Antimicrobial use metrics and benchmarking to improve stewardship outcomes: methodology, opportunities, and challenges.

Measurement of antimicrobial use before and after an intervention and the associated outcomes are key activities of antimicrobial stewardship programs. In the United States, the recommended metric for aggregate antibiotic use is days of therapy/1000 patient-days. Clinical outcomes, including response to therapy and bacterial resistance, are critical measures but are more difficult to document than economic outcomes. Interhospital benchmarking of risk adjusted antimicrobial use is possible, although several obstacles remain before it can have an impact on patient care. Many challenges for stewardship programs remain, but the methods and science to support their efforts are rapidly evolving.

Trends in aminoglycoside use and gentamicin-resistant gram-negative clinical isolates in US academic medical centers: implications for antimicrobial stewardship.

OBJECTIVE: To measure trends in aminoglycoside antibiotic use and gentamicin-resistant clinical isolates across a network of hospitals and compare network-level relationships with those of individual hospitals. DESIGN: Longitudinal observational investigation. SETTING: US academic medical centers. PARTICIPANTS: Adult inpatients. METHODS: Adult aminoglycoside use was measured from 2002 or 2003 through 2009 in 29 hospitals. Hospital-wide antibiograms assessed gentamicin resistance by proportions and incidence rates for Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, and Escherichia coli. Mixed-effects analysis of variance was used to assess the significance of changes in aminoglycoside use and changes in resistance rates and proportions. Generalized estimating equations were used to assess the relationship between aminoglycoside use and resistance. RESULTS: Mean aminoglycoside use declined by 41%, reflecting reduced gentamicin (P < .0001) and tobramycin (P < .005) use; amikacin use did not change. The rate and proportion of gentamicin-resistant P. aeruginosa decreased by 48% (P < .0001) and 31% (P < .0001), respectively. The rate and proportion of gentamicin-resistant E. coli increased by 166% and 124%, respectively (P < .0001), and they were related to increasing quinolone resistance in E. coli. Resistance among K. pneumoniae and A. baumannii did not change. Relationships between aminoglycoside use and resistance at the network level were highly variable at the individual hospital level. CONCLUSIONS: Mean aminoglycoside use declined in this network of US hospitals and was associated with significant and opposite changes in rates of resistance for some organisms and no change for others. At the individual hospital level, antibiograms appear to be an unreliable reflection of antibiotic use, at least for aminoglycosides.

Benchmarking antimicrobial drug use in hospitals.

Measuring and monitoring antibiotic use in hospitals is believed to be an important component of the strategies available to antimicrobial stewardship programs to address acquired antimicrobial resistance. Recent efforts to organize large numbers of hospitals into networks allow for interhospital comparisons of a variety of healthcare processes and outcomes, a process often called 'benchmarking'. For comparisons of antimicrobial use to be valid, usage figures must be risk-adjusted to account for differences in patient mix and hospital characteristics. The purpose of this review is to describe recent methods to benchmark antimicrobial drug use and to critically assess the potential advantages and the remaining challenges. While many methodological challenges remain, and the clinical outcomes resulting from benchmarking programs have yet to be determined, recent developments suggest that benchmarking antimicrobial drug use will become an important component of antimicrobial stewardship program activities.

Can the antibiogram be used to assess microbiologic outcomes after antimicrobial stewardship interventions? A critical review of the literature.

Hospitals are implementing antimicrobial stewardship programs (ASPs) in response to national guidelines to improve the use and to extend the utility of antiinfective drugs. An often implied purpose of ASPs is to curb or reverse the emergence of resistant bacteria. Because antibiotic use causes antibiotic resistance, there is a natural tendency to link local measures of antibiotic use to local measures of bacterial resistance, and the hospital antibiogram is a readily available measure of resistance. We performed a literature review to identify published reports that used hospitalwide and unit-specific antibiograms to assess the relationship of ASP interventions to changes in resistance. Eight studies were identified and reviewed. The relationship between hospital antibiotic use and resistance is complex, and the existing literature has several limitations. Furthermore, the antibiogram itself is neither designed nor well suited to reflect changes in hospital antimicrobial drug use. The literature on the effectiveness of ASPs in reducing resistance continues to emerge, but at this time the antibiogram bears an inconsistent relationship with changes in hospital antibiotic use and cannot be recommended to reliably evaluate an ASP intervention. Interrupted time series analysis is a superior strategy to assess the effect of an ASP intervention on bacterial resistance, but it is not widely used because of its complexity and greater data requirements. Nevertheless, before ASP efforts can be convincingly demonstrated to have a favorable impact on resistance, a more sophisticated approach that links drug use to resistance should become a priority, at least for hospitals that have sufficient resources.

Benchmarking risk-adjusted adult antibacterial drug use in 70 US academic medical center hospitals.

BACKGROUND: Antimicrobial stewardship programs are advised to measure and risk-adjust antimicrobial use to facilitate interhospital comparisons, a process called benchmarking. The purpose of this investigation was to evaluate a new benchmarking strategy for antibacterials. METHODS: Hospital-wide adult antibacterial drug use in 2009 was measured as days of therapy (DOT) and length of therapy (LOT) from billing records in 70 US academic medical centers (AMCs). Patients were assigned to 1 of 35 clinical service lines (CSL) based on their Medicare Severity Diagnosis Related Group. Expected (E) use was determined by indirect standardization and compared with observed (O) use. RESULTS: Of 1,791 ,180 discharged adults, 63.7% received antibacterial drugs; the range by CSL was 14.3% (psychiatry) to 99.7% (lung transplant). Mean ± SD hospital-wide use was 839 ± 106 DOTs (range, 594-1109) and 536 ± 53.0 LOT (range, 427-684) per 1000 patient-days. The ventilator support CSL had the most DOT per discharge, 39.4 ± 9.4 days; the LOT was 21.5 ± 4.5 days. The hospital-wide O/E ratio range was 0.7-1.45; in 5 AMCs the ratio exceeded the 90% confidence interval (CI) and was below the 90% CI in 6. Variability in use was explained by the proportion of treated patients within each CSL and mean LOT and DOT per discharge. CONCLUSIONS: Adult antibacterial drug use was benchmarked to expected use adjusted for patient mix, and outlier hospitals were identified. Differences between expected and observed use reflect usage patterns that were benchmarked and are targets for evaluation and intervention.

Diversity of antimicrobial use and resistance in 42 hospitals in the United States.

STUDY OBJECTIVE: To measure diversity (or heterogeneity) of antibiotic use in a sample of hospitals in the United States and to assess an association with bacterial resistance. DESIGN: Observational cross-sectional study. SETTING: Forty-two general medical-surgical hospitals, mostly in the Eastern United States. DATA SOURCE: Administrative claims data and hospital antibiograms during 2003. MEASUREMENTS AND MAIN RESULTS: Antibiotic use was measured by defined daily dose (DDD), and diversity was assessed by using Simpson's Index and the Shannon-Weiner Index. Aggregated antibiograms (from 17 hospitals) were used to assess resistance. There were a total of 3,655,579 patient-days during 2003, with a mean +/- SD of 87,037 +/- 62,679 patient-days/hospital. Mean +/- SD antibiotic use was 704 +/- 244 DDD/1000 patient-days/hospital, and fluoroquinolones represented the largest single class. Mean +/- SD diversity by Simpson's Index was 0.861 +/- 0.022/hospital, and a strong correlation was noted between the two diversity measures. Multivariate analysis found no significant relationship between diversity and the proportion of resistant pathogens. CONCLUSION: Diversity of aggregate antibiotic use can be measured, but additional investigations are needed to determine if it is a useful strategy to contain resistance.

Resistant gram-negative bacilli: A neglected healthcare crisis?

PURPOSE: Infections caused by drug-resistant gram-negative bacteria are a growing threat to the healthcare community and clinicians are encouraged to employ a combination of strategies for effective prevention and treatment of these difficult infections. SUMMARY: Recent epidemiological studies suggest an increase in healthcare- associated infections caused by gram-negative bacteria, particularly Klebsiella spp., Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter spp. The rising incidence of drug resistance of these pathogens presents a challenge given the few novel antimicrobial agents under development that specifically target these organisms. To combat this trend, recent guidelines promote Antimicrobial Stewardship Programs (ASP) as an effective means to possibly control the emergence and spread of antimicrobial resistance. Two key ASPs strategies include prospective audit, intervention, and feedback, and formulary restriction and preauthorization. The best methods to measure antimicrobial use and antimicrobial resistance are still being developed. In addition, using pharmacokinetics and pharmacodynamics priniciples to guide antimicrobial dosing regimens may have a role in controlling development of resistance. Finally, enforcing rigorous infection control practices can reduce the transmission of problematic pathogens within the healthcare setting. CONCLUSION: With a limited number of antimicrobial agents in development, clinicians cannot rely on new drugs alone to treat infections due to drug-resistant gram-negative bacteria but must also incorporate strategies that reduce the emergence of resistance and prevent the spread of problematic bacteria. Potentially effective interventions include antimicrobial stewardship tactics that advocate optimal use of currently available antimicrobial agents and rigorous infection control measures. Infectious diseases trained pharmacists are in a unique position to play a key role in helping control the spread of nosocomial pathogens.

Antimicrobial stewardship programs in health care systems.

Antimicrobial stewardship programs in hospitals seek to optimize antimicrobial prescribing in order to improve individual patient care as well as reduce hospital costs and slow the spread of antimicrobial resistance. With antimicrobial resistance on the rise worldwide and few new agents in development, antimicrobial stewardship programs are more important than ever in ensuring the continued efficacy of available antimicrobials. The design of antimicrobial management programs should be based on the best current understanding of the relationship between antimicrobial use and resistance. Such programs should be administered by multidisciplinary teams composed of infectious diseases physicians, clinical pharmacists, clinical microbiologists, and infection control practitioners and should be actively supported by hospital administrators. Strategies for changing antimicrobial prescribing behavior include education of prescribers regarding proper antimicrobial usage, creation of an antimicrobial formulary with restricted prescribing of targeted agents, and review of antimicrobial prescribing with feedback to prescribers. Clinical computer systems can aid in the implementation of each of these strategies, especially as expert systems able to provide patient-specific data and suggestions at the point of care. Antibiotic rotation strategies control the prescribing process by scheduled changes of antimicrobial classes used for empirical therapy. When instituting an antimicrobial stewardship program, a hospital should tailor its choice of strategies to its needs and available resources.

Pseudomonas aeruginosa, Staphylococcus aureus, and fluoroquinolone use.

Few long-term multicenter investigations have evaluated the relationships between aggregate antimicrobial drug use in hospitals and bacterial resistance. We measured fluoroquinolone use from 1999 through 2003 in a network of US hospitals. The percentages of fluoroquinolone-resistant Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) were obtained from yearly antibiograms at each hospital. Univariate linear regression showed significant associations between a hospital's volume of fluoroquinolone use and percent resistance in most individual study years (1999-2001 for P. aeruginosa, 1999-2002 for S. aureus). When the method of generalized estimating equations was used, a population-averaged longitudinal model incorporating total fluoroquinolone use and the previous year's resistance (to account for autocorrelation) did not show a significant effect of fluoroquinolone use on percent resistance for most drug-organism combinations, except for the relationship between levofloxacin use and percent MRSA. The ecologic relationship between fluoroquinolone use and resistance is complex and requires further study.