Clinical outcomes and emergence of resistance of Pseudomonas aeruginosa infections treated with ceftolozane-tazobactam versus ceftazidime-avibactam.

Few studies compare outcomes of patients with difficult-to-treat resistance (DTR) Pseudomonas aeruginosa infections treated with ceftolozane-tazobactam versus ceftazidime-avibactam. A multicenter prospective study was conducted of unique patients with DTR P. aeruginosa infections from 2018 to 2023 receiving >72 h of ceftolozane-tazobactam or ceftazidime-avibactam, with confirmation that the P. aeruginosa isolate was susceptible to the agent administered by broth microdilution. Inverse probability weighting (IPW) incorporating propensity scores was utilized to ensure balanced baseline characteristics. Regression performed on the post-IPW group determined 30-day mortality and subsequent emergence of resistance (i.e., ≥4-fold increase in MIC) to the initial treatment (i.e., ceftolozane-tazobactam or ceftazidime-avibactam). Among 186 eligible patients, 102 (55%) received ceftolozane-tazobactam and 84 (45%) received ceftazidime-avibactam. In the post-IPW cohort, balance was achieved across all variables [e.g., demographics, severity of illness, severe immunocompromise, Charlson Comorbidity Index ≥5, continuous renal replacement therapy (CRRT), source of infection, combination therapy]. Thirty-day mortality was similar between the ceftolozane-tazobactam and ceftazidime-avibactam groups [21% vs 17%; adjusted odds ratio (aOR): 1.01 (95% confidence interval, CI: 0.90-1.14)]. Emergence of resistance was higher in the ceftolozane-tazobactam group [38% vs 25%; aOR: 1.89 (95% CI: 0.98-4.88)], but did not achieve statistical significance. Prolonged treatment durations and use of CRRT were associated with increased emergence of resistance (both P = 0.04). Although the survival of patients with DTR P. aeruginosa infections appears similar regardless of whether ceftolozane-tazobactam or ceftazidime-avibactam is prescribed, the emergence of resistance may be more concerning with the former. Plausible mechanistic explanations support these findings. Modifiable risk factors were identified that may mitigate this risk.

Is Carbapenem Therapy Necessary for the Treatment of Non-CTX-M ESBL-Producing Enterobacterales Bloodstream Infections?

BACKGROUND: Investigations into antibiotics for extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E) bloodstream infections (BSIs) have focused on blaCTX-M genes. Outcomes of patients with non-CTX-M-producing ESBL-E BSIs and optimal treatment are unknown. METHODS: A multicenter observational study investigating 500 consecutive patients with ceftriaxone-resistant Enterobacterales BSIs during 2018-2022 was conducted. Broth microdilution and whole genome sequencing confirmed antibiotic susceptibilities and ESBL gene presence, respectively. Inverse probability weighting (IPW) using propensity scores was employed to ensure patients infected with non-CTX-M and CTX-M ESBL-E BSIs were similar prior to evaluation of outcomes. RESULTS: 396 patients (79.2%) were confirmed to have an ESBL-E BSI. ESBL gene family prevalence was as follows: blaCTX-M (n=370), blaSHV (n=16), blaOXY (n=12), and blaVEB (n=5). ESBL gene identification was not limited to Escherichia coli and Klebsiella species. In the IPW cohort, there was no difference in 30-day mortality or ESBL-E infection recurrence between the non-CTX-M and CTX-M groups (OR=.99, 95% CI 0.87-1.11; p=0.83) and (OR=1.10, 95% CI 0.85--1.42; p=0.47), respectively. In an exploratory analysis limited to the non-CTX-M group, 86% of the 21 patients receiving meropenem were alive on day 30; none of the 5 patients receiving piperacillin-tazobactam were alive on day 30. CONCLUSIONS: Our findings suggest that non-CTX-M and CTX-M ESBL-producing Enterobacterales BSIs are equally concerning and associated with similar clinical outcomes. Meropenem may be associated with improved survival in patients with non-CTX-M ESBL-E BSIs, underscoring the potential benefit of comprehensive molecular diagnostics to enable early antibiotic optimization for patients with ESBL-E BSI, beyond just blaCTX-M genes.

Molecular epidemiology and clinical significance of carbapenemase genes in carbapenem-resistant Acinetobacter baumannii isolates in southern Poland.

INTRODUCTION: A complex interplay between Acinetobacter spp., patients, and the environment has made it increasingly difficult to optimally treat patients infected with Acinetobacter spp., mainly due to rising antimicrobial resistance and challenges with surveillance. OBJECTIVES: This study evaluated carbapenem­resistant A. baumannii (CRAB) isolates to determine their resistance profiles and the presence of specific ß­lactamases to inform CRAB surveillance upon hospital admission and regional empiric antibiotic therapies. PATIENTS AND METHODS: The study was conducted at 4 hospitals in southern Poland between June and December 2022. Only health care-associated infections caused by A. baumannii were considered. A total of 82 CRAB isolates were included in the analysis. Species identification was performed by matrix­assisted laser desorption / ionization time­of­flight mass spectrometry, antimicrobial susceptibility was determined phenotypically, and polymerase chain reactions were carried out to identify the resistance genes. RESULTS: Depending on the hospital, the incidence of CRAB infections varied from 428.6 to 759.5 per 10 000 admissions in intensive care units (ICUs), and from 0.3 to 21 per 10 000 admissions in non­ICUs. CRAB antibiotic susceptibility was the highest for cefiderocol (100%), colistin (96%), tigecycline (77%), gentamicin (51%), and ampicillin / sulbactam (36%). The most prevalent blaOXA genes were blaOXA­66­1 (95%) and blaOXA­40 (71%), and additionally the extended­spectrum ß­lactamase gene blaTEM­1 (41%). CONCLUSION: An unexpectedly high incidence of CRAB infections occurred in Polish hospitals. There is a need for effective CRAB prevention and control that includes effective hospital screening, national surveillance, and improved treatment options.

RABIES IN RODENTS AND LAGOMORPHS IN THE USA, 2011-20.

Rabies is an acute progressive encephalitis caused by infection with rabies viruses, with reservoirs among bats and mesocarnivores, but all mammals are susceptible. Despite its distribution and abundance, cases of rabies are much less common in rodents and lagomorphs. Familiarity with current rabies prevalence data is important for informed decisions on human postexposure prophylaxis after rodent and lagomorph bites. This study is an update of rabies cases reported in rodents and lagomorphs in the US from 2011 to 2020. Rabies reports were collected passively from laboratory testing agencies in the US and Puerto Rico from 2011 to 2020. Descriptive analysis was conducted to determine the percent positivity of rabies cases by species. A total of 401 cases of rabies in rodents and lagomorphs were reported from 2011 to 2020. Most reported cases were in groundhogs (Marmota monax), representing >90% of cases, and the trend closely aligned with rabies in raccoons (Procyon lotor). In any given year, the percent positivity of rabies in rodents and lagomorphs was <2.5%, and the trend of percent positivity from 2011 to 2020 was stable. Groundhog and North American beaver (Castor canadensis) percent positivity was significantly higher than the rest of the rodents and lagomorphs. Most rabies cases occurred during the months of May-September. Documented cases of rabies in rodents and lagomorphs are generally rare, but with variation between species. Groundhogs and North American beavers had rabies percent positivity similar to high-risk species, such as bats and raccoons, and constituted 97% of all rodent and lagomorph positive cases. Since 1993, the trend in rabies cases in groundhogs has significantly declined. These results can be used to help inform public health officials on rodent and lagomorph prevention and control efforts, as well as rabies postexposure prophylaxis.

Clinical characteristics of hospitalized patients with false-negative severe acute respiratory coronavirus virus 2 (SARS-CoV-2) test results.

OBJECTIVE: To determine clinical characteristics associated with false-negative severe acute respiratory coronavirus virus 2 (SARS-CoV-2) test results to help inform coronavirus disease 2019 (COVID-19) testing practices in the inpatient setting. DESIGN: A retrospective observational cohort study. SETTING: Tertiary-care facility. PATIENTS: All patients 2 years of age and older tested for SARS-CoV-2 between March 14, 2020, and April 30, 2020, who had at least 2 SARS-CoV-2 reverse-transcriptase polymerase chain reaction tests within 7 days. METHODS: The primary outcome measure was a false-negative testing episode, which we defined as an initial negative test followed by a positive test within the subsequent 7 days. Data collected included symptoms, demographics, comorbidities, vital signs, labs, and imaging studies. Logistic regression was used to model associations between clinical variables and false-negative SARS-CoV-2 test results. RESULTS: Of the 1,009 SARS-CoV-2 test results included in the analysis, 4.0% were false-negative results. In multivariable regression analysis, compared with true-negative test results, false-negative test results were associated with anosmia or ageusia (adjusted odds ratio [aOR], 8.4; 95% confidence interval [CI], 1.4-50.5; P = .02), having had a COVID-19-positive contact (aOR, 10.5; 95% CI, 4.3-25.4; P < .0001), and having an elevated lactate dehydrogenase level (aOR, 3.3; 95% CI, 1.2-9.3; P = .03). Demographics, symptom duration, other laboratory values, and abnormal chest imaging were not significantly associated with false-negative test results in our multivariable analysis. CONCLUSIONS: Clinical features can help predict which patients are more likely to have false-negative SARS-CoV-2 test results.