Abstract

Abstract Background Nonsusceptibility of Proteus mirabilis to imipenem allows this pathogen evade surveillance for carbapenemases. Metallo-beta-lactamases of the VIM family are widespread among Enterobacterales in Europe. We identified an outbreak of P. mirabilis carrying 2 VIM enzymes among elderly patients from a medical center in Hungary. Methods A total of 16 P. mirabilis isolates were received from Hungary during 2020 as part of the SENTRY Antimicrobial Surveillance Program. Isolates were susceptibility tested by the CLSI reference broth microdilution method. Carbapenem-nonsusceptible isolates were submitted to whole genome sequencing, screened for resistance mechanisms, and evaluated for core genome multi-locus sequence typing (cgMLST). Results Among the 16 P. mirabilis isolates from Hungary, 5 carbapenem-nonsusceptible, multidrug-resistant isolates (3 from urinary tract infections and 1 each from bloodstream infection and pneumonia) were identified from patients 66-92 years old. Four of these 5 isolates were listed as community acquired. All isolates were resistant to ceftriaxone (MIC, > 8 mg/L), cefepime (16- > 32), imipenem ( > 8), gentamicin ( > 16), levofloxacin (16- > 32), nitrofurantoin ( > 64), trimethoprim/sulfamethoxazole ( > 4), and plazomicin ( > 128), but susceptible to meropenem (0.25-0.5) and ertapenem (0.03-0.25). Isolates carried blaVIM-4 and blaVIM-75 on a class 1 integron within IS26 and separated by aac(6’)-IIc. IS26 was located on a compound plasmid carrying other resistance-encoding genes, including armA. The integron structure is identical to the blaVIM-4 and blaVIM-1-carrying integron described from a Vibrio cholerae isolated from a seagull in France in 2015 (KR262557). blaVIM-75 is a single amino acid variant (Q60R) of blaVIM-1. All isolates carried mutations in the QRDR (gyrA_S83I, parC_S84I). Based on cgMLST analysis, these 5 P. mirabilis isolates were highly similar, with only 7-19 SNPs detected. Conclusion The outbreak of multidrug-resistant P. mirabilis isolates carrying blaVIM-4 and blaVIM-75 in a Hungarian medical center is a cause of concern. Surveillance should be performed to understand the spread of and treatment options for infections caused by carbapenem-nonsusceptible P. mirabilis. Disclosures Lalitagauri M. Deshpande, PhD, Melinta: Grant/Research Support|Pfizer: Grant/Research Support Katalin Burián, MD, JMI Laboratories: Grant/Research Support Ilona Dóczi Csányi, MD, JMI Laboratories: 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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