Conan MacDougall

Antimicrobial Stewardship Programs in Health Care Systems

SUMMARY 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.

Measurement of Adult Antibacterial Drug Use in 130 US Hospitals: Comparison of Defined Daily Dose and Days of Therapy

BACKGROUND Hospitals are advised to measure antibiotic use and monitor its relationship to resistance. The World Health Organizations recommended metric is the defined daily dose (DDD). An alternative measure is the number of days of therapy (DOT). The purpose of this study was to contrast these measures. METHODS We measured the use of 50 antibacterial drugs that were administered to adults who were discharged from 130 US hospitals during 1 August 2002-31 July 2003. RESULTS Of 1,795,504 patients, 1,074,174 received at least 1 dose of an antibacterial drug (59.8%). The mean (+/- standard deviation) of total antibacterial drug use measured by the number of DDDs per 1000 patient-days and the number of DOTs per 1000 patient-days were not significantly different (792+/-147 and 776+/-120, respectively; P=.137), although the correlation was poor (r=0.603). For some individual drugs, such as levofloxacin and linezolid, there was no significant difference between DDDs per 1000 patient-days and DOTs per 1000 patient-days, because the administered daily dosage was nearly equivalent to the DDD. When the administered dosage exceeded the DDD, such as for ampicillin-sulbactam and cefepime, estimates of use based on DDDs per 1000 patient-days significantly exceeded those based on DOTs per 1000 patient-days (P<.001). When the administered dosage was less than the DDD, such as for piperacillin-tazobactam and ceftriaxone, estimates of use based on DDDs per 1000 patient-days were significantly lower than those based on DOTs per 1000 patient-days (P<.001). CONCLUSION The measurement of aggregate hospital antibiotic use by DDDs per 1000 patient-days and DOTs per 1000 patient-days is discordant for many frequently used antibacterial drugs, because the administered dose is dissimilar from the DDD recommended by the World Health Organization. DDD methods are useful for benchmarking purposes but cannot be used to make inferences about the number of DOTs or relative use for many antibacterial drugs.

Trends in Antibacterial Use in US Academic Health Centers: 2002 to 2006

BACKGROUND Antibacterial drug use is a major risk factor for bacterial resistance, but little is known about antibacterial use in US hospitals. The objectives of this study were to characterize trends in antibacterial use in a sample of US hospitals and to identify predictors of use. METHODS We measured systemic antibacterial use from validated claims data at 22 university teaching hospitals from January 1, 2002, through December 31, 2006, and we examined potential predictors of use in 2006, including hospital and patient demographics and antibacterial stewardship policies. RESULTS A total of 775,731 adult patients were discharged in 35 hospitals during 2006, and 492,721 (63.5%) received an antibacterial drug. The mean (SD) total antibacterial use increased from 798 (113) days of therapy per 1000 patient days in 2002 to 855 (153) in 2006 (P < .001). Fluoroquinolones were the most commonly used antibacterial class from 2002 through 2006, and use remained stable. Piperacillin sodium-tazobactam sodium and carbapenem use increased significantly, and aminoglycoside use declined. Cefazolin sodium was the most commonly used antibacterial drug in 2002 and 2003 but was eclipsed by vancomycin hydrochloride in 2004. The strongest predictor of broad-spectrum antibacterial use was explained by differences across hospitals in the mean durations of therapy. CONCLUSIONS Total antibacterial use in adults increased significantly from 2002 through 2006 in this sample of academic health centers, driven by increases in the use of broad-spectrum agents and vancomycin. These developments have important implications for acquired resistance among nosocomial pathogens, particularly for methicillin-resistant Staphylococcus aureus (MRSA).

Hospital and Community Fluoroquinolone Use and Resistance in Staphylococcus aureus and Escherichia coli in 17 US Hospitals

BACKGROUND Fluoroquinolones are widely prescribed in hospitals and the community. Previous studies have shown associations between fluoroquinolone use and isolation of fluoroquinolone-resistant Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA). We performed an ecologic-level study to determine whether variability in hospital percentages of fluoroquinolone-resistant E. coli and MRSA were associated with fluoroquinolone use in hospitals and their surrounding communities. METHODS We measured fluoroquinolone use in 17 US hospitals and their surrounding communities in the year 2000. Data on fluoroquinolone use in hospitals was electronically extracted from billing data. Data on fluoroquinolone use in communities was obtained from IMS health data for all prescriptions filled in pharmacies within a 16-km radius of each hospital. We used hospital antibiograms to determine the percentage of isolates that were fluoroquinolone-resistant E. coli and MRSA, and we performed linear regression to determine the relationship between percentage of resistant isolates and fluoroquinolone use in hospitals and their surrounding communities. RESULTS There was a significant association between total fluoroquinolone use within hospitals and percentage of S. aureus isolates that were MRSA (r=0.77; P=.0003) and between total fluoroquinolone use in the community and percentage of E. coli isolates that were fluoroquinolone-resistant E. coli (r=0.68; P=.003). Population density within the 16-km radius also correlated with MRSA percentage (r=0.57; P=.015) and fluoroquinolone-resistant E. coli percentage (r=0.85; P=.002), but associations between total fluoroquinolone use and resistance remained significant after adjustment for population density. CONCLUSIONS In this ecologic analysis, we found associations between fluoroquinolone use in hospitals and methicillin resistance in S. aureus and between fluoroquinolone use in communities and fluoroquinolone resistance in E. coli in hospitals. Antimicrobial use in hospitals and communities may have different relative importance with regard to resistance in different pathogens encountered in hospitals.

Insights from the Society of Infectious Diseases Pharmacists on Antimicrobial Stewardship Guidelines from the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America

In 2007, the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America published a document that addressed the major considerations for the justification, description, and conduct of antimicrobial stewardship programs. Our document is intended to continue the dialogue of these formalized programmatic strategies. We briefly review the guidelines, including the two primary strategies (prospective auditing with feedback, and preauthorization), and the supplemental strategies (education, information technology, transitional therapy, deescalation or streamlining, and dose optimization). Discussions are introduced or furthered in the areas of program goals, barriers and solutions, and outcome measures. Definition and training of infectious diseases pharmacists are presented in detail. We offer keys to future success, which include continued collaboration and expanded use of information technology.

Pseudomonas aeruginosa, Staphylococcus aureus, and Fluoroquinolone Use

Increasingly resistant bacteria in sickle cell disease patients indicate need to evaluate extendedspectrum cephalosporin therapy.

Variability in rates of use of antibacterials among 130 US hospitals and risk-adjustment models for interhospital comparison.

OBJECTIVE To describe variability in rates of antibacterial use in a large sample of US hospitals and to create risk-adjusted models for interhospital comparison. METHODS We retrospectively surveyed the use of 87 antibacterial agents on the basis of electronic claims data from 130 medical-surgical hospitals in the United States for the period August 2002 to July 2003; these records represented 1,798,084 adult inpatients. Hospitals were assigned randomly to the derivation data set (65 hospitals) or the validation data set (65 hospitals). Multivariable models predicting rates of antibacterial use were created using the derivation data set. These models were then used to predict rates of antibacterial use in the validation data set, which was compared with observed rates of antibacterial use. Rates of antibacterial use was measured in days of therapy per 1,000 patient-days. RESULTS Across the surveyed hospitals, a mean of 59.3% of patients received at least 1 dose of an antimicrobial agent during hospitalization (range for individual hospitals, 44.4%-73.6%). The mean total rate of antibacterial use was 789.8 days of therapy per 1,000 patient-days (range, 454.4-1,153.4). The best model for the total rate of antibacterial use explained 31% of the variance in rates of antibacterial use and included the number of hospital beds, the number of days in the intensive care unit per 1,000 patient-days, the number of surgeries per 1,000 discharges, and the number of cases of pneumonia, bacteremia, and urinary tract infection per 1,000 discharges. Five hospitals in the validation data set were identified as having outlier rates on the basis of observed antibacterial use greater than the upper bound of the 90% prediction interval for predicted antibacterial use in that hospital. CONCLUSION Most adult inpatients receive antimicrobial agents during their hospitalization, but there is substantial variability between hospitals in the volume of antibacterials used. Risk-adjusted models can explain a significant proportion of this variation and allow for comparisons between hospitals for benchmarking purposes.

Daptomycin therapy for vancomycin-resistant enterococcal bacteremia: a retrospective case series of 30 patients.

Study Objective. To determine clinical and microbiologic outcomes of daptomycin for the treatment of bacteremia caused by vancomycin‐resistant enterococci (VRE).

Update on prevalence and treatment of methicillin-resistant Staphylococcus aureus infections

The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) is characterized by variations (sometimes extreme) by country and geographic region. The conventional association of MRSA with healthcare settings has been upset by the emergence of community-associated MRSA infections in many areas. With this surge in MRSA comes a renewed interest in alternative agents to vancomycin for treatment of MRSA infections, including older drugs, such as clindamycin, doxycycline and trimethoprim– sulfamethoxazole. Newer agents, such as linezolid and daptomycin, are aiming to improve on the poor cure rates found with vancomycin in serious MRSA infections, but definitive studies showing superiority of these drugs are not yet available. Finally, the drug-development pipeline contains a number of agents for the treatment of MRSA infections, including enhanced glycopeptides (dalbavancin, oritavancin and telavancin) and anti-MRSA cephalosporins (ceftobiprole). As MRSA becomes the ‘new normal’ in many areas, clinicians will have to sort out the proper role of a dozen or more anti-MRSA drugs.

Antimicrobial drug prescribing for pneumonia in ambulatory care.

Higher levels of fluoroquinolone use were associated with increasing age and later study year.