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Infections caused by carbapenem-resistant Enterobacterales (CRE) pose significant threats to patients and public health worldwide. Carbapenem resistance can occur through several molecular mechanisms, including enzymatic hydrolysis by carbapenemases and reduced influx via porin mutations. Identifying carbapenemase-producing isolates could enable tailored antibiotic selection to improve patient outcomes and infection control measures to prevent further carbapenemase transmission. In a large collection of CRE isolates, we found that only carbapenemase-producing CRE exhibited an inoculum effect, in which their measured resistance varies markedly with cell density, which risks misdiagnosis. Further, this inoculum effect occurred under conditions where bacteria released carbapenemases to the community upon exposure to antibiotics that resulted in cell death. Measuring this inoculum effect, or integrating other data from routine antimicrobial susceptibility testing, enhanced carbapenem resistance detection, paving the way for more effective strategies to combat this growing public health crisis.

Candida auris is an emerging, often multidrug-resistant pathogen with important public health implications. Infections are associated with high mortality, and prevention of transmission requires stringent infection control measures, making C. auris a potential barrier to transplantation. We describe the first donor-derived C. auris transmission in a lung transplant recipient.

Multidrug resistant organisms are a serious threat to human health 1 , 2 . Fast, accurate antibiotic susceptibility testing (AST) is a critical need in addressing escalating antibiotic resistance, since delays in identifying multidrug resistant organisms increase mortality 3 , 4 and use of broad-spectrum antibiotics, further selecting for resistant organisms. Yet current growth-based AST assays, such as broth microdilution 5 , require several days before informing key clinical decisions. Rapid AST would transform the care of patients with infection while ensuring that our antibiotic arsenal is deployed as efficiently as possible. Growth-based assays are fundamentally constrained in speed by doubling time of the pathogen, and genotypic assays are limited by the ever-growing diversity and complexity of bacterial antibiotic resistance mechanisms. Here we describe a rapid assay for combined genotypic and phenotypic AST through RNA detection, GoPhAST-R, that classifies strains with 94–99% accuracy by coupling machine learning analysis of early antibiotic-induced transcriptional changes with simultaneous detection of key genetic resistance determinants to increase accuracy of resistance detection, facilitate molecular epidemiology and enable early detection of emerging resistance mechanisms. This two-pronged approach provides phenotypic AST 24–36 h faster than standard workflows, with <4 h assay time on a pilot instrument for hybridization-based multiplexed RNA detection implemented directly from positive blood cultures. A new assay combining genotypic and phenotypic information accelerates accurate clinical antibiotic susceptibility testing.

To the Editor: In their Perspective article, Singhal and colleagues (Nov. 9 issue) 1 support the proposed Food and Drug Administration (FDA) rule that would end the agency’s enforcement-discretion policy for laboratory-developed tests. The authors cite the proliferation of commercial tests without clinical utility. Most laboratory-developed tests are used internally to support the care of hospitalized patients when FDA-cleared tests are unavailable. The authors speculate that lobbying by academic medical centers against the Verifying Accurate Leading-edge IVCT Development (VALID) Act of 2022 was financially motivated. In reality, laboratories at academic medical centers do not generate revenue. The authors suggest that the . . .

The first healthcare-associated transmission of mcr-1 in the United States was associated with shared exposure to a duodenoscope, despite implementation of updated reprocessing instructions and supplemental measures; this represents the first documented duodenoscope-linked transmission since publication of updated reprocessing guidelines. Abstract Background Clinicians increasingly utilize polymyxins for treatment of serious infections caused by multidrug-resistant gram-negative bacteria. Emergence of plasmid-mediated, mobile colistin resistance genes creates potential for rapid spread of polymyxin resistance. We investigated the possible transmission of Klebsiella pneumoniae carrying mcr-1 via duodenoscope and report the first documented healthcare transmission of mcr-1–harboring bacteria in the United States. Methods A field investigation, including screening targeted high-risk groups, evaluation of the duodenoscope, and genome sequencing of isolated organisms, was conducted. The study site included a tertiary care academic health center in Boston, Massachusetts, and extended to community locations in New England. Results Two patients had highly related mcr-1–positive K. pneumoniae isolated from clinical cultures; a duodenoscope was the only identified epidemiological link. Screening tests for mcr-1 in 20 healthcare contacts and 2 household contacts were negative. Klebsiella pneumoniae and Escherichia coli were recovered from the duodenoscope; neither carried mcr-1. Evaluation of the duodenoscope identified intrusion of biomaterial under the sealed distal cap; devices were recalled to repair this defect. Conclusions We identified transmission of mcr-1 in a United States acute care hospital that likely occurred via duodenoscope despite no identifiable breaches in reprocessing or infection control practices. Duodenoscope design flaws leading to transmission of multidrug-resistant organsisms persist despite recent initiatives to improve device safety. Reliable detection of colistin resistance is currently challenging for clinical laboratories, particularly given the absence of a US Food and Drug Administration–cleared test; improved clinical laboratory capacity for colistin susceptibility testing is needed to prevent the spread of mcr-carrying bacteria in healthcare settings.

Abstract Background In 2021, the Clinical and Laboratory Standards Institute revised its susceptible oxacillin minimum inhibitory concentration (MIC) breakpoint for Staphylococcus spp. other than S. aureus and S. lugdunensis (SOSA) from  ≤0.25 to  ≤0.5 µg/mL. Here, we describe the response to this breakpoint change, which at the time of this study was not yet recognized by the US Food and Drug Administration (FDA), in our laboratory, where the primary method for antimicrobial susceptibility testing (AST) of SOSA is VITEK 2. VITEK 2 uses the Automated Expert System (AES) to integrate the results of oxacillin MIC and cefoxitin screen tests into a final interpretation; our laboratory also adjudicates discordant oxacillin and cefoxitin results using a PBP2a test. Methods We retrospectively reviewed and assessed the yield of PBP2a testing for 189 SOSA isolates with discordant (when applying the FDA susceptible oxacillin breakpoint of ≤0.25 µg/mL) VITEK 2 oxacillin and cefoxitin results, and then prospectively incorporated PBP2a testing for isolates with oxacillin MICs of 0.5 µg/mL and positive cefoxitin screens into our algorithm. Results Compared with accepting the VITEK 2 AES interpretation, PBP2a testing substantially improved the accuracy of mecA-mediated resistance classification in both scenarios, especially for the ∼4.7% of isolates with oxacillin MICs ≤0.5 µg/mL and positive cefoxitin screens. Conclusions Although detection of mecA or PBP2a is the gold standard for assessment of β-lactam resistance in staphylococci, targeting a subset of isolates for mecA or PBP2a testing based on phenotypic AST results that predict an increased risk of misclassification may be a pragmatic, labor- and cost-saving approach. Targeting selected staphylococci for PBP2a testing based on VITEK 2 phenotypic susceptibility testing results is a pragmatic approach for clinical laboratories to increase the accurate classification of mecA-mediated oxacillin resistance among Staphylococcus spp. other than S. aureus and S. lugdunensis.

A 13-month-old girl presented with pneumonia. Imaging studies revealed splenomegaly, splenic lesions, and diffuse lymphadenopathy. Three months later, her mother presented with right hip pain and a lytic lesion in the femoral neck. Diagnoses were made.

To describe an investigation into 5 clinical cases of carbapenem-resistant Acinetobacter baumannii (CRAB). Epidemiological investigation supplemented by whole-genome sequencing (WGS) of clinical and environmental isolates. A tertiary-care academic health center in Boston, Massachusetts. Individuals identified with CRAB clinical infections. A detailed review of patient demographic and clinical data was conducted. Clinical isolates underwent phenotypic antimicrobial susceptibility testing and WGS. Infection control practices were evaluated, and CRAB isolates obtained through environmental sampling were assessed by WGS. Genomic relatedness was measured by single-nucleotide polymorphism (SNP) analysis. Four clinical cases spanning 4 months were linked to a single index case; isolates differed by 1-7 SNPs and belonged to a single cluster. The index patient and 3 case patients were admitted to the same room prior to their development of CRAB infection, and 2 case patients were admitted to the same room within 48 hours of admission. A fourth case patient was admitted to a different unit. Environmental sampling identified highly contaminated areas, and WGS of 5 environmental isolates revealed that they were highly related to the clinical cluster. We report a cluster of highly resistant Acinetobacter baumannii that occurred in a burn ICU over 5 months and then spread to a separate ICU. Two case patients developed infections classified as community acquired under standard epidemiological definitions, but WGS revealed clonality, highlighting the risk of burn patients for early-onset nosocomial infections. An extensive investigation identified the role of environmental reservoirs.

Developing and deploying new diagnostic tests are difficult, but the need to do so in response to a rapidly emerging pandemic such as COVID-19 is crucially important. During a pandemic, laboratories play a key role in helping healthcare providers and public health authorities detect active infection, a task most commonly achieved using nucleic acid-based assays. While the landscape of diagnostics is rapidly evolving, PCR remains the gold-standard of nucleic acid-based diagnostic assays, in part due to its reliability, flexibility and wide deployment. To address a critical local shortage of testing capacity persisting during the COVID-19 outbreak, our hospital set up a molecular-based laboratory developed test (LDT) to accurately and safely diagnose SARS-CoV-2. We describe here the process of developing an emergency-use LDT, in the hope that our experience will be useful to other laboratories in future outbreaks and will help to lower barriers to establishing fast and accurate diagnostic testing in crisis conditions.