What is the role for metronidazole in the treatment of Clostridium difficile infection? Results from a national cohort study of Veterans with initial mild disease

Background: Metronidazole may still be an appropriate therapeutic option for mild Clostridium difficile infection (CDI) in select patients, but data is limited to guide clinicians in identifying these patients. Methods: Our two-stage study included a national cohort of Veterans with a first episode of mild CDI (2010–2014). First, among those treated with metronidazole, we identified predictors of success, defined as absence of all-cause mortality or recurrence 30-days post-treatment, using multivariable unconditional logistic regression. Second, among a subgroup of patients with characteristic/s predictive of success identified in the first-stage, we compared clinical outcomes among those treated with metronidazole compared with vancomycin, using Cox proportional hazards models for time to 30-day all-cause mortality, CDI recurrence, and failure. Results: Among 3,656 patients treated with metronidazole, we identified 3,282 patients with success and 374 patients without success (failure). Younger age was the only independent predictor of success. Age ≤65 years was associated with an odds of success 1.63 times higher (95% confidence interval [CI] 1.29 – 2.06) than age \u3e65 years. Among 115 propensity-score matched pairs ≤65 years of age, no significant differences were observed between metronidazole and vancomycin (reference) for all-cause mortality (hazard ratio [HR] 0.29, 95% CI 0.06–1.38), CDI recurrence (HR 0.62, 95% CI 0.26–1.49), or failure (HR 0.50, 95% CI 0.23–1.07). Conclusion: Among patients ≤65 years of age with initial mild CDI, clinical outcomes were similar with metronidazole and vancomycin. These data suggest metronidazole may be considered for the treatment of initial mild CDI among patients 65 years of age or younger

Predictors of Clostridioides difficile recurrence across a national cohort of veterans in outpatient, acute, and long-term care settings

Purpose: The greatest challenge in treating Clostridioides difficile infection (CDI) is disease recurrence, which occurs in about 20% of patients, usually within 30 days of treatment cessation. We sought to identify independent predictors of first recurrence among a national cohort of veterans with CDI. Methods: We conducted a case-control study among acute and long-term care Veterans Affairs (VA) inpatients and outpatients with a first CDI episode (positive stool sample for C. difficile toxin[s] and receipt of at least 2 days of CDI treatment) between 2010 and 2014. Cases experienced first recurrence within 30 days from the end of treatment. Controls were those without first recurrence matched 4:1 to cases on year, facility, and severity. Multivariable conditional logistic regression was used to identify predictors of first recurrence. Results: We identified 32 predictors of first recurrence among 974 cases and 3,896 matched controls. Significant predictors included medication use prior to (probiotics, fluoroquinolones, laxatives, third- or fourth-generation cephalosporins), during (first- or second-generation cephalosporins, penicillin/amoxicillin/ampicillin, third- and fourth-generation cephalosporins), and after CDI treatment (probiotics, any antibiotic, proton pump inhibitors [PPIs], and immunosuppressants). Other predictors included current biliary tract disease, malaise/fatigue, cellulitis/abscess, solid organ cancer, medical history of HIV, multiple myeloma, abdominal pain, and ulcerative colitis. Conclusion: In a large national cohort of outpatient and acute and long-term care inpatients, treatment with certain antibiotics, PPIs, immunosuppressants, and underlying disease were among the most important risk factors for first CDI recurrence

Predictors of Mortality Among a National Cohort of Veterans With Recurrent Clostridium difficile Infection

Background: Though recurrent Clostridium difficile infection (CDI) is common and poses a major clinical concern, data are lacking regarding mortality among patients who survive their initial CDI and have subsequent recurrences. Risk factors for mortality in patients with recurrent CDI are largely unknown. Methods: Veterans Affairs patients with a first CDI (stool sample with positive C. difficile toxin(s) and ≥2 days CDI treatment) were included (2010–2014). Subsequent recurrences were defined as additional CDI episodes ≥14 days after the stool test date and within 30 days of the end of treatment. A matched (1:4) case–control analysis was conducted using multivariable conditional logistic regression to identify predictors of all-cause mortality within 30 days of the first recurrence. Results: Crude 30-day all-cause mortality rates were 10.6% for the initial CDI episode, 8.3% for the first recurrence, 4.2% for the second recurrence, and 5.9% for the third recurrence. Among 110 cases and 440 controls, 6 predictors of mortality were identified: use of proton pump inhibitors (PPIs; odds ratio [OR], 3.86; 95% confidence interval [CI], 2.14–6.96), any antibiotic (OR, 3.33; 95% CI, 1.79–6.17), respiratory failure (OR, 8.26; 95% CI, 1.71–39.92), congitive dysfunction (OR, 2.41; 95% CI, 1.02–5.72), nutrition deficiency (OR, 2.91; 95% CI, 1.37–6.21), and age (OR, 1.04; 95% CI, 1.01–1.07). Conclusions: In our national cohort of Veterans, crude mortality decreased by 44% from the initial episode to the third recurrence. Treatment with antibiotics, use of PPIs, and underlying comorbidities were important predictors of mortality in recurrent CDI. Our study assists health care providers in identifying patients at high risk of death after CDI recurrence

Treatment, Clinical Outcomes, and Predictors of Mortality among a National Cohort of Admitted Patients with Acinetobacter baumannii Infection

The objectives were to analyze treatment, clinical outcomes, and predictors of mortality in hospitalized patients with Acinetobacter baumannii infection. This was a retrospective cohort study of inpatients with A. baumannii cultures and treatment from 2010 to 2019. Patients who died during admission were compared to those who survived, to identify predictors of inpatient mortality, using multivariable unconditional logistic regression models. We identified 4,599 inpatients with A. baumannii infection; 13.6% died during admission. Fluoroquinolones (26.8%), piperacillin-tazobactam (24%), and carbapenems (15.6%) were used for treatment. Tigecycline (3%) and polymyxins (3.7%) were not used often. Predictors of inpatient mortality included current acute respiratory failure (adjusted odds ratio [aOR] 3.94), shock (aOR 3.05), and acute renal failure (aOR 2.01); blood (aOR 1.94) and respiratory (aOR 1.64) infectious source; multidrug-resistant A. baumannii (MDRAB) infection (aOR 1.66); liver disease (aOR 2.15); and inadequate initial treatment (aOR 1.30). Inpatient mortality was higher in those with MDRAB versus non-MDRAB (aOR 1.61) and in those with CRAB versus non-CRAB infection (aOR 1.68). Length of stay \u3e10 days was higher among those with MDRAB versus non-MDRAB (aOR 1.25) and in those with CRAB versus non-CRAB infection (aOR 1.31). In our national cohort of inpatients with A. baumannii infection, clinical outcomes were worse among those with MDRAB and/or CRAB infection. Predictors of inpatient mortality included several current conditions associated with severity, infectious source, underlying illness, and inappropriate treatment. Our study may assist health care providers in the early identification of admitted patients with A. baumannii infection who are at higher risk of death

National trends in hospital, long-term care and outpatient Acinetobacter baumannii resistance rates

Introduction: Acinetobacter baumannii is a top-priority pathogen of the World Health Organization (WHO) and the Centers for Disease Control (CDC) due to antibiotic resistance. Gap Statement: Trends in A. baumannii resistance rates that include community isolates are unknown. Aim: Identify trends in A. baumannii resistance rates across the Veterans Affairs (VA) Healthcare System, including isolates from patients treated in hospitals, long-term care facilities and outpatient clinics nationally. Methodology: We included A. baumannii clinical cultures collected from VA patients from 2010 to 2018. Cultures were categorized by location: VA medical centers (VAMCs), long-term care (LTC) units [community living centers (CLCs)], or outpatient. We assessed carbapenem resistance, multidrug resistance (MDR) and extensive drug resistance (XDR). Time trends were assessed with Joinpoint regression. Results: We identified 19 376 A. baumannii cultures (53% VAMCs, 4% CLCs, 43% outpatient). Respiratory cultures were the most common source of carbapenem-resistant (43 %), multidrug-resistant (49 %) and extensively drug-resistant (21 %) isolates. Over the study period, the number of A. baumannii cultures decreased significantly in VAMCs (11.9% per year). In 2018, carbapenem resistance was seen in 28% of VAMC isolates and 36% of CLC isolates, but only 6% of outpatient isolates, while MDR was found in 31% of VAMC isolates and 36% of CLC isolates, but only 8 % of outpatient isolates. Carbapenem-resistant, multidrug-resistant and extensively drug-resistant A. baumannii isolates decreased significantly in VAMCs and outpatient clinics over time (VAMCs: by 4.9, 7.2 and 6.9%; outpatient: by 11.3, 10.5 and 10.2% per year). Resistant phenotypes remained stable in CLCs. Conclusion: In the VA nationally, the prevalence of A. baumannii is decreasing, as is resistance. Carbapenem-resistant and multidrug-resistant A. baumannii remain common in VAMCs and CLCs. The focus of infection control and antimicrobial stewardship efforts to prevent transmission of resistant A. baumannii should be in hospital and LTC settings

Antibiotic Resistance Rates for Pseudomonas aeruginosa Clinical Respiratory and Bloodstream Isolates Among the Veterans Affairs Healthcare System from 2009 to 2013

Pseudomonas aeruginosa is a major cause of healthcare-associated infections and resistance among isolates is an increasing burden. The study purpose was to describe national resistance rates for clinical P. aeruginosa respiratory and bloodstream cultures and the prevalence of multidrug-resistant (MDR) P. aeruginosa within the Veterans Affairs (VA). MDR was defined as non-susceptibility to at least one drug in at least 3 of the following 5 categories: carbapenems, extended-spectrum cephalosporins, aminoglycosides, and piperacillin/tazobactam. We reviewed 24,562 P. aeruginosa respiratory and bloodstream isolates across 126 VA facilities between 2009 to 2013. Most isolates were collected from inpatient settings (82%). Resistance was highest in fluoroquinolones (33%) and exceeded 20% for all classes assessed (carbapenems, extended-spectrum cephalosporins, aminoglycosides, and piperacillin/tazobactam). Resistance was higher in inpatient settings and in respiratory isolates. Prevalence of MDR was 20% overall (22% for inpatient isolates, 11% outpatient, 21% respiratory, 17% bloodstream). Our findings are consistent with previous surveillance report

National trends in the treatment of urinary tract infections among Veterans’ Affairs Community Living Center residents

Objective: To describe urinary tract infection (UTI) treatment among Veterans’ Affairs (VA) Community Living Centers (CLCs) nationally and to assess related trends in antibiotic use. Design: Descriptive study. Setting and participants: All UTI episodes treated from 2013 through 2017 among residents in 110 VA CLCs. UTI episodes required collection of a urine culture, antibiotic treatment, and a UTI diagnosis code. UTI episodes were stratified into culture-positive and culture-negative episodes. Methods: Frequency and rate of antibiotic use were assessed for all UTI episodes overall and were stratified by culture-positive and culture-negative episodes. Joinpoint software was used for regression analyses of trends over time. Results: We identified 28,247 UTI episodes in 14,983 Veterans. The average age of Veterans was 75.7 years, and 95.9% were male. Approximately half of UTI episodes (45.7%) were culture positive and 25.7% were culture negative. Escherichia coli was recovered in 34.1% of culture-positive UTI episodes, followed by Proteus mirabilis and Klebsiellaspp, which were recovered in 24.5% and 17.4% of culture-positive UTI episodes, respectively. The rate of total antibiotic use in days of therapy (DOT) per 1,000 bed days decreased by 10.1% per year (95% CI, −13.6% to −6.5%) and fluoroquinolone use (ciprofloxacin or levofloxacin) decreased by 14.5% per year (95% CI, −20.6% to −7.8%) among UTI episodes overall. Similar reductions in rates of total antibiotic use and fluoroquinolone use were observed among culture-positive UTI episodes and among culture-negative UTI episodes. Conclusion: Over a 5-year period, antibiotic use for UTIs significantly decreased among VA CLCs, as did use of fluoroquinolones. Antibiotic stewardship efforts across VA CLCs should be applauded, and these efforts should continue

Frequency and Predictors of Suboptimal Prescribing Among a Cohort of Older Male Residents with Urinary Tract Infection

BACKGROUND Unnecessary antibiotic treatment of suspected urinary tract infection (UTI) is common in long-term care facilities (LTCFs). However, less is known about the extent of suboptimal treatment, in terms of antibiotic choice, dose, and duration, after the decision to use antibiotics has been made. METHODS We described the frequency of potentially suboptimal treatment among residents with an incident UTI (first during the study with none in the year prior) in Veterans Affairs’ (VA) Community Living Centers (CLCs, 2013-2018). Time trends were analyzed using Joinpoint regression. Residents with UTIs receiving potentially suboptimal treatment were compared to those receiving optimal treatment to identify resident characteristics predictive of suboptimal antibiotic treatment, using multivariable unconditional logistic regression models. RESULTS We identified 21,938 residents with an incident UTI treated in 120 VA CLCs, of which 96.0% were male. Potentially suboptimal antibiotic treatment was identified in 65.0% of residents and decreased 1.8% annually (p\u3c0.05). Potentially suboptimal initial drug choice was identified in 45.6% of residents, suboptimal dose frequency in 28.6%, and longer than recommended duration in 12.7%. Predictors of suboptimal antibiotic treatment included: prior fluoroquinolone exposure (adjusted odds ratio [aOR] 1.38), chronic renal disease (aOR 1.19), age \u3e85 years (aOR 1.17), prior skin infection (aOR 1.14), recent high white blood cell count (aOR 1.08), and genitourinary disorder (aOR 1.08). CONCLUSION Similar to findings in non-VA facilities, potentially suboptimal treatment was common but improving in CLC residents with an incident UTI. Predictors of suboptimal antibiotic treatment should be targeted with antibiotic stewardship interventions to improve UTI treatment

Impact of Clopidogrel on Clinical Outcomes in Patients with Staphylococcus aureus Bacteremia: a National Retrospective Cohort Study

Activated platelets have known antimicrobial activity against Staphylococcus aureus. Accelerated clearance of platelets induced by S. aureus can result in thrombocytopenia and increased mortality in patients. Recent studies suggest that P2Y12 inhibition protects platelets from accelerated clearance. We therefore evaluated the effect of P2Y12 inhibition on clinical outcomes in patients with S. aureus bacteremia across a large national cohort. Our retrospective cohort (2010 to 2018) included patients admitted to Veterans Affairs (VA) hospitals with blood cultures positive for S. aureus and treated with standard-of-care antibiotics. Employing propensity score-matched Cox proportional hazards regression models, we compared clinical outcomes in patients treated with clopidogrel for at least the 30 days prior to admission and continuing for at least 5 days after admission to patients without any P2Y12 inhibitor use in the year preceding admission. Mortality was significantly lower among clopidogrel users than P2Y12 inhibitor nonusers (n = 147 propensity score-matched pairs): the inpatient mortality hazard ratio (HR) was 0.11 (95% confidence interval [CI], 0.01 to 0.86), and 30-day mortality HR was 0.43 (95% CI, 0.19 to 0.98). There were no differences in 30-day readmission, 30-day S. aureus reinfection, microbiological clearance, or thrombocytopenia. Clopidogrel use at the time of infection reduced in-hospital mortality by 89% and 30-day mortality by 57% among a cohort of patients with S. aureus bacteremia. These results support the need to further study the use of P2Y12 inhibitors as adjunctive therapy in S. aureus bloodstream infections

Predictors of potentially suboptimal treatment of urinary tract infections in long-term care facilities

Background: Suboptimal antibiotic treatment of urinary tract infection (UTI) is high in long-term care facilities (LTCFs) and likely varies between facilities. Large-scale evaluations have not been conducted. Aim: To identify facility-level predictors of potentially suboptimal treatment of UTI in Veterans Affairs (VA) LTCFs and to quantify variation across facilities. Methods: This was a retrospective cohort study of 21,938 residents in 120 VA LTCFs (2013–2018) known as Community Living Centers (CLCs). Potentially suboptimal treatment was assessed from drug choice, dose frequency, and/or treatment duration. To identify facility characteristics predictive of suboptimal UTI treatment, LTCFs with higher and lower rates of suboptimal treatment (≥median, \u3c median) were compared using unconditional logistic regression models. Joinpoint regression models were used to quantify average percentage difference across facilities. Multilevel logistic regression models were used to quantify variation across facilities. Findings: The rate of potentially suboptimal antibiotic treatment varied from 1.7 to 34.2 per 10,000 bed-days across LTCFs. The average percentage difference in rates across facilities was 2.5% (95% confidence interval (CI): 2.4–2.7). The only facility characteristic predictive of suboptimal treatment was the incident rate of UTI per 10,000 bed-days (odds ratio: 4.9; 95% CI: 2.3–10.3). Multilevel models demonstrated that 94% of the variation between facilities was unexplained after controlling for resident and CLC characteristics. The median odds ratio for the full multilevel model was 1.37. Conclusion: Potentially suboptimal UTI treatment was variable across VA LTCFs. However, most of the variation across LTCFs was unexplained. Future research should continue to investigate factors that are driving suboptimal antibiotic treatment in LTCFs