Antibiotic Resistance: Data Gaps Will Remain Despite HHS Taking Steps to Improve Monitoring
Published: 2011-06-01T00:00:00

Fast Facts:

Highlights:
section_title: Why GAO Did This Study
paragraphs: 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 HHS's 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.
section_title: What GAO Found
paragraphs: 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 HHS's Centers for Disease Control and Prevention (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. CDC's 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. CDC's 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 CDC's monitoring of antibiotic-resistant infections limit the agency's 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 agency's 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, CDC's 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 DOI's 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.
section_title: What GAO Recommends
paragraphs: To better control the spread of resistance, GAO recommends that 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.

section_title: Letter
paragraphs: 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.
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. 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. Further, a congressional committee 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. 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. 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. 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.
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.  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.
subsections: section_title: Background
subsections: section_title: Antibiotics and the Development and Spread of Antibiotic-resistant Bacteria
paragraphs: Antibiotics are drugs that are used to treat bacterial infections.  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 app. 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. 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.
section_title: Antibiotic Disposal and Pathways for Antibiotics to Enter the Environment
paragraphs: 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. 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.
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. In addition, some areas may use onsite  septic systems to treat wastewater and in these systems wastewater is  discharged below the ground’s surface. 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.
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. 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.
section_title: Federal Agency Responsibilities
paragraphs: 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. 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) and released A Public Health  Action Plan to Combat Antimicrobial Resistance (Action Plan) in 2001.  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.
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). 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.
section_title: CDC’s Monitoring of Antibiotic Resistance in Healthcare and Community Settings
paragraphs: 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. 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. 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 app. III for additional information about each of the six systems.)
section_title: 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
paragraphs: 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.
subsections: section_title: Federal Agencies Do Not Routinely Quantify the Amount of Antibiotics Produced for Human Use
paragraphs: Federal agencies, including FDA and USITC, do not routinely quantify  antibiotic production for human use. 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. 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. 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. USITC no  longer collects and quantifies antibiotic production, but did so until 1994.
section_title: Over 7 Million Pounds of Antibiotics Were Sold in 2009 for Human Use and Most Antibiotics Sold Share Common Characteristics
subsections: section_title: Most of the 7.4 Million Pounds of Antibiotics Sold Fell into Five Antibiotic Classes
paragraphs: 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. 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.
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. Oral forms of antibiotics and injectable forms, such as  intravenous injections, together accounted for 99 percent of the total  pounds sold.
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.
section_title: 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
paragraphs: 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.
subsections: section_title: CDC Annually Collects Certain National Data on Antibiotic Prescriptions to Monitor Antibiotic Use, but Data Do Not Allow for Important Analyses
paragraphs: 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). NAMCS is based on a sample of visits  to office-based physicians and community health centers. NHAMCS is  based on a sample of visits to emergency and outpatient departments and  hospital-based ambulatory surgery locations. 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. 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.
section_title: CDC Is Taking Steps to Improve Its Monitoring of Antibiotic Use in Outpatient and Inpatient Settings, but Gaps in Information Will Remain
paragraphs: 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. 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. 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. 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. Furthermore, CDC officials do  not know if the survey will be repeated. 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. 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. 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. 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.
section_title: CDC’s Get Smart Program Promotes Appropriate Antibiotic Use to Providers and Patients
paragraphs: 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. CDC  launched its Get Smart program in 1995 with the overall goal of reducing  the increasing rate of antibiotic resistance. 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. 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. 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.
section_title: 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
paragraphs: 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. 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. 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.
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. 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. 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. 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.
section_title: NIH and FDA Activities Have Complemented CDC’s Efforts to Promote Appropriate Antibiotic Use
paragraphs: 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. 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. 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. 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. 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.
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. 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. 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.
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. 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  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.”
section_title: CDC’s Monitoring of Antibiotic-Resistant Infections Has Limitations in Assessing the Overall Problem of Antibiotic Resistance
paragraphs: 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.
subsections: section_title: Data Gaps in CDC’s Monitoring of Antibiotic- Resistant Infections in Healthcare Settings Limit Its Ability to Produce Accurate National Estimates
paragraphs: 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, 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 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.  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. 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 from their intensive care units.  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. Participating facilities may submit data about  different types of HAIs, and this includes information about whether the  HAIs are resistant to antibiotics. 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.  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. 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.
section_title: CDC’s Monitoring of Antibiotic-Resistant Infections in Community Settings Can Provide Accurate National Estimates for Some Infections
paragraphs: 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. 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. 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 infection-causing  bacteria—group A and B Streptococcus, Neisseria meningitidis,  Streptococcus pneumoniae, and MRSA. 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. 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.
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. 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. 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. 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.
section_title: 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
paragraphs: 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. 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.  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. 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. 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. 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.  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. 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.
section_title: 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
paragraphs: 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.
subsections: section_title: Federal Agencies Do Not Monitor the Disposal of Most Antibiotics Intended for Human Use, but Have Measured the Presence of Antibiotics in the Environment
paragraphs: 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. According to EPA,  antibiotics enter the environment through various pathways into water,  soil, and sediment, such as wastewater discharged from treatment plants.  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. Under this system, EPA receives  information from hazardous waste generators through the Biennial  Reporting System. 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. Erythromycin is the only antibiotic  on the third CCL list (CCL 3)—the current CCL that was published in  October 2009. 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. 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.
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. (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.  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.
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. 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. 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. 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.
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.  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. 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.
section_title: Studies Find Antibiotics Present in the Environment at Certain Concentration Levels Can Increase the Population of Resistant Bacteria Due to Selective Pressure
paragraphs: 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.
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. 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. 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. 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. 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.
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.
section_title: Conclusions
paragraphs: 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.
section_title: Recommendations
paragraphs: 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.
section_title: Agency Comments
paragraphs: 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.
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section_title: Appendix I: Methodology for Reviewing Scientific Evidence on Antibiotic Resistance in the Environment
paragraphs: 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.” 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. 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.
section_title: Appendix II: Bacteria and the Development of Antibiotic Resistance
paragraphs: 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. In addition, the  same bacteria that may cause disease in one individual may not cause  disease in another. 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. 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. 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.  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.  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. 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. 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.
section_title: Appendix III: Centers for Disease Control and Prevention’s Surveillance Systems for Monitoring Antibiotic Resistance
paragraphs: Examples of how surveillance data were used  group A and group B  Streptococcus;  Neisseria meningitidis;  Streptococcus  pneumoniae; methicillin- resistant  Staphylococcus aureus  (MRSA)
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.
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.
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.
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.
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.
CDC receives information on  each newly reported case of  tuberculosis (TB) in the  United States.
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.
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.
section_title: Appendix IV: Topical Antiseptics and Antibiotic Resistance
paragraphs: 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. Because antiseptics are intended for use in or on  humans or animals, 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. 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.
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. 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.  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. 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. (See table 6.) Each of the studies measured for the  presence of triclosan, and the study involving sewage sludge also tested  for triclocarban. 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. Triclocarban was found to  be present in all sewage sludge samples taken from wastewater treatment  plants located across the United States.
section_title: Appendix V: Comments from the Department of Health and Human Services
section_title: Appendix VI: GAO Contact and Staff Acknowledgments
subsections: section_title: GAO Contact
section_title: Acknowledgments
paragraphs: 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.