Antimicrobial Agents and Chemotherapy

HIV infection remains a critical global public health concern. A potential long-acting therapeutic agent, 4'-ethynyl-2-fluoroadenosine analog 1c (CL-197), was investigated in a first-in-human phase 1 clinical trial. This single-center, randomized, double-blind, dose-escalation, placebo-controlled study assessed the safety and pharmacokinetics (PKs) of five doses of CL-197 (1, 10, 30, 60, and 100 mg) in healthy adults aged 18-45 years. The 1 mg group was open-label (n = 4), while the other groups...

The prevalence of non-susceptibility to ceftolozane-tazobactam (C/T) among Pseudomonas aeruginosa remains low, but novel mechanisms of C/T resistance are of concern. Herein, we describe a novel P. aeruginosa genotype associated with high-level C/T resistance (>256/4 µg/mL) in a single patient. Whole-genome sequencing of the isolate was compared to that of a susceptible isolate cultured from the same patient 2 months earlier. Analysis of the sequences revealed two different P. aeruginosa...

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Treatment of symptomatic patients with coccidioidomycosis often involves the use of triazole antifungals. There is concern for reduced susceptibility of Coccidioides to fluconazole, as a high percentage of isolates were previously reported to have elevated fluconazole MICs. We reviewed our recent azole MICs against Coccidioides and examined temporal trends over a 20-year period. Our clinical laboratory database was queried for data against Coccidioides between 2006 and 2025, and trends in GM...

The global rise of antibiotic-resistant Pseudomonas aeruginosa (PA) necessitates the development of novel therapeutic approaches. Polyclonal antibodies constitute a promising approach, as they target multiple bacterial epitopes and functions. Moreover, they have recently demonstrated renewed clinical applicability in their humanized format. We developed a glyco-humanized polyclonal antibody (GH-pAb) targeting PA by immunization of pigs with five PA serotypes frequently encountered in clinical...

Piperacillin-tazobactam is commonly used in critically ill pediatric patients; however, standard dosing regimens may not reliably achieve maximally effective exposures in this population. To characterize the population pharmacokinetics of piperacillin-tazobactam in critically ill pediatric patients and evaluate the adequacy of commonly used dosing regimens, plasma concentrations were obtained around a single dose of piperacillin-tazobactam in critically ill pediatric patients aged 1 month to 12...

Nosocomial Pseudomonas aeruginosa infections are among the most challenging infections to treat, and resistance to last-line agents, including polymyxins and aztreonam-based therapies, risks a future with limited or no clinical treatment options. Bacteriophages (phages) have emerged as a promising therapeutic option, both in cocktails and when given in combination with antibiotics. In this study, we show that the synergy between a lipopolysaccharide (LPS)-specific phage and antibiotics is driven...

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Talaromyces marneffei is a thermally dimorphic fungus causing life-threatening systemic mycosis in immunocompromised patients. The emergence of azole-resistant clinical isolates, especially those with reduced susceptibility to voriconazole (VOC) and fluconazole (FLC), presents a critical therapeutic challenge. Although target-gene alterations and efflux-related mechanisms have been reported in pathogenic fungi, the broader molecular basis distinguishing high-minimum-inhibitory concentration...

A phase 1, open-label study was conducted to investigate the effect of renal impairment (RI) on pharmacokinetics (PK) and safety of funobactam plus imipenem/cilastatin. Participants were enrolled and assigned to one of five cohorts based on renal function category: normal renal function, mild RI, moderate RI, severe RI, and end-stage renal disease (ESRD) requiring hemodialysis (HD). Participants received a single-dose of funobactam with imipenem and cilastatin by intravenous infusion...

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The global spread of carbapenem-resistant Pseudomonas aeruginosa (CRPA) poses a critical clinical threat, with bla(KPC) as a key mobile carbapenem resistance gene. Here, we investigated a novel bla(KPC-2) genetic element and its transmission in clinical ST2483 isolate PA100 via whole-genome sequencing, molecular, and phenotypic testing, and vesicle analysis. A unique 4,746-bp IS26-flanked structure inserted at the chromosomal InaA/pncB2 locus was confirmed, which forms a circular transposition...

Diabetic foot infections (DFIs) are a major complication of diabetes frequently involving multidrug-resistant Staphylococcus aureus. Their persistence and therapeutic complexity underscore the urgent need for alternatives to conventional antibiotics. Phage therapy offers a promising solution, though its clinical application is often limited by the narrow host range of individual phages. Here, SAVM02, a recently characterized staphylococcal Kayvirus, was trained using directed evolution against...

Candida auris frequently demonstrates resistance to multiple antifungal classes and has been classified as a critical priority pathogen by the World Health Organization and the first fungal pathogen designated an urgent threat by the U.S. Centers for Disease Control and Prevention. Patients with skin colonization face a 7%-20% risk of invasive infection, with 30-day mortality of 30%-72%. While chlorhexidine gluconate (CHG) is widely used for general skin decolonization, it fails to reliably...

Neisseria gonorrhoeae is a major public health concern due to its high global prevalence and rapid evolution of antibiotic resistance. A first-in-class topoisomerase inhibitor, zoliflodacin (a spiropyrimidinetrione), recently received FDA approval for treatment of gonorrhea, but its potential for cross-resistance with another topoisomerase inhibitor, the fluoroquinolone antibiotic ciprofloxacin, remains poorly understood. Here, we investigated how genetic diversity in the fluoroquinolone target...