Murphy, Shannon G.

Abstract We report an eightfold increase in sulbactam-durlobactam MICs in a carbapenem-resistant Acinetobacter baumannii cerebrospinal fluid isolate recovered after 14 days of sulbactam-durlobactam plus meropenem therapy. Treatment-emergent mutations in the AdeFGH efflux system were identified, accompanied by a 166-fold increase in adeG expression. Efflux pump inhibition restored sulbactam-durlobactam susceptibility.

ABSTRACT Candida auris is an emerging pathogen known for causing invasive, multidrug-resistant infections and healthcare-associated outbreaks. Measuring the relatedness of C. auris strains is critical for detecting and preventing healthcare-associated transmission. Whole genome sequencing (WGS) and analysis of single-nucleotide polymorphisms (SNPs) offer high-resolution assessments of genetic relatedness and antifungal susceptibility; however, interpretation requires an understanding of inter- and intra-patient C. auris diversity and genotypic markers of resistance, respectively. This study aimed to define SNP thresholds for assessing C. auris relatedness in healthcare-associated outbreak investigations, predict antifungal resistance via genotypic markers, and evaluate patient risk factors to inform future surveillance strategies. WGS was performed on 68 C. auris isolates (clades I and III) obtained from 31 hospitalized patients across a healthcare system between 2021 and 2024. Using MycoSNP analysis, we observed a maximum intra-patient variation of 14 SNPs. Five probable transmission clusters were identified based on epidemiologic links, with patient isolates differing by a median of 5 SNPs (range: 0−12). Analysis with a commercial pipeline (refMLST, BugSeq) showed similar clustering patterns. All new detections occurring more than 1 month after admission were linked to a cluster, representing a highly specific indicator of healthcare-associated infection. WGS detected known genotypic markers for fluconazole (ERG11 Y132F, F126L, and MRR1 N647T) and micafungin (FKS1 F635C) resistance, with the latter emerging during antimicrobial therapy. In addition, putative FUR1 mutations (G207R and Q16::STOP) associated with flucytosine resistance were identified. These findings emphasize the utility of WGS for identifying healthcare-associated clusters of C. auris and predicting antifungal resistance. IMPORTANCE Candida auris is a difficult-to-treat yeast that causes invasive infections in vulnerable patient populations. Healthcare exposure is a key risk factor for becoming colonized or infected with C. auris , and infection prevention groups focus on curbing the spread of this organism within the healthcare environment. Whole genome sequencing approaches are key for supporting these efforts, as they can help define clusters of C. auris transmission and can also provide insight into antifungal resistance. Our work provides practical guidance for interpreting genomic data in this setting, helping infection prevention teams respond more effectively to outbreaks and expanding the use of genotypic predictions for antifungal resistance.

ABSTRACT Antimicrobial resistance mediated by carbapenemases significantly complicates treatment options. A case report by Morelan et al. (ASM Case Reports 1:e00094-25, 2025, https://doi.org/10.1128/asmcr.00094-25 ) illustrates how delayed recognition of Klebsiella pneumoniae carbapenemase (KPC) production in an Escherichia coli urinary tract infection resulted in suboptimal cefepime therapy, despite in vitro susceptibility. This case underscores the urgent need for clinical laboratories to implement on-site carbapenemase testing, as recommended by the Infectious Diseases Society of America and the Clinical and Laboratory Standards Institute (CLSI). Timely detection of KPC, coupled with reporting strategies for cefepime susceptibility results (suppression or editing results as resistant) in carbapenemase producers, may have facilitated earlier administration of a more appropriate antimicrobial and prevented recurrent infections and readmissions. In this commentary, we highlight recent updates to CLSI guidance for carbapenemase testing and antimicrobial susceptibility reporting strategies. Using this case report as an example, we outline the potential impact of these strategies on patient management and outcomes, further emphasizing the role of the clinical microbiology laboratory in antimicrobial stewardship.