Electronically Available Patient Claims Data Improve Models for Comparing Antibiotic Use Across Hospitals: Results From 576 US Facilities.

BACKGROUND: The Centers for Disease Control and Prevention (CDC) uses standardized antimicrobial administration ratios (SAARs)-that is, observed-to-predicted ratios-to compare antibiotic use across facilities. CDC models adjust for facility characteristics when predicting antibiotic use but do not include patient diagnoses and comorbidities that may also affect utilization. This study aimed to identify comorbidities causally related to appropriate antibiotic use and to compare models that include these comorbidities and other patient-level claims variables to a facility model for risk-adjusting inpatient antibiotic utilization. METHODS: The study included adults discharged from Premier Database hospitals in 2016-2017. For each admission, we extracted facility, claims, and antibiotic data. We evaluated 7 models to predict an admission's antibiotic days of therapy (DOTs): a CDC facility model, models that added patient clinical constructs in varying layers of complexity, and an external validation of a published patient-variable model. We calculated hospital-specific SAARs to quantify effects on hospital rankings. Separately, we used Delphi Consensus methodology to identify Elixhauser comorbidities associated with appropriate antibiotic use. RESULTS: The study included 11 701 326 admissions across 576 hospitals. Compared to a CDC-facility model, a model that added Delphi-selected comorbidities and a bacterial infection indicator was more accurate for all antibiotic outcomes. For total antibiotic use, it was 24% more accurate (respective mean absolute errors: 3.11 vs 2.35 DOTs), resulting in 31-33% more hospitals moving into bottom or top usage quartiles postadjustment. CONCLUSIONS: Adding electronically available patient claims data to facility models consistently improved antibiotic utilization predictions and yielded substantial movement in hospitals' utilization rankings.

Significant Regional Differences in Antibiotic Use Across 576 US Hospitals and 11 701 326 Adult Admissions, 2016-2017.

BACKGROUND: Quantifying the amount and diversity of antibiotic use in United States hospitals assists antibiotic stewardship efforts but is hampered by limited national surveillance. Our study aimed to address this knowledge gap by examining adult antibiotic use across 576 hospitals and nearly 12 million encounters in 2016-2017. METHODS: We conducted a retrospective study of patients aged ≥ 18 years discharged from hospitals in the Premier Healthcare Database between 1 January 2016 and 31 December 2017. Using daily antibiotic charge data, we mapped antibiotics to mutually exclusive classes and to spectrum of activity categories. We evaluated relationships between facility and case-mix characteristics and antibiotic use in negative binomial regression models. RESULTS: The study included 11 701 326 admissions, totaling 64 064 632 patient-days, across 576 hospitals. Overall, patients received antibiotics in 65% of hospitalizations, at a crude rate of 870 days of therapy (DOT) per 1000 patient-days. By class, use was highest among ß-lactam/ß-lactamase inhibitor combinations, third- and fourth-generation cephalosporins, and glycopeptides. Teaching hospitals averaged lower rates of total antibiotic use than nonteaching hospitals (834 vs 957 DOT per 1000 patient-days; P < .001). In adjusted models, teaching hospitals remained associated with lower use of third- and fourth-generation cephalosporins and antipseudomonal agents (adjusted incidence rate ratio [95% confidence interval], 0.92 [.86-.97] and 0.91 [.85-.98], respectively). Significant regional differences in total and class-specific antibiotic use also persisted in adjusted models. CONCLUSIONS: Adult inpatient antibiotic use remains high, driven predominantly by broad-spectrum agents. Better understanding reasons for interhospital usage differences, including by region and teaching status, may inform efforts to reduce inappropriate antibiotic prescribing.

Identifying Hospital Antimicrobial Resistance Targets via Robust Ranking.

We develop a robust ranking procedure to uncover trends in variation in antibiotic resistance (AR) rates across hospitals for some antibiotic-bacterium pairs over several years. We illustrate how the method can be used to detect potentially dangerous trends and to direct attention to hospitals' management practices. A robust method is indicated due to the fact that some unusual reported resistance rates may be due to measurement protocol differences and not any real difference in AR rates. Our proposed method is less sensitive to outlier observations than other robust methods. The application on real AR data shows how a dangerous trend in a particular AR rate would be detected. Our results indicate the potential benefits of systematic AR rate collection and AR reporting systems across hospitals.

Antibiogram compliance in University HealthSystem Consortium participating hospitals with Clinical and Laboratory Standards Institute guidelines.

PURPOSE: The degree of compliance with antibiogram guidance among University HealthSystem Consortium (UHC) hospitals was analyzed. METHODS: The UHC Pharmacy Council Pharmacy Practice Advancement Committee conducted a survey to evaluate hospital policies regarding the generation, reporting, and utilization of antibiograms among UHC hospitals. The survey was distributed via a UHC online survey tool to pharmacy directors at 237 UHC hospitals. Responses were collected from April 13 to May 14, 2010. RESULTS: Of the 237 hospitals to which surveys were sent, 49 hospitals (21%) from 28 states submitted survey responses. Forty-eight hospitals reported that they routinely generated antibiograms, and 36 reported that they adopted all or most of the standards recommended by the 2009 guidelines on antibiograms published by the Clinical and Laboratory Standards Institute (CLSI). The compliance rates to the four key CLSI recommendations were as follows: 98% reported data at least annually, 89% eliminated duplicate isolates, 83% did not include surveillance isolates, and 64% required at least 30 isolates for each reported species. Thirty-eight hospitals had an antimicrobial stewardship program; 35 of them formally reviewed antibiograms and 19 implemented new programs based on the antibiogram data. In 16 hospitals, formulary changes were made as a consequence of antibiogram results. In 30 hospitals, pharmacists had significant involvement in compiling, reviewing, and reporting antibiograms. CONCLUSION: Among respondents from 47 UHC hospitals, the compliance rates to four key CLSI recommendations for antibiograms ranged from 64% to 98%. Respondents from 30 hospitals reported significant involvement of pharmacists in compiling, reviewing, and reporting antibiograms.

Characterization of continued antibacterial therapy after diagnosis of hospital-onset Clostridium difficile infection: implications for antimicrobial stewardship.

STUDY OBJECTIVES: To determine the proportion of hospitalized adults with hospital-onset Clostridium difficile infection (CDI) who continued to receive concomitant non-CDI antibacterial agents, to characterize the antibacterial therapy that these patients received before and after the diagnosis of CDI, and to compare hospital outcomes between those patients who did and those who did not have their previous antibacterial therapy discontinued after CDI diagnosis. DESIGN: Retrospective cohort study. DATA SOURCE: Drug use and administrative discharge data from 42 United States academic medical centers. PATIENTS: A total of 5968 adult inpatients with hospital-onset CDI between January 1, 2002, and June 30, 2006. MEASUREMENTS AND MAIN RESULTS: We characterized patient-level antibacterial agent use before and after CDI diagnosis. Overall, 3479 patients (58.3%) continued antibacterial therapy for 2 or more days after CDI diagnosis (interhospital range 6.7-72.2%). Although the number of different antibacterial agents received in the week preceding CDI diagnosis was positively associated with continued antibacterial therapy, the relationship between continuation and severity of illness was statistically significant but nonlinear. Patients who were receiving oral vancomycin alone were less likely to have antibacterial therapy continued (28/61 patients [45.9%]) than patients receiving metronidazole alone (1154/2333 patients [49.5%]) or receiving both metronidazole and oral vancomycin (2297/3576 [64.2%]). After adjusting for confounders, patients who continued to receive antibacterial therapy had a 62.7% (95% confidence interval [CI] 48.6-78.0%, p<0.001) longer length of hospital stay after CDI diagnosis than those who did not continue therapy; the adjusted odds of mortality and odds of readmission were 1.7 (95% CI 1.4-2.1, p<0.001) and 1.2 (95% CI 1.1-1.5, p=0.025) times higher, respectively, with continued antibacterial therapy. CONCLUSION: A majority of patients with CDI continued to receive antibacterial agents after their CDI diagnosis, although the interhospital range was large. Compared with patients who did not continue therapy, hospital length of study, mortality, and subsequent admissions among patients who continued their antibacterial therapy remained significantly higher after adjusting for confounders. The adverse outcomes associated with continued therapy likely reflect the severity of the underlying primary infection and/or a poorer response to CDI therapy, suggesting an opportunity for antimicrobial stewardship programs to make important contributions to patient care.

Economic impact of Clostridium difficile infection in a multihospital cohort of academic health centers.

STUDY OBJECTIVE: To assess the economic impact of Clostridium difficile infection (CDI) in a large multihospital cohort. DESIGN: Retrospective case-control study. DATA SOURCE: Administrative claims data from 45 academic medical centers. PATIENTS: A total of 10,857 patients who developed health care-associated CDI and were discharged between April 1, 2002, and March 31, 2007 (cases); each case patient was matched by hospital, age, quarter and year of hospital discharge, and diagnosis related group to at least one control patient who did not develop health care-associated CDI (19,214 controls). MEASUREMENTS AND MAIN RESULTS: Patients with health care-associated CDI were identified by using a previously validated method combining the International Classification of Diseases, Ninth Revision, Clinical Modification code for CDI with specific CDI drug therapy (oral or intravenous metronidazole, or oral vancomycin). Costs were determined from charges by using standardized cost:charges ratios and were adjusted for age, All Patient Refined-Diagnosis Related Group (APR-DRG) severity of illness level, race, and sex with use of multivariable linear regression. The adjusted mean cost for cases was significantly higher than that for controls ($55,769 vs $28,609), and adjusted mean length of stay was twice as long (21.1 vs 10.0 days). The interaction between CDI and APR-DRG severity of illness level was significant; the effect of CDI on costs and length of stay decreased as severity of illness increased. CONCLUSION: This large CDI economic evaluation confirms that health care-associated cases of CDI are associated with significantly higher mean cost and longer length of stay than those of matched controls, with the greatest effect on costs at the lowest level of severity of illness.

Perceived barriers to scholarship and research among pharmacy practice faculty: survey report from the AACP Scholarship/Research Faculty Development Task Force.

OBJECTIVES: To identify problems that pharmacy practice faculty members face in pursuing scholarship and to develop and recommend solutions. METHODS: Department chairs were asked to forward a Web-based survey instrument to their faculty members. Global responses and responses stratified by demographics were summarized and analyzed. RESULTS: Between 312 and 340 faculty members answered questions that identified barriers to scholarship and recommended corrective strategies to these barriers. The most common barrier was insufficient time (57%), and the most common recommendation was for help to "identify a research question and how to answer it." Sixty percent reported that scholarship was required for advancement but only 32% thought scholarship should be required. Forty-one percent reported that the importance of scholarship is overemphasized. CONCLUSIONS: These survey results provide guidance to improve the quantity and quality of scholarship for faculty members who wish to pursue scholarship, although many of the survey respondents indicated they did not regard scholarship as a priority.

Trends in antibacterial use in hospitalized pediatric patients in United States academic health centers.

Trends in pediatric antibacterial use were examined in 20 academic health centers during the period 2002-2007. There was a significant increase in the use of linezolid (P < .001) and of macrolides (P = .001) and a significant decrease in the use of aminoglycosides (P < .001) and of first-generation cephalosporins (P < .001).

Relationship of carbapenem restriction in 22 university teaching hospitals to carbapenem use and carbapenem-resistant Pseudomonas aeruginosa.

Many hospital antimicrobial stewardship programs restrict the availability of selected drugs by requiring prior approval. Carbapenems may be among the restricted drugs, but it is unclear if hospitals that restrict availability actually use fewer carbapenems than hospitals that do not restrict use. Nor is it clear if restriction is related to resistance. We evaluated the relationship between carbapenem restriction and the volume of carbapenem use and both the incidence rate and proportion of carbapenem-resistant Pseudomonas aeruginosa isolates from 2002 through 2006 in a retrospective, longitudinal, multicenter analysis among a consortium of academic health centers. Carbapenem use was measured from billing records as days of therapy per 1,000 patient days. Hospital antibiograms were used to determine both the incidence rate and proportion of carbapenem-resistant P. aeruginosa isolates. A survey inquired about restriction policies for antibiotics, including carbapenems. General linear mixed models were used to examine study outcomes. Among 22 hospitals with sufficient data for analysis, overall carbapenem use increased significantly over the 5 years of study (P < 0.0001), although overall carbapenem resistance in P. aeruginosa did not change. Hospitals that restricted carbapenems (n = 8; 36%) used significantly fewer carbapenems (P = 0.04) and reported lower incidence rates of carbapenem-resistant P. aeruginosa (P = 0.01) for all study years. Fluoroquinolone use was a potential confounder of these relationships, but hospitals that restricted carbapenems actually used fewer fluoroquinolones than those that did not. Restriction of carbapenems is associated with both lower use and lower incidence rates of carbapenem resistance in P. aeruginosa.

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).

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.

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 Organization's 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.

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.

Predicting hospital rates of fluoroquinolone-resistant Pseudomonas aeruginosa from fluoroquinolone use in US hospitals and their surrounding communities.

Rates of fluoroquinolone resistance among Pseudomonas aeruginosa in hospitals are increasing, but interhospital variability is great. We sought to determine whether this variability correlated to fluoroquinolone use in hospitals and in the surrounding community. Hospital quinolone use in 1999 (24 hospitals) through 2001 (35 hospitals) was determined from billing records. The number of fluoroquinolone prescriptions within a 10-mile (approximately 16-km) radius of each hospital was determined for 1999 and 2000. Hospital fluoroquinolone use increased from 1999 through 2001, from 137 to 163 defined daily doses (DDD)/1000 patient-days (P=.01). The rate of community fluoroquinolone use also increased, from 2.3 to 2.8 DDD/1000 inhabitant-days (P<.001). Rates of fluoroquinolone-resistant P. aeruginosa increased from 29% in 1999 to 36% in 2001 (P=.003). Both community and hospital fluoroquinolone use were predictive of rates of fluoroquinolone-resistant P. aeruginosa. Levofloxacin was associated with resistance, but ciprofloxacin was not. Most of the variability in resistance rates is explained by volume of fluoroquinolone use, both in the hospital and the surrounding community.

Reduction in broad-spectrum antimicrobial use associated with no improvement in hospital antibiogram.

OBJECTIVE: To evaluate the effect of an antimicrobial management programme on broad-spectrum antimicrobial use and antimicrobial susceptibilities of common nosocomial pathogens at a tertiary-care teaching hospital. METHODS: Review of hospital charts of patients who had been prescribed broad-spectrum antimicrobials 48 h earlier. Recommendations to streamline or discontinue antimicrobials were made based on results of available microbiology data, radiography studies, as well as the working diagnosis at the time of review. The charts were reviewed again on the following day to assess acceptance or rejection of the recommendations. Antimicrobial use, measured as defined daily dose per 1000 patient days (DDD/1000 PD), was determined before and after the antimicrobial management programme was started and was assessed as the mean quarterly use in the six quarters preceding implementation of the programme compared to the most recent six quarters that the programme has been in existence. Antibiotic susceptibilities were obtained from the clinical microbiology laboratory. RESULTS: Compared to the six quarters before the programme, broad-spectrum antibiotic use decreased by 28% (693 DDD/1000 PD to 502 DDD/1000 PD, P = 0.003). Total antifungal agent use decreased by a similar amount, i.e. 28% (144 DDD/1000 PD to 103 DDD/1000 PD, P = 0.02). Total antimicrobial use decreased by 27% (1461 DDD/1000 PD to 1069 DDD/1000 PD, P = 0.0007). Susceptibilities of common nosocomial Gram-negative organisms to commonly prescribed antibiotics did not change significantly over the 3 years of the programme. The rate of methicillin-resistant Staphylococcus aureus increased significantly in the non-intensive care areas of the hospital (P = 0.02) and decreased significantly in the intensive care areas of the hospital (P = 0.009) over the 4 year period from 2000 to 2003. CONCLUSION: Implementation of an antibiotic management programme resulted in substantial reductions in both broad-spectrum and total antimicrobial consumption without having a significant impact on antibiotic susceptibilities of common Gram-negative microorganisms within the institution. The changes in MRSA rate in the non-ICU and ICU settings may reflect infection control measures that were in place during the study period.

Antimicrobial formularies: can they minimize antimicrobial resistance?

The relationship between antimicrobial drug use and resistance rates and the implications for antimicrobial formularies are described. Efforts to restrict antimicrobial drug use to reduce resistance in certain microorganisms have been accompanied by increases in resistance in other microorganisms. Random cycling of a variety of antimicrobial agents to treat infections caused by the same microorganism in different patients within a health care institution has been advocated as a means to reduce antimicrobial resistance. Analysis of actual antimicrobial drug use and resistance data from a network of 40 hospitals revealed wide variability in antimicrobial use. The specific type and volume of antimicrobial agents used appear to play key roles in determining resistance rates. It may be feasible to optimize diversity in antimicrobial drug use and minimize resistance by making judicious changes to the antimicrobial formulary.