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Antimicrobial Resistance Interagency Task Force
2007 Annual Report (Released June 2008)

Action Items 1–2

Focus Area I: Surveillance

Action Item #1: Determine Which Organisms and Susceptibility to Specific Antimicrobial Drugs Should Be under Surveillance and Create a Mechanism for Periodic Updating of This List.

Project Title: Public Health Surveillance

• Agency: CDC, USDA, FDA, DoD, VA
• Description: Organisms currently under public health surveillance for antimicrobial resistance include: Campylobacter, E. coli O157:H7, Gram negative and Gram positive organisms causing health care associated infections, group A Streptococcus, group B Streptococcus, Haemophilis influenzae, Helicobacter pylori, HIV, Influenza, Malaria, Mycobacterium tuberculosis, Neisseria gonorrhoeae, Neisseria meningitidis, Salmonella, Shigella, Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Trichomonas vaginalis, and Vancomycin Resistant Enterococcus. Organisms are added to this list when resistance emerges as a public health problem, as tools are developed for detecting resistance, and when there is capacity at the appropriate level. On August 30, 2006, FDA cleared a new test for the detection of vancomycin resistant Enterococci (VRE) by detecting vanA and vanB genes using an automated real-time PCR Instrument. It is indicated for use for patients at risk for VRE colonization.
• Results: Ongoing. See Executive Summary and Surveillance Data (to be released following public comment period, summer 2007).

Project: CDC Antimicrobial Resistance Surveillance Activities Meeting

• Agency: CDC
• Description: The CDC Office of Antimicrobial Resistance, in response to the recently held Antimicrobial Resistance Task Force consultants meeting, convened an internal AR surveillance meeting to explore ways for programs to strengthen and enhance their current surveillance efforts. By sharing successes and failures and exploring potential collaborations, we may be able to increase the impact and utility of our overall surveillance programs.
• Results: Meeting held May 15, 2008 at CDC. Approximately 100 attended from the agency. System/activity overviews presented included: GISP, GASP Collaborations, ABCs, NARMS, NHSN, Fungal Surveillance, AIDS, HIV/AIDS, Hepatitis, Malaria, and Neglected Tropical diseases and International Emerging Infectious Diseases.

**TOP PRIORITY**

Action Item #2: With Partners, Design and Implement a National AR Surveillance Plan.

Project Title: Expansion and enhancement of the National Antimicrobial Resistance Monitoring System (NARMS) for enteric bacteria

• Agency: CDC, FDA, USDA
• Description: NARMS is a collaboration among FDA (Center for Veterinary Medicine), CDC and U.S. Department of Agriculture. The NARMS program has three components or “arms” (human, retail, and animal) from which select foodborne bacteria are characterized from human clinical cases, retail meats, and food animals at federally inspected slaughter and processing plants. .  Additionally, ten state laboratories, who also participate in FoodNet, submit a proportion of Campylobacter isolates to the CDC NARMS laboratory. Currently, nine participating FoodNet states plus Pennsylvania test grocery store meat products for the presence of select enteric bacteria and corresponding antimicrobial susceptibility profiles. Salmonella slaughter isolates recovered from chickens, turkeys, cattle, and swine were submitted to the NARMS animal program through the USDA Food Safety and Inspection Service (FSIS) Salmonella HACCP Verification Testing Program.
• Results: NARMS now includes all 50 states, providing national surveillance for antimicrobial resistance among select foodborne pathogens.  Campylobacter sampling in the nine FoodNet states has been changed to allow for burden estimates and a plan for further expanding to more sites in underway.  Five additional sites send enterococci and E. coli isolated from outpatient stools to CDC NARMS for antimicrobial susceptibility testing. FDA, CDC, & USDA NARMS staff also met in Atlanta September 17-18, 2007 for a strategic planning conference to discuss how to implement the recommendations put forward in the FDA Science Board summary report.

Project Title: Coordination of Surveillance Efforts

• Agency: CDC, FDA
• Description: Coordinate surveillance activities.
• Results: The NARMS program just completed in 2007 an extensive review by the FDA Science Board, focusing on 4 major areas: sampling strategies, data reporting and harmonization, coordinated research, and international surveillance activities. FDA responded to the Board's recommendations, and is prioritizing recommendations for improving the program. A strategic planning meeting was held at CDC, September 17-18, 2007 focusing on how best to implement the Science Board recommendations where appropriate. NARMS scientists are also currently partnering with scientists at the University of Maryland to investigate the presence of MRSA in retail meats in the greater Washington DC area. Findings of this MRSA retail meat study may direct a larger study with the FoodNet program looking at a larger sample size obtained from the National Antimicrobial Resistance Monitoring System.

Project Title: Enhanced Surveillance for Multidrug-resistant (MDR TB) and Extensively Drug Resistant Tuberculosis (XDR TB) in the United States. Supplemental funded project for 4 TB programs.

• Agency: CDC
• Description: The purpose of this pilot exercise is to provide additional surveillance data for TB cases reported as MDR or XDR. Data not currently collected on the Report of a Verified Case of TB (RVCT), such as additional drug susceptibility test results, culture results, treatment and outcome data and information about hospitalization, are requested from 4 TB programs (CA, NYC, FL, TX), which provide about 55% of the reported MDR TB cases in the U.S. The results of this pilot will provide important additional clinical and diagnostic information on MDR TB. It will also inform CDC on how a nationwide supplemental registry for MDR/XDR TB would work, what information we can expect to collect, and the usefulness and reliability of that information.
• Results: Data collection is ongoing and should be completed by May 2008. Analysis and reporting will occur in Summer 2008.

Project Title: Treatment Practices, Outcomes and Cost of Multidrug-resistant (MDR TB) and Extensively Drug Resistant Tuberculosis (XDR TB) in the United States.

• Agency: CDC
• Description: The purpose of this proposed project is to provide detailed observational data on the current treatment characteristics, outcomes and costs of multidrug resistant (MDR) and extensively drug resistant XDR TB cases in the United States. The study collects treatment, outcome, and cost data which are generalizable to the U.S. population of MDR and XDR TB cases. The objectives of the project are to describe the clinical and case management practices currently employed to manage MDR TB and XDR TB cases, determine the frequency and contributing factors of further acquired drug resistance during treatment among MDR TB cases, describe factors associated with favorable MDR/XDR TB patient outcomes, and determine costs and payer sources for treatment and case management of MDR and XDR TB for a population representative of the US MDR TB case population.
• Results: Project is being announced by CDC for extramural funding in Spring 2008. Selection process for awards will begin June, 2008.

Project Title: Federal TB Task Force Response to Extensively Drug-resistant (XDR) TB

• Agency: CDC
• Description: In November of 2006, the Federal TB TF convened to discuss the possible U.S. government response to the global threat of XDR TB. It was decided that the TB TF would draft an action plan describing the potential U.S. government (USG) response to XDR domestically and internationally. The TB TF divided into 8 workgroups to draft each section (Surveillance, epidemiology and outbreak investigation; laboratory; infection control; clinical and programmatic; research; communications and education; partnerships; and cost analysis). The 1992 National Action Plan to Combat MDR TB was used as a model. In April 2007, an initial draft was completed and is undergoing review.
• Results: A draft of the plan has been entered into multiple agency USG clearance.

Project Title: An analysis of molecular epidemiology of multi-drug resistant M. tuberculosis in the United States

• Agency: CDC
• Description: The purpose of this research project is to develop a comprehensive national tuberculosis (TB) genotyping registry for TB case-patients with multidrug-resistant M. tuberculosis (MDR-TB) and to assess the molecular epidemiology of MDR-TB in the United States (U.S.). Through this investigation, the Division of TB Elimination (DTBE) at the Centers for Disease Control and Prevention (CDC) will work with 14 selected U.S. TB Epidemiologic Studies Consortium (TBESC) sites to collect epidemiologic and genotyping data from all MDR-TB case-patients in the U.S. This will be a five-year cross-sectional population based study design where recruitment and data collection are handled prospectively starting on October 1, 2005 through 2010.
• Results: Project is currently enrolling patients at all 14 sites.

Project Title: National Tuberculosis Surveillance System (NTSS)

• Agency: CDC
• Description: Ongoing collection, analysis, and communication of national tuberculosis surveillance information; expanded in 1993 to include the frequency and type of antimicrobial resistance, enabling strategically focused tuberculosis control and elimination efforts.  The expanded national TB surveillance system has proven its usefulness in assisting in the evaluation of the success of TB control efforts and monitoring the status of the epidemic, particularly through the collection of data on initial drug susceptibility.  Information on the use of initial regimens of four first-line drugs, directly observed therapy, and completion of therapy in one year or less have been used as measures to evaluate program success.  As future efforts towards TB elimination increase, both existing and new surveillance systems at the national, state, and local levels will become even more critical to monitor the burden and impact of TB, evaluate the success of control and prevention efforts, and direct planning and policy development.
• Results: Data collection and analysis are gathered on a continuous basis. The proportion of patients with primary MDR TB decreased from 2.4% to 1.0% in 2001. After an increase to 1.2% in 2002, the proportion has decreased to 0.9% in 2006. In 2006, the percentage of U.S.-born persons with MDR was 0.4 %. The percentage of foreign-born persons with MDR was much greater, at 1.3%. Of the total number of reported MDR TB cases, the proportion occurring in foreign-born persons increased from 25% in 1993 to 80% in 2006. The CDC annual TB surveillance report, Reported Tuberculosis in the United States, 2006, provides detailed summaries of anti-TB drug resistance from the national surveillance data. This report and other publications and recommendations based on these data are available on the internet. http://www.cdc.gov/tb/surv/surv2006/default.htm

Project Title: Gonococcal Isolate Surveillance Project (GISP)

• Agency: CDC, DoD
• Description: Sentinel surveillance system for monitoring antimicrobial resistance of Neisseria gonorrhoeae in the US, established in 1986. Male urethral gonococcal isolates are submitted for susceptibility testing together with clinical and demographic patient data each month from STD clinics in 25-30 cities in the US. GISP data has demonstrated the ongoing and increasing spread of fluoroquinolone-resistance N. gonorrhoeae and the emergence of N. gonorrhoeae with decreased susceptibility to azithromycin in the U.S. Currently, there is only one class of antibiotics that is recommended and available for treatment of all gonococcal infections in the US; and with the continued decrease in the capacity for local/state public health laboratories to maintain culture capacity and to perform local antimicrobial susceptibility testing, GISP data have become even more important.
• Results: GISP data are published in an annual report and periodically in the MMWR and other peer-reviewed journals. GISP annual reports from 1998-2005, as well as important reference and link resources can be found at http://www.cdc.gov/std/gisp. GISP data were used to update and revise the 2007 CDC's Sexually Transmitted Diseases Treatment Guidelines (Update to CDC's STD Treatment Guidelines, 2006: Fluoroquinolones NO Longer Recommended for Treatment of Gonococcal Infections. MMWR, April 13, 2007, 54 (14).) Location-specific (city, state, region) alerts and guidelines are regularly updated on the CDC's GISP website.

Project Title: Azithromycin Resistance in Syphilis in the United States

• Agency: CDC
• Description: This sentinel surveillance project for monitoring azithromycin-resistant syphilis in the United States was initiated in early 2008. Residual clinical specimens from genital ulcers and other moist lesions from men and women, along with demographic data, are submitted to CDC from STD clinic sites in 11 cities. Specimens are tested by PCR for Treponema pallidum. When positive, the DNA is screened for mutations in 23S RNA associated with resistance to azithromycin. The objectives are to monitor and track the epidemiology of azithromycin-resistant syphilis for each participating geographic locale.
• Results: Specimen and data submission is underway.

Project Title: Surveillance for HIV Drug Resistance

• Agency: CDC
• Description: CDC maintains a national surveillance system that provides data for national, state, and local public health HIV prevention program planning and evaluation. The variant, atypical, and resistant HIV surveillance (VARHS) system is an extension of CDC's HIV/AIDS reporting system in select surveillance areas. It uses remnant HIV diagnostic sera or plasma to amplify and sequence relevant genes of the HIV pol region and collects electronic amino acid sequence data from private laboratories performing genotyping to evaluate HIV-1 drug resistance and HIV-1 subtypes and associated factors among persons newly diagnosed and reported with HIV. Data will be useful for future evaluations of trends associated with the transmission of HIV drug resistant mutations and subtype distribution. Ongoing data collection and analyses through routine surveillance also will inform HIV prevention and treatment program planning and vaccine development efforts and alert to the spread or clustering of atypical strains.
• Results: National surveillance for HIV drug resistance is ongoing. Currently (2008), eleven (11) surveillance areas participate.

Project Title: Surveillance for Emerging Antimicrobial Resistance Connected to Healthcare (SEARCH)

• Agency: CDC
• Description: The SEARCH program started as a network of voluntary participants (i.e., hospitals, private industries, professional organizations, and state health departments) to enhance detection and reporting of vancomycin-resistant Staphylococcus aureus (VRSA). All U.S. healthcare organizations and practitioners are encouraged to report such isolates to CDC through SEARCH and, after notifying their state health department, to send the isolates to CDC for confirmatory testing.
• Results: As of April 2008, CDC has confirmed ten VRSAs in the U.S.

Project Title: Enhanced collection and electronic transfer of data on Antimicrobial Use and Resistance (AUR)

• Agency: CDC
• Description: A cooperative study of enhanced collection, compilation, and transmission of data on antimicrobial use and resistance from  automated laboratory instrumentation systems in healthcare settings to CDC and other public health systems using architecture fully compatible with the Public Health Information Network (PHIN).  This will create a database that will facilitate benchmarking and performance feedback to promote local AR improvement efforts; development of regional, state, and national data about patterns of use and resistance; and evaluation of prevention programs.
• Results:During 2007, microbiology, pharmacy and admission/discharge/transfer (ADT) data in the electronic HL7 Version 3 message format were received from 5 pilot healthcare facilities. The validation of these data in the medications-associated module of the National Healthcare Safety Network continue. In December 2007, collaboration with the National Center for Public Heath Informatics (NCPHI) BioSense Project was undertaken to leverage their infrastructure to expand to additional pilot healthcare facilities using a more widely accepted message format called HL7 V2.5.

Project Title: Surveillance for Invasive Methicillin-Resistant Staphylococcus aureus through the Active Bacterial Core surveillance (ABCs), Emerging Infections Program

• Agency: CDC
• Description: ABCs, part of CDC's Emerging Infections Program, conducts ongoing, active, population-based surveillance for invasive pathogens, including MRSA, in selected areas of the United States. Population-based surveillance occurs at 9 ABCs sites (California, Colorado, Georgia, Maryland, Minnesota, New York, Oregon and Tennessee) for both community-associated and healthcare-associated invasive MRSA disease. Data collected are used to determine incidence rates for invasive MRSA disease, detect at-risk populations, and explore strain characteristics through collection of MRSA isolates.
• Results: In 2008, two surveillance sites expanded. Maryland now includes the Baltimore metro area and Minnesota includes 2 counties for a total population under surveillance of approximately 18 million persons. All cases of invasive MRSA reported during 2005 and 2006 were analyzed, population based incidence rates were calculated and annual summaries were completed (http://www.cdc.gov/ncidod/dbmd/abcs/survreports.htm). A preliminary analysis of trends in invasive disease between 2005 and 2006 were performed.

Project Title: Surveillance of Multi-drug resistant infections through National Healthcare Safety Network (NHSN)

• Agency: CDC
• Description: Surveillance of healthcare associated infections and their antimicrobial resistance patterns.
• Results: The first NHSN Antimicrobial Resistance Report has been submitted to peer review for publication. Analysis of trends includes incidence of MRSA central line bloodstream infection. Development and implementation of a new module to monitor multi-drug resistant pathogens is scheduled to be launched in July 2008.

Project Title: Assessing Prevention Measures for Antimicrobial Resistant Invasive Pneumococcal Disease

• Agency: CDC
• Description: Streptococcus pneumoniae is a common cause of pneumonia, meningitis, and otitis media in the U.S. Incidence of drug-resistant S. pneumoniae increased steadily during the 1990s but then decreased after the introduction of pneumococcal conjugate vaccine (PCV7) in 2000. CDC's Active Bacterial Core surveillance (ABCs) has followed trends in invasive pneumococcal disease (IPD) to evaluate the impact of PCV7 introduction. This project has five goals: 1. Assess and improve use of pneumococcal conjugate vaccines; 2. Evaluate trends in outpatient antibiotic use for drugs likely to select for DRSP; 3. Monitor trends in DRSP using conventional and molecular means to inform the development of new pneumococcal vaccines and monitor effect of prevention measures; 4. Develop PCR-based approaches for detecting antibiotic resistant pneumococci; 5. Provide ABCs data to partners developing or evaluating prevention measures.
• Results: Held monthly conference calls with ACIP Pneumococcal Working Group to identify key areas of existing pneumococcal vaccine recommendations in need of updating; 2. Analyzed IMS data on antibiotic use to characterize geographic differences in antibiotic use and the relationship between use and resistance (compiled from ABCs data); 3. Characterized over 500 serotype 19A strains and determined that this serotype, the one serotype with the greatest increase in IPD incidence, is becoming much more genetically diverse and antibiotic resistant; 4. Partnered with colleagues in the UK and around the U.S. (e.g., Cleveland, Boston) to describe molecular mechanisms of antibiotic resistance; 5. Provided ABCs data to multiple external partners, including colleagues from Emory and Harvard Universities, GlaxoSmithKline, the Swedish Institute of Health Economics, and the Clinical and Laboratory Standards Institute.

Project Title: National molecular surveillance of antibiotic-resistant Streptococcus pneumoniae

• Agency: CDC
• Description: The Respiratory Diseases Branch (RDB) and our collaborators at the Emory Rollins School of Public health will establish a national laboratory for the molecular surveillance of invasive Streptococcus pneumoniae (Spn). We will provide front-line information concerning established and newly emerging antibiotic resistance mechanisms, clonal types, and serotypes of ABCs Spn isolates. We will monitor effects of currently used vaccines and antibiotics on the emergence and distribution of antibiotic-resistant strains.
• Results: Since introduction of the 7 valent conjugate vaccine (PCV7), serotype 19A has become the predominant invasive serotype and the primary source of antibiotic resistance; multilocus sequence typing (MLST) indicates that this is due to the emergence of new resistant strains. We have characterized at the molecular level the first example recorded in nature of a serotype switch event (resulting in 19A serotype) with concurrent conversion to penicillin-nonsusceptibility due to a single genetic event. We have also noted increases in antibiotic-nonsusceptible strains of other serotypes not targeted by PCV7 and are completing MLST analysis of these isolates. An increase in beta-lactam resistance has been documented over the past 2 years and this is probably due to the increase in penicillin nonsusceptibility among serotype 19A.

Project Title: National surveillance for the impact of pneumococcal conjugate vaccine use and appropriate antibiotic use campaigns on drug-resistant Streptococcus pneumoniae

• Agency: CDC
• Description: CDC's Active Bacterial Core surveillance (ABCs) is a high-quality, active, population-based system operating in 10 states with a population of over 20 million persons under surveillance. ABCs has tracked drug-resistant S. pneumoniae since 1995, collecting approximately 3000 invasive disease strains yearly for susceptibility testing and serotyping. Data analyses by serotype can evaluate the ongoing impact of conjugate vaccine use on resistance; by linking to data on antibiotic use inferences can also be made about a possible impact of appropriate use measures. ABCs is CDC's main system for tracking drug-resistant pneumococcus and the impact of interventions.
• Results: In 2006, approximately 3000 cases of invasive disease were identified through ABCs and serotyping and susceptibility testing of isolates is nearing completion.

Project Title: Antimicrobial resistant neonatal sepsis in the era of prophylaxis for GBS infection

• Agency: CDC
• Description: Increased use of antibiotic prophylaxis during labor and delivery to prevent perinatal group B streptococcal (GBS) disease has decreased the rate of early-onset GBS infections by 81%, but a potentially alarming increase has been detected in ampicillin resistance among selected other neonatal pathogens, especially in the low birth weight or preterm newborn. Because higher mortality is associated with ampicillin resistant gram negative infections, preliminary data on these was investigated. CDC's Emerging Infections Program network, through ABCs, provides an opportunity to monitor longer term, wider-spread trends in sepsis in the first week of life and correlate ampicillin-resistant E. coli infections with maternal receipt of intrapartum antibiotics. Enhancement of the neonatal sepsis surveillance activities in four EIPs address the impact of recent recommendations for use of vancomycin for penicillin allergy among women who carry group B streptococcus resistant to clindamycin.
• Results: ABCs surveillance since 1998 shows that E. coli is the number 2 pathogen causing invasive neonatal sepsis, after group B streptococcus. In 2006, our most recent year of analyzed surveillance, some surveillance areas have a higher incidence of E. coli sepsis than GBS sepsis. This is due to declines in GBS sepsis. E. coli sepsis incidence appears stable with a trend towards an increased incidence among preterm incidence. In 2005 and 2006 46% of E. coli isolates identified by ABCs had documented ampicillin resistance. Analysis found that exposure to at least four hours of intrapartum antibiotic prophylaxis was protective among term infants. Among preterm infants, exposure to intrapartum antibiotics was not associated with E. coli sepsis and for ampicillin-resistance E. coli sepsis. Preterm delivery was the strongest single risk factor for E. coli sepsis and for ampicillin-resistance E. coli sepsis, with an adjusted population attributable risk of 59%. To date in ABCs neonatal sepsis surveillance only 1 case infant had a sterile site MRSA isolate identified.

Project Title: Characterization of mutations in groups A and B streptococci causing decreased susceptibility to penicillin.

• Agency: CDC
• Description: Our primary objective is to screen invasive GAS and GBS isolates collected by the Active Bacterial Core surveillance (ABCs), a multistate population-based surveillance system, for susceptibility to beta-lactam agents and to characterize isolates that express unusually high MICs. These organisms could be accumulating combinations of mutations required for full resistance to penicillin. In S. pneumoniae, changes within 3 key penicillin binding protein (PBP) genes, pbp1a, pbp2x, and pbp2b lead to resistance to beta-lactam agents. Our immediate objective is to examine key PBP gene sequences from 41 national surveillance isolates (40 GBS, 1 GAS) identified so far with elevated MICs to identify the molecular genetic basis of these phenotypes. All isolates will be tested for potential beta- lactamase activity.
• Results: Three different penicillin binding protein (PBP) gene mutants in invasive GBS isolates are putatively responsible for the elevated MICs to beta lactam antibiotics. Wild type MICs were restored after PBP gene replacement with the wild type allele. Identical results were obtained through introducing the wild type PBP gene allele into this mutant on a multicopy plasmid.

Project Title: Surveillance and detection of antimicrobial resistant invasive fungal infections among stem cell and lung transplant recipients

• Agency: CDC
• Description: Goals of this project are to detect and monitor trends in emerging antimicrobial resistance among invasive fungal infections, and develop a collection of such strains for applied research by CDC and other researchers. There are currently six transplant centers involved in a sentinel network collecting surveillance data and fungal isolates, related to invasive fungal infections among persons who have received stem cell or lung transplants. This population is at highest risk for anti-fungal resistant Candida spp. and mold infections. There is no current system to track emerging anti-fungal resistance among fungal infections nationally.
• Results: University of Pittsburgh, Washington University, Cleveland Clinic, University of Alabama, University of Michigan, and the University of Pennsylvania are currently contributing to surveillance. Patient enrollment into the cohort began in April 2006. Patients are being followed for 18 months. A total of 437 patients have been enrolled to date. There have been a total of 23 invasive fungal infections, susceptibility analysis is ongoing.

Project Title: MRSA disease in Alaska

• Agency: CDC
• Description: Laboratory surveillance was established to collect isolates from the first 5 MRSA infections each month in two sites: rural southwest where MRSA comprises 85% of all S. aureus infections and at the Alaska Native Medical Center in- and outpatient services, where 50% of S. aureus infections are due to MRSA.
• Results: Isolates of MRSA from southwest Alaska are predominantly ST1 or USA400. This differs from the predominant strain in the rest of the US which is ST8 or USA300. Typing of surveillance strains from urban Anchorage is pending.

Project Title: Alaska Sentinel Surveillance for Antimicrobial Resistance in Helicobacter pylori isolates from Alaska Natives

• Agency: CDC
• Description: The Alaska H. pylori surveillance is a sentinel lab-based system that serves hospitals located in five regions of Alaska. Gastric biopsies are obtained from patients undergoing routine diagnostic esophagogastroduodenoscopy (EGD), and sent to the CDC Arctic Investigations Program (AIP) laboratory for H. pylori culture and antimicrobial susceptibility testing. Among Alaska Natives, 80% of adults have H. pylori infection and gastric cancer mortality are 2-4 times higher than the general US population.
• Results: Ongoing specimen collection and analysis. Most recent summary publication ins "Alaska sentinel surveillance for antimicrobial resistance in Helicobacter pylori isolates from Alaska native persons, 1999-2003." Helicobacter 2006; 11: 581-88. Metronidazole resistance was found in 44% of persons, clarithromycin resistance in 31%, amoxicillin resistance in 2% persons. The proportion of resistant isolates has been stable over this time period. In 2006, we added levofloxacin susceptibility testing and found 10% of isolates resistant, with resistance associated with prior fluoroquinolone use. Ref: Clin Infect Dis. 2007 Jan 15;44(2):e5-8. Epub 2006 Dec 7.

Project Title: Enhanced surveillance of influenza viruses for resistance to licensed drugs and development of tests for rapid detection of drug-resistant strains with pandemic potential

• Agency: CDC
• Description: Improved molecular tests for rapid diagnosis of mutants resistant to both the old and new drugs are needed for pandemic preparedness as well as for interpandemic control of influenza.  This project studies avian influenza viruses of different subtypes, which will improve pandemic preparedness.  In addition, it will evaluate existing biochemical tests and develop new molecular techniques for detecting influenza A and B mutants resistant to neuraminidase inhibitors (NIs), which will improve surveillance for drug-resistant variants among human influenza viruses.
• Results: In 2006, surveillance data for resistance to licensed drugs (M2 blockers: amantadine and rimantadine) in human isolates from the US and other countries was reviewed. In the US the percentage of influenza A(H3N2) viruses resistant to amantadine/rimantadine was much higher (14%) than in previous years. Continued analysis of different subtypes of influenza virus isolates resistant to amantadine/rimantadine did not reveal their antigenic difference from viruses sensitive to the drugs.

Project Title: Development of a DoD AR surveillance plan consistent with the national AR surveillance plan

• Agency: DoD
• Description: Establish an overarching framework for facilitating the implementation, operation, and evaluation of activities in AR surveillance within DoD.
• Results: In February 2007 DoD & CDC sponsored a US Medicine Institute for Health Studies (USMI) roundtable meeting entitled, "Addressing Antimicrobial Resistance"; an executive summary, transcript and speaker presentations are available on the USMI website at http://www.usminstitute.org/index.html (from the home page, click on the tab "Roundtable" and scroll down to this date). New ways to capture microbiological (including resistance) clinical lab data from military treatment facilities' electronic medical records, standardization of Acinetobacter PFGE techniques with improved specimen sharing among certain medical centers, and a significant research effort by DoD and NIAID focusing on infections (e.g., wounds, burns, etc) with multidrug resistant organisms at collaborating medical centers are areas of progress in 2007.

Project Title: DoD antimicrobial resistance surveillance network

• Agency: DoD
• Description: Under a Cooperative Research and Development Agreement (CRADA) with private industry, developing a DoD-wide AR surveillance network for identifying AR occurrences and trends within the military population. The cornerstones of this mechanism are: 1) the provision of daily, independent quality-assurance review and feedback of a military laboratory's susceptibility test results by experts in the field, 2) the continuous generation of up-to-date antibiograms based on an individual medical facility's AR patterns, 3) access to validated information on antimicrobial resistance occurrences and trends in the facility's geographic region for evaluating their implications for military personnel, and 4) facilitation of DoD-wide monitoring of AR trends to improve evidence-based decision and policy making on antibiotic usage and patient care, and 5) to enhance DoD ability to identify and respond to AR events of military significance in a timely manner.
• Results: Ongoing. Electronic antimicrobial susceptibility testing quality assurance and analysis system TSN from Focus-Bio-Innova (now Eurofins Medinet) is being used in 4 DoD pilot sites, 3 in the US and 1 in Europe. Expansion to additional sites has been proposed. TSN is viewed by its parent company as "mature" and is not seeking to add additional sites, but has not ruled out additional DoD participation. Linkage of these sites into a DoD network (pilot sites plus DoD-GEIS) for information aggregation, sharing and analysis of AR trends was accomplished in 2006.

Project Title: Emerging Pathogens Initiative (EPI)

• Agency: VA
• Description: The Veterans Health Administration (VHA) currently has an ongoing and well-defined AR surveillance plan (the EPI, a laboratory-based automated surveillance system) . The VHA uses standardized definitions and methods to set local parameters for surveillance in the EPI system. EPI data regarding some AR organisms have been returned to the Veterans Integrated Service Networks with reporting station specific data included. National quartiles have also been provided for use at the Network and local level. Confidentiality is a key element in any activity undertaken by the VHA. Great effort has been put forth to maintain confidentiality of the Emerging Pathogens Initiative surveillance data set. Access is strictly limited for any data with unique identifiers.
• Results: Currently over 158 VHA facilities across the country transmit data to the EPI monthly. The data collected by the EPI are being reviewed by the Infectious Diseases Program Office and reported to the Veterans Integrated Service Networks (VISNs = VA regional offices).  Enhancements that acquire additional information on antimicrobial resistance of specified organisms were distributed to reporting stations in July 2004 and continue to function as requested with ongoing enhancements to acquire even more information have been requested and are currently in process. Review of process for reporting information back to VISNs was undertaken and determined it should continue with annual reports; this review is still in process and will continue.

Project Title: Review of commercially available computer software to be used for infection prevention, control and containment 

• Agency: VA
• Description: VA is actively reviewing computer off-the-shelf software products to assist in infection control processes for prevention and control of infectious diseases including antimicrobial resistant organisms; computer-assisted decision support systems will be a key element in VA's choice of product.
• Results: Review and evaluation of off-the-shelf products remains in process for issue of antibiotic resistance, as well as having features that will assist in evaluation of healthcare-associated infection analysis. At this time, one vendor product has been selected for further development nationwide that will include antibiogram monitoring and possibly decision support regarding antibiotic choices. Provided successful pilot and beta-site testing, systemwide implementation would be anticipated within 3 years.

Next Section: Action Items 3—7 —>

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