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

Action Items 3—7

Action Item #3: Develop Standards and Methodologies.

Project Title: Analytical Methods Development for Ecologically Relevant Pharmaceuticals and Metabolites

• Agency: EPA
• Description: Evaluate sample volumes, sample preservation options, and extraction techniques for LC/MS/MS analyses in order to achieve the detection limits necessary to measure environmentally relevant or informatically predicted levels of the 65 pharmaceuticals in water, sediment, and tissues.
• Results: Manuscript on LC/MS/MS and water extraction methods by the end of FY07. Manuscript on LC/MS/MS and sediment and tissue extraction methods by the end of FY08. FY10 Report on chemical methods developed for ecologically relevant pharmaceuticals.

Project Title: Development and Single Lab Validation of Methods for Pharmaceuticals and Personal Care Products

• Agency: EPA
• Description: Project designed to develop and refine methods of detection for pharmaceuticals, pesticides, steroids and hormones. Several antibiotics are included in the most recently published method. Ultimately the goal is to produce refined methods with high accuracy and precision.
• Results: Ongoing. "Method 1694: Pharmaceuticals and Personal Care Products in Water, Soil, Sediment, and Biosolids by HPLC/MS/MS" was published in December of 2007. This publication includes methods for numerous antibiotics.

Project Title: Development of CLSI/NCCLS testing standards

• Agency: FDA
• Description: Campylobacter is one of the primary foodborne pathogens under surveillance in NARMS. Additionally, many bacteria that cause disease in aquatic animals require growth conditions that vary substantially from routine terrestrial bacterial pathogens, thus the need for development of standardized testing methods.
• Results: Completed development of a standardized in vitro susceptibility testing method for Campylobacter including the determination of quality control ranges for fourteen antimicrobial agents of human and veterinary importance. This method was incorporated into the Clinical and Laboratory Standards Institute (CLSI) M45-A guideline “Methods for Antimicrobial Dilution and Disk Susceptibility Testing of Infrequently Isolated or Fastidious Bacteria”. Also completed a multi-laboratory study to evaluate the use of disk diffusion for screening Campylobacter isolates for resistance to ciprofloxacin and erythromycin which has been incorporated in the CLSI M45 guideline. Completed development of standardized in vitro susceptibility testing methods for bacteria isolated from aquatic animals. These methods were incorporated into the Clinical and Laboratory Standards Institute (CLSI) M42-A guideline “Methods for Broth Dilution Susceptibility Testing of Bacteria Isolated from Aquatic Animals”, and M49-A guideline “Methods for Antimicrobial Disk Susceptibility Testing of Bacteria Isolated from Aquatic Animals”.

Project Title: Antimicrobial susceptibility testing for Listeria

• Agency: USDA
• Description: Methodologies and standards for antimicrobial susceptibility testing of Listeria are being developed and implemented.
• Results: A new Listeria broth microdilution plate was constructed and tested in 2007. A manuscript has been submitted for publication. Bacterial Epidemiology and Antimicrobial Resistance Research Unit, ARS, Athens, GA.

Action Item #4: Address Additional Surveillance Issues Unique to AR.

Project Title: Estimating the public health and economic burden of disease caused by drug resistant Group A streptococcus

• Agency: CDC
• Description: The goal of this project is to estimate the burden of disease caused by Drug-Resistant Group A streptococcus (GAS). The project will draw from estimates of the prevalence of resistance among GAS isolates from CDC's Active Bacterial Core surveillance as well as the scientific literature on resistance. Burden of disease will be estimated from national databases of health care visits and hospitalizations as well as ABCs data on disease rates.
• Results: Progress has been made on two components of the study. Approximately 900 invasive GAS isolates obtained from CDC's active surveillance (ABCs) during 2006 have been received at CDC; antibiotic susceptibility testing of these is nearly complete. Preliminary estimates of the burden of noninvasive GAS infections (e.g., skin infections such as cellulitis and impetigo, pharyngitis) obtained from two national databases (National Ambulatory Medical Care Survey or NAMCS and the National Hospital Ambulatory Medical Care Survey or NHAMCS) have been calculated: annual visits for GAS cellulitis=1.4-5.0 million; GAS pharyngitis=4.4-9.0 million. Next steps: complete antibiotic susceptibility testing of ABCs 2007 GAS isolates; finalize national estimates of noninvasive GAS disease; calculate annual burden of macrolide resistant invasive GAS infections as identified through ABCs and use sensitivity estimates to generate high and low estimates of the total annual number of resistant noninvasive GAS infections.

Project Title: National Burden of antimicrobial resistant neonatal sepsis

• Agency: CDC
• Description: Neonatal sepsis, including bloodstream infections, meningitis, pneumonia and clinical sepsis, is a leading cause of illness in early life that can result in long-term disability and death. The emergence of antimicrobial resistance among common neonatal pathogens, particularly Escherichia coli and Staphylococcus aureus, threatens successful treatment of these infections and has raised concerns about overuse of intrapartum antibiotics. Recent studies have detected vaginal MRSA colonization in up to 11% of pregnant women late in pregnancy. However, there are no precise estimates of the overall burden of disease caused by drug-resistant neonatal pathogens upon which to base clinical guidelines and policy decisions. This project is a collaboration between 3 CDC centers, Emory University, and the National Institute of Child Health and Development's (NICHD) neonatal network. Through CDC's Active Bacterial Core surveillance (ABCs) and NICHD's neonatal network, we will conduct active surveillance for early-onset neonatal sepsis from 2007-2009.
• Results: Accomplishments to date include identification of 175 neonatal sepsis cases in the participating ABCs areas in 2007 (data not finalized) suggesting a slight decline in overall incidence from 2006. No additional early-onset MRSA cases in ABCs were confirmed in 2007. The NICHD 2007 data are not finalized; from 2006-first 6 months of 2007 NICHD identified 221 early-onset sepsis cases; GBS was the leading cause (33%) followed by E. coli (27%). From ABCs we documented that 32% of births in the era of universal GBS screening are exposed to intrapartum antibiotics; penicillin and ampillin are the most common agents (77%) followed by clindamycin. For newborns only sepsis associated hospitalizations declined from 25-21 hospitalizations /1000 live births; for all infants <3 months of age, sepsis-associated hospitalizations declined form 35-31 hospitalizations/1000 live births.

Project Title: Population-based surveillance for antimicrobial resistance among candida bloodstream infections.

• Agency: CDC
• Description: Conduct population-based surveillance for antimicrobial resistance among candida bloodstream infections in Baltimore and surrounding area and Atlanta and surrounding area (limited by funding to two sites). Sites will collect epidemiologic data and submit candida isolates to CDC for speciation and susceptibility results. Surveillance will be conducted for two years and compared with previous surveillance data from the same areas in order to assess changing trends. There are no national surveillance programs for monitoring susceptibility in candida infections.
• Results: Approximately 100 isolates have been received to date from Atlanta metropolitan area sites. Demographic and detailed clinical data collection for case patients is also underway in the Atlanta area. Of 70 cases for whom data have been received, 50% have candidemia due to C. albicans, and 30% have candidemia due to C. glabrata (12% of candidemia cases were due to C. glabrata in 1992-1993 Atlanta metropolitan area candidemia surveillance). Species confirmation is underway at CDC, and susceptibility testing will be performed. Isolate collection has recently begun in Baltimore City and Baltimore County. More funding is being sought in order to expand the surveillance network.

Project Title: Clinical Outcomes in Multi-Drug Resistant non-Typhi Salmonella Serotypes

• Agency: CDC
• Description: Enhanced surveillance for non-Typhi Salmonella to investigate the impact of multi-drug resistance on clinical outcomes.
• Results: 8 of 10 sites completed 2 years of data/isolate collection. Participants submitted approximately 350 isolates for susceptibility testing to NARMS lab at CDC. Participants and CDC epidemiologists conducted teleconferences to finalize analysis scheme.

Project Title: Implementation of the Collaboration in Animal Health and Food Safety Epidemiology (CAHFSE).

• Agency: USDA
• Description: Collaboration in Animal Health, Food Safety, and Epidemiology (CAHFSE) is a comprehensive USDA program designed to address animal health and food safety issues, including antimicrobial resistance, utilizing continual tracking of the selected data points. This program includes on-farm sample collection and data and risk factor analysis (APHIS), research efforts with molecular and phenotypic characterization of isolates, pathogenesis and development of intervention strategies (ARS), and in-plant efforts for sample collection, data analysis and risk assessment (Food Safety and Inspection Service (FSIS).
• Results: As of 2007, a total of 1209 on-farm swine fecal samples from 31 farms were analyzed for Salmonella. A total of 516 of these samples were analyzed for the presence of Campylobacter, E. coli, and enterococci. The incidence of Salmonella, Campylobacter, E. coli, and enterococci was 7%, 27%, 87%, and 60%, respectively. The incidence of Salmonella, E. coli, and enterococci was consistent with previous years, while the level of Campylobacter was almost 50% less than in previous years. The predominant serotypes of Salmonella were S. Derby, S. Typhimurium 5(-), S. Heidelberg, and, S. Mbandaka.

Project Title: Participation in the Regional Dairy Quality Management Alliance (RDQMA).

• Agency: USDA
• Description: The mission of the RDQMA is to assure a healthful and safe food supply by advocating the adoption of best management practices (BMPs), which promote animal health and welfare, improve productivity and profitability of dairy farms and encourages environmental stewardship. The RDQMA utilizes the New York State Cattle Health Assurance Program (NYSCHAP) herd risk assessment model and this model has been adopted for use in all participating states. The USDA is responsible for addressing specific issues such as Johne's Disease, salmonellosis, antimicrobial resistance and mastitis/milk quality. The RDQMA is being considered as the pilot program prior to implementation of a dairy component of the CAHFSE program.
• Results: Ongoing. Blood, manure, weekly bulk milk tank samples, environmental samples, management data surveys, economic data, nutrient management data and carcass data are being gathered from 2 farms in the northeastern US. Samples are being analyzed for the presence of Mycobacterium avium spp. paratuberculosis, Salmonella spp., E. coli 0157:H7 and generic E. coli, Listeria monocytogenes, Campylobacter, and Enterococci. Bacterial Epidemiology and Antimicrobial Resistance Research Unit, ARS, Athens, GA. This program is in the early stages of data collection.

Project Title: Implementation of a dairy pilot program in the Midwest.

• Agency: USDA
• Description: Prior to implementation of a dairy component of the CAHFSE program, and in addition to the RDQMA described above, APHIS and ARS have undertaken a pilot study on 5 dairy farms in the midwest for comparison to the RDQMA program.
  Currently, samples are being cultured for Salmonella, Campylobacter, E. coli and Enterococci, (zoonotic and commensal bacteria).  Sera are being banked for future testing. Samples and health/management data are being collected from each farm monthly.
• Results: Completed-2007. Bacterial Epidemiology and Antimicrobial Resistance Research Unit, ARS, Athens, GA. From the APHIS dairy study, a total of approximately 500 fecal and environmental samples were analyzed for Salmonella with one-fourth of these sampled for the other bacteria. The incidence of Salmonella, E. coli, and enterococci was consistent with previous years, while the level of Campylobacter was almost 50% less than in previous years. The predominant serotypes of Salmonella from swine samples were S. Derby, S. Typhimurium 5(-), S. Heidelberg, and, S. Mbandaka.

Project Title: Implementation of USDA VetNet.

• Agency: USDA
• Description: USDA VetNet was established in 2003 and was modeled after PulseNet USA, the national molecular subtyping network for food-borne disease surveillance. The objectives of USDA VetNet are to use PFGE to subtype zoonotic pathogens submitted to the animal arm of the National Antimicrobial Resistance Monitoring System (NARMS), compare USDA VetNet and PulseNet PFGE patterns, and to use the comparative data for surveillance and investigation of food-borne illness outbreaks. Whereas PulseNet subtypes seven food borne disease-causing bacteria: E. coli O157:H7, nontyphoidal Salmonella, Shigella, Listeria monocytogenes, Campylobacter, Yersinia pestis, and Vibrio cholerae, VetNet, at present, subtypes nontyphoidal Salmonella serotypes and Campylobacter from animals including diagnostic specimens, healthy farm animals, and carcasses of food-producing animals at slaughter.
• Results: Ongoing. Bacterial Epidemiology and Antimicrobial Resistance Research Unit, ARS, Athens, GA. VetNet has two functioning databases including the NARMS Salmonella and Campylobacter databases. The Salmonella database contains over 13,000 Salmonella isolates, while the Campylobacter database contains over 900 Campylobacter isolates. Both databases contain the PFGE Tagged Image File Format (TIFF) images, demographic information, and the antimicrobial resistance profiles assigned by NARMS.

** TOP PRIORITY **

Action Item #5: Develop and Implement Procedures for Monitoring Antimicrobial Use In Human Medicine, Agriculture, Veterinary Medicine, and Consumer Products.

Project Title: Comprehensive demonstration project: building regional coalitions to prevent methicillin-resistant Staphylococcus aureus in healthcare facilities

• Agency: CDC
• Description: This project supports the development and implementation of comprehensive programs to reduce the incidence of  MRSA infections in states and/or large regional networks acute phase and nonacute phase healthcare facilities.  The Pittsburgh Regional Healthcare Initiative (PRHI) was recruited as a collaborating partner for this project.  PRHI is a coalition of regional healthcare facilities and civic, corporate, and healthcare leaders in the Pittsburgh area dedicated to improving the quality of healthcare delivery in southwestern Pennsylvania. 
• Results: 2007 milestones include: 1) National Veteran's Health Affairs MRSA Prevention Initiative-building on the work at VA Pittsburgh, a national pilot program was initiated in August 2006 to determine if results could be replicated in 17 other VA hospitals; CDC's NHSN is being used to measure the impact. In January 2007 plans were announced to initiate MRSA prevention programs in all VA hospitals. CDC continues to actively participate in that national task force. 2) Plexus Institute Initiative (funded by Robert Woods Johnson Foundation-another expansion of Pittsburgh VA work, this project examines use of a social/cultural change improvement model (“positive deviance') applied to MRSA prevention in 6 funded sites. CDC is providing in-kind support and assistance. 3) Maryland Patient Safety Center Initiative has initiated a regional voluntary MRSA prevention program of 16 Maryland Hospitals that will implement MRSA prevention initiatives using the “positive deviance” change model. CDC is providing in-kind support and assistance in using NHSN as the outcome measurement tool.

Project Title: National Ambulatory Medical Care Survey (NAMCS) and National Hospital Ambulatory Medical Care Survey (NHAMCS)

• Agency: CDC
• Description: NAMCS is an annual national survey that collects data on the utilization of ambulatory medical care services provided by office-based physicians in the United States. Findings are based on a sample of visits to nonfederally employed office-based physicians who are primarily engaged in direct patient care. NAMCS monitors trends in prescription of antimicrobial drugs in the physician office setting.
  NHAMCS is an annual national survey that collects data on the utilization of ambulatory medical care services provided by hospital emergency and outpatient departments in the United States. Findings are based on a sample of visits to emergency departments and outpatient clinics. NHAMCS monitors trends in prescription of antimicrobial drugs in hospital emergency and outpatient departments.
• Results: During 2007, presented poster on "Antimicrobial Use at Respiratory-related U.S. Ambulatory Care Visits Before and After Issuance of Performance Measures for Community-acquired Pneumonia" at the 2007 Annual Meeting of the Infectious Diseases Society of America. Antimicrobial prescribing in ambulatory care settings decreased from 154 antimicrobials per 1,000 visits in 1993-94 to 123 antimicrobials per 1,000 visits in 2005-06 (down by 20%). This decline was observed in all age groups, except for persons 15-24 years of age. Among children and adolescents under 15 years of age, decreasing trends in antimicrobial prescribing rates were found in the physician office and emergency department (ED) settings, but not in the hospital outpatient department (OPD). For persons 15 years of age and over, antimicrobial prescribing rates increased by 29% in the OPD and 15% in the ED; no change was observed in physician offices.

Project Title: Prescription databases

• Agency: DoD
• Description: Use of the prescription database (PDTS) is being piloted for gastrointestinal and respiratory outbreak detections.
• Results: 17 additional VA hospitals nationwide are now participating in a pilot program to evaluate the reproducibility of the initial results, and the group has elected to use CDC's National Healthcare Safety Network (NHSN) for data collection. Data submission is underway in those hospitals.

Action Item #6: Identify and Evaluate Methods for Collecting (e.g., Optimal Sampling Methods) and Disseminating the Surveillance Data on Antimicrobial Drug Use.

Project Title: Monitoring Trends in Prescriptions of Antimicrobials in the Alaska Native Health Care System

• Agency: CDC
• Description: In Alaska, where many patients are seen and treated in locations far from a hospital and where substantial delays may occur in transporting ill patients to definitive care, little is known about changes in prescribing rates. We have developed a method for extracting prescriptions from the Indian Health Service to measure rates of antimicrobial prescriptions over time.
• Results: Final analysis and write-up of prescribing data from Anchorage and Bristol Bay regional clinical services for 1992- 2004. The overall visit-based prescribing rate of oral antimicrobials in <18 year olds was lower than rates reported from a similar age group in US but decreases in prescribing rates seen in other regions of the US since the mid-1990's have not been seen in Alaska.

Project Title: Emerging Pathogens Initiative (EPI)

• Agency: VA
• Description: Resistance data are being gathered in the EPI, an automated surveillance system, at the reporting site level and can be used for comparisons based on geographic areas and can be linked to ICD-9-CM diagnostic codes. In addition, drug use data can be linked to laboratory testing and diagnoses for a significant emerging disease.
• Results: This item is already underway in the VHA with reporting from facilities across the country. 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. Request for enhancements to capture ICD-9-CM coding from outpatient encounters associated with presence of antimicrobial resistance has been submitted, as has request for ability to delineate differences of data from sites that have consolidated administrative services and reporting mechanisms.

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: Commercially available software are being tested in clinical settings including some VA medical centers. 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. 

Action Item #7: Work With Accrediting Agencies To Address Antimicrobial Drug-Use As Part Of Quality Assurance In Health Care Delivery Systems.

Project Title: Get Smart: Know When Antibiotics Work-Development and testing of Health Plan Employer Data and Information Set (HEDIS) measures for appropriate antibiotic use

• Agency: CDC
• Description: HEDIS is a performance measurement tool used by purchasers and consumers to compare many of the nation's leading health plans.  In this project, CDC epidemiologists collaborate with experts in the development and testing of HEDIS measures to develop and test one or more measures of appropriate antimicrobial use in children. Measures include rate of prescribing antimicrobial drugs for acute upper respiratory infections and bronchitis; rate of prescribing antimicrobial drugs for pharyngitis where no throat culture or rapid streptococcal antigen test was performed; and episodes of otitis media treated with a recommended first-line agent. When the measure is incorporated into HEDIS, the measure and its impact on physician and patient awareness of appropriate antimicrobial use will be evaluated. Additionally, two new measures were developed and tested during 2004 for adults; the treatment of acute bronchitis and all upper respiratory infections.
• Results: NCQA was presented with specifications for two potential measures relating to Appropriate Antibiotic Prescribing for Respiratory Infections for Children. Two measures for children were agreed upon, developed and tested following NCQA's specifications. In 2003 these two measures; one on pharyngitis and one on upper respiratory infections were pilot tested. NCQA reviewed and accepted these measures and they were incorporated into the 2004 HEDIS set. The two adult measures were included in the HEDIS set beginning in 2006. The 2006 pilot year of the acute bronchitis measure showed that on average, both Commercial and Medicaid plans showed high rates of inappropriate antibiotic use (66% and 70%, respectively). The antibiotic utilization measure was not approved for public reporting because of the type of information collected (e.g. total number of antibiotics prescribed not broken down by diagnosis); the committee approved this measure for 2008 HEDIS.

Project Title: Surgical Site Infection Antibiotic Prophylaxis plan in conjunction with the Joint Commission ORYX aggregate

• Agency: VA
• Description: VHA has introduced surgical site antibiotic prophylaxis (including both timing and appropriateness of choices, as well as timely cessation) as a performance measure for VHA systems nationwide. These performance measures constitute 50% of the annual evaluation for Executive Career Field (ECF) performance plans for VHA regional directors and individual medical center directors.
• Results: In Federal Fiscal Year 2005, VHA introduced surgical site antibiotic prophylaxis as a performance measure for VHA systems nationwide--ongoing into FY 2008 (considered a "mission critical" measure. Data from VHA's Office of Quality and Performance reveal that for Performance Measures SIP1a (Prophylactic antibiotic started timely) comparing national numbers from the third and 4th quarters from FY 2005, FY 2006 and FY 2007, the percent starting timely was 78.7%, 88.6% and 90.6%, respectively. Additionally, for the measure of SIP10a (Correct Antibiotic ALL surgeries) comparing national numbers for fourth quarter FY 2006 and FY 2007, percent with correct antibiotics was 93.7% and 95.8%, respectively.

Project Title: Community-acquired pneumonia performance measures in conjunction with the Joint Commission ORYX aggregate

• Agency: VA
• Description: Along with b above, VHA Office of Quality and Performance has initiated quality measures for timing, diagnostics and treatment of community-acquired pneumonia.  
• Results: Data from VHA's Office of Quality and Performance reveal that for Performance Measures CAP11 (Initial antibiotic started within 8 hours of presentation) comparing national numbers from 2005, 2006, and 2006, percent of community acquired pneumonia cases admitted to inpatient status received initial antibiotics within 8 hours of presentation for 73.5%, 88.9% and 94.4% of the time respectively. For CAP12 (Initial antibiotic started within 4 hours), the numbers are 44.4%, 68.7% and 80.9%, respectively for FY 2005, 2006 and 2007. CAP14 (Appropriate initial antibiotic for immunocompromised, non-ICU admissions) was 69.7%, 82.2% and 89.0%, respectively for FY 2005, 2006 and 2007. And, CAP10 (Blood culture obtained before initial dose of antibiotic) for community acquired pneumonia admitted, quarters 2, 3 and 4 for FY 2005, 2006, and 2007 respectively, revealed rates of 87.5%, 90.3% and 92.7%, respectively.

Project Title: Transformational measures for VHA-Infection Rate Reduction

• Agency: VA
• Description: VHA Office of Quality and Performance has espoused as Transformational Measure 1, Infection Rate Reduction which included central line-associated bloodstream infections, ventilator-associated pneumonias and methicillin-resistant Staphylococcus aureus prevention. Transformational measures are incremental measures designed to support long term strategic goals. They are visionary and identify areas of significant system impact, but may not be attainable in a single performance year.
• Results: Formally adopted as transformational measures for FY 2008. Ventilator-associated pneumonia and central-line-associated bloodstream infections in the ICUs have been in effect since FY 2006 through the VA Inpatient Evaluation Center (IPEC). MRSA Prevention Initaitive started in FY 2007. All are ongoing. Transformational measures indicates that no definitive measures have been selected, but the issue is of such significance to the organization that individual ones are being reviewed for inclusion in the next set of performance measures.

Project Title: Participation in the Institute for Healthcare Improvement's 5 Million Lives Campaign

• Agency: VA
• Description: Relative to antibiotic resistance the individual campaigns 'Reduce Methicillin-Resistant Staphylococcus aureus (MRSA) Infection,' 'Prevent Surgical Site Infections,' 'Prevent Central Line-Associated Bloodstream Infections,' and 'Prevent Ventilator-Associated Pneumonia' have been espoused.
• Results: Establishment of performance measures as part of the annual evaluation for the Executive Career Field (ECF) performance plans for VHA regional directors and individual medical center directors. These will be transformational measures for the organization. Transformational measures indicates that no definitive measures have been selected, but the issue is of such significance to the organization that individual ones are being reviewed for inclusion in the next set of performance measures.

<— Previous Section: Action Items 1–2        Next Section: Action Items 8—20 —>

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