Antimicrobial Agents and Chemotherapy

In this issue, B. Gaglani, T. M. Andermann, C. Wate, J. Oldan, et al. (Antimicrob Agents Chemother 70:e01542-25, 2026, https://doi.org/10.1128/aac.01542-25) describe a recurrent Burkholderia cenocepacia infection successfully treated with cefiderocol plus sulbactam-durlobactam. Treatment decisions are often made with incomplete microbiological and pharmacological data, even as interest in mechanism-based β-lactam combination strategies continues to grow. This case supports the utility of...

Achieving antibiotic pharmacodynamic targets is critical to surviving sepsis. The purpose of this study was to determine the achievement of pharmacodynamic target-free minimum plasma concentration (fCmin)-during the first 2 days of high-dose 6-h intravenous meropenem or piperacillin-tazobactam in critically ill children, and to identify its predictors. This was a prospective observational study conducted in two pediatric intensive care units of children admitted between 2022 and 2023 who were...

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Human adenovirus (HAdV) is one of the most infectious pathogens that can cause diseases affecting multiple organ systems, posing a significant threat to public health. Currently, there are no specific antiviral therapies available for HAdV infection. In this study, three folate antagonists aminopterin (AMT), pralatrexate (PDX), and methotrexate (MTX) with potent antiviral activity against HAdV infection have been identified through a drug repurposing screening strategy. The three drugs showed...

Combination antimicrobial treatment for endocarditis secondary to Enterobacterales may be associated with clinical benefits, but this benefit comes with an increased risk of adverse drug reactions (ADRs). We hypothesized that short-course combination therapy would optimize clinical benefits while minimizing ADRs. This was a retrospective, multicenter study of adult patients with definitive endocarditis secondary to Enterobacterales. Short-course combination treatment was defined as receipt of...

Strain diversity in Mycobacterium tuberculosis (Mtb) underlies distinct clinical presentations and outcomes, but the range of drug susceptibility phenotypes among clinical isolates is poorly understood. We aimed to identify drug response patterns in phylogenetically diverse clinical isolates to combination treatment. We selected 13 strains out of 641 drug-sensitive clinical isolates that capture local and global phylogenetic diversity and included Erdman ATCC-35801 as a reference. We treated...

Studies have shown there is minimal risk of cephalosporin cross-reactivity with penicillin (PCN), though avoidance in practice still occurs. Avoidance of cephalosporins due to reported PCN allergies can result in negative clinical outcomes. Removal of cross-reactivity alerts from the electronic health record (EHR) may increase cephalosporin utilization. The objective of this study was to evaluate cephalosporin utilization in those with documented intermediate-, high-, and severe-risk allergies...

Novel β-lactam/β-lactamase inhibitors (βL/βLIs) are important therapies for carbapenem-resistant Pseudomonas aeruginosa (CRPA). However, the global extent of resistance to these agents and the impact of resistance on patient outcomes are unclear. We therefore evaluated patients with CRPA isolates at 35 hospitals (nine countries) from December 2018 to November 2019. Antimicrobial susceptibility testing was performed at a central laboratory by agar dilution for ceftolozane-tazobactam (C/T) and...

Pseudomonas aeruginosa thrive to survive in harsh conditions imposed by the host. We have previously described two Zn^(2+)-transporting members of the Cation Diffusion Facilitator family, YiiP and CzcD, inhibiting susceptibility to imipenem by decreasing the expression of the outer membrane porin OprD (A. Salusso and D. Raimunda, Front Cell Infect Microbiol 7:84, 2017, https://doi.org/10.3389/fcimb.2017.00084). Here, we provide evidence that a protein encoded in yiiP's operon, PA3962, is...

This study assessed whether voriconazole (VRC) gradient diffusion results can be extrapolated to isavuconazole (ISA) and posaconazole (PSC) in Aspergillus fumigatus and Aspergillus terreus by comparison with the Clinical and Laboratory Standards Institute (CLSI) broth microdilution (BMD) and cyp51A sequencing. Agreement with CLSI BMD was highest at 48 h, but remained limited for some azole-species combinations. VRC-PSC extrapolation was reliable in both species, whereas VRC-ISA extrapolation was...

Ceftazidime-avibactam (CAZ-AVI) is a crucial treatment for multidrug-resistant (MDR) gram-negative infections; however, the impact of treatment timing and outcomes in real-world practice remains unclear. This study evaluated CAZ-AVI use across diverse U.S. centers, with emphasis on early initiation. We conducted a retrospective cohort study at 22 U.S. medical centers (2019-2025), including adults with MDR gram-negative infections who received CAZ-AVI ≥ 72 h. The primary outcome was composite...

To determine midostaurin and posaconazole plasma concentrations and investigate adverse events (AEs) resembling drug-drug interactions (DDI) when both drugs were administered concomitantly during induction chemotherapy for acute myeloid leukemia (AML). Patients with FLT3-mutated AML who received midostaurin and posaconazole concomitantly between May 2019 and December 2022 were included and followed up to March 2023. Twice-weekly trough levels for midostaurin and posaconazole were measured with...

The emergence of Klebsiella pneumoniae species complex (KpSC) with tet(X4) in aquatic products poses a public health risk. Among 442 aquatic products sampled in Hainan, 14 tet(X4)-positive isolates were identified with multidrug-resistant profiles. IncFII(pCRY)_v, a previously uncharacterized plasmid, emerged as the dominant tet(X4) carrier in this study, transferable by conjugation and widely present in KpSC, and particularly prevalent among clinical isolates. These findings call for One Health...

Candida albicans remains the predominant cause of invasive candidiasis worldwide, yet comprehensive global analyses of its antifungal susceptibility trends remain scarce. In this decade-long study, we evaluated 6,342 C. albicans isolates collected between 2015 and 2024 through the Antimicrobial Testing Leadership and Surveillance global surveillance program, representing 41 countries across four continents. Europe accounted for more than half of all isolates, followed by North America,...

Molecular markers give evidence of Plasmodium falciparum resistance to antimalarials. We determined the spatial and temporal distribution of antimalarial drug resistance markers in the P. falciparum population in Ghana using targeted amplicon deep sequencing. We contextualized our findings within the framework that duration of drug exposure and transmission intensity drive trends in molecular markers. About 87% (901/1,037) of samples collected from children ≤9 years with uncomplicated malaria...