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The current antimicrobial market and old (pre-2000) in vitro antimicrobial susceptibility test interpretative criteria (STIC) are not working properly. Malfunctioning susceptibility breakpoints and antimicrobial markets have serious implications for both patients (ie, from a safety and efficacy perspective) and antibiotic-focused pharmaceutical and biotechnology company economic viability. Poorly functioning STIC fail both patients and clinicians since they do not discriminate between likely effective and ineffective antimicrobial regimens. Poor economic viability fails patients and clinicians as it decreases the industry's ability to develop antimicrobial agents that clinicians and patients urgently require now and in the future. Herein, we review how STIC for older antimicrobial agents were determined and how their correction can impact the perceived utility of old relative to new antimicrobial agents. Moreover, we describe the data and analysis needs to systematically reevaluate older STIC values. We call for professional infectious diseases societies, government agencies, and other consensus bodies interested in the appropriate use of antimicrobial agents to join an effort to systematically evaluate and, where warranted, correct STIC for all relevant antimicrobial agents. This effort will amplify the effects of other measures designed to increase appropriate antimicrobial use (ie, good antimicrobial stewardship), development, and regulation.

Among consecutive patients with multidrug-resistant Pseudomonas aeruginosa bacteremia or pneumonia we found those treated with ceftazidime-avibactam were more likely to develop resistance (defined as ≥4-fold increased MIC) than those treated with ceftolozane-tazobactam (40% vs 10%; P =.002). Ceftazidime-avibactam resistance was associated with new mutations in ampC and efflux regulatory pathways. [ABSTRACT FROM AUTHOR]

The in vitro susceptibility testing interpretive criteria (STIC) for piperacillin/tazobactam (TZP) against Enterobacterales were recently updated by the US Food and Drug Administration, Clinical and Laboratory Standards Institute, and European Committee on Antimicrobial Susceptibility Testing. The United States Committee on Antimicrobial Susceptibility Testing (USCAST) also recently reviewed TZP STIC for Enterobacterales and arrived at different STIC for Enterobacterales. Here, we explain our recommendations and rationale behind them. Based on our review of the available data, USCAST does not recommend TZP STIC for certain Enterobacterales species that have a moderate to high likelihood of clinically significant AmpC production (Enterobacter cloacae , Citrobacter freundii , and Klebsiella aerogenes only) or for third-generation cephalosporin-nonsusceptible Enterobacterales. USCAST recommends a TZP susceptibility breakpoint of ≤ 16/4 mg/L for third-generation cephalosporin-susceptible Enterobacterales and only endorses the use of extended infusion TZP regimens for patients with infections due to these pathogens. [ABSTRACT FROM AUTHOR]

Background Guidelines suggest dual antipseudomonal therapy for empiric treatment of pneumonia caused by gram-negative bacteria in intensive care unit (ICU) patients. Additionally, consideration of local susceptibility data and patient-specific risk factors for resistance is recommended for selecting optimal empiric regimens. However, data assessing how to best do this are lacking, and it is unclear whether a local susceptibility data–based or a patient-specific risk factor–based approach will better drive appropriate empiric treatment. This study aims to compare these 2 strategies. Methods This retrospective study was divided into 2 periods. In period I, gram-negative respiratory cultures from ICU patients were used to develop unit-specific combination antibiograms, and individual patient charts were reviewed to assess the impact of risk factors on antimicrobial susceptibility to develop a risk factor–based treatment algorithm. Optimal empiric regimens based on these 2 strategies were then defined. In period II, these regimens were hypothetically applied to patients to compare rates of appropriate empiric therapy and overuse by the 2 methods. Results Risk factor–based regimens had a higher appropriateness rate compared to regimens derived from antibiograms (89.9% vs 83.7%). Additionally, applying antibiogram-based regimens resulted in a higher prevalence of antibiotic overuse than a patient-specific risk factor–based approach (69.8% vs 40.3%), with excess overuse driven by a higher frequency of unnecessary use of combination therapy. Conclusions Both strategies provided high rates of appropriateness in empiric antibiotic selection. However, the patient-specific risk factor–based approach demonstrated a higher rate of appropriate therapy and offered advantages in reducing rates of unnecessary combination therapy. [ABSTRACT FROM AUTHOR]

We report identification of 5 patients with infections caused by NDM-5-producing Escherichia coli harboring PBP3 mutations that showed reduced susceptibility to aztreonam-avibactam and cefiderocol. Durlobactam, a novel diazabicyclooctane β-lactamase inhibitor, demonstrated minimum inhibitory concentrations ranging from 0.5 to 2 µg/mL supporting future investigations into a potential role in clinical management. [ABSTRACT FROM AUTHOR]

Objectives To assess risk factors for carbapenem-resistant Pseudomonas aeruginosa (CR) and extended-β-lactam-resistant P. aeruginosa (EBR) infection/colonization, and to develop and compare tools for predicting isolation of CR and EBR from clinical cultures. Methods This retrospective study analysed hospitalized patients with positive P. aeruginosa cultures between 2015 and 2021. Two case–control analyses were performed to identify risk factors and develop scoring tools for distinguishing patients with CR versus carbapenem-susceptible (CS) P. aeruginosa and EBR versus CS P. aeruginosa. The performance of institutionally derived scores, externally derived scores and the presence/absence of key risk factors to predict CR and EBR were then compared. Results A total of 2379 patients were included. Of these, 8.3% had a positive culture for CR, 5.0% for EBR and 86.7% for CS P. aeruginosa. There was substantial overlap in risk factors for CR and EBR. Institutional risk scores demonstrated modestly higher area under the ROC curve values than external scores for predicting CR (0.67 versus 0.58) and EBR (0.76 versus 0.70). Assessing the presence/absence of ≥1 of the two strongest predictors (prior carbapenem use or CR isolation within 90 days) was slightly inferior to scoring tools for predicting CR, and comparable for predicting EBR. Conclusions Clinicians concerned about CR in P. aeruginosa should consider the likelihood of EBR when making treatment decisions. A simple approach of assessing recent history of CR isolation or carbapenem usage performed similarly to more complex scoring tools and offers a more pragmatic way of identifying patients who require coverage for resistant P. aeruginosa. [ABSTRACT FROM AUTHOR]