In vitro activity of sulbactam-durlobactam against colistin-resistant and/or cefiderocol-non-susceptible, carbapenem-resistant Acinetobacter baumannii collected in U.S. hospitals.

The activity of a novel ß-lactamase inhibitor combination, sulbactam-durlobactam (SUL-DUR), was tested against 87 colistin-resistant and/or cefiderocol-non-susceptible carbapenem-resistant Acinetobacter baumannii clinical isolates collected from U.S. hospitals between 2017 and 2019. Among them, 89% and 97% were susceptible to SUL-DUR and imipenem plus SUL-DUR, with MIC50/MIC90 values of 2 µg/mL/8 µg/mL and 1 µg/mL/4 µg/mL, respectively. The presence of amino acid substitutions in penicillin-binding protein 3, including previously reported A515V or T526S, was associated with SUL-DUR non-susceptibility.

Molecular characterization of clinical carbapenem-resistant Enterobacterales from Qatar.

One hundred forty-nine carbapenem-resistant Enterobacterales from clinical samples obtained between April 2014 and November 2017 were subjected to whole genome sequencing and multi-locus sequence typing. Klebsiella pneumoniae (81, 54.4%) and Escherichia coli (38, 25.5%) were the most common species. Genes encoding metallo-ß-lactamases were detected in 68 (45.8%) isolates, and OXA-48-like enzymes in 60 (40.3%). blaNDM-1 (45; 30.2%) and blaOXA-48 (29; 19.5%) were the most frequent. KPC-encoding genes were identified in 5 (3.6%) isolates. Most common sequence types were E. coli ST410 (8; 21.1%) and ST38 (7; 18.4%), and K. pneumoniae ST147 (13; 16%) and ST231 (7; 8.6%).

A Prospective Study of Acinetobacter baumannii Complex Isolates and Colistin Susceptibility Monitoring by Mass Spectrometry of Microbial Membrane Glycolipids.

Acinetobacter baumannii is a prevalent nosocomial pathogen with a high incidence of multidrug resistance. Treatment of infections due to this organism with colistin, a last-resort antibiotic of the polymyxin class, can result in the emergence of colistin-resistant strains. Colistin resistance primarily occurs via modifications of the terminal phosphate moieties of lipopolysaccharide-derived lipid A, which reduces overall membrane electronegativity. These modifications are readily identified by mass spectrometry (MS). In this study, we prospectively collected Acinetobacter baumannii complex clinical isolates from a hospital system in Pennsylvania over a 3-year period. All isolates were evaluated for colistin resistance using standard MIC testing by both agar dilution and broth microdilution, as well as genospecies identification and lipid A profiling using MS analyses. Overall, an excellent correlation between colistin susceptibility and resistance, determined by MIC testing, and the presence of a lipid A modification, determined by MS, was observed with a sensitivity of 92.9% and a specificity of 94.0%. Additionally, glycolipid profiling was able to differentiate A. baumannii complex organisms based on their membrane lipids. With the growth of MS use in clinical laboratories, a reliable MS-based glycolipid phenotyping method that identifies colistin resistance in A. baumannii complex clinical isolates, as well as other Gram-negative organisms, represents an alternative or complementary approach to existing diagnostics.

In Vitro Evolution of Cefiderocol Resistance in an NDM-Producing Klebsiella pneumoniae Due to Functional Loss of CirA.

By serially exposing an NDM-producing Klebsiella pneumoniae clinical strain to cefiderocol, we obtained a mutant with cefiderocol MIC of >128 µg/ml. The mutant contained an early stop codon in the iron transporter gene cirA, and its complementation fully restored susceptibility. The cirA-deficient mutant was competed out by the parental strain in vitro, suggesting reduced fitness. IMPORTANCE Cefiderocol, a newly approved cephalosporin agent with an extensive spectrum of activity against Gram-negative bacteria, is a siderophore cephalosporin that utilizes iron transporters to access the bacterial periplasm. Loss of functional CirA, an iron transporter, has been associated with cefiderocol resistance. Here, we show that such genetic change can be selected under selective pressure and cause high-level cefiderocol resistance, but with a high fitness cost. Whether these resistant mutants can survive beyond selective pressure will inform stewardship of this agent in the clinic.

Epidemiology of carbapenem-resistant Enterobacteriaceae in hospitals of a large healthcare system in Miami, Florida from 2012 to 2016: Five years of experience with an internal registry.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) is an urgent public health threat globally. Limited data are available regarding the epidemiology of CRE in South Florida. We describe the epidemiology of CRE within a large public healthcare system in Miami, FL, the experience with an internal registry, active surveillance testing, and the impact of infection prevention practices. METHODS: Retrospective cohort study in 4 hospitals from a large healthcare system in Miami-Dade County, FL from 2012 to 2016. The internal registry included all CRE cases from active surveillance testing from rectal and/or tracheal screening occurring in the intensive care units of 2 of the hospitals and clinical cultures across the healthcare system. All CRE cases were tagged in the electronic medical record and automatically entered into a platform for automatic infection control surveillance. The system alerted about new cases, readmissions, and transfers. RESULTS: A total of 371 CRE cases were identified. The overall prevalence was 0.077 cases per 100 patient-admissions; the admission prevalence was 0.019 per 100 patient-admissions, and the incidence density was 1.46 cases per 10,000 patient-days. Rates increased during the first 3 years of the study and declined later to a lower level than at the beginning of study period. CONCLUSIONS: Active surveillance testing and the use of an internal registry facilitated prompt identification of cases contributing to control increasing rates of CRE by rapid implementation of infection prevention strategies.