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VIM-type-producing Gram-negative bacteria (GNB) infections are difficult to treat. This is a retrospective single-center study of 34 patients who received cefiderocol for the treatment of VIM-type-producing GNB infections, including 25 Pseudomonas spp., 7 Enterobacterales , and 5 Achromobacter sp. Primary outcomes were clinical failure (defined as death, lack of clinical improvement, or a switch to another drug) at day 14 and 30-day all-cause mortality. The median age was 59 years (IQR 53.7-73.4), and the median Charlson comorbidity index was 3.5 (IQR 2-5). The main infections were respiratory tract infections ( n = 9, 27%) and skin and soft tissue infections ( n = 9, 27%). Eight patients exhibited bacteremia. In 9/17 patients with a drainable focus, drainage was performed. The median cefiderocol treatment duration was 13 days (IQR 8-24). Five patients (15%) experienced clinical failure on day 14, and the thirty-day mortality rate was 9/34 (27%); two cases occurred because of an uncontrolled infection source, and one was due to a new infection caused by the same bacteria. The other six deaths were unrelated to the index infection. Five patients experienced microbiological recurrence within three months. Susceptibility testing revealed the development of cefiderocol resistance in 1/7 cases with persistent or recurrent positive cultures. Cefiderocol, even in monotherapy, could be considered for the treatment of VIM-type-producing GNB infections.

In the context of difficult-to-treat carbapenem-resistant Pseudomonas aeruginosa infections, we evaluated imipenem, meropenem, and doripenem combinations against eleven carbapenemase-producing P. aeruginosa isolates. According to the widespread global distribution of high-risk clones and carbapenemases, four representative isolates were selected: ST175 (OXA-2/VIM-20), ST175 (VIM-2), ST235 (GES-5), and ST111 (IMP-33), for efficacy studies using a sepsis murine model. Minimum inhibitory concentration (mg/L) ranges were 64-256 for imipenem and 16-128 for meropenem and doripenem. In vitro, imipenem plus meropenem was synergistic against 72% of isolates and doripenem plus meropenem or imipenem against 55% and 45%, respectively. All combinations were synergistic against the ST175, ST235, and ST155 clones. In vivo, meropenem diminished the spleen and blood bacterial concentrations of four and three isolates, respectively, with better efficacy than imipenem or doripenem. The combinations did not show efficacy compared with the more active monotherapies, except for imipenem plus meropenem, which reduced the ST235 bacterial spleen concentration. Mortality decreased with imipenem plus meropenem or doripenem for the ST175 isolate. Results suggest that carbapenem combinations are not an alternative for severe infections by carbapenemase-producing P. aeruginosa . Meropenem monotherapy showed in vivo efficacy despite its high MIC, probably because its dosage allowed a sufficient antimicrobial exposure at the infection sites., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.