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.

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.

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.