Exploring variations in recommended first-choice therapy for complicated urinary tract infections in males: Insights from outpatient settings across age, race, and ethnicity.

INTRODUCTION: There are known disparities in the treatment of infectious diseases. However, disparities in treatment of complicated urinary tract infections (UTIs) are largely uninvestigated. OBJECTIVES: We characterized UTI treatment among males in Veterans Affairs (VA) outpatient settings by age, race, and ethnicity and identified demographic characteristics predictive of recommended first-choice antibiotic therapy. METHODS: We conducted a national, retrospective cohort study of male VA patients diagnosed with a UTI and dispensed an outpatient antibiotic from January 2010 through December 2020. Recommended first-choice therapy for complicated UTI was defined as use of a recommended first-line antibiotic drug choice regardless of area of involvement (ciprofloxacin, levofloxacin, or sulfamethoxazole/trimethoprim) and a recommended duration of 7 to 10 days of therapy. Multivariable models were used to identify demographic predictors of recommended first-choice therapy (adjusted odds ratio [aOR] > 1). RESULTS: We identified a total of 157,898 males diagnosed and treated for a UTI in the outpatient setting. The average antibiotic duration was 9.4 days (±standard deviation [SD] 4.6), and 47.6% of patients were treated with ciprofloxacin, 25.1% with sulfamethoxazole/trimethoprim, 7.6% with nitrofurantoin, and 6.6% with levofloxacin. Only half of the male patients (50.6%, n = 79,928) were treated with recommended first-choice therapy (first-line drug choice and appropriate duration); 77.6% (n = 122,590) were treated with a recommended antibiotic choice and 65.9% (n = 104,070) with a recommended duration. Age 18-49 years (aOR 1.07, 95% confidence interval [CI] 1.03-1.11) versus age ≥65 years was the only demographic factor predictive of recommended first-choice therapy. CONCLUSIONS: Nearly half of the patients included in this study did not receive recommended first-choice therapies; however, racial and ethnic disparities were not identified. Underutilization of recommended first-choice antibiotic therapy in complicated UTIs continues to be an area of focus for antimicrobial stewardship programs.

Real-world utilization of ceftazidime/avibactam among inpatients in the national Veterans Affairs Healthcare System.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Multidrug-resistant (MDR) infections are challenging to treat due to underlying patient conditions, pathogen characteristics, and high antibiotic resistance rates. As newer antibiotic therapies come to market, limited data exist about their real-world utilization. METHODS: This was a national retrospective cohort study of ceftazidime/avibactam (approved in 2015) utilization among inpatients from the Veterans Affairs (VA) Healthcare System, from 2015 through 2021. Joinpoint regression was used to estimate time trends in utilization. RESULTS: Ceftazidime/avibactam use increased by 52.3% each year (days of therapy per 1,000 bed days; 95% confidence interval, 12.4%-106.4%). We identified 1,048 unique predominantly male (98.3%) and white (66.2%; Black, 27.7%) patients treated with ceftazidime/avibactam, with a mean (SD) age of 71.5 (11.9) years. The most commonly isolated organisms were Pseudomonas aeruginosa (36.3%; carbapenem resistant, 80.6%; MDR, 65.0%) and Klebsiella species (34.1%; carbapenem resistant, 78.4%; extended-spectrum cephalosporin resistant, 90.7%). Common comorbid conditions included hypertension (74.8%), nervous system disorders (60.2%), diabetes mellitus (48.7%), and cancer (45.1%). Median time to ceftazidime/avibactam initiation from admission was 6 days, with a median of 3 changes in therapy before ceftazidime/avibactam initiation and a subsequent median length of inpatient stay of 14 days (median of 8 days of ceftazidime/avibactam therapy). Treatment heterogeneity was high, both before ceftazidime/avibactam initiation (89.6%) and during ceftazidime/avibactam treatment (85.6%), and common concomitant antibiotics included vancomycin (41.4%), meropenem (24.1%), cefepime (15.2%), and piperacillin/tazobactam (15.2%). The inpatient mortality rate was 23.6%, and 20.8% of patients had a subsequent admission with ceftazidime/avibactam treatment. CONCLUSION: Utilization of ceftazidime/avibactam increased from 2015 to 2021 in the national VA Healthcare System. Ceftazidime/avibactam was utilized in complex, difficult-to-treat patients, with substantial treatment heterogeneity and variation in the causative organism and culture site.

Nirmatrelvir/Ritonavir Utilization for the Treatment of Non-hospitalized Adults with COVID-19 in the National Veterans Affairs (VA) Healthcare System.

INTRODUCTION: Limited data exist regarding real-world utilization of nirmatrelvir/ritonavir. We identified predictors of nirmatrelvir/ritonavir use among Veterans Affairs (VA) outpatients nationally. METHODS: We conducted a retrospective cohort study among outpatients with coronavirus disease 2019 (COVID-19) who were eligible to receive nirmatrelvir/ritonavir between January and December of 2022, to identify factors associated with nirmatrelvir/ritonavir use (i.e., demographics, medical history, prior medication and healthcare exposures, frailty, and other clinical characteristics) using multivariable logistic regression. RESULTS: We included 309,755 outpatients with COVID-19 who were eligible for nirmatrelvir/ritonavir, of whom 12.2% received nirmatrelvir/ritonavir. Nirmatrelvir/ritonavir uptake increased from 1.1% to 23.2% over the study period. Factors associated with nirmatrelvir/ritonavir receipt included receiving a COVID-19 booster vs. none (adjusted odds ratio [aOR] 2.19 [95% confidence interval [CI] 2.12-2.26]), age ≥ 50 vs. 18-49 years (aORs > 1.5 for all age groups ≥ 50 years), having HIV (aOR 1.36 [1.22-1.51]), being non-frail vs. severely frail (aOR 1.22 [1.13-1.33]), and having rheumatoid arthritis (aOR 1.12 [1.04-1.21). Those with concomitant use of potentially interacting antiarrhythmics (aOR 0.35 [0.28-0.45]), anticoagulants/antiplatelets (aOR 0.42 [0.40-0.45]), and/or psychiatric/sedatives (aOR 0.84 [0.81-0.87]) were less likely to receive nirmatrelvir/ritonavir. CONCLUSIONS: Despite increases over time, overall utilization of nirmatrelvir/ritonavir was low. Predictors of nirmatrelvir/ritonavir utilization were consistent with known risk factors for progression to severe COVID-19, including older age and underlying medical conditions. Unvaccinated and undervaccinated patients and those receiving potentially interacting medications for cardiovascular or mental health conditions (antiarrhythmic, alpha-1 antagonist, anticoagulant/antiplatelet, sedative/hypnotic/psychiatric) were less likely to receive nirmatrelvir/ritonavir. Further education of prescribers and patients about nirmatrelvir/ritonavir treatment guidelines is needed to improve overall uptake and utilization in certain high-risk subpopulations.

Advancements in Novel Live Biotherapeutic Products for Clostridioides difficile Infection Prevention.

The profound impact of the human microbiome on health and disease has captivated the interest of clinical and scientific communities. The human body hosts a vast array of microorganisms collectively forming the human microbiome, which significantly influences various physiological processes and profoundly shapes overall well-being. Notably, the gut stands out as an exceptional reservoir, harboring the most significant concentration of microorganisms, akin to an organ in itself. The gut microbiome's composition and function are influenced by genetics, environment, age, underlying conditions, and antibiotic usage, leading to dysbiosis and pathogenesis, such as Clostridioides difficile infection (CDI). Conventional CDI treatment, involving antibiotics like oral vancomycin and fidaxomicin, fails to address dysbiosis and may further disrupt gut microbial communities. Consequently, emerging therapeutic strategies are focused on targeting dysbiosis and restoring gut microbiota to advance CDI therapeutics. Fecal microbiota transplantation (FMT) has demonstrated remarkable efficacy in treating recurrent CDI by transferring processed stool from a healthy donor to a recipient, restoring gut dysbiosis and enhancing bacterial diversity. Moreover, 2 newer Food and Drug Administration (FDA)-approved live biotherapeutic products (LBP), namely, Fecal Microbiota Live-JSLM and Fecal Microbiota Spores Live-BRPK, have shown promise in preventing CDI recurrence. This review explores the role of the gut microbiota in preventing and treating CDI, with an emphasis on gut-based interventions like FMT and fecal microbiota-based products that hold potential for gut restoration and prevention of CDI recurrence. Understanding the microbiome's impact on CDI prevention and treatment offers valuable insights for advancing future CDI therapeutics.

Decreasing Antibiotic Resistance Trends Nationally in Gram-Negative Bacteria Across United States Veterans Affairs Medical Centers, 2011-2020.

INTRODUCTION: Gram-negative resistance is a well-acknowledged public health threat. Surveillance data can be used to monitor resistance trends and identify strategies to mitigate their threat. The objective of this study was to assess antibiotic resistance trends in Gram-negative bacteria. METHODS: The first cultures of Pseudomonas aeruginosa, Citrobacter, Escherichia coli, Enterobacter, Klebsiella, Morganella morganii, Proteus mirabilis, and Serratia marcescens per hospitalized patient per month collected from 125 Veterans Affairs Medical Centers (VAMCs) between 2011 to 2020 were included. Time trends of resistance phenotypes (carbapenem, fluoroquinolone, extended-spectrum cephalosporin, multi-drug, and difficult-to-treat) were analyzed with Joinpoint regression to estimate average annual percent changes (AAPC) with 95% confidence intervals and p values. A 2020 antibiogram of reported antibiotic percent susceptibilities was also created to evaluate resistance rates at the beginning of the COVID-19 pandemic. RESULTS: Among 40 antimicrobial resistance phenotype trends assessed in 494,593 Gram-negative isolates, there were no noted increases; significant decreases were observed in 87.5% (n = 35), including in all P. aeruginosa, Citrobacter, Klebsiella, M. morganii, and S. marcescens phenotypes (p < 0.05). The largest decreases were seen in carbapenem-resistant phenotypes of P. mirabilis, Klebsiella, and M. morganii (AAPCs: - 22.9%, - 20.7%, and - 20.6%, respectively). In 2020, percent susceptibility was over 80% for all organisms tested against aminoglycosides, cefepime, ertapenem, meropenem, ceftazidime-avibactam, ceftolozane-tazobactam, and meropenem-vaborbactam. CONCLUSION: We observed significant decreases in antibiotic resistance for P. aeruginosa and Enterobacterales over the past decade. According to the 2020 antibiogram, in vitro antimicrobial activity was observed for most treatment options. These results may be related to the robust infection control and antimicrobial stewardship programs instituted nationally among VAMCs.

Student pharmacists delivering academic detailing on adult pneumococcal vaccination to community pharmacists.

BACKGROUND: Academic detailing is an educational outreach approach to disseminate evidence-based information to health care professionals and improve clinical decision making. Pharmacists and physicians are recognized as the most qualified individuals to perform academic detailing; however, trained student pharmacists may also serve as suitable academic detailers. OBJECTIVES: To describe our academic detailing intervention that used trained student pharmacists to disseminate an updated pneumococcal vaccination clinical pathway (i.e., decision-support tool) and education to community pharmacists in Rhode Island and Massachusetts. METHODS: We updated an academic detailing initiative that included a pneumococcal vaccination clinical pathway and education for community pharmacists in 2021. Two University of Rhode Island (URI) College of Pharmacy pharmacist faculty members trained 6 student pharmacists to perform academic detailing. Student pharmacists visited URI-affiliated community pharmacies throughout Rhode Island and Massachusetts. After each session, each participant received a 6-question anonymous paper survey to assess the effectiveness of the updated pathway and academic detailing session. The survey used a 5-point Likert-type scale. We assessed the percentage agreement with each question. RESULTS: Academic detailing was delivered to 76 community pharmacists from May to August 2021. Most respondents agreed (89.2%, 58/65) that their knowledge of which patient populations met eligibility for the pneumococcal conjugate vaccine or pneumococcal polysaccharide vaccine improved. Respondents were confident they could apply the knowledge gained (93.8%, 61/65) and intended to apply the pathway (93.8%, 61/65) to clinical practice. Most respondents expected vaccination practices to change because of the academic detailing and education materials received (83.6%, 51/61). Almost all respondents (95.4%, 62/65) found the educational materials easy to understand. CONCLUSION: Trained student pharmacists can deliver academic detailing regarding adult pneumococcal vaccination to community pharmacists. Enlisting the help of student pharmacists may be a sustainable approach to academic detailing and provides students with valuable opportunities to practice delivering educational outreach to community pharmacists.

Antibiotic Prescribing in Outpatient Settings: Rural Patients Are More Likely to Receive Fluoroquinolones and Longer Antibiotic Courses.

Suboptimal antibiotic prescribing may be more common in patients living in rural versus urban areas due to various factors such as decreased access to care and diagnostic testing equipment. Prior work demonstrated a rural health disparity of overprescribing antibiotics and longer durations of antibiotic therapy in the United States; however, large-scale evaluations are limited. We evaluated the association of rural residence with suboptimal outpatient antibiotic use in the national Veterans Affairs (VA) system. Outpatient antibiotic dispensing was assessed for the veterans diagnosed with an upper respiratory tract infection (URI), pneumonia (PNA), urinary tract infection (UTI), or skin and soft tissue infection (SSTI) in 2010-2020. Rural-urban status was determined using rural-urban commuting area codes. Suboptimal antibiotic use was defined as (1) outpatient fluoroquinolone dispensing and (2) longer antibiotic courses (>ten days). Geographic variation in suboptimal antibiotic use was mapped. Time trends in suboptimal antibiotic use were assessed with Joinpoint regression. While controlling for confounding, the association of rurality and suboptimal antibiotic use was assessed with generalized linear mixed models with a binary distribution and logit link, accounting for clustering by region and year. Of the 1,405,642 veterans diagnosed with a URI, PNA, UTI, or SSTI and dispensed an outpatient antibiotic, 22.8% were rural-residing. In 2010-2020, in the rural- and urban-residing veterans, the proportion of dispensed fluoroquinolones declined by 9.9% and 10.6% per year, respectively. The rural-residing veterans were more likely to be prescribed fluoroquinolones (19.0% vs. 17.5%; adjusted odds ratio (aOR), 1.03; 95% confidence interval (CI), 1.02-1.04) and longer antibiotic courses (53.8% vs. 48.5%; aOR, 1.19, 95% CI, 1.18-1.20) than the urban-residing veterans. Among a large national cohort of veterans diagnosed with URIs, PNA, UTIs, and SSTIs, fluoroquinolone use and longer antibiotic courses were disproportionally more common among rural- as compared to urban-residing veterans. Outpatient antibiotic prescribing must be improved, particularly for rural-residing patients. There are many possible solutions, of which antibiotic stewardship interventions are but one.

Trends in Stenotrophomonas maltophilia antibiotic resistance rates in the United States Veterans Affairs Health System.

Introduction. Stenotrophomonas maltophilia is an important multidrug-resistant Gram-negative pathogen. While largely a hospital-acquired pathogen, there have been increasing reports of the pathogen in the community.Gap Statement. Trends in S. maltophilia prevalence and resistance rates that include outpatient isolates are unknown.Aim. We described recent trends in prevalence and resistance of S. maltophilia in the national Veterans Affairs (VA) Healthcare system.Methodology. The study identified positive S. maltophilia clinical cultures among VA adult patients from 2010 to 2018 across all VA hospitals, long-term care facilities/units, and outpatient settings. Annual S. maltophilia resistance rates were evaluated. Multidrug resistant (MDR) was defined as resistance to sulfamethoxazole/trimethoprim (SMX/TMP) and minocycline or levofloxacin. Time trends were assessed with regression analyses to estimate annual average percent changes (AAPC) with 95 % confidence intervals using Joinpoint software.Results. Over the 9 year study period, 18 285 S. maltophilia cultures were identified (57 % hospital, 3 % long-term care, 40 % outpatient). The most common source of S. maltophilia cultures were respiratory cultures (34.6 %) followed by urine cultures (30.4 %). In VA hospitals and long-term care facilities, the number of S. maltophilia cultures decreased significantly (by 5.4% and 8.4 % per year respectively). Overall, 3.1 % of isolates were MDR which remained stable over the study period. Resistance to other antibiotics assessed mostly remained stable, except SMX/TMP resistance decreased significantly by 8.5 % (2010, 15 %; 2018, 6 %) per year in VA hospitals.Conclusion. While previous work has recognized S. maltophilia as primarily a nosocomial pathogen, the present study found that 40 % of cultures collected were among outpatients. Between 2010 and 2018, the number of positive S. maltophilia cultures decreased significantly in the national VA Healthcare System. Resistance to SMX/TMP decreased over the study period in VA hospitals and now more closely reflects previously reported resistance rates worldwide (0-10 %). MDR S. maltophilia remained stable and low in the national VA Healthcare System.

Path of least recurrence: A systematic review and meta-analysis of fidaxomicin versus vancomycin for Clostridioides difficile infection.

STUDY OBJECTIVE: Current Clostridioides difficile infection (CDI) treatment guidelines recommend either fidaxomicin or vancomycin as first-line therapy for initial and recurrent CDI. The objective of this study was to compare recurrence rates of fidaxomicin and vancomycin for the treatment of CDI in clinically relevant and real-world subgroups via systematic review and meta-analysis. DESIGN & DATA SOURCES: A systematic literature review was performed by searching PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to September 1, 2021, for randomized and observational studies comparing vancomycin and fidaxomicin for CDI treatment in adults. The meta-analysis was performed with Review Manager 5.4 software (Cochrane Library, Oxford, United Kingdom) using a random-effects model. The primary end point was CDI recurrence after treatment with fidaxomicin or vancomycin. Subgroup analyses were conducted. PATIENTS, INTERVENTION, MEASUREMENTS & MAIN RESULTS: The literature search identified six randomized controlled trials and eight observational trials, with a total of 3944 patients (fidaxomicin 32%; vancomycin 68%) included in the meta-analysis. The mean age of study patients ranged from 46 to 75 years. The CDI recurrence rate was 22.4% (fidaxomicin 16.1%, vancomycin 25.4%). Compared to vancomycin, treatment with fidaxomicin was associated with a 31% reduction in the risk of recurrence (risk ratio 0.69; 95% confidence interval: 0.52-0.91, I2  = 62%). This reduction in recurrence risk was also seen in subgroup analyses for patients with initial CDI, first recurrent CDI, non-severe and severe CDI, and in both inpatient and outpatient settings. CONCLUSION: Our systematic review and meta-analysis found fidaxomicin was consistently associated with a lower risk of CDI recurrence than vancomycin. These results confirm CDI guideline recommendations and indicate that fidaxomicin may be preferred over vancomycin to minimize CDI recurrence across multiple clinical scenarios, although further studies are warranted.

Treatment Heterogeneity in Pseudomonas aeruginosa Pneumonia.

We have previously identified substantial antibiotic treatment heterogeneity, even among organism-specific and site-specific infections with treatment guidelines. Therefore, we sought to quantify the extent of treatment heterogeneity among patients hospitalized with P. aeruginosa pneumonia in the national Veterans Affairs Healthcare System from Jan-2015 to Apr-2018. Daily antibiotic exposures were mapped from three days prior to culture collection until discharge. Heterogeneity was defined as unique patterns of antibiotic treatment (drug and duration) not shared by any other patient. Our study included 5300 patients, of whom 87.5% had unique patterns of antibiotic drug and duration. Among patients receiving any initial antibiotic/s with a change to at least one anti-pseudomonal antibiotic (n = 3530, 66.6%) heterogeneity was 97.2%, while heterogeneity was 91.5% in those changing from any initial antibiotic/s to only anti-pseudomonal antibiotics (n = 576, 10.9%). When assessing heterogeneity of anti-pseudomonal antibiotic classes, irrespective of other antibiotic/s received (n = 4542, 85.7%), 50.5% had unique patterns of antibiotic class and duration, with median time to first change of three days, and a median of two changes. Real-world evidence is needed to inform the development of treatment pathways and antibiotic stewardship initiatives based on clinical outcome data, which is currently lacking in the presence of such treatment heterogeneity.

Assessing Rates of Co-Resistance and Patient Outcomes in Multidrug-Resistant Pseudomonas aeruginosa.

Multidrug-resistant (MDR) Pseudomonas aeruginosa infections are associated with poor patient outcomes due to complex co-resistance patterns. We described common co-resistance patterns, clinical characteristics, and associated outcomes in patients admitted with an MDR P. aeruginosa. This national, multicenter, retrospective cohort study within the Veterans Affairs included adults hospitalized with a MDR P. aeruginosa infection (January 2015-December 2020) per Centers for Disease Control definition. Clinical outcomes were compared among those with differing MDR P. aeruginosa co-resistance: resistant to carbapenems and extended-spectrum cephalosporins and piperacillin-tazobactam (CARB/ESC/PT) versus without CARB/ESC/PT resistance; resistant to carbapenems and extended-spectrum cephalosporins and fluoroquinolone (CARB/ESC/FQ) versus without CARB/ESC/FQ resistance. We included 3,763 hospitalized patients. Co-resistance to CARB/ESC/PT was observed in 42.7%, and to CARB/ESC/FQ in 40.7%. The lowest co-resistance rates were observed with ceftolozane-tazobactam (6.2%, n = 6/97; 12.5%, n = 10/80, respectively) and ceftazidime-avibactam (5.2%, n = 5/97; 12.5%, n = 10/80, respectively). Overall, 14.2% of patients died during hospitalization, 59.7% had an extended length of stay, and 14.9% had reinfection with hospitalization. Outcomes were similar between patients with MDR P. aeruginosa strains with and without co-resistance to CARB/ESC/PT and CARB/ESC/FQ. Among a national cohort of patients hospitalized with MDR P. aeruginosa infections, co-resistance to three classes of standard of care antibiotics, such as carbapenem, extended-spectrum cephalosporins, and piperacillin-tazobactam or fluoroquinolones, exceeded 40% in our study population, posing great concerns for selecting appropriate empirical therapy. Clinical outcomes were poor for all patients, regardless of different co-resistance patterns. New treatment options are needed for hospitalized patients with suspected or confirmed MDR P. aeruginosa infections. IMPORTANCE We studied antibiotic co-resistance patterns in a national group of hospitalized patients with infections due to multidrug-resistant (MDR) Pseudomonas aeruginosa, a type of bacteria that resists treatment to at least three classes of antibiotics. Co-resistance to antibiotic classes most typically used for treatment was common, which makes selecting appropriate antibiotics to successfully treat the infections difficult. Outcomes, including death, were poor for all patients in our study, regardless of the different patterns of co-resistance to common antibiotic classes. New antibiotics are needed to help treat hospitalized patients with MDR P. aeruginosa infections.

The Comparative Effectiveness of Ceftolozane/Tazobactam versus Aminoglycoside- or Polymyxin-Based Regimens in Multi-Drug-Resistant Pseudomonas aeruginosa Infections.

Pseudomonas aeruginosa infections are challenging to treat due to multi-drug resistance (MDR) and the complexity of the patients affected by these serious infections. As new antibiotic therapies come on the market, limited data exist about the effectiveness of such treatments in clinical practice. In this comparative effectiveness study of ceftolozane/tazobactam versus aminoglycoside- or polymyxin-based therapies among hospitalized patients with positive MDR P. aeruginosa cultures, we identified 57 patients treated with ceftolozane/tazobactam compared with 155 patients treated with aminoglycoside- or polymyxin-based regimens. Patients treated with ceftolozane/tazobactam were younger (mean age 67.5 vs. 71.1, p = 0.03) and had a higher comorbidity burden prior to hospitalization (median Charlson 5 vs. 3, p = 0.01) as well as higher rates of spinal cord injury (38.6% vs. 21.9%, p = 0.02) and P. aeruginosa-positive bone/joint cultures (12.3% vs. 0.7%, p < 0.0001). Inpatient mortality was significantly lower in the ceftolozane/tazobactam group compared with aminoglycosides or polymyxins (15.8% vs. 27.7%, adjusted odds ratio 0.39, 95% confidence interval 0.16−0.93). There were no significant differences observed for the other outcomes assessed. In hospitalized patients with MDR P. aeruginosa, inpatient mortality was 61% lower among patients treated with ceftolozane/tazobactam compared to those treated with aminoglycoside- or polymyxin-based regimens.

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.

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 >10 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.

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.

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

BACKGROUND: Unnecessary antibiotic treatment of suspected urinary tract infections (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 (the first during the study with none in the year prior) in Department of 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 with 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 whom 96.0% were male. Potentially suboptimal antibiotic treatment was identified in 65.0% of residents and decreased 1.8% annually (P < .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, 1.38), chronic renal disease (1.19), age ≥85 years (1.17), prior skin infection (1.14), recent high white blood cell count (1.08), and genitourinary disorder (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.

Antibiograms Cannot Be Used Interchangeably Between Acute Care Medical Centers and Affiliated Nursing Homes.

OBJECTIVE: To determine whether antibiograms for Veterans Affairs (VA) nursing homes (NHs), termed Community Living Centers, are similar to those from their affiliated acute care medical centers. DESIGN: Descriptive study. SETTING AND PARTICIPANTS: We compared the 2017 antibiograms for VA NHs to their affiliated VA medical centers (VAMCs). Antibiograms included antibiotic susceptibility rates for commonly observed bacteria in this setting (Staphylococcus aureus, Enterococcus spp, Escherichia coli, Klebsiella spp, Proteus mirabilis, and Pseudomonas aeruginosa). METHODS: Antibiograms were considered to be in complete agreement when the overall susceptibility rate between the NH and affiliated VAMC was either at or above 80% or below 80% across all bacteria and antibiotics. Average percentage of bacteria-antibiotic comparisons in disagreement per facility pair, and number of facilities with agreement for specific bacteria-antibiotic comparisons were also assessed. The chi-square test was used to compare disagreement between NH-VAMC facilities based on geographic proximity of the NH to the VAMC, culture source, and bed size. RESULTS: A total of 119 NH-VAMC affiliate pairs were included in this analysis, with 71% (84/119) on the same campus and 29% (35/119) on geographically distinct campuses. None of the NH-VAMC pairs demonstrated complete agreement (all bacteria vs all antibiotics) between their antibiograms. On average, 20% of the bacteria-antibiotic comparisons from the antibiogram disagreed clinically per NH-VAMC pair, and almost twice as often the nursing home had lower susceptibility (higher resistance) than the acute care facility. Some bacteria-antibiotic comparisons agreed in all facilities (eg, E coli-imipenem; S aureus-linezolid; S aureus-vancomycin), while others showed greater disagreement (eg, Klebsiella spp-cefazolin; Klebsiella spp-ampicillin-sulbactam; P aeruginosa-ciprofloxacin). Rates of clinical disagreement were similar by geographic proximity of the NH to the VAMC, culture source, and bed size. CONCLUSIONS AND IMPLICATIONS: Overall, this study showed a moderate lack of agreement between VA NH antibiograms and their affiliate VAMC antibiograms. Our data suggest that antibiograms of acute care facilities are often not accurate approximations of the nursing home resistance patterns and therefore should be used with caution (if at all) in guiding empiric antibiotic therapy.

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.

Facilitators and Barriers to Antibiotic Stewardship: A Qualitative Study of Pharmacists' Perspectives.

Background: The Veterans Affairs (VA) is a leader in the implementation and advancement of antibiotic stewardship programs throughout the nation. The Centers for Disease Control and Prevention (CDC) has also led national antibiotic stewardship efforts and has outlined core elements to improve antibiotic use in hospitals, long-term care, and outpatient settings. Many facilities still face challenges to the implementation and maintenance of successful programs, particularly in nonacute care settings. The objective of this study was to identify barriers and facilitators to antibiotic stewardship within the VA medical centers through qualitative interviews with pharmacists. Methods: Eight semi-structured telephone interviews were conducted with pharmacists from 6 VA medical centers within VA New England Healthcare System. Pharmacist respondents were either pharmacy champions (for medical centers with established programs) or pharmacists with responsibilities in making antibiotic recommendations (locations without established programs). All interviews were audio recorded and transcribed verbatim. NVivo 8 was used for data coding and analysis. Results: Pharmacists from all 8 medical centers were contacted for interviews and pharmacists from 6 medical centers agreed to interviews (75% VA New England medical center participation). Three main themes regarding antibiotic stewardship were identified from the interviews with pharmacists. Respondents described the importance of (1) a supportive organizational culture, (2) protected time for antibiotic stewardship, and (3) a cohesive organizational structure in the success of antibiotic stewardship programs. Conclusions: Our findings support the CDC core elements for antibiotic stewardship, in particular the importance of leadership commitment in the creation of a culture that supports antibiotic stewardship and in ensuring staff are given sufficient time for antibiotic stewardship efforts. Although a strong supportive culture has been built, strategies focused on fostering increased protected time for antibiotic stewardship and a cohesive organizational structure may be helpful in advancing and sustaining successful antibiotic stewardship programs that improve patient outcomes.