Whole-genome sequencing of Providencia rettgeri co-producing NDM-1 and VIM-1 carbapenemases in clinical settings: genomic insights, therapeutic considerations, and literature overview

Abstract Background Providencia rettgeri is an emerging nosocomial pathogen with expected resistant phenotype to colistin and tigecycline and an increasing capacity to acquire clinically relevant carbapenemases. Although metallo-β-lactamase-producing P. rettgeri has been reported, co-production of NDM and VIM among highly genomically related isolates remains uncommon and warrants detailed genomic characterization. Methods Five clinical P. rettgeri isolates recovered between January 2024 and December 2025 through routine diagnostic and regional antimicrobial resistance surveillance activities in Latium, Italy, were analyzed. Antimicrobial susceptibility testing, phenotypic carbapenemase detection, whole-genome sequencing, resistome analysis, plasmid replicon typing, and clonal relationship assessment were performed. A structured literature overview was conducted to contextualize available evidence on NDM/VIM-producing P. rettgeri . Results Four Intensive Care Unit (ICU)-associated isolates collected in 2025, PR-1 to PR-4, co-produced NDM-1 and VIM-1 and shared an extensive multidrug-resistance profile, IncA/C and IncFIB(pQil) replicons, and the same ribosomal sequence type, rST219654. Core-genome multi-locus sequence typing (cgMLST) showed that these isolates differed by 0 to 13 alleles, supporting their description as an ICU-associated group of highly genomically related isolates. They were resistant to carbapenems and most β-lactam/β-lactamase inhibitor combinations. Gentamicin and amikacin retained in vitro activity. Aztreonam was categorized as susceptible (S) for PR-1 and susceptible, increased exposure (I) for PR-2 to PR-4 according to the retrospective EUCAST (v16.0) interpretation. Conclusions Comparative genomic analysis identified an ICU-associated group of highly genomically related P. rettgeri isolates co-producing NDM-1 and VIM-1 in Italy. These findings highlight the role of uncommon Enterobacterales species as reservoirs of mobile carbapenemase determinants and support the integration of whole-genome sequencing into antimicrobial resistance surveillance and infection-control programs. In critically ill patients, NDM/VIM-producing P. rettgeri should be regarded as an emerging multidrug-resistant nosocomial pathogen of clinical concern with limited therapeutic options.