Abstract
Abstract Background Patients undergoing treatment for cancer or an organ transplant are often immunosuppressed and particularly susceptible to infections caused by Gram-negative pathogens, including resistant isolates. Meropenem-vaborbactam is a combination of a carbapenem and a beta-lactamase inhibitor that is effective against serine-beta-lactamases, including KPC carbapenemase. We evaluated the activity of meropenem-vaborbactam (MEV) and comparators against Enterobacterales isolates collected in the US during 2014-2021 from patients in hematology, oncology, or transplant units (H/T). Activity of meropenem-vaborbactam and comparator antimicrobial agents tested against Enterobacterales isolates and CRE collected from medical centers in the US Methods A total of 2,185 clinical isolates were consecutively collected from patients in H/T units in 33 hospitals in all 9 US Census Divisions. Isolates were tested using CLSI broth microdilution methodology. Results were interpreted using CLSI breakpoints. Carbapenem-resistant Enterobacterales (CRE) were characterized as having MIC values ≥ 4 mg/L to imipenem and/or meropenem (MER). A subset of CREs were genotypically characterized for carbapenemase genes by PCR or whole genome sequencing. Results The most common species isolated were Escherichia coli (n=863), Klebsiella pneumoniae (n=518), and Enterobacter cloacae complex (n=284). The most common infection type was bloodstream infection (n=1,057), followed by urinary tract infection (n=347). Susceptibility was 99.6% to MEV, 98.5% to MER, and 83.4% to piperacillin-tazobactam (Table). 28 isolates (1.3%) were CRE; the susceptibility of these isolates to MEV was 71.4% while their susceptibilities to levofloxacin and piperacillin-tazobactam were 25.0% and 0.0%, respectively (Table). Of the 28 CRE, 19 were genotypically characterized. 13 isolates produced KPC, 3 produced OXA-48/232, and 1 had NDM-5. All KPC-producing isolates were MEV susceptible, and the 3 OXA-48/232 and 1 NDM were resistant. Conclusion MEV was very active against isolates causing infections in H/T patients, including isolates that were KPC-producing CREs. These in vitro data suggest that MEV would be an effective treatment option for H/T patients with Gram-negative infections. Disclosures Dee Shortridge, PhD, AbbVie: Grant/Research Support|JMI Laboratory: Employee|Melinta: Grant/Research Support|Menarini: Grant/Research Support|Shionogi: Grant/Research Support Lalitagauri M. Deshpande, PhD, Melinta: Grant/Research Support|Pfizer: Grant/Research Support Cecilia G. Carvalhaes, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support.
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