Antimicrobial Agents and Chemotherapy

N⁶-methyladenosine (m⁶A) is a major epitranscriptomic modification that regulates RNA metabolism and affects the replication and latency reversal of human immunodeficiency virus type 1 (HIV-1) in cells. Methyltransferase-like 3 (METTL3) is the principal catalytic enzyme responsible for m⁶A deposition, and its pharmacological inhibition has emerged as a potential therapeutic strategy for cancer and viral infections. However, the relative potency of METTL3 inhibitors in reducing m⁶A levels and...

Hand, foot, and mouth disease (HFMD) is primarily caused by Enterovirus 71 (EV71) and Coxsackievirus A16 (CA16), while excessive inflammatory responses induced by viral infection are the main cause of severe conditions. Hence, it is important to develop agents with both antiviral and anti-inflammatory activities for clinical treatment. In this study, we synthesized 20 compounds based on the hybridization of nonsteroidal anti-inflammatory drugs (NSAIDs) and organoselenium and found that YSN-1-167...

We investigated sequences of the penicillin-binding protein 2x (PBP2x) among 902 Streptococcus pyogenes isolates from children with pharyngitis. Twenty-five pharyngeal isolates carried variants associated with reduced β-lactam susceptibility. Penicillin and ampicillin susceptibility testing confirmed reduced susceptibility among PBP2x variant isolates relative to those with the wild-type sequence.

The KPC family of serine β-lactamases comprises more than 260 members. Some variants are associated with ceftazidime-avibactam resistance in clinical isolates, often linked to substitutions and/or insertions/deletions (i.e., INDELs) in three distinct loops of the KPC sequence: (i) the 164-179 loop (i.e., the Ω loop); (ii) the 237-243 loop; and (iii) the 267-275 loop. Inconsistencies in residue numbering across published reports, however, complicate the accurate annotation of KPC variants. We...

We aimed to characterize OXA-1054, a novel carbapenem-hydrolyzing class D β-lactamase (CHDL) detected in a multidrug-resistant Pseudomonas aeruginosa clinical isolate. Antimicrobial susceptibility was determined by broth microdilution, and carbapenemase activity was confirmed by hydrolysis assays. Whole-genome sequencing via Illumina and PacBio platforms enabled comprehensive analysis of the resistome and plasmid architecture. The bla(OXA-1054) gene was cloned in parallel with bla(OXA-48) and...

Urinary tract infections (UTIs) impose a large healthcare burden, with escalating antimicrobial resistance (AMR), and treatment failure. Proteus mirabilis is an undercharacterized and challenging UTI pathogen due to intrinsic resistance and biofilm formation. To understand P. mirabilis population genomics, we combined pangenome analysis, in silico AMR prediction, and phenotypic antimicrobial susceptibility testing (AST) across 1,027 P. mirabilis genomes derived from human urine specimens. This...

Next-generation sequencing techniques have revolutionized the epidemiology and understanding of Campylobacter spp. infections. In this study, we present the results of a next-generation sequencing (NGS) analysis conducted in 2024 on 2,360 Campylobacter spp. strains isolated in France, including 1,959 Campylobacter jejuni, 358 Campylobacter coli, and 43 Campylobacter fetus strains. We describe the diversity of circulating strains and provide an overview of the main mechanisms of antibiotic...

We evaluated the activity of ceftibuten combinations with avibactam, ledaborbactam, and xeruborbactam against isogenic Escherichia coli and clinical Enterobacterales isolates producing broad-spectrum β-lactamases. Avibactam and ledaborbactam enhanced ceftibuten activity against transformants producing serine-β-lactamases. Ceftibuten/xeruborbactam was also active against VIM and some IMP producers. All combinations were active against OXA-48- and KPC-producing clinical isolates....

Ceftazidime is an effective antipseudomonal antibiotic, used commonly in cystic fibrosis. Continuous 24-hour intravenous infusion allows children to receive daily treatment at home. However, the instability of 24-h ceftazidime infusions and production of toxic pyridine has led to recommendations not to use them. We aimed to determine a suitable target temperature to limit degradation of ceftazidime in 24-h infusions and assess effectiveness of simple temperature control. For in vitro...

Cefazolin serves as the antibiotic choice for surgical prophylaxis to prevent surgical site infection, yet consensus on dosing guidelines for patients with obesity is not well defined. To quantify cefazolin exposure in plasma and subcutaneous adipose tissue during abdominal surgery, and to build a popPK model comparing standard anthropometrics, calculated body-composition metrics, and directly measured body-composition values as predictors of interindividual variability. A single center...

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...