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

Heterogeneity in the treatment of bloodstream infections identified from antibiotic exposure mapping

Purpose: As changes in antibiotic therapy are common, intent‐to‐treat and definitive therapy exposure definitions in infectious disease clinical trials and observational studies may not accurately reflect all antibiotics received over the course of the infection. Therefore, we sought to describe changes in antibiotic therapy and unique treatment patterns among patients with bacteremia. Methods: We conducted a retrospective cohort study of hospitalizations from Veterans Affairs (VA) Medical Centers (January 2002‐September 2015) and community hospitals (de‐identified Optum Clinformatics DataMart with matched Premier Hospital data; October 2009‐March 2013). In the VA population, antibiotic exposures were mapped from the culture collection date among those with positive Staphylococcus aureus cultures. In the Optum‐Premier population, exposures were mapped from the admission date among those with a primary diagnosis of bacteremia. Results: Our study included 50 467 bacteremia admissions, with only 14% of admissions having the same treatment pattern as another admission. For every 100 bacteremia admissions, 89 had changes in antibiotic therapy. For every 100 bacteremia admissions with changes in therapy, 95 had unique antibiotic treatment patterns. These findings were consistent in both populations, over time, and among different facilities within study populations. The median time to first therapy change was 2 days after initial therapy, with a median of three changes. Conclusions: Changes in antibiotic therapy for bloodstream infections were nearly universal regardless of hospital setting. Based on our findings, common antibiotic exposure definitions of intent‐to‐treat and definitive therapy would misclassify exposure in 86% of admissions, which highlights the need for better operational definitions of exposure in infectious diseases research

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

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

Clinical and genetic risk factors for biofilm-forming Staphylococcus aureus

The molecular and clinical factors associated with biofilm-forming methicillin-resistant Staphylococcus aureus (MRSA) are incompletely understood. Biofilm production for 182 MRSA isolates obtained from clinical culture sites (2004 to 2013) was quantified. Microbiological toxins, pigmentation, and genotypes were evaluated, and patient demographics were collected. Logistic regression was used to quantify the effect of strong biofilm production (versus weak biofilm production) on clinical outcomes and independent predictors of a strong biofilm. Of the isolates evaluated, 25.8% (47/182) produced strong biofilms and 40.7% (74/182) produced weak biofilms. Strong biofilm-producing isolates were more likely to be from multilocus sequence typing (MLST) clonal complex 8 (CC8) (34.0% versus 14.9%; P = 0.01) but less likely to be from MLST CC5 (48.9% versus 73.0%; P = 0.007). Predictors for strong biofilms were spa type t008 (adjusted odds ratio [aOR], 4.54; 95% confidence interval [CI], 1.21 to 17.1) and receipt of chemotherapy or immunosuppressants in the previous 90 days (aOR, 33.6; 95% CI, 1.68 to 673). Conversely, patients with high serum creatinine concentrations (aOR, 0.33; 95% CI, 0.15 to 0.72) or who previously received vancomycin (aOR, 0.03; 95% CI, 0.002 to 0.39) were less likely to harbor strong biofilm-producing MRSA. Beta-toxin-producing isolates (aOR, 0.31; 95% CI, 0.11 to 0.89) and isolates with spa type t895 (aOR, 0.02 95% CI

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

Trends in Collection of Microbiological Cultures Across Veterans Affairs Community Living Centers in the United States Over 8 Years

Objectives: To describe and evaluate changes in the collection of microbiological cultures across Veterans Affairs (VA) Community Living Centers (CLCs) nationally. Design: Descriptive study. Setting: 146 VA CLCs. Participants: We identified both positive and negative microbiological cultures collected during VA CLC admissions from January 2010 through December 2017. Measures: We measured the average annual percentage change (AAPC) in the rate of cultures collected per 1000 bed days and per admission, overall and stratified by culture type (ie, urine, blood, skin and soft tissue, and respiratory tract). AAPCs were also calculated for the proportion and rate of positive cultures collected, overall and stratified by culture type and organism (ie, Escherichia coli, Proteus mirabilis, Staphylococcus aureus, Enterococcus spp, Pseudomonas aeruginosa, Klebsiella spp, Enterobacter spp, Morganella morganii, Citrobacter spp, Serratia marcescens, and Streptococcus pneumoniae). Joinpoint regression software was used to assess trends and estimate AAPCs and 95% confidence intervals (CIs). Results: Over 8 years, 355,329 cultures were collected. The rate of cultures collected per 1000 bed days of care decreased significantly by 6.0% per year (95% CI –8.7%, −3.2%). The proportion of positive cultures decreased by 0.9% (95% CI –1.4%, −0.4%). The most common culture types were urine (48.4%), followed by blood (27.7%). The rate of cultures collected per 1000 bed days of care decreased per year by 6.3% for urine, 5.0% for blood, 4.4% for skin and soft tissue, and 4.9% for respiratory tract. In 2010, S aureus was the most common organism identified, and in all subsequent years E coli was the most common. Conclusion and implications: We identified a significant reduction in the number of cultures collected over time among VA CLCs. Our findings may be explained by decreases in the collection of unnecessary cultures in VA CLCs nationally due to increased antibiotic stewardship efforts targeting unnecessary culturing and antibiotic treatment

Poor clinical outcomes associated with suboptimal antibiotic treatment among older long-term care facility residents with urinary tract infection: a retrospective cohort study

Background: Antibiotic use is associated with several antibiotic-related harms in vulnerable, older long-term care (LTC) residents. Suboptimal antibiotic use may also be associated with harms but has not yet been investigated. The aim of this work was to compare rates of poor clinical outcomes among LTC residents with UTI receiving suboptimal versus optimal antibiotic treatment. Methods: We conducted a retrospective cohort study among residents with an incident urinary tract infection (UTI) treated in Veterans Affairs LTC units (2013–2018). Potentially suboptimal antibiotic treatment was defined as use of a suboptimal initial antibiotic drug choice, dose frequency, and/or excessive treatment duration. The primary outcome was time to a composite measure of poor clinical outcome, defined as UTI recurrence, acute care hospitalization/emergency department visit, adverse drug event, Clostridioides difficile infection (CDI), or death within 30 days of antibiotic discontinuation. Shared frailty Cox proportional hazard regression models were used to compare the time-to-event between suboptimal and optimal treatment. Results: Among 19,701 LTC residents with an incident UTI, 64.6% received potentially suboptimal antibiotic treatment and 35.4% experienced a poor clinical outcome. In adjusted analyses, potentially suboptimal antibiotic treatment was associated with a small increased hazard of poor clinical outcome (aHR 1.06, 95% CI 1.01–1.11) as compared with optimal treatment, driven by an increased hazard of CDI (aHR 1.94, 95% CI 1.54–2.44). Conclusion: In this national cohort study, suboptimal antibiotic treatment was associated with a 6% increased risk of the composite measure of poor clinical outcomes, in particular, a 94% increased risk of CDI. Beyond the decision to use antibiotics, clinicians should also consider the potential harms of suboptimal treatment choices with regards to drug type, dose frequency, and duration used