Antibiotic Prescribing Choices and Their Comparative C. Difficile Infection Risks: A Longitudinal Case-Cohort Study.

BACKGROUND: Antibiotic use is the strongest modifiable risk factor for the development of Clostridioides difficile infection, but prescribers lack quantitative information on comparative risks of specific antibiotic courses. Our objective was to estimate risks of C. difficile infection associated with receipt of specific antibiotic courses. METHODS: We conducted a longitudinal case-cohort analysis representing over 90% of Ontario nursing home residents, between 2012 and 2017. Our primary exposure was days of antibiotic receipt in the prior 90 days. Adjustment covariates included: age, sex, prior emergency department or acute care stay, Charlson comorbidity index, prior C. difficile infection, acid suppressant use, device use, and functional status. We examined incident C. difficile infection, including cases identified within the nursing home, and those identified during subsequent hospital admissions. Adjusted and unadjusted regression models were used to measure risk associated with 5- to 14-day courses of 18 different antibiotics. RESULTS: We identified 1708 cases of C. difficile infection (1.27 per 100 000 resident-days). Longer antibiotic duration was associated with increased risk: 10- and 14-day courses incurred 12% (adjusted relative risk [ARR] = 1.12, 95% confidence interval [CI]: 1.09, 1.14) and 27% (ARR = 1.27, 95% CI: 1.21,1.30) more risk compared to 7-day courses. Among 7-day courses with similar indications: moxifloxacin resulted in 121% more risk than amoxicillin (ARR = 2.21, 95% CI: 1.67, 3.08), ciprofloxacin engendered 89% more risk than nitrofurantoin (ARR = 1.89, 95% CI: 1.45, 2.68), and clindamycin resulted in 112% (ARR = 2.12, 95% CI: 1.32, 3.78) more risk than cloxacillin. CONCLUSIONS: C. difficile infection risk increases with antibiotic duration, and there are wide disparities in risks associated with antibiotic courses used for similar indications.

The Urine-culturing Cascade: Variation in Nursing Home Urine Culturing and Association With Antibiotic Use and Clostridiodes difficile Infection.

BACKGROUND: Rates of antibiotic use vary widely across nursing homes and cannot be explained by resident characteristics. Antibiotic prescribing for a presumed urinary tract infection is often preceded by inappropriate urine culturing. We examined nursing home urine-culturing practices and their association with antibiotic use. METHODS: We conducted a longitudinal, multilevel, retrospective cohort study based on quarterly nursing home assessments between April 2014 and January 2017 in 591 nursing homes and covering >90% of nursing home residents in Ontario, Canada. Nursing home urine culturing was measured as the proportion of residents with a urine culture in the prior 14 days. Outcomes included receipt of any systemic antibiotic and any urinary antibiotic (eg, nitrofurantoin, trimethoprim/sulfonamides, ciprofloxacin) in the 30 days after the assessment and Clostridiodes difficile infection in the 90 days after the assessment. Adjusted Poisson regression models accounted for 14 resident covariates. RESULTS: A total of 131 218 residents in 591 nursing homes were included; 7.9% of resident assessments had a urine culture in the prior 14 days; this proportion was highly variable across the 591 nursing homes (10th percentile = 3.4%, 90th percentile = 14.3%). Before and after adjusting for 14 resident characteristics, nursing home urine culturing predicted total antibiotic use (adjusted risk ratio [RR] per doubling of urine culturing, 1.21; 95% confidence interval [CI], 1.18-1.23), urinary antibiotic use (RR, 1.33; 95% CI, 1.28-1.38), and C. difficile infection (incidence rate ratio, 1.18; 95% CI, 1.07-1.31). CONCLUSIONS: Nursing homes have highly divergent urine culturing rates; this variability is associated with higher antibiotic use and rates of C. difficile infection.

The Drivers of Acute and Long-term Care Clostridium difficile Infection Rates: A Retrospective Multilevel Cohort Study of 251 Facilities.

Background: Drivers of differences in Clostridium difficile incidence across acute and long-term care facilities are poorly understood. We sought to obtain a comprehensive picture of C. difficile incidence and risk factors in acute and long-term care. Methods: We conducted a case-cohort study of persons spending at least 3 days in one of 131 acute care or 120 long-term care facilities managed by the United States Veterans Health Administration between 2006 and 2012. Patient (n = 8) and facility factors (n = 5) were included in analyses. The outcome was the incidence of facility-onset laboratory-identified C. difficile infection (CDI), defined as a person with a positive C. difficile test without a positive test in the prior 8 weeks. Results: CDI incidence in acute care was 5 times that observed in long-term care (median, 15.6 vs 3.2 per 10000 person-days). History of antibiotic use was greater in acute care compared to long-term care (median, 739 vs 513 per 1000 person-days) and explained 72% of the variation in C. difficile rates. Importation of C. difficile cases (acute care: patients with recent long-term care attributable infection; long-term care: residents with recent acute care attributable infection) was 3 times higher in long-term care as compared to acute care (median, 52.3 vs 16.2 per 10000 person-days). Conclusions: Facility-level antibiotic use was the main factor driving differences in CDI incidence between acute and long-term care. Importation of acute care C. difficile cases was a greater concern for long-term care as compared to importation of long-term care cases for acute care.

Trends in Antibiotic Use and Nosocomial Pathogens in Hospitalized Veterans With Pneumonia at 128 Medical Centers, 2006-2010.

BACKGROUND: In 2005, pneumonia practice guidelines recommended broad-spectrum antibiotics for patients with risk factors for nosocomial pathogens. The impact of these recommendations on the ability of providers to match treatment with nosocomial pathogens is unknown. METHODS: Among hospitalizations with a principal diagnosis of pneumonia at 128 Department of Veterans Affairs medical centers from 2006 through 2010, we measured annual trends in antibiotic selection; initial blood or respiratory cultures positive for methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and Acinetobacter species; and alignment between antibiotic coverage and culture results for MRSA and P. aeruginosa, calculating sensitivity, specificity, and diagnostic odds ratio using a 2 × 2 contingency table. RESULTS: In 95 511 hospitalizations for pneumonia, initial use of vancomycin increased from 16% in 2006 to 31% in 2010, and piperacillin-tazobactam increased from 16% to 27%, and there was a decrease in both ceftriaxone (from 39% to 33%) and azithromycin (change from 39% to 36%) (P < .001 for all). The proportion of hospitalizations with cultures positive for MRSA decreased (from 2.5% to 2.0%; P < .001); no change was seen for P. aeruginosa (1.9% to 2.0%; P = .14) or Acinetobacter spp. (0.2% to 0.2%; P = .17). For both MRSA and P. aeruginosa, sensitivity increased (from 46% to 65% and 54% to 63%, respectively; P < .001) and specificity decreased (from 85% to 69% and 76% to 68%; P < .001), with no significant changes in diagnostic odds ratio (decreases from 4.6 to 4.1 [P = .57] and 3.7 to 3.2 [P = .95], respectively). CONCLUSIONS: Between 2006 and 2010, we found a substantial increase in the use of broad-spectrum antibiotics for pneumonia despite no increase in nosocomial pathogens. The ability of providers to accurately match antibiotic coverage to nosocomial pathogens remains low.

Virtual learning collaboratives to improve urine culturing and antibiotic prescribing in long-term care: controlled before-and-after study.

BACKGROUND: Urine culturing practices are highly variable in long-term care and contribute to overprescribing of antibiotics for presumed urinary tract infections. The purpose of this study was to evaluate the use of virtual learning collaboratives to support long-term care homes in implementing a quality improvement programme focused on reducing unnecessary urine culturing and antibiotic overprescribing. METHODS: Over a 4-month period (May 2018-August 2018), 45 long-term care homes were self-selected from five regions to participate in virtual learning collaborative sessions, which provided an orientation to a quality improvement programme and guidance for implementation. A process evaluation complemented the use of a controlled before-and-after study with a propensity score matched control group (n=127) and a difference-in-difference analysis. Primary outcomes included rates of urine cultures performed and urinary antibiotic prescriptions. Secondary outcomes included rates of emergency department visits, hospital admission and mortality. An 18-month baseline period was compared with a 16-month postimplementation period with the use of administrative data sources. RESULTS: Rates of urine culturing and urinary antibiotic prescriptions per 1000 resident days decreased significantly more among long-term care homes that participated in learning collaboratives compared with matched controls (differential reductions of 19% and 13%, respectively, p<0.0001). There was no statistically significant changes to rates of emergency department visits, hospital admissions or mortality. These outcomes were observed with moderate adherence to the programme model. CONCLUSIONS: Rates of urine culturing and urinary antibiotic prescriptions declined among long-term care homes that participated in a virtual learning collaborative to support implementation of a quality improvement programme. The results of this study have refined a model to scale this programme in long-term care.

Reducing unnecessary urine culturing and antibiotic overprescribing in long-term care: a before-and-after analysis.

BACKGROUND: Antibiotic use in long-term care homes is highly variable. High rates of antibiotic use are associated with antibiotic resistance and Clostridium difficile infection. We asked 2 questions regarding a program designed to improve diagnosis and management of urinary tract infections in long-term care: whether the program decreased urine culturing and antibiotic prescribing rates and whether specific strategies of the program were more or less likely to be adopted. METHODS: The study included 10 long-term care homes in Ontario, Canada, between December 2015 and May 2017. We assessed the implementation of the program's 9 strategies via semistructured interviews with key informants. Using a before-and-after study design, and on the basis of monthly facility-level records, we measured changes in the rates of urine specimens sent for culture and susceptibility testing, prescriptions for antibiotics commonly used to treat urinary tract infections and total antibiotic prescriptions, using Poisson regression. RESULTS: Participating homes implemented an average of 6.1 of the 9 strategies. Urine culturing decreased from 3.20 to 2.09 per 1000 resident-days from the baseline to the intervention phase (adjusted incidence rate ratio [IRRadjusted] = 0.72, 95% confidence interval [CI] 0.63-0.82), urinary antibiotic prescriptions fell from 1.52 to 0.83 per 1000 resident-days (IRRadjusted = 0.60, 95% CI 0.47-0.74) and total antibiotic prescriptions fell from 3.85 to 2.60 per 1000 resident-days (IRRadjusted = 0.74, 95% CI 0.65-0.83). After adjusting for secular trends, these reductions were not statistically significant. INTERPRETATION: We demonstrated a reduction in urine culturing and antibiotic use following implementation of the Urinary Tract Infection Program. This initial analysis supports a broader implementation of this program, although ongoing evaluation is required to monitor secular trends in urine culturing and antibiotic use.

Regional variability in outpatient antibiotic use in Ontario, Canada: a retrospective cross-sectional study.

BACKGROUND: Regional variability in antibiotic use is associated with both antibiotic overuse and antimicrobial resistance. Our objectives were to benchmark outpatient antibiotic use and to evaluate geographic variability among health regions in the province of Ontario, Canada. METHODS: This was a cross-sectional study of antibiotics dispensed from outpatient retail pharmacies in Ontario between March 2016 and February 2017. We analyzed variability in the number of antibiotic prescriptions dispensed per 1000 population among Ontario's 14 health regions with crude and adjusted Poisson regression models. Adjusted models controlled for rurality, 4 physician characteristics and 6 population characteristics. RESULTS: There were 8 352 578 antibiotics dispensed during the 1-year study period or 621 per 1000 population. The most commonly prescribed antibiotic classes were narrow-spectrum penicillins, macrolides, first-generation cephalosporins and second-generation fluoroquinolones, with adult women receiving the highest rate of prescriptions: 985 antibiotic prescriptions per 1000 population. There was geographic variability in total and class-specific antibiotic use. In the health region with the highest use 778 antibiotics were dispensed per 1000 population whereas in the health region with the lowest use 534 antibiotics were dispensed per 1000 population. The adjusted marginal standardized antibiotic prescription rates for the health regions with the highest and lowest use were 787 (95% confidence interval [CI] 658-934) and 546 (95% CI 494-606) antibiotic prescriptions per 1000 population, respectively. INTERPRETATION: We described baseline antibiotic usage in Ontario over a 12-month period, noting variability among some health regions. Our findings highlight the need for interventions to optimize antibiotic use and slow the emergence of antimicrobial resistance.

Increased environmental sample area and recovery of Clostridium difficile spores from hospital surfaces by quantitative PCR and enrichment culture.

OBJECTIVE: Clostridium difficile spores play an important role in transmission and can survive in the environment for several months. Optimal methods for measuring environmental C. difficile are unknown. We sought to determine whether increased sample surface area improved detection of C. difficile from environmental samples. SETTING: Samples were collected from 12 patient rooms in a tertiary-care hospital in Toronto, Canada. METHODS: Samples represented small surface-area and large surface-area floor and bedrail pairs from single-bed rooms of patients with low (without prior antibiotics), medium (with prior antibiotics), and high (C. difficile infected) shedding risk. Presence of C. difficile in samples was measured using quantitative polymerase chain reaction (qPCR) with targets on the 16S rRNA and toxin B genes and using enrichment culture. RESULTS: Of the 48 samples, 64·6% were positive by 16S qPCR (geometric mean, 13·8 spores); 39·6% were positive by toxin B qPCR (geometric mean, 1·9 spores); and 43·8% were positive by enrichment culture. By 16S qPCR, each 10-fold increase in sample surface area yielded 6·6 times (95% CI, 3·2-13) more spores. Floor surfaces yielded 27 times (95% CI, 4·9-181) more spores than bedrails, and rooms of C. difficile-positive patients yielded 11 times (95% CI, 0·55-164) more spores than those of patients without prior antibiotics. Toxin B qPCR and enrichment culture returned analogous findings. CONCLUSIONS: Clostridium difficile spores were identified in most floor and bedrail samples, and increased surface area improved detection. Future research aiming to understand the role of environmental C. difficile in transmission should prefer samples with large surface areas.

Variation in Empiric Coverage Versus Detection of Methicillin-Resistant Staphylococcus aureus and Pseudomonas aeruginosa in Hospitalizations for Community-Onset Pneumonia Across 128 US Veterans Affairs Medical Centers.

OBJECTIVE To examine variation in antibiotic coverage and detection of resistant pathogens in community-onset pneumonia. DESIGN Cross-sectional study. SETTING A total of 128 hospitals in the Veterans Affairs health system. PARTICIPANTS Hospitalizations with a principal diagnosis of pneumonia from 2009 through 2010. METHODS We examined proportions of hospitalizations with empiric antibiotic coverage for methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PAER) and with initial detection in blood or respiratory cultures. We compared lowest- versus highest-decile hospitals, and we estimated adjusted probabilities (AP) for patient- and hospital-level factors predicting coverage and detection using hierarchical regression modeling. RESULTS Among 38,473 hospitalizations, empiric coverage varied widely across hospitals (MRSA lowest vs highest, 8.2% vs 42.0%; PAER lowest vs highest, 13.9% vs 44.4%). Detection rates also varied (MRSA lowest vs highest, 0.5% vs 3.6%; PAER lowest vs highest, 0.6% vs 3.7%). Whereas coverage was greatest among patients with recent hospitalizations (AP for anti-MRSA, 54%; AP for anti-PAER, 59%) and long-term care (AP for anti-MRSA, 60%; AP for anti-PAER, 66%), detection was greatest in patients with a previous history of a positive culture (AP for MRSA, 7.9%; AP for PAER, 11.9%) and in hospitals with a high prevalence of the organism in pneumonia (AP for MRSA, 3.9%; AP for PAER, 3.2%). Low hospital complexity and rural setting were strong negative predictors of coverage but not of detection. CONCLUSIONS Hospitals demonstrated widespread variation in both coverage and detection of MRSA and PAER, but probability of coverage correlated poorly with probability of detection. Factors associated with empiric coverage (eg, healthcare exposure) were different from those associated with detection (eg, microbiology history). Providing microbiology data during empiric antibiotic decision making could better align coverage to risk for resistant pathogens and could promote more judicious use of broad-spectrum antibiotics. Infect Control Hosp Epidemiol 2017;38:937-944.