This is the accessible text file for GAO report number GAO-11-406 
entitled 'Antibiotic Resistance: Data Gaps Will Remain Despite HHS 
Taking Steps to Improve Monitoring' which was released on July 1, 
2011. 

This text file was formatted by the U.S. Government Accountability 
Office (GAO) to be accessible to users with visual impairments, as 
part of a longer term project to improve GAO products' accessibility. 
Every attempt has been made to maintain the structural and data 
integrity of the original printed product. Accessibility features, 
such as text descriptions of tables, consecutively numbered footnotes 
placed at the end of the file, and the text of agency comment letters, 
are provided but may not exactly duplicate the presentation or format 
of the printed version. The portable document format (PDF) file is an 
exact electronic replica of the printed version. We welcome your 
feedback. Please E-mail your comments regarding the contents or 
accessibility features of this document to Webmaster@gao.gov. 

This is a work of the U.S. government and is not subject to copyright 
protection in the United States. It may be reproduced and distributed 
in its entirety without further permission from GAO. Because this work 
may contain copyrighted images or other material, permission from the 
copyright holder may be necessary if you wish to reproduce this 
material separately. 

United States Government Accountability Office: 
GAO: 

Report to the Committee on Agriculture, House of Representatives: 

June 2011: 

Antibiotic Resistance: 

Data Gaps Will Remain Despite HHS Taking Steps to Improve Monitoring: 

GAO-11-406: 

GAO Highlights: 

Highlights of GAO-11-406, a report to the Committee on Agriculture, 
House of Representatives. 

Why GAO Did This Study: 

Infections that were once treatable have become more difficult to 
treat because of antibiotic resistance. Resistance occurs naturally 
but is accelerated by inappropriate antibiotic use in people, among 
other things. Questions have been raised about whether agencies such 
as the Department of Health and Human Services (HHS) have adequately 
assessed the effects of antibiotic use and disposal on resistance in 
humans. GAO was asked to (1) describe federal efforts to quantify the 
amount of antibiotics produced, (2) evaluate HHSs monitoring of 
antibiotic use and efforts to promote appropriate use, (3) examine HHS
s monitoring of antibiotic-resistant infections, and (4) describe 
federal efforts to monitor antibiotic disposal and antibiotics in the 
environment, and describe research on antibiotics in the development 
of resistance in the environment. GAO reviewed documents and 
interviewed officials, conducted a literature review, and analyzed 
antibiotic sales data. 

What GAO Found: 

Federal agencies do not routinely quantify the amount of antibiotics 
that are produced in the United States for human use. However, sales 
data can be used as an estimate of production, and these show that 
over 7 million pounds of antibiotics were sold for human use in 2009. 
Most of the antibiotics that were sold have common characteristics, 
such as belonging to the same five antibiotic classes. The class of 
penicillins was the largest group of antibiotics sold for human use in 
2009, representing about 45 percent of antibiotics sold. 

HHS performs limited monitoring of antibiotic use in humans and has 
implemented efforts to promote their appropriate use, but gaps in data 
on use will remain despite efforts to improve monitoring. Although CDC 
monitors use in outpatient healthcare settings, there are gaps in data 
on inpatient antibiotic use and geographic patterns of use. CDC is 
taking steps to improve its monitoring, but gaps such as information 
about overall antibiotic use will remain. Because use contributes to 
resistance, more complete information could help policymakers 
determine what portion of antibiotic resistance is attributed to human 
antibiotic use, and set priorities for action to control the spread of 
resistance. CDCs Get Smart program promotes appropriate antibiotic 
use; CDC has observed declines in inappropriate prescribing, but it is 
unclear to what extent the declines were due to the program or to 
other factors. CDCs program has been complemented by efforts by the 
National Institutes of Health and the Food and Drug Administration, 
such as supporting studies to develop tests to quickly diagnose 
bacterial infections. 

Gaps in CDCs monitoring of antibiotic-resistant infections limit the 
agencys ability to assess the overall problem of antibiotic 
resistance. There are data gaps in monitoring of such infections that 
occur in healthcare facilities; CDC does not collect data on all types 
of resistant infections to make facilitywide estimates and the 
agencys information is not nationally representative. CDC can provide 
accurate national estimates for certain resistant infections that 
develop in the community, including tuberculosis. Although CDC is 
taking steps to improve its monitoring, these efforts will not allow 
CDC to accurately assess the overall problem of antibiotic resistance 
because they do not fill gaps in information. Without more 
comprehensive data, CDCs ability to assess the overall scope of the 
public health problem and plan and implement preventive activities 
will be impeded. 

Federal agencies do not monitor the disposal of most antibiotics 
intended for human use, but they have detected them, as well as 
antibiotics for animal use, in the environment, which results partly 
from their disposal. EPA and DOIs United States Geological Survey 
have examined the presence of certain antibiotics in environmental 
settings such as streams. Studies conducted by scientists have found 
that antibiotics present in the environment at certain concentrations 
can increase the population of resistant bacteria. 

What GAO Recommends: 

To better control the spread of resistance, GAO recommends that HHSs 
Centers for Disease Control and Prevention (CDC) develop and implement 
strategies to improve its monitoring of (1) antibiotic use and (2) 
antibiotic-resistant infections. HHS generally agreed with our 
recommendations. HHS, the Environmental Protection Agency (EPA) and 
the Department of the Interior (DOI) provided technical comments, 
which we incorporated as appropriate. 

View [hyperlink, http://www.gao.gov/products/GAO-11-406] or key 
components. For more information, contact Marcia Crosse at (202) 512-
7114 or crossem@gao.gov. 

[End of section] 

Contents: 

Letter: 

Background: 

Federal Agencies Do Not Routinely Quantify Amount of Antibiotics 
Produced for Human Use, but Sales Data Show Over 7 Million Pounds of 
Antibiotics Were Sold in 2009: 

Data Gaps Remain Despite CDC's Efforts to Expand Its Limited 
Monitoring of Antibiotic Use; CDC, NIH, and FDA Have Implemented 
Efforts to Promote Appropriate Use: 

CDC's Monitoring of Antibiotic-Resistant Infections Has Limitations in 
Assessing the Overall Problem of Antibiotic Resistance: 

Federal Agencies Do Not Monitor Antibiotic Disposal, but Have Examined 
the Presence of Antibiotics in the Environment, and Studies Find that 
Such Antibiotics Can Increase the Population of Resistant Bacteria: 

Conclusions: 

Recommendations: 

Agency Comments: 

Appendix I: Methodology for Reviewing Scientific Evidence on 
Antibiotic Resistance in the Environment: 

Appendix II: Bacteria and the Development of Antibiotic Resistance: 

Appendix III: Centers for Disease Control and Prevention's 
Surveillance Systems for Monitoring Antibiotic Resistance: 

Appendix IV: Topical Antiseptics and Antibiotic Resistance: 

Appendix V: Comments from the Department of Health and Human Services: 

Appendix VI: GAO Contact and Staff Acknowledgments: 

Tables: 

Table 1: CDC's Six Surveillance Systems that Provide Information to 
Monitor Antibiotic Resistance, by System Purpose and Infection 
Transmission Setting: 

Table 2: Amount of Antibiotics Sold in 2009 and Additional 
Information, by Antibiotic Class: 

Table 3: Amount of Antibiotics Sold in 2009, by Route of 
Administration: 

Table 4: Amount of Antibiotics Sold in 2009, by Type of Purchaser: 

Table 5: Five National Studies that Measured the Presence of 
Antibiotics in the Environment, Conducted by EPA and USGS: 

Table 6: CDC's Surveillance Systems for Monitoring Antibiotic 
Resistance, by Bacteria, Geographic Coverage, and Examples of Data Use: 

Table 7: Five National Studies that Measured the Presence of 
Antiseptic Active Ingredients in the Environment, Conducted by EPA and 
USGS: 

Abbreviations: 

ABCs: Active Bacterial Core Surveillance: 

ANDA: Abbreviated New Drug Application: 

CCL: Contaminant Candidate List: 

CDC: Centers for Disease Control and Prevention: 

CMS: Centers for Medicare & Medicaid Services: 

DOI: Department of the Interior: 

EIP: Emerging Infections Programs: 

EPA: Environmental Protection Agency: 

FDA: Food and Drug Administration: 

GISP: Gonococcal Isolate Surveillance Project: 

HAI: healthcare-associated infection: 

HHS: Department of Health and Human Services: 

MDRO: multidrug-resistant organism: 

MIC: minimum inhibitory concentration: 

MRSA: Methicillin-resistant Staphylococcus aureus: 

NAMCS: National Ambulatory Medical Care Survey: 

NARMS: EB: National Antimicrobial Resistance Monitoring System: 
Enteric Bacteria: 

NCQA: National Committee for Quality Assurance: 

NDA: New Drug Application: 

NHAMCS: National Hospital Ambulatory Medical Care Survey: 

NHSN: National Healthcare Safety Network: 

NIH: National Institutes of Health: 

NNDSS: National Notifiable Diseases Surveillance System: 

NTSS: National Tuberculosis Surveillance System: 

PhRMA: Pharmaceutical Research and Manufacturers of America: 

RCRA: Resource Conservation and Recovery Act: 

SDWA: Safe Drinking Water Act: 

TB: tuberculosis: 

UCMR: Unregulated Contaminant Monitoring Rule: 

USGS: United States Geological Survey: 

USITC: United States International Trade Commission: 

[End of section] 

United States Government Accountability Office: 
Washington, DC 20548: 

June 1, 2011: 

The Honorable Frank D. Lucas: 
Chairman: 
The Honorable Collin Peterson: 
Ranking Member: 
Committee on Agriculture: 
House of Representatives: 

Over 60 years ago penicillin was the first antibiotic introduced to 
treat bacterial infections, leading to a dramatic drop in deaths from 
bacterial infections that were previously untreatable, as well as 
significant gains in life expectancy. The eventual emergence and 
spread of bacterial infections that are resistant to antibiotics, 
however, has jeopardized these gains because infections that were once 
easy to cure with antibiotics are becoming difficult, if not 
impossible, to treat. Some bacterial infections, such as certain types 
of pneumonia and gonorrhea that are acquired in the community, have 
developed resistance to almost all currently available antibiotics. 
Furthermore, the bacterial infections that contribute most to human 
disease are also those in which antibiotic resistance is most common, 
such as respiratory tract infections and infections acquired in 
hospitals. Although not all infections acquired in hospitals are 
resistant to antibiotics, individuals with resistant infections are 
more likely to have a poor prognosis and to remain in the hospital for 
a longer time, resulting in greater medical costs.[Footnote 1] 

While the development of antibiotic resistance is not new, as 
resistance is a natural biological phenomenon and can occur when any 
antibiotic is present, it is accelerated by a variety of factors 
including the inappropriate use of antibiotics in the absence of a 
bacterial infection and the prolonged use of antibiotics to treat 
patients who are critically ill. Antibiotic-resistant bacteria that 
are present in the human body can be spread to others. In addition, 
antibiotic-resistant bacteria that occur in the environment, either 
from natural causes or their discharge into soil or bodies of water, 
may spread their resistance to other bacteria. 

Scientists, public health officials, and clinicians agree that 
antibiotic resistance has become a national and global health 
challenge. While there are various causes of antibiotic resistance-- 
including the use of antibiotics in humans and animals--the actual 
scope of the overall problem is not clear and there is uncertainty 
about the relative contributions of each cause.[Footnote 2] 
Recommendations for government action to address antibiotic resistance 
have been made by various organizations and scientific experts, 
including a task force made up of federal agencies, and there is 
agreement that, among other things, improved surveillance of 
antibiotic use and antibiotic-resistant infections is needed to 
adequately understand antibiotic resistance and implement effective 
strategies to help control this complex problem.[Footnote 3] Further, 
a congressional committee[Footnote 4] and others have made 
recommendations to increase the geographic coverage of existing 
federal agency surveillance to address concerns such as gaps in the 
ability to track and monitor certain antibiotic-resistant infections, 
such as methicillin-resistant Staphylococcus aureus (MRSA). 

Questions have been raised as to whether federal agencies, including 
the Department of Health and Human Services (HHS), have adequately 
assessed the relationship among the volume of antibiotics produced for 
human use, the human use of antibiotics, the presence of antibiotics 
in the environment, and the problem of antibiotic resistance. The 
House Committee on Agriculture asked us to evaluate how federal 
agencies track the occurrence of antibiotic resistance and the use and 
disposal of antibiotics into the environment. In this report, we (1) 
describe efforts by federal agencies to quantify the amount of 
antibiotics produced for human use, (2) describe and evaluate HHS 
efforts to monitor antibiotic use and promote the appropriate use of 
antibiotics by humans, (3) examine HHS efforts to monitor cases of 
antibiotic-resistant infections in humans in the United States, and 
(4) describe federal efforts to monitor the disposal of antibiotics 
intended for human use, federal efforts to monitor the presence of 
antibiotics in the environment, and the scientific evidence regarding 
the role of antibiotics in the development of antibiotic-resistant 
bacteria in the environment. 

To describe efforts to quantify the amount of antibiotics produced for 
human use by federal agencies, we interviewed HHS officials to 
determine whether HHS collects information about, and quantifies, the 
amount of antibiotics that are produced for human use. We also 
reviewed documents from HHS and the U.S. International Trade 
Commission (USITC)--a federal agency that collects and analyzes trade 
data to inform U.S. trade policy--to learn about federal efforts to 
quantify antibiotic production in the United States. We purchased 2009 
national sales data for antibiotics from IMS Health to estimate the 
volume of antibiotics produced in the United States for human use. 
[Footnote 5] IMS Health provided us the total volume of antibiotics, 
in kilograms, that were sold, based on all antibiotic drugs that were 
included in the Red Book Advanced database, as of April 2010.[Footnote 
6] We converted the total volume from kilograms to pounds. To further 
describe the antibiotics that were sold in 2009, we classified the 
total volume of antibiotics by antibiotic class, the route of 
administration (e.g., oral), and the types of pharmacies that 
purchased antibiotics (e.g., chain store pharmacy). To assess the 
reliability of IMS Health data, we reviewed existing information about 
the data and interviewed officials knowledgeable about the data to 
assess their completeness.[Footnote 7] We determined that the data 
were sufficiently reliable for their use in this report. 

To describe HHS efforts to monitor the use of antibiotics in humans, 
we reviewed HHS documents and interviewed HHS officials. We reviewed 
HHS documents describing the various surveys that HHS uses to 
routinely collect data about antibiotic use, including information 
about the survey samples, the types of data that are gathered, and how 
antibiotic use is measured. We also reviewed agency documents that 
summarize trends in antibiotic use, based on the surveys. We 
interviewed HHS officials with responsibility for the surveys about 
the strengths and limitations of each survey and how the agency uses 
the collected data to monitor antibiotic use. To evaluate HHS's 
efforts to monitor antibiotic use, we compared HHS's data collection 
and monitoring activities with broad guidelines for monitoring 
antibiotic use, which we identified by reviewing relevant HHS 
documents and expert organization (e.g., World Health Organization) 
guidelines. To describe HHS efforts to promote the appropriate use of 
antibiotics, we reviewed documents from HHS about programs and 
activities focused specifically on decreasing inappropriate antibiotic 
use. We also interviewed officials from HHS about the objectives and 
implementation of these programs and activities. To evaluate HHS's 
efforts to promote the appropriate use of antibiotics, we reviewed 
relevant HHS documents and research articles in peer-reviewed journals 
about the effectiveness of intervention programs to reduce 
inappropriate antibiotic use and we interviewed HHS officials about 
the strengths and limitations of its program to promote appropriate 
antibiotic use and how the agency has evaluated its program. 

To examine HHS efforts to monitor cases of antibiotic-resistant 
infections in humans, we reviewed agency documents from HHS and 
interviewed HHS officials and representatives from an HHS advisory 
committee on healthcare infection control. We reviewed HHS documents 
describing each of the agency's surveillance systems that are used to 
monitor antibiotic resistance. The documents described the purpose and 
objectives of each system, and what surveillance data are collected 
and how the data are collected; the documents also provided annual 
summary information about monitored infections. We interviewed HHS 
officials with responsibility for each of the surveillance systems 
about the strengths and limitations of each system and how the data 
gathered by each system are used by the agency. We also interviewed 
four members of a federal advisory committee that provides guidance to 
HHS regarding infection control, surveillance, and prevention, as well 
as officials from three organizations that serve as liaisons to the 
committee, to obtain their opinions of the strengths and limitations 
of HHS's surveillance systems.[Footnote 8] 

To describe federal efforts to monitor the disposal of antibiotics 
intended for human use, we interviewed officials from the 
Environmental Protection Agency (EPA), HHS, and the Department of the 
Interior's (DOI) United States Geological Survey (USGS) to determine 
if these agencies collect data about the disposal of antibiotics and, 
if applicable, how they use such data for monitoring. We also reviewed 
relevant federal laws under which EPA may have responsibility to 
regulate disposal of certain antibiotics and to monitor certain 
antibiotics in drinking water, as well as a Food and Drug 
Administration (FDA) consumer guidance document describing recommended 
disposal practices for unused drugs. We interviewed officials from the 
Pharmaceutical Research and Manufacturers of America (PhRMA) to learn 
about the drug disposal practices that are commonly used by 
pharmaceutical manufacturers.[Footnote 9] To describe federal efforts 
to monitor the presence of antibiotics found in the environment, we 
reviewed documents describing relevant studies conducted by EPA and 
USGS, including methods for selecting study sample sites and the study 
findings. We focused on the extent to which antibiotics were present 
in environmental settings, including soil, sediment, and bodies of 
water, and in certain pathways to the environment, such as waste water 
in treatment plants. We interviewed EPA and USGS officials to obtain 
background information and context about the studies as well as EPA's 
use of the study findings. We also interviewed EPA and USGS officials 
about their plans for further related studies. 

To describe the scientific evidence regarding the role of antibiotics 
in the development of antibiotic-resistant bacteria in the 
environment, we conducted a literature review and interviewed agency 
officials. Our literature review included 105 articles that met 
defined search criteria on antibiotic resistance in the environment, 
published on or between January 1, 2007, and July 8, 2010. The 
articles included those published in peer-reviewed journals. In our 
review, we analyzed the scientific findings reported about antibiotic 
concentrations that induce environmental bacteria to become resistant 
and the ability of environmental bacteria to spread resistance through 
the transfer of resistance genes. We also interviewed EPA and USGS 
agency officials to obtain context for the scientific evidence 
presented in the articles. For a detailed description of our 
literature review, see appendix I. 

We conducted our performance audit from March 2010 to June 2011 in 
accordance with generally accepted government auditing standards. 
Those standards require that we plan and perform the audit to obtain 
sufficient, appropriate evidence to provide a reasonable basis for our 
findings and conclusions based on our audit objectives. We believe 
that the evidence obtained provides a reasonable basis for our 
findings and conclusions based on our audit objectives. 

Background: 

Antibiotics and the Development and Spread of Antibiotic-resistant 
Bacteria: 

Antibiotics are drugs that are used to treat bacterial infections. 
[Footnote 10] Antibiotics work by killing or slowing the growth of 
bacteria and they are not effective against nonbacterial infections, 
such as those caused by viruses. Antibiotic resistance is the result 
of bacteria changing in ways that reduce or eliminate the 
effectiveness of antibiotics to cure infection. Antibiotic use forces 
bacteria to either adapt or die in a process known as "selective 
pressure." Selective pressure means that when an antibiotic is used, 
some bacteria will be killed by the antibiotic while other bacteria 
will survive. Bacteria are able to survive, in part, because they have 
certain genetic material that allows them to avoid the effects of the 
antibiotic. The surviving bacteria will multiply and pass on to future 
generations their genetic material that is coded for resistance to 
antibiotics. Any use of antibiotics--appropriate and inappropriate-- 
creates selective pressure among bacteria. (For more information on 
resistant bacteria, see appendix II). 

The inappropriate use of antibiotics, or the additional use of 
antibiotics that could have been avoided, can occur when healthcare 
providers prescribe antibiotics when they are not beneficial, such as 
to treat a viral infection, or when antibiotic treatments are not 
targeted to the specific bacteria causing the infection.[Footnote 11] 
Inappropriate antibiotic use also occurs when healthcare providers do 
not prescribe the correct antibiotic dose and duration of treatment. 
Further, inappropriate use includes when patients do not complete a 
full course of prescribed antibiotics. 

Antibiotic Disposal and Pathways for Antibiotics to Enter the 
Environment: 

Individual consumers, health care facilities, pharmacies, and 
pharmaceutical manufacturers dispose of unused antibiotics using 
various methods. For the purposes of this report, the disposal of 
antibiotics refers to the discard of unused antibiotics by consumers, 
companies, and others. Common disposal methods for individual 
consumers include throwing unused antibiotics in the trash, flushing 
them down the toilet, and pouring them down the drain.[Footnote 12] 
According to EPA officials, healthcare facilities and pharmacies often 
return unused or expired drugs to contracted companies, known as 
reverse distributors, for manufacturer credit. The reverse distributor 
is then instructed by the manufacturer to return the unused drug to 
the manufacturer, or in most cases, the reverse distributor is 
instructed to dispose of the drugs. The unused drugs are then most 
likely incinerated as solid waste, subject to state and local 
environmental regulations. The federal guidelines on how consumers 
should properly dispose of their unused drugs, including antibiotics, 
recommend that consumers dispose of their unused drugs either by 
returning them through a drug take-back program, where available, or 
by mixing them with coffee grounds or kitty litter and throwing them 
in the household trash.[Footnote 13] 

Unused antibiotics intended for human use may enter the environment 
through various pathways such as sewage systems and landfills, 
depending upon the method of disposal and other factors. Unused 
antibiotics enter sewage systems after they are flushed down the 
toilet or poured down the drain. Unused antibiotics that enter the 
sewage system then flow to wastewater treatment plants where, if not 
removed during the treatment process, they are released into the 
environment, such as in rivers and streams, as wastewater effluent. 
[Footnote 14] In addition, some areas may use onsite septic systems to 
treat wastewater and in these systems wastewater is discharged below 
the ground's surface.[Footnote 15] Unused antibiotics that are 
disposed of in the trash could enter the environment if landfills were 
to leak. Although modern landfills are designed with liners and 
systems to limit this process by rerouting leachate, that is, liquid 
generated in landfills, to wastewater treatment plants, the 
antibiotics that are contained in the leachate may ultimately enter 
the environment. This can occur if antibiotics are not removed during 
the wastewater treatment process. In general, wastewater treatment 
plants are not designed to remove low concentrations of drug 
contaminants, such as antibiotics.[Footnote 16],[Footnote 17] 

In addition, antibiotics that have been used by humans to treat 
infections can also enter the environment. Most used antibiotics enter 
the sewage systems after they are ingested and excreted by individuals 
because antibiotics are not fully absorbed by the human body.[Footnote 
18] Like unused antibiotics that enter the sewage systems, used 
antibiotics flow from sewage systems to wastewater treatment plants 
and may be released into the environment as wastewater effluent or 
biosolids. Agricultural manure is another potential source of 
antibiotics entering the environment; some antibiotics used for 
agriculture are similar to those used by humans.[Footnote 19] 

Federal Agency Responsibilities: 

Within HHS, the Centers for Disease Control and Prevention (CDC), FDA, 
and the National Institutes of Health (NIH) have responsibilities for 
protecting Americans from health risk, including risk associated with 
antibiotic-resistant infections. These agencies have a variety of 
responsibilities related to the surveillance, prevention, and research 
of infectious disease. CDC has a primary responsibility to protect the 
public health through the prevention of disease and health promotion. 
One of CDC's primary roles is to monitor health, and part of this role 
involves monitoring antibiotic-resistant infections and the use of 
antibiotics. CDC's statutory authority to conduct such surveillance 
derives from the Public Health Service Act.[Footnote 20] Tracking the 
emergence of antibiotic resistance, and limiting its spread, is also 
part of CDC's mission. Consistent with this mission, CDC implements 
prevention strategies, such as educational programs, that are designed 
to limit the development and spread of antibiotic resistance and the 
agency monitors antibiotic prescriptions in humans to help reduce the 
spread of antibiotic resistance. 

Part of FDA's responsibility for protecting the public health involves 
assuring the safety and efficacy of human drugs. FDA reviews and 
approves labels for antibiotics and provides educational information 
to consumers and healthcare providers about the appropriate use of 
antibiotics, and the risk of the development of antibiotic resistance 
associated with their inappropriate use. FDA also licenses vaccines 
for use in humans to prevent bacterial infections--including certain 
antibiotic-resistant infections--as well as viral infections and has 
the authority for the review of diagnostics, including tests to detect 
bacterial infections. As the nation's medical research agency, NIH is 
responsible for conducting and funding medical research to improve 
human health and save lives. According to its research agenda on 
antibiotic resistance, NIH supports and conducts research on many 
aspects of antibiotic resistance, including studies of how bacteria 
develop resistance, the development of diagnostic tests for bacterial 
infections that are or are likely to become resistant to antibiotics, 
as well as clinical trials such as those to study the effective 
duration for antibiotic treatments. 

CDC, FDA, and NIH are also co-chairs of the Interagency Task Force on 
Antimicrobial Resistance (Task Force)[Footnote 21] and released A 
Public Health Action Plan to Combat Antimicrobial Resistance (Action 
Plan) in 2001.[Footnote 22] The Action Plan identified actions needed 
to address the emerging threat of antibiotic resistance and 
highlighted the need to improve federal agencies' ongoing monitoring 
of antibiotic use and of antibiotic-resistant infections. 
Specifically, the Action Plan stated that establishing a national 
surveillance plan for antibiotic-resistant infections should be a high 
priority, and that improved monitoring of such infections was needed 
to identify emerging trends and assess changing patterns of antibiotic 
resistance as well as to target and evaluate prevention and control 
efforts. The Action Plan also specifically stated that surveillance of 
antibiotic use in humans should be a high priority and was needed to 
better understand the relationship between antibiotic use and 
antibiotic resistance. For example, identifying a specific pattern of 
antibiotic use associated with increased antibiotic resistance could 
support a response from policymakers, such as to affect change in 
antibiotic use practices. Further, improved antibiotic use monitoring 
would help identify prevention activities and anticipate gaps in the 
availability of existing antibiotics effective in treating bacterial 
infections. A revised draft Action Plan was published for public 
comment on March 16, 2011.[Footnote 23] 

EPA's mission includes protecting Americans from significant 
environmental health risks. As part of its role, EPA sets national 
standards for the disposal of solid and hazardous waste and the 
quality of drinking water. EPA generally regulates the disposal of 
waste, including some unused or expired drugs, under the Resource 
Conservation and Recovery Act (RCRA).[Footnote 24] EPA also 
promulgates national requirements for drinking water quality of public 
water systems under the Safe Drinking Water Act (SDWA). EPA conducts 
research on topics related to human health and the environment, 
including research aimed at understanding drug disposal practices and 
the potential human and ecological health risks of drugs, such as 
antibiotics, found in the environment. 

Within DOI, USGS is responsible for providing scientific information 
to better understand the health of the environment, including our 
water resources. USGS conducts large-scale studies to gather 
information that can provide a basis for evaluating the effectiveness 
of specific policies; these studies can also be used to support 
decision making at the local and national levels--for example, 
decisions related to protecting water quality. In 1998, USGS initiated 
the Emerging Contaminants Project to improve the scientific 
understanding of the release of emerging contaminants to the 
environment, including where these contaminants originate and whether 
they have adverse effects on the environment. As part of the project, 
USGS has conducted national studies to measure the presence of 
unregulated contaminants, including antibiotics, in the environment, 
and conducts targeted local studies to assess the impact of specific 
pathways by which antibiotics can enter the environment. 

CDC's Monitoring of Antibiotic Resistance in Healthcare and Community 
Settings: 

CDC has six surveillance systems that provide information to monitor 
antibiotic resistance that occurs in healthcare and community 
settings. According to CDC, public health surveillance is the ongoing 
and systematic collection, analysis, and interpretation of data for 
use in the planning, implementation, and evaluation of public health 
practice.[Footnote 25] The surveillance systems collect information 
about antibiotic resistance among certain bacteria that cause 
infections in humans, and the infections are transmitted either in 
healthcare settings or in the community. For example, CDC's National 
Healthcare Safety Network (NHSN) monitors infections that occur in 
healthcare settings, including those that are resistant to 
antibiotics, such as MRSA, while CDC's Active Bacterial Core 
Surveillance (ABCs) system monitors bacterial infections such as 
meningitis and pneumonia that are spread in the community or in 
healthcare settings.[Footnote 26] Table 1 provides information about 
the purpose of each CDC surveillance system that monitors antibiotic 
resistance and summarizes the settings in which the monitored 
infections are spread. (See appendix III for additional information 
about each of the six systems.) 

Table 1: CDC's Six Surveillance Systems that Provide Information to 
Monitor Antibiotic Resistance, by System Purpose and Infection 
Transmission Setting: 

Surveillance system: National Healthcare Safety Network (NHSN); 
Purpose of surveillance system and role in monitoring antibiotic 
resistance: To provide a database for healthcare facilities to report 
their healthcare-associated infection (HAI) and antibiotic resistance 
surveillance data to allow them to estimate the occurrence of such 
events, monitor trends, and identify patient safety problems.[A] CDC 
compiles data on antibiotic resistance across participating facilities; 
Infection transmission setting: Spread in healthcare settings, such as 
from healthcare personnel to patient or from patient to patient. 

Surveillance system: Active Bacterial Core Surveillance (ABCs) [of the 
Emerging Infections Programs (EIP) Network][B]; 
Purpose of surveillance system and role in monitoring antibiotic 
resistance: To monitor trends in disease and deaths caused by invasive 
bacterial infections of public health importance, such as meningitis 
caused by Neisseria meningitidis. ABCs is also used to monitor trends 
in antibiotic resistance, track new resistance mechanisms, and 
evaluate the effect of public health interventions; 
Infection transmission setting: Spread in the community, from person 
to person (e.g., by exchange of respiratory secretions), or in 
healthcare settings, such as from healthcare personnel to patient or 
from patient to patient. 

Surveillance system: National Antimicrobial Resistance Monitoring 
System: Enteric Bacteria (NARMS: EB); 
Purpose of surveillance system and role in monitoring antibiotic 
resistance: To monitor trends in antibiotic resistance among enteric 
bacteria from humans and to conduct research to better understand the 
emergence, persistence, and spread of antibiotic resistance.[C] NARMS: 
EB is also used to provide data to assist FDA in making decisions 
related to the approval of safe and effective antibiotic drugs for 
animals and to promote interventions to reduce resistance; 
Infection transmission setting: Spread in the community and in other 
settings, such as through eating food contaminated with fecal matter 
or eating undercooked poultry. 

Surveillance system: Gonococcal Isolate Surveillance Project (GISP); 
Purpose of surveillance system and role in monitoring antibiotic 
resistance: To monitor trends in antibiotic resistance in Neisseria 
gonorrhoeae--the bacterium that causes gonorrhea--in order to 
establish a basis for selecting treatment guidelines for gonorrhea; 
Infection transmission setting: Spread in the community, from person 
to person, through sexual contact. 

Surveillance system: National Tuberculosis Surveillance System (NTSS); 
Purpose of surveillance system and role in monitoring antibiotic 
resistance: To monitor national trends in tuberculosis (TB), including 
groups at risk for TB, and to evaluate outcomes of TB cases. CDC also 
uses NTSS to monitor antibiotic resistance in Mycobacterium 
tuberculosis--the bacterium that causes tuberculosis; 
Infection transmission setting: Spread in the community, from person 
to person, by breathing infected air during close contact. 

Surveillance system: National Notifiable Diseases Surveillance System 
(NNDSS); 
Purpose of surveillance system and role in monitoring antibiotic 
resistance: To monitor certain infectious diseases, such as human 
immunodeficiency virus infection and measles. CDC also uses NNDSS to 
monitor antibiotic resistance in the bacteria Streptococcus 
pneumoniae, with a focus on assessing the impact of immunization 
against invasive Streptococcus pneumoniae infection. Streptococcus 
pneumoniae causes infections such as pneumonia and meningitis; 
Infection transmission setting: Spread in the community, from person 
to person, such as by exchange of respiratory secretions. 

Source: GAO analysis of CDC information and scientific literature. 

[A] NHSN also allows facilities to report on 'laboratory-identified' 
event surveillance data for certain HAIs that are resistant to 
multiple drugs--such as multidrug-resistant Klebsiella infections--as 
well as Clostridium difficile infections; such data are more easily 
obtained because they come primarily from laboratory test results 
without clinical evaluation of patients. Clostridium difficile 
infections may develop due to the prolonged use of antibiotics during 
healthcare treatment. 

[B] As part of EIP's Healthcare Associated Infections Surveillance, 
CDC has monitored Clostridium difficile infections in healthcare and 
community settings since 2009. 

[C] FDA coordinates the NARMS program and works with CDC to manage 
NARMS: EB, the human component of the program. FDA and the United 
States Department of Agriculture test for antibiotic-resistant enteric 
bacteria in retail meats and food animals, respectively. Enteric 
bacteria are found in the intestinal tracts of humans and animals. 

[End of table] 

Federal Agencies Do Not Routinely Quantify Amount of Antibiotics 
Produced for Human Use, but Sales Data Show Over 7 Million Pounds of 
Antibiotics Were Sold in 2009: 

Federal agencies do not routinely quantify the amount of antibiotics 
that are produced in the United States for human use, but sales data, 
which can be used to estimate the quantity of antibiotic production, 
show that over 7 million pounds of antibiotics were sold in 2009 for 
human use in the United States. These data indicate that most of the 
antibiotics sold have common characteristics, such as belonging to 
five antibiotic classes. 

Federal Agencies Do Not Routinely Quantify the Amount of Antibiotics 
Produced for Human Use: 

Federal agencies, including FDA and USITC, do not routinely quantify 
antibiotic production for human use.[Footnote 27] FDA does collect 
annual information on the quantity of drugs that manufacturers 
distribute from new drug application (NDA) and abbreviated new drug 
application (ANDA) holders, but the data are not readily accessible. 
[Footnote 28] For each approved drug, NDA and ANDA holders are 
required to report annually to FDA the total number of dosage units of 
each strength or potency of the drug that was distributed (e.g., 
100,000 5 milligram tablets) for domestic and foreign use.[Footnote 
29] This information must be submitted to FDA each year--within 60 
days of the anniversary date of approval of the drug application--for 
as long as the NDA or ANDA is active. The data that NDA and ANDA 
holders submit to FDA on the quantity of distributed drugs are not 
readily accessible because, according to an FDA official, they are 
submitted as part of an annual report in the form of a table and the 
agency does not enter the data electronically. In addition, because 
the anniversary dates of approval vary by NDA and ANDA, the reporting 
periods are not comparable. For drugs with an active ingredient for 
which there are multiple NDA and ANDA applications, FDA officials 
stated that one would also need to aggregate the data across multiple 
applications in order to determine the total quantity of the 
particular active ingredient. An FDA official told us that the agency 
rarely uses these data for analyses of drug utilization, drug safety, 
and drug shortages because other sources of data provide FDA 
information that is more detailed and timely about the quantities of 
certain drugs that are available in the market. For example, FDA uses 
drug sales data, which are available on a monthly basis, to evaluate 
and address drug safety and drug shortage problems.[Footnote 30] USITC 
no longer collects and quantifies antibiotic production, but did so 
until 1994.[Footnote 31] 

Over 7 Million Pounds of Antibiotics Were Sold in 2009 for Human Use 
and Most Antibiotics Sold Share Common Characteristics: 

Most of the 7.4 Million Pounds of Antibiotics Sold Fell into Five 
Antibiotic Classes: 

In 2009, approximately 7.4 million pounds of antibiotics were sold for 
human use--which can be used as an estimate of the quantity of 
antibiotics produced for human use in the United States--and most sold 
share common characteristics, such as antibiotic classes. Most of the 
7.4 million pounds, or about 89 percent, of antibiotics that were sold 
in 2009 fell into five antibiotic classes: penicillins, cephems, 
folate pathway inhibitors, quinolones, and macrolides (see table 2). 
The class of penicillins was the largest group of antibiotics sold in 
2009.[Footnote 32] About 3.3 million pounds of penicillins were sold, 
which represents 45.2 percent of all antibiotics sold in 2009. 
Penicillins, such as amoxicillin, are used to treat bacterial 
infections that include pneumonia and urinary tract infections. 

Table 2: Amount of Antibiotics Sold in 2009 and Additional 
Information, by Antibiotic Class: 

Antibiotic class: Penicillins; 
Amount sold (in pounds): 3,336,890; 
Amount sold (in kilograms): 1,516,768; 
Percentage of total antibiotics sold: 45.2; 
Examples of drugs within antibiotic class: Penicillin, Amoxicillin, 
Oxacillin, Piperacillin; 
Examples of bacterial infections treated by some drugs within 
antibiotic class: Group A Streptococcal infections, some pneumonia 
infections caused by Streptococcus pneumoniae, bacterial ear 
infections, some urinary tract infections caused by Escherichia coli, 
and some Staphylococcus aureus infections. 

Antibiotic class: Cephems; 
Amount sold (in pounds): 1,094,681; 
Amount sold (in kilograms): 497,582; 
Percentage of total antibiotics sold: 14.8; 
Examples of drugs within antibiotic class: Cephalexin, Cefuroxime, 
Cefotetan, Cefixime, Ceftriaxone; 
Examples of bacterial infections treated by some drugs within 
antibiotic class: Skin infections, respiratory tract infections, intra-
abdominal infections, gonorrhea, and bacterial meningitis. 

Antibiotic class: Folate Pathway Inhibitors; 
Amount sold (in pounds): 1,064,456; 
Amount sold (in kilograms): 483,843; 
Percentage of total antibiotics sold: 14.4; 
Examples of drugs within antibiotic class: Sulfonamides, Trimethoprim-
Sulfamethoxazole; 
Examples of bacterial infections treated by some drugs within 
antibiotic class: Urinary tract infections and other types of 
infections. 

Antibiotic class: Quinolones; 
Amount sold (in pounds): 664,894; 
Amount sold (in kilograms): 302,225; 
Percentage of total antibiotics sold: 9.0; 
Examples of drugs within antibiotic class: Ciprofloxacin, Levofloxacin; 
Examples of bacterial infections treated by some drugs within 
antibiotic class: Urinary tract infections, respiratory tract 
infections, and other infections. 

Antibiotic class: Macrolides; 
Amount sold (in pounds): 382,139; 
Amount sold (in kilograms): 173,700; 
Percentage of total antibiotics sold: 5.2; 
Examples of drugs within antibiotic class: Erythromycin, Azithromycin; 
Examples of bacterial infections treated by some drugs within 
antibiotic class: Some respiratory tract infections. 

Antibiotic class: Other; 
Amount sold (in pounds): 844,467; 
Amount sold (in kilograms): 383,849; 
Percentage of total antibiotics sold: 11.4; 
Examples of drugs within antibiotic class: Tetracyclines, 
Oxazolidinones, Aminoglycosides, and other classes; 
Examples of bacterial infections treated by some drugs within 
antibiotic class: Skin infections and other infections. 

Antibiotic class: Total; 
Amount sold (in pounds): 7,387,527; 
Amount sold (in kilograms): 3,357,967; 
Percentage of total antibiotics sold: 100.0; 
Examples of drugs within antibiotic class: [Empty]; 
Examples of bacterial infections treated by some drugs within 
antibiotic class: [Empty]. 

Source: GAO analysis of IMS Health data and summary of CDC and NIH 
information. 

Notes: Classes are identified according to the Clinical and Laboratory 
Standards Institute classification system. According to this 
classification system, certain antibiotic classes can be further 
classified into subclasses. For example, the cephem class includes the 
subclass of cephalosporins. The total amount of antibiotics sold does 
not take into account the dose, which varies by individual antibiotic, 
or the total number of individuals who were prescribed or treated with 
antibiotics. 

[End of table] 

The Majority of Antibiotics Sold for Human Use in 2009 Were for Oral 
Administration and for Use in Outpatient Settings: 

Most of the antibiotics that were sold for human use in 2009 were for 
oral administration and for use in outpatient settings. As shown in 
table 3, about 6.5 million pounds, or 87.4 percent, of all antibiotics 
sold for human use in 2009 were intended for oral administration, for 
example, in the form of pills.[Footnote 33] Oral forms of antibiotics 
and injectable forms, such as intravenous injections, together 
accounted for 99 percent of the total pounds sold. 

Table 3: Amount of Antibiotics Sold in 2009, by Route of 
Administration: 

Route of administration: Oral; 
Amount sold (in pounds): 6,454,670; 
Amount sold (in kilograms): 2,933,941; 
Percentage of total antibiotics sold: 87.4%. 

Route of administration: Injection; 
Amount sold (in pounds): 854,281; 
Amount sold (in kilograms): 388,310; 
Percentage of total antibiotics sold: 11.6%. 

Route of administration: Other[A]; 
Amount sold (in pounds): 78,576; 
Amount sold (in kilograms): 35,717; 
Percentage of total antibiotics sold: 1.1%. 

Route of administration: Total; 
Amount sold (in pounds): 7,387,527; 
Amount sold (in kilograms): 3,357,967; 
Percentage of total antibiotics sold: 100.0%. 

Source: GAO analysis of IMS Health data. 

Note: Individual entries may not sum to totals because of rounding. 

[A] Examples of other routes include administration by ear drops or 
inhalation. 

[End of table] 

About 5.8 million pounds, or 78.6 percent, of all antibiotics sold for 
human use in 2009 were purchased by chain store pharmacies, 
independent pharmacies, food store pharmacies, and clinics (see table 
4). This suggests that most of the antibiotics that were purchased in 
2009 were intended for use in outpatient settings. 

Table 4: Amount of Antibiotics Sold in 2009, by Type of Purchaser: 

Type of purchaser: Chain store pharmacies[A]; 
Amount sold (in pounds): 3,906,132; 
Amount sold (in kilograms): 1,775,515; 
Percentage of total antibiotics sold: 52.9%. 

Type of purchaser: Independent pharmacies[B]; 
Amount sold (in pounds): 923,770; 
Amount sold (in kilograms): 419,896; 
Percentage of total antibiotics sold: 12.5%. 

Type of purchaser: Nonfederal hospitals; 
Amount sold (in pounds): 852,247; 
Amount sold (in kilograms): 387,385; 
Percentage of total antibiotics sold: 11.5%. 

Type of purchaser: Food store pharmacies[C]; 
Amount sold (in pounds): 745,526; 
Amount sold (in kilograms): 338,876; 
Percentage of total antibiotics sold: 10.1%. 

Type of purchaser: Clinics; 
Amount sold (in pounds): 232,672; 
Amount sold (in kilograms): 105,760; 
Percentage of total antibiotics sold: 3.1%. 

Type of purchaser: Long-term care facilities; 
Amount sold (in pounds): 228,662; 
Amount sold (in kilograms): 103,937; 
Percentage of total antibiotics sold: 3.1%. 

Type of purchaser: Federal facilities[D]; 
Amount sold (in pounds): 219,533; 
Amount sold (in kilograms): 99,788; 
Percentage of total antibiotics sold: 3.0%. 

Type of purchaser: Other[E]; 
Amount sold (in pounds): 278,984; 
Amount sold (in kilograms): 126,811; 
Percentage of total antibiotics sold: 3.8%. 

Type of purchaser: Total; 
Amount sold (in pounds): 7,387,527; 
Amount sold (in kilograms): 3,357,967; 
Percentage of total antibiotics sold: 100.0%. 

Source: GAO analysis of IMS Health data. 

[A] Chain store pharmacies include businesses that consist of four or 
more stores with the same name that are owned and operated by the same 
organization. 

[B] Independent pharmacies are privately owned pharmacies that operate 
fewer than four stores. 

[C] Food store pharmacies include pharmacies that are located in 
grocery stores. 

[D] Federal facilities include, for example, Department of Veterans 
Affairs hospitals and public health outpatient facilities. 

[E] Other includes mail order pharmacies and pharmacies located in 
such entities as health maintenance organizations and prisons. 

[End of table] 

Data Gaps Remain Despite CDC's Efforts to Expand Its Limited 
Monitoring of Antibiotic Use; CDC, NIH, and FDA Have Implemented 
Efforts to Promote Appropriate Use: 

Although CDC annually collects certain national data on antibiotic 
prescriptions to monitor the use of antibiotics, these data have 
limitations and do not allow for important analyses. CDC is taking 
steps to improve its monitoring of antibiotic use by collecting and 
purchasing additional data, but gaps in information will remain. CDC's 
Get Smart program promotes the appropriate use of antibiotics and the 
agency has observed recent national declines in inappropriate 
antibiotic prescribing; however, it is unclear to what extent its 
program contributed to the recent declines. NIH and FDA activities 
have complemented CDC's efforts to promote the appropriate use of 
antibiotics. 

CDC Annually Collects Certain National Data on Antibiotic 
Prescriptions to Monitor Antibiotic Use, but Data Do Not Allow for 
Important Analyses: 

CDC conducts two national health care surveys that gather data, 
annually, on antibiotic prescribing in outpatient settings--the 
National Ambulatory Medical Care Survey (NAMCS) and the National 
Hospital Ambulatory Medical Care Survey (NHAMCS).[Footnote 34] NAMCS 
is based on a sample of visits to office-based physicians and 
community health centers.[Footnote 35] NHAMCS is based on a sample of 
visits to emergency and outpatient departments and hospital-based 
ambulatory surgery locations.[Footnote 36],[Footnote 37] Both surveys 
obtain data from healthcare provider records on patient symptoms, 
provider diagnoses, and the names of specific drugs, including 
antibiotics, that were prescribed during the patient visits.[Footnote 
38] CDC officials stated that, among their purposes, CDC uses NAMCS 
and NHAMCS to monitor antibiotic use in outpatient settings for 
patient conditions that do not usually require antibiotics for 
treatment, such as antibiotic prescribing rates for upper respiratory 
infections, such as the common cold. 

NAMCS and NHAMCS are limited because they do not capture information 
about the use of antibiotics in inpatient settings. In inpatient 
settings, such as hospitals, antibiotics are often used, multiple 
antibiotics may be used in the same patient, and use may be prolonged. 
Monitoring overall antibiotic use (i.e., in inpatient and outpatient 
settings) over time is important for understanding patterns in 
antibiotic resistance. Information about overall antibiotic use in 
humans is also needed to routinely assess the contribution that human 
antibiotic use makes to the overall problem of antibiotic resistance 
in humans, relative to other contributing factors. For example, 
monitoring what portion of antibiotic use is attributed to humans 
versus animals is important to understanding antibiotic resistance. 
CDC officials told us that more complete information about antibiotic 
use by humans and animals is needed to help interpret trends from 
surveillance data and to inform on possible strategies to control the 
spread of antibiotic resistance, such as through changing antibiotic 
use practices. 

NAMCS and NHAMCS data are further limited because they do not allow 
the agency to assess geographic patterns in antibiotic prescribing 
practices in outpatient settings. CDC officials told us that the 
survey samples were designed to obtain national, not state-level 
estimates. As a result, CDC cannot currently assess the potential 
effects of geographic variation at the state level in antibiotic 
prescribing rates on patterns of antibiotic resistance or identify 
states or other geographic areas in the United States, for instance, 
which have higher than average antibiotic prescribing for conditions 
that do not usually require antibiotics for treatment. Information 
about geographic variation in antibiotic prescribing would allow CDC 
to anticipate future patterns in antibiotic resistance, given that the 
use of antibiotics has a direct effect on antibiotic resistance. Such 
information, according to CDC officials, would also allow CDC to 
target prevention efforts, such as those aimed at reducing 
inappropriate antibiotic use. 

CDC Is Taking Steps to Improve Its Monitoring of Antibiotic Use in 
Outpatient and Inpatient Settings, but Gaps in Information Will Remain: 

CDC is taking steps to improve its monitoring of antibiotic use, but 
gaps in information about the use of antibiotics will remain. To 
address the agency's lack of data on inpatient antibiotic use, CDC is 
planning to gather information on antibiotic use with a prevalence 
survey of U.S. acute care hospitals in 2011.[Footnote 39] The survey 
will be conducted during a single time period on a single day and will 
collect some patient information about the reasons for the antibiotic 
use, which include treating an active infection or using antibiotics 
to prevent infection associated with a medical or surgical procedure. 
[Footnote 40] According to CDC officials, these data will fill in the 
gap in its data by providing information about the prevalence of 
inpatient antibiotic use. CDC officials further stated that having 
data on the baseline amount of inpatient antibiotic use, and the 
reasons for that use, will allow the agency to target and evaluate its 
own prevention efforts.[Footnote 41] However, the survey findings will 
not be representative of hospitals nationwide, because the survey 
sample is limited to selected hospitals located within five entire 
states and urban areas in five other states.[Footnote 42] Furthermore, 
CDC officials do not know if the survey will be repeated.[Footnote 43] 
Without periodic data collection and monitoring, CDC cannot assess 
trends in inpatient antibiotic use or evaluate the effects that 
changes in antibiotic use may have on antibiotic resistance. 

Additionally, in 2011, CDC officials told us that the agency plans to 
reinstate a module of NHSN that will allow participating facilities to 
report their inpatient antibiotic use, which will provide CDC with 
some inpatient antibiotic use data, but these data will not be 
nationally representative.[Footnote 44] In 2009, CDC temporarily 
discontinued this module because, according to CDC officials, it was 
not sustainable due to the high burden on facilities to report such 
data. Footnote 45] CDC has redesigned the module to reduce the 
reporting burden on facilities; for example, CDC officials told us 
that, instead of relying on manual entry, facilities will be able to 
electronically capture and automatically send their data to NHSN. 
[Footnote 46] While the module will allow facilities in NHSN to 
monitor their own antibiotic use, the data will not provide the agency 
with information about the prevalence of inpatient antibiotic use 
because NHSN is not based on a nationally representative sample of 
facilities. 

To improve CDC's monitoring of antibiotic use in outpatient settings, 
CDC officials told us that they are finalizing a contract with a 
private data vendor to obtain 5 years of national data on antibiotic 
prescribing in outpatient settings by antibiotic drug, county, and 
type of provider. According to CDC officials, these data will help the 
agency understand relationships between antibiotic use and antibiotic 
resistance in certain geographic areas. CDC officials further stated 
that these data would help guide the agency's prevention efforts. With 
preliminary data on outpatient prescriptions for the antibiotic 
subclass of fluoroquinolones, CDC has shown wide variation in 
prescribing across states. Further, CDC plans to increase the size of 
the NAMCS sample at least fourfold in 2012, which would allow CDC to 
produce antibiotic prescribing rates for some states that year. 
[Footnote 47] 

CDC's Get Smart Program Promotes Appropriate Antibiotic Use to 
Providers and Patients: 

CDC's Get Smart: Know When Antibiotics Work (Get Smart) program 
promotes appropriate antibiotic use, which is aimed specifically at 
healthcare providers, patients, and parents of young children. 
[Footnote 48] CDC launched its Get Smart program in 1995 with the 
overall goal of reducing the increasing rate of antibiotic resistance. 
[Footnote 49] The program is primarily focused on upper respiratory 
infections because, according to CDC, such infections account for over 
half of all antibiotics prescribed by office-based physicians. The Get 
Smart program works with partners, such as certain health insurance 
companies, to develop and distribute educational materials. Footnote 
50] With the goal of educating healthcare providers and the public, 
the Get Smart educational materials are aimed directly at these 
populations. For example, the Get Smart program supported the 
development of an online training program for healthcare providers to 
improve their knowledge and diagnosing of middle ear disease. The Get 
Smart program developed and launched a national media campaign in 
2003, in partnership with FDA, to provide a coordinated message on 
appropriate antibiotic use to the public and this message has been 
disseminated through print, television, radio, and other media. 
[Footnote 51] For example, CDC developed a podcast for parents of 
young children, available on CDC's Web site, to communicate its 
message. In the podcast, a pharmacist counsels a frustrated mother 
about appropriate antibiotic use and symptomatic relief options for 
her son's cold. Some materials are aimed at healthcare providers with 
the goal of educating their patients; for example, the Get Smart 
program developed a prescription pad for symptoms of viral infections. 
Healthcare providers can use the communication tool to acknowledge 
patient discomfort and recommend strategies to their patients for the 
relief of symptoms associated with viral illnesses--without 
prescribing an antibiotic unnecessarily. The prescription sheet 
includes the Get Smart logo and provides information for patients 
about the appropriate use of antibiotics to treat bacterial infections. 

CDC has continued to update and expand its materials for the Get Smart 
program. For example, CDC officials stated that the agency has 
expanded its educational materials by partnering with Wake Forest 
University to develop a curriculum for medical students related to 
appropriate antibiotic prescribing, and the impact of antibiotic use 
and its inappropriate use on antibiotic resistance, and the agency has 
developed a continuing education course for pharmacists. CDC officials 
told us that pharmacists serve as one of the most important health 
care professionals in promoting appropriate antibiotic use, for 
example by educating patients about the importance of taking 
antibiotics exactly as directed. In November 2010, CDC launched 
another Get Smart program, called Get Smart for Healthcare. This 
program focuses on improving antibiotic use in inpatient healthcare 
settings--including hospitals and nursing homes--through antimicrobial 
stewardship. 

CDC Has Observed Declines in Inappropriate Antibiotic Prescribing, but 
It Is Unclear to What Extent Its Program to Promote Appropriate 
Antibiotic Use Contributed to Recent Trends: 

CDC has observed declines in inappropriate antibiotic prescribing in 
outpatient settings since its Get Smart program began in 1995, but it 
is unclear to what extent this program contributed to these trends. 
For example, using NAMCS and NHAMCS data, CDC found about a 26 percent 
decline in the number of courses of antibiotics prescribed per 100 
children younger than 5 years old for ear infections between 1996-1997 
and 2006. Further, CDC reported about a 53 percent decrease in the 
antibiotic prescription rate for the common cold among all persons 
between 1996-1997 and 2006.[Footnote 52] A similar trend in antibiotic 
prescribing among children has also been observed with data from the 
National Committee for Quality Assurance (NCQA). NCQA monitors trends 
in antibiotic prescribing for the purpose of comparing the performance 
of healthcare plans.[Footnote 53] NCQA monitors the percentage of 
children 3 months to 18 years of age who were diagnosed with an upper 
respiratory infection and did not receive an antibiotic prescription 
within 3 days of the office visit, and this measure has shown 
improvement (i.e., percentage increases in appropriate treatment) 
between 2003 and 2008.[Footnote 54] 

The measures that CDC uses to evaluate the effectiveness of the Get 
Smart program do not necessarily reflect the effect of the program 
because they do not capture information about individuals who were 
exposed to the Get Smart program, compared to those who were not. As a 
result, it is unclear if the declines in the inappropriate antibiotic 
prescribing were due to exposure to Get Smart messages and educational 
materials or from other factors, such as efforts to measure healthcare 
performance with antibiotic prescribing indicators (e.g., NCQA 
measures) or the recommended use of influenza vaccines among young 
children, since 2004.[Footnote 55] CDC officials told us that they 
believe the NCQA measures have helped to improve appropriate 
antibiotic prescribing by improving knowledge of treatment guidelines 
by physicians and practitioners. In addition, reducing the number of 
cases of influenza among children is likely to have contributed to 
declines in inappropriate antibiotic prescriptions because antibiotics 
are often prescribed in patients with influenza symptoms. The measures 
that CDC uses to evaluate the effectiveness of the Get Smart program 
also do not allow CDC to determine, for example, whether declines in 
inappropriate antibiotic prescribing are attributable to a decrease in 
demand for antibiotics by patients, or to improved adherence to 
appropriate prescribing guidelines by healthcare providers. The 
measures are further limited because they do not allow CDC to 
determine whether the observed declines are consistent across the 
United States or are due to decreases in certain geographic areas. 

CDC officials told us that they rely on other indicators to 
demonstrate the effectiveness of the Get Smart Program, such as 
interest in CDC's Get Smart Web site and media materials. According to 
these officials, studies examining the impact of educational 
materials, including Get Smart materials, further demonstrate the 
effectiveness of the Get Smart program. For example, CDC officials 
cited a study in Massachusetts where educational materials, including 
Get Smart materials, were distributed to physicians and their patients 
in several communities.[Footnote 56] Findings indicate that in 
communities where educational and promotional materials about 
appropriate antibiotic use--including Get Smart materials--were 
distributed, antibiotic prescribing rates for children declined. 
Declines were also observed in communities where these educational and 
promotional materials were not distributed.[Footnote 57] These 
findings indicate that factors other than educational and promotional 
materials focused on the appropriate use of antibiotics may also have 
led to declines in inappropriate antibiotic prescribing. Without 
information about which are the most effective ways to reduce 
inappropriate antibiotic prescribing in outpatient and inpatient 
settings, CDC cannot target its resources on these preventive 
approaches. 

NIH and FDA Activities Have Complemented CDC's Efforts to Promote 
Appropriate Antibiotic Use: 

NIH and FDA have complemented CDC's efforts to promote the appropriate 
use of antibiotics in humans through various activities. NIH supports 
research specifically aimed at decreasing the inappropriate use of 
antibiotics as part of its research agenda to target antibiotic 
resistance. NIH-funded studies focus on establishing appropriate 
antibiotic treatment courses, using off-patent antibiotics to treat 
infections, and developing rapid diagnostic tests to help healthcare 
providers choose an appropriate antibiotic for treatment.[Footnote 58] 
For example, in 2009, NIH began funding a clinical trial to determine 
whether the standard 2-week antibiotic treatment course for children 
with urinary tract infections can remain effective if shortened, 
thereby decreasing the likelihood of antibiotic resistance and 
preserving the effectiveness of existing antibiotics.[Footnote 59] In 
2007, NIH awarded two 5-year contracts to study whether off-patent 
antibiotics such as clindamycin and a combination of the drugs 
trimethoprim and sulfamethoxazole can be used to treat certain skin 
infections instead of the more recently developed antibiotics, such as 
Linezolid and Vancomycin, in order to preserve the newer drugs' 
effectiveness.[Footnote 60] Further, since 2002, NIH has supported the 
development of a new test to rapidly diagnose TB. It currently takes 
up to 3 months to accurately diagnose TB and to determine its 
resistance to antibiotics, according to NIH officials. Findings from a 
recent clinical trial study reported that, within 2 hours, the new 
test can diagnose a TB infection and determine if it is resistant to 
the antibiotic rifampin, which is commonly used to treat TB.[Footnote 
61] NIH officials stated that the test is being recommended by the 
World Health Organization for the early diagnosis of TB and NIH is 
currently supporting research to improve the test and expand its 
capabilities.[Footnote 62] 

Research on the development of vaccines for bacterial and viral 
infections is also part of NIH's research agenda to decrease the 
inappropriate use of antibiotics, according to an NIH official. An NIH 
official stated that the agency has funded the discovery and 
development of several staphylococcal vaccine candidates, for example, 
through investigator-initiated grants.[Footnote 63] In addition, an 
NIH official told us that NIH conducted preclinical animal studies 
that provided data for the development of a multivalent staphylococcal 
vaccine candidate, which allowed the candidate to advance to clinical 
testing.[Footnote 64] NIH also supports the development of vaccines 
for viral infections. According to an NIH official, decreasing the 
occurrence of influenza infections with influenza vaccines may 
decrease the inappropriate use of antibiotics. Many healthcare 
providers inappropriately treat viral respiratory infections with 
antibiotics, so preventing influenza reduces the opportunities for 
unnecessary antibiotic treatment.[Footnote 65] 

FDA activities also complement CDC's efforts to promote the 
appropriate use of antibiotics in humans. According to an FDA 
official, the agency collaborated with CDC on certain Get Smart 
activities, such as developing an appropriate antibiotic use message 
for the national media campaign, and amended its drug labeling 
regulations in 2003 to require that all oral or intravenous 
antibiotics for human use include additional information on their 
appropriate use.[Footnote 66],[Footnote 67] FDA's labeling requirement 
is intended to encourage physicians to prescribe antibiotics only when 
clinically necessary and to encourage them to counsel their patients 
about the proper use of such drugs and the importance of taking them 
exactly as directed. For example, the amended regulation requires that 
antibiotic labeling include the statement that "prescribing [the 
antibiotic] in the absence of a proven or strongly suspected bacterial 
infection is unlikely to benefit the patient and increases the risk of 
the development of drug-resistant bacteria." 

CDC's Monitoring of Antibiotic-Resistant Infections Has Limitations in 
Assessing the Overall Problem of Antibiotic Resistance: 

CDC's monitoring of antibiotic-resistant infections has limitations in 
assessing the overall problem of antibiotic resistance. The agency's 
monitoring of antibiotic-resistant infections in healthcare facilities 
has data gaps that limit CDC's ability to produce accurate national 
estimates of such infections. For some of these infections monitored 
by CDC in community settings, in comparison, CDC can provide accurate 
national estimates. CDC is taking steps to improve its monitoring of 
antibiotic-resistant infections in healthcare settings, but these 
efforts will not improve CDC's ability to assess the overall problem 
of antibiotic resistance. 

Data Gaps in CDC's Monitoring of Antibiotic-Resistant Infections in 
Healthcare Settings Limit Its Ability to Produce Accurate National 
Estimates: 

A sample of healthcare facilities that is not representative--and 
incomplete information about the entire scope of healthcare-associated 
infections (HAIs) that are resistant to antibiotics--present data gaps 
that limit CDC's ability to produce accurate national estimates of 
antibiotic resistant HAIs in healthcare settings. Some infections are 
acquired as a result of medical treatment in a healthcare setting, 
such as a hospital or outpatient unit, while others are transmitted in 
the community, such as respiratory infections that are spread in 
schools and the workplace. According to CDC officials, healthcare 
settings contribute to the development of antibiotic resistance 
because of their high volume of susceptible patients, large number of 
disease-causing bacteria, and high antibiotic usage. CDC uses NHSN to 
monitor HAIs,[Footnote 68] including antibiotic-resistant HAIs, at a 
national level, but the facilities that participate are not a 
nationally representative sample. Facility enrollment and 
participation in NHSN[Footnote 69] is either voluntary, required 
because of a state mandate, or obligated as a condition of 
participation in HHS' Centers for Medicare & Medicaid Services (CMS) 
Hospital Inpatient Quality Reporting program.[Footnote 70] According 
to CDC officials, as of January 2011, 23 states and territories 
required, or had plans to require, healthcare facilities to use NHSN 
for their reporting mandate.[Footnote 71] As of January 1, 2011, all 
acute care hospitals participating in the CMS Hospital Inpatient 
Quality Reporting Program are obligated to report into NHSN central-
line associated bloodstream infections for certain procedures[Footnote 
72] from their intensive care units.[Footnote 73] Although the number 
of participating facilities has increased substantially, because 
healthcare facilities enroll voluntarily or by mandate, this group of 
facilities is not representative of facilities nationwide, as a random 
sample would be. Participating healthcare facilities in states with 
mandated participation are more likely to be overrepresented in the 
sample, while facilities in states without mandates are more likely to 
be underrepresented. 

The data that participating healthcare facilities supply to NHSN do 
not reflect the full scope of HAIs that occur within these facilities, 
further limiting CDC's ability to provide accurate national estimates 
about antibiotic-resistant HAIs.[Footnote 74] Participating facilities 
may submit data about different types of HAIs, and this includes 
information about whether the HAIs are resistant to antibiotics. 
[Footnote 75] For example, some facilities report data to NHSN on 
central-line associated bloodstream infections but not other infection 
types, such as catheter-associated urinary tract infections.[Footnote 
76] Further, participating healthcare facilities may report HAI data 
to NHSN for certain units within facilities. For example, 
participating facilities may report data to NHSN on infections that 
occur in intensive care units but not those that occur in specialty 
care areas. CDC depends on the microbiology data provided by 
participating facilities to determine, among reported cases, the 
number and percentage of certain types of HAIs with resistance to 
certain antibiotics.[Footnote 77] Without an accurate national 
estimate of antibiotic-resistant HAIs, CDC cannot assess the magnitude 
and types of such infections that occur in all patient populations 
(i.e., facilitywide) within healthcare settings. 

CDC's Monitoring of Antibiotic-Resistant Infections in Community 
Settings Can Provide Accurate National Estimates for Some Infections: 

CDC's monitoring of antibiotic-resistant infections in community 
settings can provide accurate national estimates of antibiotic- 
resistant infections that are caused by 5 of the 12 bacteria that the 
agency monitors. These 5 are captured by two surveillance systems, the 
National Antimicrobial Resistance Monitoring System for Enteric 
Bacteria (NARMS: EB) and the National Tuberculosis Surveillance System 
(NTSS), which collect nationally representative data about certain 
antibiotic-resistant infections; these infections can occur in 
community settings. 

Both systems employ sampling strategies that can provide accurate 
national estimates by collecting representative case information from 
all 50 states.[Footnote 78] For NARMS: EB, health departments in all 
50 states submit a representative sample of four of the five bacteria 
it monitors--non-typhoidal Salmonella, typhoidal Salmonella, Shigella, 
and Escherichia coli O157 cases to NARMS: EB for antibiotic 
susceptibility testing. To ensure adequate sample size and a random 
sample for testing, the health departments systematically select and 
submit to NARMS: EB every 20th non-typhoidal Salmonella, Shigella, and 
Escherichia coli O157 case as well as every typhoidal Salmonella case 
received at their laboratories. NARMS: EB cannot produce an accurate 
national estimate for one of the five bacteria it monitors-- 
Campylobacter--because according to CDC officials, the system collects 
a sample of the bacteria in 10 states.[Footnote 79] CDC uses NTSS to 
collect information about each newly reported case of tuberculosis 
infection in the United States, including information on drug 
susceptibility results for the majority of cases that test positive 
for tuberculosis. 

CDC's monitoring of other bacteria that cause antibiotic-resistant 
infections in community settings cannot provide estimates that are 
nationally representative because they are derived from samples that 
do not accurately represent the entire United States. Through ABCs, 
CDC conducts antibiotic resistance surveillance of five[Footnote 80] 
infection-causing bacteria--group A and B Streptococcus, Neisseria 
meningitidis, Streptococcus pneumoniae, and MRSA.[Footnote 81], 
[Footnote 82] According to CDC officials, these bacteria cause 
bloodstream infections, sepsis, meningitis, and pneumonia. ABCs is a 
collaboration between CDC, state health departments, and universities 
in 10 states.[Footnote 83] CDC officials told us that for each 
identified case of infection within their surveillance populations, 
the ABCs sites conduct a chart review to collect a variety of 
information, such as underlying disease and risk factors, vaccination 
history, and demographic information. This information is entered into 
a case report form and submitted to CDC along with bacterial isolates 
for additional testing, including tests for antibiotic 
resistance.[Footnote 84] 

ABCs' monitoring of cases of resistant infections is limited to 
surveillance areas in 10 states, and the surveillance areas vary 
somewhat depending on the infection-causing bacterium that is 
monitored. For example, Neisseria meningitidis is monitored in 6 
entire states and in primarily urban areas in 4 other states while 
MRSA is monitored in 1 entire state and primarily urban areas in 8 
other states.[Footnote 85] According to CDC's Web site, the population 
included in the ABCs surveillance areas is roughly representative of 
the U.S. population on the basis of certain demographic 
characteristics (e.g., race and age) and urban residence. However, 
ABCs cannot provide estimates that are nationally representative for 
rural residence, and some experts have raised concerns because of the 
underrepresentation of rural areas.[Footnote 86],[Footnote 87] 
Further, since surveillance is critical to providing early warning of 
emerging resistance problems, limited geographic coverage among 
monitored infection-causing bacteria impedes CDC's ability to detect 
emerging problems. 

The Gonococcal Isolate Surveillance Project (GISP), which CDC uses to 
monitor antibiotic resistance in Neisseria gonorrhoeae, the bacterium 
that causes gonorrhea, cannot provide accurate national estimates of 
cases of antibiotic-resistant gonorrhea because it collects 
information only on selected patient populations. Each month, GISP 
collects case samples from the first 25 men diagnosed with urethral 
gonorrhea in each participating sexually transmitted disease clinic. 
The clinics are located in 24 states and they send these samples to 
designated laboratories for antibiotic susceptibility 
testing.[Footnote 88] However, according to CDC officials, most cases 
of gonorrhea in the United States are not treated in sexually 
transmitted disease clinics, and are more likely treated in a variety 
of healthcare settings, such as primary care physicians' offices. 
Further, since GISP collects information on cases of gonorrhea from 
male patients only, the data cannot represent the total U.S. 
population in order to provide an accurate national estimate of 
resistant gonorrhea cases.[Footnote 89] 

CDC Is Taking Steps to Improve Its Monitoring of Antibiotic-Resistant 
Infections in Healthcare Facilities, but These Steps Will Not Improve 
CDC's Ability to Assess the Overall Problem of Antibiotic Resistance: 

CDC is taking steps to improve its monitoring of antibiotic-resistant 
infections in healthcare facilities, but CDC's ability to assess the 
overall problem of antibiotic resistance will not be improved. With a 
prevalence survey, CDC is planning to collect additional data in 2011 
about HAIs, which may provide more comprehensive information about 
certain types of HAIs that are resistant to antibiotics. According to 
CDC officials, the survey of U.S. acute care hospitals--which will 
also provide data on antibiotic use, as described previously--will 
allow the agency to more accurately assess the burden of HAIs and 
antibiotic resistance among those HAIs in healthcare settings. 
[Footnote 90] Unlike NHSN, the survey is designed to allow CDC to 
assess the magnitude and types of HAIs occurring in all patient 
populations within the sample of acute care hospitals. The survey will 
collect information about types of infection (e.g., urinary tract 
infection, bloodstream infection), bacteria causing HAIs, and test 
results regarding antibiotic resistance. The survey will not collect 
resistance information for all bacteria that cause HAIs. However, 
according to CDC officials, the survey will collect resistance 
information for some of the most common bacteria that cause HAIs, 
including Acinetobacter, Enterococcus faecalis, Enterococcus faecium, 
Escherichia coli, Klebsiella, Pseudomonas aeruginosa, and 
Staphylococcus aureus.[Footnote 91] While the survey may provide more 
comprehensive information about certain types of HAIs that are 
resistant to antibiotics because it is designed to cover all patient 
populations in the sampled hospitals, the survey will not be able to 
provide information about the prevalence of all antibiotic-resistant 
HAIs that occur in U.S. acute care hospitals. A further limitation is 
that the sample is not representative of U.S. acute care hospitals. As 
described earlier, this is because the survey is based on a sample of 
acute care hospitals located within the EIP surveillance areas, 
according to CDC officials. 

CDC also plans to enhance its monitoring of HAIs by expanding the 
geographic coverage of its surveillance of Clostridium difficile 
infections and CDC officials told us that the agency is piloting 
additional surveillance for gram-negative infections through the EIP 
network.[Footnote 92] According to CDC, the agency began monitoring 
Clostridium difficile infections through EIP in 2009 in 7 surveillance 
areas, to obtain more comprehensive and representative information 
about this infection, including for antibiotic resistance.[Footnote 
93] CDC officials stated that the agency plans to expand its 
Clostridium difficile monitoring to 10 surveillance areas by summer 
2011. In 2 of the 10 surveillance areas (i.e., Oregon and Minnesota), 
surveillance will occur in rural areas only. CDC officials stated that 
the data will allow the agency, among other things, to detect 
Clostridium difficile infections that occur prior to admission to a 
healthcare facility and to identify new populations at risk.[Footnote 
94] CDC officials also told us that the agency is piloting 
surveillance for gram-negative infections that are resistant to 
multiple antibiotics, through the EIP network, as an exploratory 
effort and feasibility study on how to improve the agency's monitoring 
of these infections in healthcare settings. 

In addition, CDC anticipates that the number of acute care hospitals 
participating in NHSN will expand in 2011 stemming from the CMS 
Hospital Inpatient Quality Reporting Program obligation to do so. The 
expanded participation will, CDC officials believe, result in more 
representative data about certain HAIs and antibiotic-resistant 
infections.[Footnote 95] CMS has expanded its quality data measures to 
include two HAI measures that will be reported through NHSN. As stated 
previously, as of January 1, 2011, hospitals are obligated to report 
on central-line bloodstream infections associated with certain 
procedures from their intensive care units and on January 1, 2012, 
hospitals will be obligated to report on surgical site infections. 
[Footnote 96] Hospitals will also need to report on antibiotic 
resistance associated with these two types of infections, given NHSN's 
reporting requirements for participation. As part of CDC's protocols, 
facilities submit microbiological data for each HAI identified, which 
includes the type of bacteria causing the infection and test results 
regarding antibiotic resistance. 

Federal Agencies Do Not Monitor Antibiotic Disposal, but Have Examined 
the Presence of Antibiotics in the Environment, and Studies Find that 
Such Antibiotics Can Increase the Population of Resistant Bacteria: 

Federal agencies do not collect data regarding the disposal of most 
antibiotics intended for human use, but EPA and USGS have measured the 
presence of certain antibiotics in the environment due, in part, to 
their disposal. Studies conducted by scientists have found that 
antibiotics that are present in the environment at certain 
concentration levels can increase the population of resistant bacteria 
due to selective pressure. 

Federal Agencies Do Not Monitor the Disposal of Most Antibiotics 
Intended for Human Use, but Have Measured the Presence of Antibiotics 
in the Environment: 

EPA does not monitor the disposal of most antibiotics intended for 
human use, but EPA and USGS have measured the presence of antibiotics 
in the environment, including water, soil, and sediment.[Footnote 97] 
According to EPA, antibiotics enter the environment through various 
pathways into water, soil, and sediment, such as wastewater discharged 
from treatment plants.[Footnote 98] The disposal of hazardous waste, 
such as chemicals that are harmful to human health when ingested, is 
regulated by EPA. Under RCRA, EPA has established a system by which 
hazardous waste is regulated from the time it is produced until it is 
disposed.[Footnote 99] Under this system, EPA receives information 
from hazardous waste generators through the Biennial Reporting System. 
[Footnote 100] EPA officials told us that antibiotics in general do 
not fall under RCRA's definition of hazardous waste; as a result, EPA 
does not generally receive information about the disposal of 
antibiotics. EPA officials further stated that the agency would 
receive limited information about antibiotics if they fell under 
RCRA's definition of hazardous waste. However, in part because it is 
the responsibility of the person disposing of a waste to determine 
whether or not it is hazardous, agency officials could not identify 
any specific antibiotics that fall under EPA's regulatory definition 
of hazardous waste and therefore concluded that it would be a rare 
occurrence for the agency to receive information on the disposal of 
antibiotics. 

Under SDWA, EPA is authorized to regulate contaminants in public 
drinking water systems. EPA generally requires public water systems to 
monitor certain contaminants for which there are national primary 
drinking water regulations--standards limiting the concentration of a 
contaminant or requiring certain treatment. EPA has not promulgated 
any drinking water regulation for an antibiotic. EPA is required to 
identify and publish a list every 5 years of unregulated contaminants 
that may require regulation, known as the Contaminant Candidate List 
(CCL). EPA generally uses this list to select contaminants for its 
periodic regulatory determinations, by which the agency decides 
whether to regulate a contaminant, but contaminants may remain on the 
CCL for many years before EPA makes such a decision.[Footnote 101] 
Erythromycin is the only antibiotic on the third CCL list (CCL 3)--the 
current CCL that was published in October 2009.[Footnote 102] 
According to EPA officials, the agency is in the process of evaluating 
CCL 3 contaminants, including erythromycin, and plans to determine 
whether or not regulation is required for at least five contaminants 
from the CCL 3 by 2013. EPA's determination to promulgate a national 
primary drinking water regulation for a contaminant is made based on 
three criteria established under SDWA, including that the contaminant 
may have an adverse effect on human health.[Footnote 103] To provide 
information such as that needed to determine whether to regulate the 
contaminant, EPA has the authority to require a subset of public water 
systems to monitor a limited number of unregulated contaminants, which 
the agency has implemented through the Unregulated Contaminant 
Monitoring Rule (UCMR). On March 3, 2011, EPA proposed the list of 
contaminants (primarily from the CCL 3) to be monitored under the 
third UCMR (UCMR 3). Erythromycin was not included on the proposed 
UCMR 3 list of contaminants, because according to EPA officials, 
further development of an analytical method that can be used for 
national monitoring of erythromycin is needed. EPA officials stated 
that the agency is in the initial stages of development of an 
analytical method for a number of pharmaceuticals, including 
erythromycin, and will evaluate the readiness of this analytical 
method for future UCMR efforts. EPA officials further stated that the 
agency will continue to evaluate unregulated contaminants, such as 
erythromycin, for future CCLs and will utilize any new data that 
become available.[Footnote 104] 

EPA and USGS have conducted several studies to measure the presence of 
antibiotics in the environment, which results partly from their 
disposal. According to EPA and USGS officials, there is no specific 
statutory mandate requiring the agencies to collect information about 
the presence of antibiotics in the environment. However, from 1999 
through 2007, the agencies conducted five national studies measuring 
the presence and concentration of certain antibiotics in streams, 
groundwater, untreated drinking water, sewage sludge, and wastewater 
effluent as part of their efforts to study emerging contaminants. 
[Footnote 105],[Footnote 106] (See table 5.) These studies were 
generally designed to determine whether certain contaminants, 
including antibiotics, were entering the environment and as a result, 
some study sites were selected based on being susceptible to 
contamination.[Footnote 107] For example, the study examining the 
presence of antibiotics, and other contaminants, in streams in 30 
states was designed to determine whether these contaminants were 
entering the environment. Therefore, USGS purposely selected study 
sites susceptible to contamination by humans, industry, and 
agricultural wastewater. 

Table 5: Five National Studies that Measured the Presence of 
Antibiotics in the Environment, Conducted by EPA and USGS: 

Name of study (agency that conducted the study): Pharmaceuticals, 
Hormones, and Other Organic Wastewater Contaminants in U.S. Streams, 
1999-2000: A National Reconnaissance (USGS); 
Year(s) study was conducted: 1999-2000; 
Description of study sites: 139 streams across 30 states; 
Examples of antibiotics detected[A]: Ciprofloxacin, Erythromycin, 
Tetracycline. 

Name of study (agency that conducted the study): A National 
Reconnaissance of Pharmaceuticals and Other Organic Wastewater 
Contaminants in the United States - I) Groundwater (USGS); 
Year(s) study was conducted: 2000; 
Description of study sites: 47 groundwater sites across 18 states; 
Examples of antibiotics detected[A]: Lincomycin, Sulfamethazine, 
Sulfamethoxazole. 

Name of study (agency that conducted the study): A National 
Reconnaissance for Pharmaceuticals and Other Organic Wastewater 
Contaminants in the United States - II) Untreated Drinking Water 
Sources (USGS); 
Year(s) study was conducted: 2001; 
Description of study sites: 25 ground-and 49 surface-water sources of 
drinking water in 25 states and Puerto Rico; 
Examples of antibiotics detected[A]: Azithromycin, Ciprofloxacin, 
Erythromycin. 

Name of study (agency that conducted the study): Targeted National 
Sewage Sludge Survey (EPA); 
Year(s) study was conducted: 2006-2007; 
Description of study sites: 74 publicly owned plants that treat 
wastewater in 35 states; 
Examples of antibiotics detected[A]: Azithromycin, Ciprofloxacin, 
Erythromycin. 

Name of study (agency that conducted the study): Transport of 
Chemicals from Wastewater Effluents (EPA and USGS); 
Year(s) study was conducted: 2002; 
Description of study sites: 10 wastewater treatment plants in 10 
states; 
Examples of antibiotics detected[A]: Erythromycin, Sulfamethoxazole, 
Trimethoprim. 

Source: GAO analysis and summary of EPA and USGS information. 

[A] Detected antibiotics include those used for treatment by both 
animals and humans. 

[End of table] 

In all five studies antibiotics were found to be present. For example, 
erythromycin was detected in multiple samples tested in four studies 
and ciprofloxacin was detected in three studies.[Footnote 108] 
According to EPA and USGS officials, the antibiotic concentrations 
detected in streams, groundwater, and untreated drinking water are low 
relative to the maximum recommended therapeutic doses approved by FDA 
for most antibiotics. In contrast, antibiotics were found in 
relatively higher concentrations in sewage sludge. For example, the 
maximum concentration level of ciprofloxacin that was detected in 
streams or untreated drinking water sources was .03 micrograms per 
liter of water.[Footnote 109] In comparison, ciprofloxacin was 
detected in sewage sludge sampled from large publicly owned treatment 
plants at concentrations ranging from 74.5 to 47,000 micrograms per 
kilogram of sewage sludge.[Footnote 110] The maximum recommended 
therapeutic dose for ciprofloxacin is about 13,000 micrograms per 
kilogram of weight. According to USGS officials, waste from humans and 
domestic animals that receive antibiotics (i.e., therapeutic or 
subtherapeutic doses) are likely to contain antibiotics as a 
substantial portion of such antibiotic treatments are not fully 
absorbed through the body.[Footnote 111] 

EPA and USGS also have two ongoing studies that measure the presence 
of antibiotics in wastewater and drinking water. First, EPA is 
assessing the concentration of pharmaceuticals and other contaminants 
in municipal wastewater because past studies have suggested that 
municipal wastewater is a likely source of human pharmaceuticals 
entering the environment. According to EPA officials, EPA is 
collecting samples from 50 of the largest municipal wastewater plants 
in the United States and testing their treated effluents for 
contaminants, including 12 antibiotics.[Footnote 112] The study's 
findings are expected to be made available sometime in 2012 and may 
help EPA develop new standards for municipal wastewater treatment, 
according to EPA officials. Second, EPA and USGS are collaborating on 
a study to measure the presence of several antibiotics (e.g., 
erythromycin) and other contaminants in raw and finished drinking 
water to better determine human exposures to these contaminants 
through drinking water.[Footnote 113] During 2011, researchers will 
take samples from between 20 and 25 drinking water treatment plants 
across the United States and according to EPA officials, the 
information will be used to inform EPA decision making about the focus 
of future monitoring efforts. EPA and USGS officials anticipate the 
study's findings to be made available sometime in 2012. 

Studies Find Antibiotics Present in the Environment at Certain 
Concentration Levels Can Increase the Population of Resistant Bacteria 
Due to Selective Pressure: 

Scientific evidence gathered in our literature review shows that, at 
certain concentration levels, antibiotics present in the environment-- 
in water and soil--can increase the population of resistant bacteria, 
due to selective pressure. Of the 15 studies we identified that 
examined this association, 5 examined water-related environments and 
10 examined soil-related environments. Among these 15 studies, 11 
provided evidence to support the association. Support for this 
association means that antibiotics present in these environments 
increased the population of resistant bacteria through selective 
pressure because bacteria containing resistance genes survived and 
multiplied.[Footnote 114] 

Results for the five studies examining water-related environments 
generally support an association between the presence of antibiotics 
and an increase in the population of resistant bacteria caused by 
selective pressure, although only one tested concentration levels of 
antibiotics as low as those that have been detected in national 
studies of U.S. streams, groundwater, and source drinking water. The 
results of this study were inconclusive as to whether low antibiotic 
concentration levels, such as levels measured at or below 1.7 
micrograms per liter of water, led to an increase in the population of 
resistant bacteria.[Footnote 115] Among the four other studies that 
supported an association between the presence of antibiotics and an 
increase in the population of resistant bacteria, the lowest 
concentration level associated with an increase was 20 micrograms of 
oxytetracycline per liter of water--over 50 times higher than maximum 
antibiotic concentration levels detected in stream water across the 
United States.[Footnote 116] Another of these four studies found that 
chlortetracycline was associated with an increase in the population of 
resistant bacteria, but only at concentration levels over 1000 times 
higher than those that have been detected in streams across the United 
States.[Footnote 117] According to USGS officials, scientists 
generally agree that the population of resistant bacteria would 
increase in water if the concentration levels of antibiotics that are 
present were to reach the minimum level that is known to induce 
antibiotic resistance in a clinical setting.[Footnote 118],[Footnote 
119] USGS officials further stated that higher concentrations of 
antibiotics have been found, for example, in waters near to 
pharmaceutical manufacturing facilities in countries outside of the 
United States.[Footnote 120] 

Results for the 10 studies examining antibiotic resistance in soil- 
related environments, such as soil and sediment, were more mixed, and 
we cannot draw comparisons between concentration levels tested in 
these studies and those that have been found in such environments 
across the United States. Seven of the 10 studies found evidence to 
support an association between the presence of antibiotics and an 
increase in the population of resistant bacteria due to selective 
pressure, and the association existed at all concentration levels 
studied. No association existed among the antibiotic concentration 
levels in the other 3 studies. Because national data about the 
presence and concentration levels of antibiotics in soil and sediment 
are not available, we cannot draw comparisons between concentration 
levels tested in these studies and those commonly found in such 
environments across the United States. As with water-related 
environments, USGS officials stated that scientists generally agree 
that the population of resistant bacteria would increase in soil if 
the concentration levels of antibiotics that are present were to reach 
the minimum level that is known to induce antibiotic resistance in 
clinical settings. USGS officials further stated that antibiotic 
concentration levels in soils where human and animal waste have been 
applied as fertilizer are likely to be directly related to the 
antibiotic concentration levels in these sources.[Footnote 121] 

Conclusions: 

Antibiotics have been widely prescribed to treat bacterial infections 
in humans and their use contributes to the development of antibiotic 
resistance, which is an increasing public health problem in the United 
States and worldwide. Monitoring the use of antibiotics in humans and 
preventing their inappropriate use, such as prescribing an antibiotic 
to treat a viral infection, is critically important because the use of 
antibiotics for any reason contributes to the development and spread 
of antibiotic resistance. Establishing patterns of antibiotic use is 
necessary for understanding current--and predicting future--patterns 
of antibiotic resistance. Monitoring overall antibiotic use in humans, 
including in inpatient and outpatient healthcare settings, is also 
needed to evaluate the contribution of such use--relative to other 
causes, such as animal use--to the overall problem of antibiotic 
resistance. Such information could help policymakers set priorities 
for actions to control the spread of antibiotic resistance. 

CDC is collecting data on antibiotic use and the occurrence of 
resistance, but the agency's data sources have limited ability to 
provide accurate national estimates and do not allow it to assess 
associations between use and resistance. CDC does not monitor the use 
of antibiotics in inpatient settings--where antibiotic use is often 
intensive and prolonged and thus, the risk of antibiotic resistance is 
greater--although the agency believes such information would help it 
target and evaluate its own prevention efforts to reduce the 
occurrence of resistance. Although the agency collects annual data in 
the United States about the use of antibiotics in outpatient settings, 
the data do not allow CDC to assess geographic patterns of use in 
those settings. Similarly, CDC's monitoring of antibiotic-resistant 
infections does not allow the agency to assess the overall problem of 
antibiotic resistance because of gaps in the data it collects. Without 
more comprehensive information about the occurrence of cases of 
antibiotic-resistant infections and the use of antibiotics, the 
agency's ability to understand the overall scope of the public health 
problem, detect emerging trends, and plan and implement prevention 
activities is impeded. Further, the lack of comprehensive information 
about antibiotic-resistant infections and antibiotic use, and the most 
effective ways to reduce inappropriate prescribing, impedes CDC's 
ability to strategically target its resources directed at reducing the 
occurrence of antibiotic-resistant infections. 

CDC is attempting to address the gaps in its data on antibiotic use in 
humans and on antibiotic-resistant infections by obtaining additional 
data, but it is not clear whether the steps it is taking will result 
in more comprehensive information from which the agency could assess 
the public health impact of antibiotic resistance. Further, it is not 
clear whether these steps will provide CDC with the information it 
needs to identify what actions are needed to reduce the occurrence of 
antibiotic-resistant infections. 

Recommendations: 

To better prevent and control the spread of antibiotic resistance, we 
recommend that the Director of CDC take the following two actions: 

* Develop and implement a strategy to improve CDC's monitoring of 
antibiotic use in humans, for example, by identifying available 
sources of antibiotic use information; and: 

* develop and implement a strategy to improve CDC's monitoring of 
antibiotic-resistant infections in inpatient healthcare facilities to 
more accurately estimate the national occurrence of such infections. 

Agency Comments: 

We provided a draft of this report for review to HHS, EPA, and DOI. 
HHS provided written comments, which are reproduced in appendix V. 
HHS, EPA, and DOI provided technical comments, which we incorporated 
as appropriate. 

In its written comments, HHS generally agreed with the actions we 
recommend it take to improve its monitoring of antibiotic use and 
resistance. HHS says that steps are being taken to address existing 
gaps in CDC's monitoring of antibiotic use and the occurrence of 
antibiotic-resistant infections, and HHS noted that such monitoring is 
critically important in preventing the development and spread of 
antibiotic resistance. HHS highlighted examples of the steps CDC is 
taking, or plans to undertake, to address gaps in CDC's monitoring of 
antibiotic use and antibiotic-resistant infections, such as a planned 
survey of acute care hospitals in the United States. HHS noted that 
other planned activities to improve the monitoring of antibiotic use 
and antibiotic-resistant infections are described in the revised draft 
Action Plan, developed by the Interagency Task Force on Antimicrobial 
Resistance. HHS stated that CDC believes that the successful, timely 
accomplishment of its planned and ongoing activities to improve 
monitoring will result in information that is sufficiently 
comprehensive for a full and complete assessment of the public health 
impact of antibiotic resistance, and that this assessment will provide 
federal agencies with appropriate information to identify necessary 
actions to reduce the occurrence of antibiotic-resistant infections. 
HHS stated that it would provide updates on its progress toward the 
accomplishment of its steps to improve monitoring in the 2010 annual 
progress report on the Action Plan, scheduled for public release this 
summer. HHS also commented that it has initiated the process of 
developing a strategic plan for preventing the emergence and spread of 
antibiotic-resistant infections, and a primary component of this 
strategic plan is the monitoring of antibiotic use and resistance. We 
support this effort and encourage HHS, as it develops its strategic 
plan, to continue to examine approaches for improving its monitoring 
of antibiotic use and antibiotic-resistant infections that will help 
provide the agency with information that is needed to more accurately 
estimate the national occurrence of antibiotic-resistant infections. 

As agreed with your offices, unless you publicly announce the contents 
of this report earlier, we plan no further distribution until 30 days 
from the report date. At that time, we will send copies to the 
Secretaries of the Department of Health and Human Services and the 
Department of the Interior, the Administrator of the Environmental 
Protection Agency, and other interested parties. In addition, the 
report will be available at no charge on the GAO Web site at 
[hyperlink, http://www.gao.gov]. 

If you or your staff have any questions about this report, please 
contact me at (202) 512-7114 or crossem@gao.gov. Contact points for 
our Offices of Congressional Relations and Public Affairs may be found 
on the last page of this report. GAO staff who made major 
contributions to this report are listed in appendix VI. 

Signed by: 

Marcia Crosse: 
Director, Health Care: 

[End of section] 

Appendix I: Methodology for Reviewing Scientific Evidence on 
Antibiotic Resistance in the Environment: 

To describe the scientific evidence on the development of antibiotic- 
resistant bacteria in the environment, we conducted a literature 
review. We identified literature made available since 2007 that 
reported scientific findings on antibiotic concentrations that induce 
bacteria located in the environment to become resistant as well as the 
ability of bacteria to spread resistance. We conducted a key word 
search of 39 databases, such as Elsevier Biobase and MEDLINE that 
included peer-reviewed journals and other periodicals to capture 
articles published on or between January 1, 2007, and July 8, 2010. We 
searched these databases for articles with key words in their title or 
abstract related to both antibiotic resistance and the environment, 
such as combinations and variations of the words "resistance," 
"antibiotic," and "environment," and descriptive words for different 
environmental settings, such as "water," "sediment," "soil," and 
"sewage."[Footnote 122] From these sources, we identified 241 
articles, publications, and reports (which we call articles) published 
from January 1, 2007, through July 8, 2010. Of these 241 articles, we 
then excluded articles that (1) were not published in English, (2) 
were available only in an abstract form or in books or book chapters, 
(3) were not peer-reviewed, (4) contained only a review of past 
literature, or (5) were unrelated to antibiotic resistance found in 
the environment such as articles that focused on the effects of 
antibiotic resistance found mainly in clinical settings.[Footnote 123] 
In total, we included 105 articles in our literature review. We 
supplemented the scientific findings analyzed in our literature review 
with contextual and background information gathered from articles that 
were identified as a result of our interviews with officials from the 
Environmental Protection Agency and the United States Geological 
Survey. 

[End of section] 

Appendix II: Bacteria and the Development of Antibiotic Resistance: 

Bacteria are single-celled organisms that live in water, soil, and in 
the bodies of humans, animals, and plants. Bacteria compete with each 
other for resources, such as nutrients, oxygen, and space, and those 
that do not compete successfully will not survive. Most bacteria that 
are present in humans, such as those found on the skin and in the 
intestines, are harmless because of the protective effects of the 
human immune system, and a few bacteria are beneficial. However, some 
bacteria are capable of causing disease. For example, Escherichia coli 
O157--which can be found in the feces of animals, such as cattle, and 
can transfer to people through contaminated undercooked meat--produce 
a toxin that causes severe stomach and bowel disorders, and death in 
some cases.[Footnote 124] In addition, the same bacteria that may 
cause disease in one individual may not cause disease in another. 
[Footnote 125] For example, Streptococcus pneumoniae is a bacterium 
that is often found in the noses and throats of healthy persons 
without causing disease, but it can also cause mild illness, such as 
sinus infections, as well as life-threatening infections such as 
meningitis. Furthermore, when the immune system is weakened, infection 
may be caused by certain bacteria that would not generally result in 
an infection in a healthy human. 

Like other living things, as bacteria grow and multiply, they also 
evolve and adapt to changes in their surroundings. Bacteria adapt to 
their surroundings through selective pressure, which is created by, 
among other things, the presence of antibiotics.[Footnote 126] 
Selective pressure means that when an antibiotic is introduced into a 
bacterial environment, some bacteria will be killed by the antibiotic 
while other bacteria will survive.[Footnote 127] Bacteria are able to 
survive because they have certain genetic material that is coded for 
resistance--allowing them to avoid the effects of the antibiotic. The 
surviving bacteria that are resistant to antibiotics will multiply and 
quickly become the dominant bacterial type. Bacteria that are 
susceptible to the effects of antibiotics may become resistant to such 
antibiotics after acquiring resistant genetic material from bacteria 
that are resistant through horizontal gene transfer. Horizontal gene 
transfer is the movement of genetic material between bacteria, and can 
occur within a species of bacteria and can sometimes occur between 
certain species of bacteria.[Footnote 128] Close proximity between 
bacteria, which allows certain genetic material to be shared, can 
facilitate gene transfer. 

The movement of antibiotic-resistant bacteria around the world is 
accelerated because of international travel and global trade. 
Individuals can contract bacterial strains--that is, distinct types of 
bacteria--that are resistant to antibiotics abroad during travel, 
whether as active infections or as unaffected carriers, and then 
spread such strains to others at home.[Footnote 129] The bacterial 
strains in different parts of the world may also contain different 
resistance genes than bacterial strains found domestically. For 
example, in 2010, the Centers for Disease Control and Prevention 
reported that three bacterial strains included a resistance gene 
identified for the first time in the United States. The emergence of 
the resistance gene was traced to patients who had received recent 
medical care in India.[Footnote 130] Further, international trade of 
food and livestock may accelerate the movement of antibiotic-resistant 
bacteria because food and livestock also carry resistant bacterial 
strains that can be contracted by humans through consumption. 

To determine whether bacteria are resistant, tests are performed that 
measure the susceptibility of pathogenic bacteria to particular 
antibiotics. The test results can predict the success or failure of an 
antibiotic treatment, and thus, guide healthcare providers' choice of 
antibiotics to treat bacterial infections. The test results include a 
numeric value, which is then interpreted according to established 
ranges.[Footnote 131] For example, a value may be categorized as 
'resistant,' meaning that the pathogenic bacterium is not inhibited by 
the concentration of the antibiotic that usually results in growth 
inhibition.[Footnote 132] 

[End of section] 

Appendix III: Centers for Disease Control and Prevention's 
Surveillance Systems for Monitoring Antibiotic Resistance: 

Table 6: CDC's Surveillance Systems for Monitoring Antibiotic 
Resistance, by Bacteria, Geographic Coverage, and Examples of Data Use: 

Surveillance system: Active Bacterial Core Surveillance (ABCs) [of the 
Emerging Infections Programs (EIP) Network[A]]; 
Bacteria monitored for antibiotic resistance: group A and group B 
Streptococcus; Neisseria meningitidis; Streptococcus pneumoniae; 
methicillin-resistant Staphylococcus aureus (MRSA)[B]; 
Geographic coverage of surveillance: 10 surveillance areas in 
California, Colorado, Connecticut, Georgia, Maryland, Minnesota, New 
Mexico, New York, Oregon, and Tennessee for group A and B 
Streptococcus; Neisseria meningitidis; and Streptococcus pneumoniae; 
9 surveillance areas in California, Colorado, Connecticut, Georgia, 
Maryland, Minnesota, New York, Oregon, and Tennessee for MRSA; 
Examples of how surveillance data were used: ABCs data were used to 
show that rates of invasive pneumococcal infections, including 
antibiotic-resistant infections among children and adults, have 
declined since a pneumococcal conjugate vaccine was introduced for 
children in 2000. ABCs data have also shown a decline in the incidence 
of pneumococcal meningitis resistant to antibiotics. ABCs data on 
MRSA, collected between 2005 and 2008, were used to identify the 
genetic makeup of MRSA strains showing unusual patterns of resistance. 
This information provided the Centers for Disease Control and 
Prevention (CDC) with evidence that mechanisms of resistance in MRSA 
were being transferred from healthcare-associated to community- 
associated strains. 

Surveillance system: Gonococcal Isolate Surveillance Project (GISP); 
Bacteria monitored for antibiotic resistance: Neisseria gonorrhoeae; 
Geographic coverage of surveillance: 29 sexually transmitted disease 
clinics located in the West, Midwest, Northeast, and South; 
Examples of how surveillance data were used: Based on GISP data, CDC 
announced in 2007 that fluoroquinolones were no longer recommended to 
treat gonorrhea because of antibiotic resistance and that the 
recommended treatment for gonorrhea was limited to only cephalosporin 
antibiotics. Neisseria gonorrhoeae isolates collected through GISP 
have been used to support research on the mechanisms used to resist 
the effects of antibiotics, according to a CDC official. 

Surveillance system: National Antimicrobial Resistance Monitoring 
System: Enteric Bacteria (NARMS: EB); 
Bacteria monitored for antibiotic resistance: Shigella, Escherichia 
coli O157, Campylobacter, typhoidal Salmonella, and non-typhoidal 
Salmonella[C]; 
Geographic coverage of surveillance: 50 states for Shigella, typhoidal 
Salmonella, non-typhoidal Salmonella, and Escherichia coli O157; 
10 states for Campylobacter--California, Colorado, Connecticut, 
Georgia, Maryland, Minnesota, New Mexico, New York, Oregon, and 
Tennessee; 
Examples of how surveillance data were used: NARMS: EB data were used 
in 2005 to support the Food and Drug Administration's (FDA) withdrawal 
of approval for the use of enrofloxacin in chickens and turkeys. 
Enrofloxacin, a fluoroquinolone, marketed under the trade name 
Baytril, had been approved for use in poultry production. In September 
2005, FDA withdrew its approval because of concerns about the spread 
of fluoroquinolone-resistant Campylobacter from poultry to humans. 
NARMS: EB data from 1996-2006 were used to identify mechanisms of 
resistance to cephalosporins among specific types of Salmonella. 

Surveillance system: National Healthcare Safety Network (NHSN); 
Bacteria monitored for antibiotic resistance: Includes, among others, 
Enterococcus faecalis; Enterococcus faecium; Staphylococcus aureus; 
Acinetobacter; Escherichia coli; Enterobacter; Klebsiella oxytoca; 
Klebsiella pneumoniae; Pseudomonas aeruginosa; and Clostridium 
difficile; 
Geographic coverage of surveillance: Participating healthcare 
facilities across the United States; 
Examples of how surveillance data were used: Participating facilities 
have used NHSN data to assess their own healthcare-associated 
infection (HAI) rates, by comparing their rates with national rates. 
CDC also compiled 2006-2007 data on antibiotic resistance across 
participating facilities and reported, for example, that as many as 16 
percent of all HAIs observed in NHSN were associated with nine 
multidrug-resistant bacteria, such as MRSA. 

Surveillance system: National Notifiable Diseases Surveillance System 
(NNDSS); 
Bacteria monitored for antibiotic resistance: Streptococcus pneumoniae; 
Geographic coverage of surveillance: Health departments in the 50 
states, 5 territories, New York City, and the District of Columbia 
voluntarily report cases to CDC; 
Examples of how surveillance data were used: CDC has determined that 
NNDSS data are likely to be used to assess the impact of a vaccine 
that was approved in 2010 to prevent additional strains of 
Streptococcus pneumoniae. 

Surveillance system: National Tuberculosis Surveillance System (NTSS); 
Bacteria monitored for antibiotic resistance: Mycobacterium 
tuberculosis; 
Geographic coverage of surveillance: CDC receives information on each 
newly reported case of tuberculosis (TB) in the United States; 
Examples of how surveillance data were used: In 2010, after expanding 
the NTSS data collection with the TB Genotyping Information Management 
System, CDC officials used genotypes identified with the system to 
assist an investigation of a TB outbreak among healthcare workers. As 
a result of the investigation, the probable source for the TB outbreak 
was identified. 

Source: GAO analysis and summary of CDC information. 

[A] Since 2009, CDC has monitored Clostridium difficile infections in 
healthcare and community settings through EIP (as part of its 
Healthcare Associated Infections Surveillance). CDC officials stated 
that these data complement the Clostridium difficile data that are 
captured through the National Healthcare Safety Network and will, 
among other things, inform vaccine development. 

[B] Haemophilus influenzae are monitored for antibiotic resistance 
periodically. 

[C] According to CDC officials, NARMS: EB collects data on Enterococci 
from 2 states and has a pilot study to monitor Escherichia coli in 1 
state. 

[End of table] 

[End of section] 

Appendix IV: Topical Antiseptics and Antibiotic Resistance: 

Topical antiseptics are products that are used to reduce the risk of 
infection by killing or inhibiting the growth of microorganisms, such 
as bacteria, on the skin. Topical antiseptic products are diverse, and 
include those targeted for healthcare settings, such as surgical hand 
scrubs and patient preoperative skin preparations; products targeted 
to consumers for general body cleansing include antibacterial soaps; 
and products specifically intended for use by food handlers. Topical 
antiseptics contain a variety of active ingredients; for example, 
triclosan and triclocarban are commonly used in antibacterial liquid 
and bar soaps, while alcohol is used in leave-on handwashes.[Footnote 
133] Because antiseptics are intended for use in or on humans or 
animals,[Footnote 134] they are considered drugs and are approved and 
regulated as nonprescription drugs by the Food and Drug Administration 
(FDA) under the Federal Food, Drug, and Cosmetic Act.[Footnote 135] 
There are concerns by public officials, and others, about the 
possibility that the use of, or exposure to, topical antiseptics 
causes antibiotic resistance in bacteria. This process is called cross-
resistance.[Footnote 136] 

FDA has conducted a review of the scientific literature regarding the 
relationship between exposure to active ingredients in topical 
antiseptics--including triclosan or triclocarban--and cross- 
resistance. According to the available scientific evidence that FDA 
has reviewed, bacteria are able to develop resistance to both 
antiseptics and antibiotics in the laboratory setting, but the 
relationship outside of the laboratory setting is not clear. For 
example, a laboratory study has shown that when certain strains of the 
bacteria Escherichia coli (E. coli) are exposed to triclosan, the E. 
coli not only acquire a high level of resistance to triclosan, but 
also demonstrate cross-resistance to various antibiotics, such as 
erythromycin and tetracycline.[Footnote 137] However, a study that 
examined household use of certain antiseptic products did not show an 
association between their use and the development of antibiotic 
resistance.[Footnote 138] According to FDA, the possibility that 
bacteria can develop cross-resistance to antibiotics from exposure to 
antiseptics warrants further evaluation. FDA will seek additional data 
regarding the safety of topical antiseptic products, for example, on 
the effects of antiseptics on cross-resistance, when it issues a 
proposed rule to amend the current monograph for antiseptic drug 
products. FDA officials told us that they expect the proposed rule to 
be published for public comment sometime in 2011. 

The Environmental Protection Agency (EPA) and the United States 
Geological Survey (USGS) conducted five national studies between 1999 
and 2007 that measured for the presence of the antiseptic active 
ingredients triclosan and triclocarban in the environment.[Footnote 
139] These studies tested for the presence and concentration of the 
antiseptic active ingredients along with other contaminants including 
antibiotics, in streams, groundwater, untreated drinking water, sewage 
sludge, and wastewater effluent.[Footnote 140] (See table 6.) Each of 
the studies measured for the presence of triclosan, and the study 
involving sewage sludge also tested for triclocarban.[Footnote 141] 
Triclosan was found to be present in 94 percent of sewage sludge 
samples, 100 percent of wastewater effluent samples, and 57.6 percent 
of stream samples tested from sites across the United States. It was 
also detected in 14.9 percent of groundwater samples and 8.1 percent 
of untreated drinking water samples.[Footnote 142] Triclocarban was 
found to be present in all sewage sludge samples taken from wastewater 
treatment plants located across the United States.: 

Table 7: Five National Studies that Measured the Presence of 
Antiseptic Active Ingredients in the Environment, Conducted by EPA and 
USGS: 

Name of study (agency that conducted the study): Pharmaceuticals, 
Hormones, and Other Organic Wastewater Contaminants in U.S. Streams, 
1999-2000: A National Reconnaissance (USGS); 
Year(s) study was conducted: 1999-2000; 
Description of study sites: 139 streams across 30 states; 
Examples of antiseptic active ingredients tested: Triclosan. 

Name of study (agency that conducted the study): A National 
Reconnaissance of Pharmaceuticals and Other Organic Wastewater 
Contaminants in the United States - I) Groundwater (USGS); 
Year(s) study was conducted: 2000; 
Description of study sites: 47 groundwater sites across 18 states; 
Examples of antiseptic active ingredients tested: Triclosan. 

Name of study (agency that conducted the study): A National 
Reconnaissance for Pharmaceuticals and Other Organic Wastewater 
Contaminants in the United States - II) Untreated Drinking Water 
Sources (USGS); 
Year(s) study was conducted: 2001; 
Description of study sites: 25 ground-and 49 surface-water sources of 
drinking water in 25 states and Puerto Rico; 
Examples of antiseptic active ingredients tested: Triclosan. 

Name of study (agency that conducted the study): Targeted National 
Sewage Sludge Survey (EPA); 
Year(s) study was conducted: 2006-2007; 
Description of study sites: 74 publicly owned plants that treat 
wastewater in 35 states; 
Examples of antiseptic active ingredients tested: Triclosan and 
Triclocarban. 

Name of study (agency that conducted the study): Transport of 
Chemicals from Wastewater Effluents (EPA and USGS); 
Year(s) study was conducted: 2002; 
Description of study sites: 10 wastewater treatment plants in 10 
states; 
Examples of antiseptic active ingredients tested: Triclosan. 

Source: GAO analysis and summary of EPA and USGS information. 

[End of table] 

[End of section] 

Appendix V: Comments from the Department of Health and Human Services: 

Department Of Health And Human Services:	
Office Of The Secretary: 
Assistant Secretary for Legislation: 
Washington, DC 20201: 

May 13 2011: 

Marcia Crosse: 
Director, Health Care: 
U.S. Government Accountability Office: 
441 G Street N.W. 
Washington, DC 20548: 

Dear Ms. Crosse: 

Attached are comments on the U.S. Government Accountability Office's 
(GAO) draft report entitled, "Antibiotic Resistance: Data Gaps Will 
Remain Despite HHS Taking Steps to Improve Monitoring" (GA0-11-406). 

The Department appreciates the opportunity to review this report 
before its publication. 

Sincerely, 

Signed by: 

Jim R. Esquea: 
Assistant Secretary for Legislation: 

Attachment: 

[End of letter] 

General Comments Of The Department Of Health And Human Services (HHS) 
On The Government Accountability Office's (GAO) Draft Report Entitled, 
"Antibiotic Resistance: Data Gaps Will Remain Despite HHS Taking Steps 
To Improve Monitoring" (GAO 11-406) 

The Department appreciates the opportunity to review and comment on 
this draft report. 

The Centers for Disease Control and Prevention (CDC) agrees with the 
GAO that monitoring and surveillance of antimicrobial use and the 
occurrence of resistant infections are critically important in 
preventing the development and spread of antibiotic resistance. 

As GAO notes, CDC has previously recognized gaps in the monitoring and 
surveillance of antimicrobial use and resistance and is taking 
specific steps to address these gaps. As noted in the report, these 
steps include: 

* The planned prevalence survey of U.S. acute care hospitals; 

* Addition of the antimicrobial use and resistance module to NHSN; 

* Increase in sample size of the National Ambulatory Medical Care 
Survey; 

* Acquisition of antimicrobial use data from private vendors; 

* Sharing of data among Federal agencies, including FDA, NIH and CMS, 
which is expanding its own data collections in collaboration with 
CDC's NHSN; 

* Continued growth of the NHSN and the enhancement of components which 
collect data from outpatient facilities. 

Additional CDC activities, not specifically mentioned in the GAO 
report, are described in the draft document A Public Health Action 
Plan to Combat Antimicrobial Resistance produced by
the Interagency Task Force on Antimicrobial Resistance [hyperlink, 
(http://www.cdc.gov/drugresistance/pdf/2010/Interagency-Action-Plan-
PreClearance-03-2011.pdf]. This document identifies over 50 specific 
actions being undertaken by Task Force members to improve monitoring 
and surveillance of antimicrobial use and resistant infections; for 
the majority of these actions, CDC is the lead agency. Among these 
actions are: 

* Enhancements to the National Antimicrobial Monitoring System; 

* Enhancements to the Gonococcal Isolate Surveillance Project; 

* Enhancements to antimicrobial resistance monitoring conducted 
through the Emerging Infections Program; 

* Enhancements to the Active Bacterial Core Surveillance system; 

* Enhancements to the national tuberculosis reporting system; 

* Collaborations with non-Federal public health agencies (state and 
local health departments, the Conference of State and Territorial 
Epidemiologists, the Association of Public Health Laboratories), non-
governmental organizations (e.g., the Clinical and Laboratory 
Standards Institute), and international organizations (e.g., World 
Health Organization) to improve monitoring and surveillance of 
antimicrobial resistance. 

Updates on CDC's progress toward successful accomplishment of these 
action steps will be further documented in the 2010 annual progress 
report on the Action Plan, scheduled for release this summer. 

CDC believes that the successful, timely accomplishment of the 
numerous action steps currently in process and planned by CDC and in 
collaboration with Federal and non-Federal partners will result in the 
Federal agencies having sufficiently comprehensive information for a 
full and complete assessment of the public health impact of antibiotic 
resistance and will provide Federal agencies with appropriate 
information to identify necessary actions to reduce the occurrence of 
antibiotic-resistant infections. 

Finally, CDC has initiated the process of developing a strategic plan 
for preventing the emergence and spread of antimicrobial resistant 
infections, of which a primary component is the monitoring and 
surveillance of antimicrobial use and resistance. 

[End of section] 

Appendix VI: GAO Contact and Staff Acknowledgments: 

GAO Contact: 

Marcia Crosse, (202) 512-7114 or crossem@gao.gov: 

Acknowledgments: 

In addition to the contact named above, Robert Copeland, Assistant 
Director; Elizabeth Beardsley; Pamela Dooley; Cathy Hamann; Toni 
Harrison; Elise Pressma; and Hemi Tewarson made key contributions to 
this report. 

[End of section] 

Footnotes: 

[1] For example, the medical costs attributable to the treatment of an 
antibiotic-resistant infection ranged from about $19,000 to $29,000 
per patient in a study of one hospital. In addition, the excess 
duration of a hospital stay was about 6 to 13 days and the death rate 
was twofold higher among those patients who were treated for such 
infections. See R.R. Roberts et al., "Hospital and Societal Costs of 
Antimicrobial-Resistant Infections in a Chicago Teaching Hospital: 
Implications for Antibiotic Stewardship, Clinical Infectious Diseases, 
vol. 49 (2009), pp. 1175-1184. 

[2] GAO has ongoing work examining antibiotic use in food animals. 

[3] For example, a recent report from the American Academy of 
Microbiology outlined several recommendations to help control the 
development and spread of antibiotic resistance, including improved 
surveillance to better assess the actual scope of the problem. See 
American Academy of Microbiology, Antibiotic Resistance: An Ecological 
Perspective on an Old Problem (Washington, D.C.: 2009). 

[4] See House of Representatives, Departments of Labor, Health, and 
Human Services, and Education, and Related Agencies Appropriations 
Bill, 2010: Report of the Committee on Appropriations together with 
Minority Views, Report 111-220 (Washington, D.C.: July 22, 2009). 

[5] The company IMS Health, on a monthly basis, collects data on drugs-
-including antibiotics--purchased by retail pharmacies from about 100 
drug manufacturers and about 500 distribution centers. These 
manufacturers and distribution centers provide data to IMS Health on 
the number of units sold. 

[6] The Red Book Advanced database includes a comprehensive list of 
drug products approved for use by the Food and Drug Administration. 

[7] IMS Health conducts detailed data reliability assessments, which 
include comparing monthly data from drug manufacturers and 
distribution centers to data from the prior month and the prior year 
in order to ensure consistency. 

[8] The Healthcare Infection Control Practices Advisory Committee is 
comprised of public infection control experts, as well as nonvoting 
federal agency representatives and nonvoting liaison representatives 
of several national organizations. The committee is charged with 
providing advice and guidance to the Secretary of HHS and the Centers 
for Disease Control and Prevention, among others, regarding the 
practice of healthcare infection control, strategies for surveillance, 
and prevention and control of healthcare-associated infections in U.S. 
healthcare facilities. The officials we interviewed from the three 
liaison organizations represented the Association of Professionals of 
Infection Control and Epidemiology, Inc., the Infectious Diseases 
Society of America, and the Society for Healthcare Epidemiology of 
America. 

[9] PhRMA officials provided us information on how pharmaceutical 
manufacturers dispose of unused drugs, such as those that are expired 
or were recalled, and active ingredients that do not get used in the 
manufacturing process. 

[10] Antibiotics are a type of antimicrobial. Antimicrobials are drugs 
or other chemicals that kill or slow the growth of organisms such as 
bacteria, viruses, and fungi. 

[11] Diagnostic tests are used to determine the types of bacteria that 
cause infection and this information can be used by healthcare 
providers to choose an appropriate antibiotic. Different antibiotics 
target different types of bacteria. 

[12] In addition, some communities conduct pharmaceutical take-back 
programs that allow the public to bring unused or expired drugs to a 
central location for disposal. 

[13] The guidance, available on the FDA Web site, states that 
consumers should follow these guidelines unless the drug's label 
directs consumers to flush the unused drug down the toilet. FDA 
recommends flushing for a small number of drugs to prevent life-
threatening risks from accidental use. See [hyperlink, 
http://www.fda.gov/forconsumers/consumerupdates/ucm101653.htm], 
downloaded on March 31, 2011. 

[14] Wastewater that leaves a treatment plant is known as effluent. 
Solid, semisolid, or liquid organic materials that leave a wastewater 
treatment plant are known as sewage sludge or biosolids. Sewage sludge 
is often applied to land as fertilizer, subject to EPA regulations. 

[15] Inadequately treated sewage from such septic systems can be a 
cause of groundwater contamination. 

[16] In general, a contaminant is any substance or matter in the 
environment such as those that have an adverse effect on air, water, 
soil, or human health. 

[17] For a discussion of wastewater treatment plants and their ability 
to remove low concentrations of antibiotics, see J.R. Lefkowitz and M. 
Duran, "Changes in Antibiotic Resistance Patterns of Escherichia coli 
during Domestic Wastewater Treatment," Water Environment Research, 
vol. 81 (2009), pp. 878-885. 

[18] Antibiotics can also enter sewage systems as a result of bathing 
and washing. Bathing and washing may release antibiotic ingredients 
remaining on the skin from the use of topical applications or from 
excretion to the skin through sweating. 

[19] Antibiotics may also enter the environment as a result of their 
use in aquaculture and orchards (e.g., antibiotics may be sprayed on 
apple or pear trees to prevent certain infections). 

[20] CDC officials told us that the act has been interpreted broadly 
to include CDC's surveillance of antibiotic-resistant infections and 
the use of antibiotics. See Public Health Service Act, as amended,  
301(a), codified at 42 U.S.C.  241(a) (2011). 

[21] The Public Health Improvement Act required that the Secretary of 
HHS establish the Task Force to provide advice and recommendations 
related to antibiotic resistance. Under the act, the secretary--in 
consultation with the Task Force and state and local public health 
officials--is required to develop, improve, coordinate, or enhance 
participation in a surveillance plan to detect and monitor emerging 
antibiotic resistance. The act also states that the secretary, in 
consultation with the Task Force and others, shall develop and 
implement educational programs for the general public to increase 
awareness of the appropriate use of antibiotics and to instruct 
healthcare professionals in the prudent use of antibiotics. See 42 
U.S.C.  247d-5 (2011). 

[22] The Task Force includes eight other federal agency members. These 
members are the Agency for Healthcare Research and Quality, Centers 
for Medicare & Medicaid Services, Health Resources and Services 
Administration, HHS Office of the Assistant Secretary for Preparedness 
and Response, Department of Agriculture, Department of Defense, 
Department of Veterans Affairs, and EPA. 

[23] The revised draft Action Plan includes the same focus areas-- 
surveillance, prevention and control, research, and product 
development--as the 2001 Action Plan, along with specific projects or 
implementation steps for many of the action items. The revised draft 
Action Plan includes expected completion dates for projects or 
implementation steps, unlike the 2001 Action Plan. 

[24] Hazardous waste has properties, such as being toxic, that make it 
dangerous or potentially harmful to human health or the environment. 

[25] Surveillance systems include the timely dissemination of data to 
persons who can undertake effective prevention and control activities, 
such as public health personnel and clinicians. 

[26] MRSA infections can also spread in the community, for example, by 
having close skin-to-skin contact or by exposure to contaminated items 
and surfaces. ABCs monitors MRSA that is spread in the community as 
well as in healthcare settings. 

[27] In contrast, FDA recently issued a report summarizing data on 
antibiotics sold or distributed for use in food-producing animals, as 
required by the Animal Drug User Fee Amendments of 2008. This report 
indicated that 28.7 million pounds of antibiotics were sold or 
distributed for use in food-producing animals in the United States in 
2009. This number includes the antibiotic class ionophores, which are 
not used in human medicine. Excluding ionophores, the total amount of 
pounds of antibiotics that were sold or distributed for use in food- 
producing animals in the United States in 2009 was 20.5 million 
pounds. According to FDA, these data are limited because they combine 
therapeutic and subtherapeutic uses of antibiotics and all species of 
animals. Further, these data do not take into account the dose size, 
which varies by individual antibiotic and species of animal, or the 
total number of animals that received antibiotics. Due to such 
limitations in the data, FDA officials noted that comparisons of 
antibiotic use between food-producing animals and humans are 
problematic. See FDA, 2009 Summary Report on Antimicrobials Sold or 
Distributed for Use in Food-Producing Animals (Rockville, Md: 2010). 
Available at [hypelink, 
http://www.fda.gov/downloads/ForIndustry/UserFees/AnimalDrugUserFeeActAD
UFA/UCM231851.pdf]. 

[28] NDAs and ANDAs are submitted to FDA by drug sponsors to obtain 
approval for their drug to be marketed in the United States. 

[29] 21 C.F.R.  314.81(b)(2)(ii)(a), 314.98(c) (2011). Generally, 
only aggregated drug distribution data can be made publicly available. 
21 C.F.R.  314.430(g)(2) (2011). 

[30] In April 2011, in response to a request from a Member of 
Congress, FDA used drug sales data to provide information about the 
amount of antibiotics that were sold in the United States in 2009 for 
human use, which it provided in correspondence to the Member. 

[31] The USITC data on antibiotic production reflected the amount of 
antibiotics that were produced--for human and animal use--in the 
United States and for sale within or outside of the United States. 
USITC began reporting on the production of antibiotics, and other 
organic chemicals at the request of the House Committee on Ways and 
Means. In 1995, the committee requested that USITC stop its data 
collection on production because it determined that this effort was no 
longer cost effective or essential for ensuring the competitiveness of 
the U.S. industry. 

[32] A limitation of comparing total weights across antibiotic classes 
is that dosages for antibiotics can vary by antibiotic class. 
According to FDA officials, comparing weights within antibiotic class 
may also be difficult, but the degree to which antibiotic dosages may 
vary within the same class is less than that across classes. 

[33] A drug is delivered to the body through oral administration when 
taken by mouth (e.g., a pill) and by injectable administration when 
delivered to the body through a needle. 

[34] NAMCS and NHAMCS are national probability sample surveys that are 
designed to provide information about medical care services in the 
United States. 

[35] The NAMCS sample does not include visits to office-based 
physicians who are employed by the federal government. 

[36] The NHAMCS sample includes nonfederal short-stay hospitals (i.e., 
average stay of fewer than 30 days) whose specialty is general (i.e., 
medical or surgical) or children's general. The NHAMCS sample also 
includes ambulatory surgery centers that are freestanding. Ambulatory 
surgery centers are medical facilities where surgical and other 
procedures not requiring an overnight hospital stay are performed. 

[37] According to CDC officials, CDC is planning to merge NHAMCS with 
its current survey on inpatient care (i.e., the National Hospital 
Discharge Survey), into one survey called the National Hospital Care 
Survey, in 2011. In the integrated survey, data collection for 
antibiotic prescriptions will continue for outpatient visits. 

[38] The surveys do not collect information on whether the 
prescriptions were filled or whether the prescribed treatment course 
was completed by the patient. According to CDC officials, this is 
because individual patients in the surveys are never identified or 
contacted. 

[39] Acute care hospitals provide inpatient medical care and other 
related services for surgery, acute medical conditions, or injuries, 
usually for a short-term illness or condition. 

[40] Some antibiotics are used to prevent infections, such as prior to 
having certain kinds of surgery that carry a high risk of infection. 

[41] CDC officials also stated that information about inpatient 
antibiotic use could inform recommendations about antibiotic treatment 
by professional groups, such as the Infectious Diseases Society of 
America. 

[42] The survey is based on a sample of acute care hospitals located 
within the 10 EIP surveillance areas (also known as 'catchment' 
areas). According to a CDC official, the survey will be representative 
of hospitals within the EIP surveillance areas. 

[43] CDC officials stated that a decision to repeat the survey will 
depend on available resources, and would be better made after the 
original survey has been completed. CDC expects to begin data 
collection in 2011 and complete its analysis in 2012. 

[44] In NHSN, similar types of surveillance information are grouped 
into modules. For example, there is a module that captures surgical 
site infections. 

[45] To illustrate, facilities reported on about 75 commonly used 
antibiotics as well as combinations of these antibiotics. 

[46] CDC officials also told us that with the redesigned module, 
facilities will be able to immediately use their data to evaluate 
antibiotic use rates for antimicrobial stewardship activities. 
Antimicrobial stewardship includes interventions and programs designed 
to improve antibiotic use. 

[47] CDC officials stated that there are no plans to provide state- 
level estimates with NHAMCS. 

[48] Otherwise healthy adults under 50 years old are an additional 
target audience. 

[49] According to CDC officials, the program was originally named the 
National Campaign for Appropriate Antibiotic Use in the Community and 
was renamed Get Smart in 2003. 

[50] In addition to health insurance companies, other Get Smart 
partners include businesses, pharmaceutical companies, foundations, 
and professional associations. As an example of how CDC collaborates 
with its partners, a health insurance company mailed Get Smart 
promotional materials to 320,000 of its customers with children ages 3 
to 10 years old. CDC also provided technical support to this company 
to develop educational kits that were sent to about 30,000 pediatric, 
family practice, and internal medicine offices. 

[51] In 2005, CDC launched two additional components of the national 
media campaign. These include materials for healthy adults, Spanish 
speakers, and American Indians. In 2008, the campaign coordinated its 
first national observance, Get Smart About Antibiotics Week, and 
through a variety of activities and resources, the messages of the Get 
Smart program were delivered to the public. 

[52] Both measures are used by HHS, as part of Healthy People 2010, to 
assess national progress related to disease prevention. 

[53] NCQA is a private organization whose mission is to improve 
healthcare quality. As part of its mission, NCQA develops quality 
standards and performance measures for a broad range of healthcare 
entities. The NCQA measures are used by more than 90 percent of U.S. 
health plans to measure performance. CDC officials helped NCQA write 
the measures on antibiotic prescribing. 

[54] NCQA also measures the percentage of healthy adults (18 to 64 
years of age) who did not receive an antibiotic prescription with a 
diagnosis of acute bronchitis, characterized by a cough that can last 
for up to 3 weeks. Performance on this measure declined between 2005 
and 2008 because the percentage decreased. 

[55] The American Academy of Pediatrics has recommended influenza 
vaccination for healthy children 6 through 24 months of age since 
2004. Currently, the American Academy of Pediatrics recommends the 
influenza vaccination for healthy children 6 months of age and older. 

[56] See J.A. Finkelstein et al., "Impact of a 16-Community Trial to 
Promote Judicious Antibiotic Use in Massachusetts," Pediatrics, vol. 
121 (2008), pp. e15-e23. 

[57] Antibiotic prescribing rates decreased in all three age groups of 
children included in the study, regardless of whether educational and 
promotional materials were distributed. For example, rates decreased 
by 14.5 percent among children 2 years old to less than 4 years old in 
communities with educational and promotional materials, and by 10.3 
percent in communities without such materials. The greater declines in 
antibiotic prescribing rates in communities with educational and 
promotional materials were statistically significant in two of the 
three age groups. 

[58] When a medication is first sold, the drug manufacturer has 
exclusive rights, or a patent, to produce that drug for a certain 
number of years. After the patent has expired, the drug becomes an off-
patent medication and can be reproduced by other drug manufacturers. 

[59] As of March 2011, this study is ongoing, according to an NIH 
official. 

[60] As of March 2011, both studies are ongoing and continue to enroll 
participants, according to an NIH official. 

[61] See C.C. Boehme et al., "Rapid Molecular Detection of 
Tuberculosis and Rifampin Resistance," New England Journal of 
Medicine, vol. 363, no. 1 (2010), pp. 1005-1015. 

[62] The test is also being recommended for the early diagnosis of 
multidrug-resistant TB and TB in individuals infected with human 
immunodeficiency virus. 

[63] As part of this effort, NIH has funded basic research, proof-of- 
concept studies, and preclinical research, according to an NIH 
official. 

[64] This candidate is currently in the first phase of clinical 
testing, which is supported by a company. A multivalent staphylococcal 
vaccine would provide broader protection against a variety of 
Staphylococcus aureus strains. 

[65] An NIH official further explained that the influenza virus causes 
lung damage that often predisposes individuals to bacterial pneumonia. 
Thus, fewer cases of influenza would lead to fewer secondary bacterial 
infections requiring antibiotic treatment. 

[66] See 21  CFR 201.24 (2011), 68 Fed. Reg. 6081 (Feb. 6, 2003). The 
amended drug labeling requirement applies only to antibiotics that are 
administered orally or intravenously. Antibiotics that are 
administered via a different route, such as those that are applied 
topically, are excluded from the labeling requirement. 

[67] For FDA information related to antibiotic use, see [hyperlink, 
http://www.fda.gov/NewsEvents/PublicHealthFocus/ucm235649.htm] 
(downloaded on March 17, 2011). 

[68] With laboratory-identified event surveillance data from NHSN, CDC 
also monitors certain HAIs caused by multidrug-resistant organisms 
(MDRO) as well as Clostridium difficile infections. 

[69] Enrollment in NHSN is open to all types of healthcare facilities 
in the United States, including acute care hospitals, psychiatric 
hospitals, rehabilitation hospitals, outpatient dialysis centers, 
ambulatory surgery centers, and long-term-care facilities. 

[70] CMS is the agency that, among other activities, administers 
Medicare, a health insurance program that helps pay for inpatient care 
in hospitals. 

[71] CDC officials said that as of January 2011, approximately 4,000 
hospitals and other healthcare facilities participated in NHSN. In 
comparison, we reported in 2008 that approximately 1,000 hospitals 
were participating in NHSN, as of December 2007. See GAO, Health-Care- 
Associated Infections in Hospitals: Leadership Needed from HHS to 
Prioritize Prevention Practices and Improve Data on These Infections, 
[hyperlink, http://www.gao.gov/products/GAO-08-283] (Washington, D.C.: 
Mar. 31, 2008). NHSN opened enrollment to all types of healthcare 
facilities in 2008. According to the American Hospital Association's 
2009 annual survey of hospitals, there are approximately 5,800 
hospitals in the United States. 

[72] The procedures include, for example, coronary artery bypass graft 
and other cardiac surgery, and hip or knee arthroplasty. 

[73] Acute care hospitals electing to participate in the Hospital 
Inpatient Quality Reporting Program are obligated to report certain 
quality data measures to CMS; those that do not participate are 
penalized by a reduction in the increase they would otherwise receive 
to their annual payments for providing inpatient services to Medicare 
beneficiaries. Under the Hospital Inpatient Quality Reporting Program, 
NHSN was designated by CMS to serve as the reporting mechanism for 
certain HAIs. 

[74] In 2008, we similarly stated that NHSN was limited in terms of 
its inability to produce reliable national estimates on the frequency 
of all HAIs--not just antibiotic-resistant HAIs. This is because NHSN 
data do not reflect the full scope of HAIs and the sample is not 
representative of facilities nationwide. See GAO-08-283. 

[75] Facilities may report on different types of HAIs for which NHSN 
has developed detailed definitions and protocols. As part of the 
protocols, facilities submit microbiological data for each HAI 
identified, provided by the facility's designated clinical 
microbiology laboratory. These data include information about the type 
of bacteria causing the infection and test results regarding 
antibiotic resistance. NHSN also has a protocol for reporting MDROs 
and Clostridium difficile infections as laboratory-identified events 
and, according to CDC officials, the test results regarding antibiotic 
resistance are used to determine whether such cases should be reported. 

[76] Central line-associated bloodstream infections, catheter- 
associated urinary tract infections, and ventilator-associated 
pneumonia are device-associated infections that can be reported 
through NHSN. Surgical site infections and postprocedure pneumonia are 
procedure-associated infections that can also be reported. MDRO and 
Clostridium difficile infections can be reported into NHSN as HAIs or 
as laboratory-identified events. 

[77] Laboratory-identified event surveillance data from NHSN also 
allow CDC to determine, among reported cases, the number of MDRO and 
Clostridium difficile infections. 

[78] NARMS: EB also collects cases from the District of Columbia, and 
NTSS reporting includes the District of Columbia, Puerto Rico, and 
other U.S. jurisdictions in the Pacific and Caribbean. 

[79] NARMS: EB collects every case, every other case, or every fifth 
case of Campylobacter from each of the 10 state health departments, 
depending on the number of cases each health department receives. 

[80] CDC also monitors Haemophilus influenzae with ABCs, but CDC 
officials stated that they do not routinely collect antibiotic 
susceptibility testing data for cases of Haemophilus influenzae 
infection, in part, because of constraints on time and resources at 
CDC's laboratories, but that the agency does conduct some testing for 
clusters of cases. 

[81] CDC uses ABCs to monitor community-and healthcare-associated 
cases of MRSA. CDC also monitors healthcare-associated MRSA through 
NHSN. 

[82] In addition to ABCs, CDC monitors cases of Streptococcus 
pneumoniae through NNDSS. CDC officials told us that NNDSS is used to 
monitor cases in areas not covered by ABCs' surveillance. NNDSS relies 
on the voluntary submission of case reports and it is considered a 
passive surveillance system. In comparison, ABCs is considered an 
active surveillance system because it relies on the active 
identification and collection of cases on a regular basis. 

[83] The 10 states are California, Colorado, Connecticut, Georgia, 
Maryland, Minnesota, New Mexico, New York, Oregon, and Tennessee. 
CDC's surveillance of Streptococcus pneumoniae, Neisseria 
meningitidis, and group A and B Streptococcus is based on geographic 
areas located in these 10 states and surveillance of MRSA is based on 
geographic areas located in 9 of the 10 states. 

[84] Bacterial isolates are sent to CDC and other laboratories for 
testing. CDC officials told us that antibiotic susceptibility testing 
is conducted on all cases of Neisseria meningitidis, Streptococcus 
pneumoniae, group A Streptococcus, and MRSA, as well as a subset of 
group B Streptococcus cases that are submitted to ABCs from 8 of the 
10 sites. 

[85] To illustrate the population sizes covered by ABCs surveillance, 
the population for Neisseria meningitidis surveillance is about 41 
million and the population for MRSA surveillance is about 19 million, 
as of January 2010. 

[86] CDC uses ABCs data to calculate national estimates of certain 
diseases, based on race and age information from ABCs surveillance 
areas and the 2009 U.S. population. 

[87] CDC officials stated that the selection of catchment areas in 
urban areas allows the agency to capture a significant percentage of 
the population in the state. 

[88] GISP surveillance collects information about gonorrhea cases from 
more locations in the West because CDC officials said they expect 
antibiotic resistance in gonorrhea to emerge first in the western 
United States and then to spread eastward. 

[89] A CDC official told us that he does not believe there are 
significant differences between men and women in the frequency of 
antibiotic resistance among cases of gonorrhea. 

[90] The survey will also be used to inform decision making regarding, 
for example, appropriate targets and strategies for preventing HAIs 
and the emergence of antibiotic-resistant infections. 

[91] The survey will collect information about different species of 
Acinetobacter and Klebsiella. 

[92] Gram-negative infections include those caused by Klebsiella, 
Acinetobacter, Pseudomonas aeruginosa, and Escherichia coli, and are 
increasingly resistant to most available antibiotics. 

[93] CDC also monitors Clostridium difficile infections through NHSN. 

[94] CDC officials also stated that these data will complement the 
data on Clostridium difficile infections that are collected through 
NHSN. 

[95] CDC officials noted that since more than 90 percent of acute care 
hospitals (excluding critical access hospitals) participate in CMS's 
Hospital Inpatient Quality Reporting Program, NHSN data will be more 
representative by 2012. 

[96] See 75 Fed. Reg. 50042 (Aug. 16, 2010). Collection and reporting 
of data on bloodstream infections associated with central lines is 
required for the fiscal year 2013 payment determination and collection 
and reporting of surgical site infections is required for the fiscal 
year 2014 payment determination. 

[97] GAO has ongoing work on pharmaceuticals in drinking water. 

[98] Treatment plants include, for example, municipal treatment plants 
that treat domestic sewage as well as healthcare and pharmaceutical 
manufacturing facility treatment plants. 

[99] RCRA's implementing regulations define hazardous waste as 
including those wastes specifically listed by EPA as well as those 
wastes exhibiting any of several characteristics. 

[100] A hazardous waste generator is any person whose processes and 
actions produce hazardous waste. 

[101] For many contaminants, EPA lacks sufficient information to allow 
EPA to make a regulatory determination. See GAO, Safe Drinking Water 
Act: EPA Should Improve Implementation of Requirements on Whether to 
Regulate Additional Contaminants, GAO-11-254 (Washington, D.C.: May 
27, 2011). 

[102] 74 Fed. Reg. 51,850, 51,852 (Oct. 8, 2009). 

[103] The other two criteria are: "the contaminant is known to occur, 
or there is a substantial likelihood that the contaminant will occur, 
in public water systems with a frequency and at levels of public 
health concern" and "in the sole judgment of the Administrator, 
regulation of such a contaminant presents a meaningful opportunity for 
health risk reduction for persons served by public water systems." 42 
U.S.C.  300g-1(b)(1)(A),(b)(1)(B)(ii) (2011). 

[104] EPA expects to publish the next CCL by 2014. 

[105] In addition, USGS has completed a national study of streambed 
sediment in about 50 streams that are located in 17 states but the 
results have not been made available. USGS officials told us that the 
agency expects to issue a report in 2012. However, some of the data 
have been published and show, for example, that trimethoprim, an 
antibiotic, occurred in higher concentrations in streambed sediment, 
compared to the overlying stream water. See E.T. Furlong et al., 
"Distributions of Organic Wastewater Contaminants between Water and 
Sediment in Surface-Water Samples in the United States," Proceedings 
of the 3rd International Conference on Pharmaceuticals and Endocrine 
Disrupting Chemicals in Water (2003), pp. 60-62. 

[106] The five national studies also measured the presence of the 
antiseptic active ingredient triclosan in the environment. (For more 
information on triclosan, see app. IV). 

[107] In comparison, EPA's targeted national sewage sludge study 
sample was designed to be representative of U.S. publicly owned 
treatment plants that treat more than one million gallons of 
wastewater per day. 

[108] Few antibiotics were detected in groundwater. For example, 
neither ciprofloxacin nor erythromycin was detected in groundwater. 
According to USGS officials, while antibiotics were generally less 
likely to be detected in groundwater compared to surface water 
systems, the USGS groundwater study's findings document that at least 
some antibiotics are able to enter groundwater. 

[109] Among the national studies of streams, groundwater, and 
untreated drinking water, the maximum antibiotic concentration level 
detected was 1.9 micrograms per liter of water--for sulfamethoxazole 
detected in streams. A concentration level of 1 microgram per liter of 
water is also referred to as 1 part per billion and a detection level 
of 1 milligram per liter of water is also referred to as 1 part per 
million. 

[110] Ciprofloxacin was not detected in the wastewater effluent study. 
Other antibiotics were detected in the treated effluent samples, 
including sulfamethoxazole and trimethoprim; the maximum concentration 
level for sulfamethoxazole was .589 micrograms per liter of water and 
the maximum concentration level for trimethoprim was .353 micrograms 
per liter of water. 

[111] In addition to the wastewater effluent study, USGS has conducted 
other, generally smaller-scale studies that examined levels of 
antibiotics in various sources of human and animal waste. For example, 
in one study USGS found chlortetracycline concentrations ranging from 
68 to 1000 micrograms per liter of swine waste lagoon samples. See 
Campagnolo et al., "Antimicrobial residues in animal waste and water 
resources proximal to large-scale swine and poultry feeding 
operations," The Science of the Total Environment, vol. 299 (2002), 
pp. 89-95. 

[112] EPA officials stated that they selected wastewater treatment 
plants that primarily receive wastewater from municipal sources and 
that discharge effluent to surface water. 

[113] EPA officials stated that while this study will provide the 
agency with information that will be useful in terms of the occurrence 
frequency and concentration of erythromycin, additional method 
development work will be required to produce a method that can be used 
for regulatory purposes. 

[114] Horizontal gene transfer--the process in which bacteria exchange 
genes that are coded for resistance--can also lead to an increase in 
the population of antibiotic-resistant bacteria in the environment 
because bacteria that were previously nonresistant become resistant. 
Studies have shown that concentrated animal feeding operations and 
wastewater treatment plants have high densities of antibiotics, as 
well as antibiotic-resistant bacteria, and that both characteristics 
facilitate gene transfer. For example, one study found that when swine 
waste was applied to fertilize soil, resistant bacteria found in the 
waste transferred their resistance genes to other bacteria in the 
soil. See H. Heuer et al., "Spreading antibiotic resistance through 
spread manure: characteristics of a novel plasmid type with low %G+C 
content," Environmental Microbiology (2009), vol. 11, pp. 937-949. 

[115] See S. Castiglioni, et al., "Novel homologs of the multiple 
resistance regulator marA in antibiotic-contaminated environments," 
Water Research, vol. 42 (2008), pp. 4271-4280. 

[116] See C.W. Knapp et al., "Indirect Evidence of Transposon-Mediated 
Selection of Antibiotic Resistance Genes in Aquatic Systems at Low- 
Level Oxytetracycline Exposures," Environmental Science & Technology, 
vol. 42 (2008), pp. 5348-5353. 

[117] See J. Munoz-Aguayo et al., "Evaluating the Effects of 
Chlortetracycline on the Proliferation of Antibiotic-Resistant 
Bacteria in a Simulated River Water Ecosystem," Applied and 
Environmental Microbiology, vol. 73 (2007), pp. 5421-5425. 

[118] The antibiotic concentration level that is known to increase the 
population of resistant bacteria because of selective pressure is 
referred to as a minimum inhibitory concentration (MIC) level. MIC 
levels are determined for specific types of bacteria and antibiotics 
and a MIC level reflects the lowest concentration of an antibiotic 
that prevents visible growth of a bacterium in two types of laboratory 
tests. MIC levels are used to predict the success or failure of an 
antibiotic treatment in a clinical setting, and thus, guide healthcare 
providers' choice of antibiotics to treat bacterial infections. 
According to a USGS official, the low concentration levels of 
antibiotics in the environment that have been detected in national 
studies are generally characterized as such because they are below MIC 
levels. 

[119] USGS officials further stated that there is evidence that 
antibiotic concentration levels lower than MIC levels can affect, 
among other things, bacterial growth in the environment. See J.C. 
Underwood et al., "Effects of the Antimicrobial Sulfamethoxazole on 
Groundwater Bacterial Enrichment," Environmental Science and 
Technology, vol. 45 (2011), pp. 3096-3101. 

[120] For example, see J. Fick et al., "Pharmaceuticals and Personal 
Care Products in the Environment: Contamination of Surface, Ground, 
and Drinking Water from Pharmaceutical Production," Environmental 
Toxicology and Chemistry, vol. 28 (2009), pp. 2522-2527. This study 
showed high concentrations of certain antibiotics in rivers and lakes 
near a wastewater treatment plant in India that receives wastewater 
from approximately 90 drug manufacturers. USGS officials told us that 
they are currently designing a national study of pharmaceutical 
manufacturing facilities that will examine antibiotic concentration 
levels in areas proximal to such facilities. 

[121] For example, one study, not conducted by USGS, has documented 
that triclocarban, an antiseptic active ingredient, persists and 
bioaccumulates in soils amended with treated sewage sludge. See C.P. 
Higgins et al., "Persistence of Triclocarban and Triclosan in Soils 
after Land Application of Biosolids and Bioaccumulation in Eisenia 
Foetida," Environmental Toxicology and Chemistry, vol. 30 (2010), pp. 
556-563. 

[122] A complete list of search terms was variations on the phrases 
"antibiotic resistance" or "antimicrobial resistance" found in 
combination with any of the following terms: "environment," "ground 
water," "surface water," "drinking water," "waste water," "effluent," 
"hospital effluent," "municipal sewage," "animal feeding operation," 
"ecotoxicity," "pharmaceutical plant," "sediment," and "soil." 

[123] For the purposes of our literature review, we defined the 
environment as water, soil, and sediment, as well as certain 
wastewater treatment-related settings and certain agricultural-related 
settings that serve as pathways into water, soil, and sediment. 

[124] Escherichia coli O157 can also spread through human feces. In 
addition to consuming contaminated meat, exposure to Escherichia coli 
O157 can occur by consuming other contaminated foods (e.g., milk and 
lettuce) or by having direct contact with infected carriers. 

[125] Bacteria that cause disease are referred to as pathogenic 
bacteria. In order to cause disease, pathogens must be able to enter 
the body, which can occur, for example, through the mouth, eyes, or 
wounds that tear the skin. 

[126] Some bacteria have developed resistance to antibiotics 
naturally, long before the development of commercial antibiotics. 

[127] Any use of antibiotics--appropriate and inappropriate--creates 
selective pressure among bacteria. 

[128] A species is a group of organisms--including bacteria--with 
common traits, such as similar genetic characteristics. 

[129] As an example, Escherichia coli O157 is a strain of the 
Escherichia coli species. 

[130] The resistance gene was found in cases of Escherichia coli, 
Klebsiella pneumoniae, and Enterobacter cloacae infections. The 
presence of this particular gene resulted in resistance to certain 
antibiotics including the carbapenems subclass; for certain bacterial 
infections, carbapenems are considered antibiotics of last resort. 

[131] The Clinical and Laboratory Standards Institute, a nonfederal 
entity, establishes ranges for the interpretation of test results for 
antibiotic resistance. 

[132] Test values may also fall into ranges for the 'susceptible' and 
'intermediate' categories. 

[133] Other active ingredients include iodine and chloroxylenol. 

[134] In contrast, disinfectants are used on inanimate surfaces or 
objects to destroy or inactivate infectious microorganisms. 
Consequently, disinfectants, even if they contain the same active 
ingredient as an antiseptic, are regulated as chemicals by the 
Environmental Protection Agency. 

[135] Federal Food, Drug, and Cosmetic Act of 1938, codified as 
amended at 21 U.S.C.  301 & scattered sections (2011). To be 
considered a drug, a product must be intended for use in the 
diagnosis, cure, mitigation, treatment, or prevention of disease in 
humans or animals, or it must be intended to affect the structure or 
any function of the body of humans or other animals. Most antiseptic 
products are currently being marketed under the Tentative Final 
Monograph for over-the-counter Healthcare Antiseptic Drug Products, 
published in 1994. See 59 Fed. Reg. 31,402 (June 17, 1994). 

[136] Since bacteria use similar mechanisms to resist the effects of 
antiseptics and antibiotics, scientists believe that it may be 
possible that exposure and development of resistance to antiseptics 
could also result in resistance to antibiotics. 

[137] M. Braoudaki and A.C. Hilton, "Adaptive Resistance to Biocides 
in Salmonella enterica and Escherichia coli O157 and Cross-Resistance 
to Antimicrobial Agents," Journal of Clinical Microbiology, Vol. 42 
(2004), pp. 73-78. 

[138] E.C. Cole, et al., "Investigation of antibiotic and 
antibacterial agent cross-resistance in target bacteria from homes of 
antibacterial product users and nonusers," Journal of Applied 
Microbiology, Vol. 95 (2003), pp. 664-676. 

[139] Officials from FDA and the Centers for Disease Control and 
Prevention told us that they do not collect information about the 
amounts of antiseptics produced or used in the United States. 
According to FDA officials, however, FDA collects annual drug 
distribution data for chlorhexidine gluconate products, which are used 
as topical antiseptics, but are not covered under FDA's monograph for 
antiseptic drug products. 

[140] In addition, USGS has completed a national study of streambed 
sediment in about 50 streams that are located in 17 states but the 
results have not been made available. USGS officials told us that the 
agency expects to issue a report in 2012. According to USGS officials, 
the national study of streambed sediment also tested for the presence 
of triclosan. 

[141] As part of an ongoing study, EPA and USGS are measuring for the 
presence of triclosan and triclocarban in treated drinking water. 
According to EPA officials, findings are expected to be made available 
sometime in 2012. 

[142] According to USGS officials, the laboratory method used for 
measuring triclosan in the agency's stream study was different than 
the method used in subsequent USGS studies. USGS officials further 
stated that this change in methodology resulted in higher triclosan 
detection frequencies in the stream study, compared to subsequent USGS 
studies. 

[143] Triclosan has been detected in other USGS studies involving 
human waste sources. For example, see C.A. Kinney et al., "Survey of 
Organic Wastewater Contaminants in Biosolids Destined for Land 
Application," Environmental Science and Technology, vol. 40 (2006), 
pp. 7207-7215. 

[End of section] 

GAO's Mission: 

The Government Accountability Office, the audit, evaluation and 
investigative arm of Congress, exists to support Congress in meeting 
its constitutional responsibilities and to help improve the performance 
and accountability of the federal government for the American people. 
GAO examines the use of public funds; evaluates federal programs and 
policies; and provides analyses, recommendations, and other assistance 
to help Congress make informed oversight, policy, and funding 
decisions. GAO's commitment to good government is reflected in its core 
values of accountability, integrity, and reliability. 

Obtaining Copies of GAO Reports and Testimony: 

The fastest and easiest way to obtain copies of GAO documents at no 
cost is through GAO's Web site [hyperlink, http://www.gao.gov]. Each 
weekday, GAO posts newly released reports, testimony, and 
correspondence on its Web site. To have GAO e-mail you a list of newly 
posted products every afternoon, go to [hyperlink, http://www.gao.gov] 
and select "E-mail Updates." 

Order by Phone: 

The price of each GAO publication reflects GAOs actual cost of
production and distribution and depends on the number of pages in the
publication and whether the publication is printed in color or black and
white. Pricing and ordering information is posted on GAOs Web site, 
[hyperlink, http://www.gao.gov/ordering.htm]. 

Place orders by calling (202) 512-6000, toll free (866) 801-7077, or
TDD (202) 512-2537. 

Orders may be paid for using American Express, Discover Card,
MasterCard, Visa, check, or money order. Call for additional 
information. 

To Report Fraud, Waste, and Abuse in Federal Programs: 

Contact: 

Web site: [hyperlink, http://www.gao.gov/fraudnet/fraudnet.htm]: 
E-mail: fraudnet@gao.gov: 
Automated answering system: (800) 424-5454 or (202) 512-7470: 

Congressional Relations: 

Ralph Dawn, Managing Director, dawnr@gao.gov: 
(202) 512-4400: 
U.S. Government Accountability Office: 
441 G Street NW, Room 7125: 
Washington, D.C. 20548: 

Public Affairs: 

Chuck Young, Managing Director, youngc1@gao.gov: 
(202) 512-4800: 
U.S. Government Accountability Office: 
441 G Street NW, Room 7149: 
Washington, D.C. 20548: