Cefepime resistance with preserved ceftriaxone susceptibility in Proteus mirabilis osteomyelitis associated with bla OXA-1 gene amplification: Two case reports with genomic analysis
Abstract
Objective: Retrospective case series to describe an unusual cefepime-resistant, ceftriaxone-susceptible phenotype in Proteus mirabilis osteomyelitis associated with bla OXA-1 gene amplification.
Patients: Two adult patients with diabetes mellitus and chronic osteomyelitis, one with diabetic foot ulcer and one with infected hip prosthesis, both with prolonged antibiotic treatment.
Methods: Clinical data and antimicrobial susceptibility results were reviewed. Whole-genome sequencing was performed using short-read and long-read platforms with hybrid assembly. Resistance gene identification, phylogenetic analysis, and gene copy number estimation were conducted.
Results: Three isolates of P. mirabilis from two patients demonstrated an unusual phenotype of cefepime resistance (MIC 16-32 μg/mL) with susceptibility to ceftriaxone. Hybrid assembly and coverage analysis demonstrated amplification of the bla OXA-1-containing cassette, with approximately 16- and 24-fold duplication in patient 1 and 6-fold duplication in patient 2. Increased copy number correlated with cefepime resistance. All isolates harbored the multidrug resistance cassette containing bla OXA-1 within an IS6-family (IS26-like) transposon, which are found to widely circulate in plasmids or chromosomes of P. mirabilis and many other Enterobacterales species.
Conclusions: This study showed that duplication of a transposon-associated bla OXA-1-containting cassette in P. mirabilis can confer cefepime resistance while…
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Evidence Hub reads this as a case series, done in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
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