Carbapenem and colistin-resistant Klebsiella pneumoniae co-producing NDM-5 and OXA-48 in a teaching hospital from Tunisia

Abstract Objectives Carbapenemase-producing Klebsiella pneumoniae (CPKp) represents a major public health threat due to limited treatment options, especially in low- and middle-income countries where colistin often remains the last active antibiotic. Here we investigated clinical carbapenem and colistin-resistant Kp isolates (CCoRKp) from Tunisia between January and June 2023. Materials and methods Kp isolates were identified by MALDI-TOF, broth microdilution susceptibility testing, NG-Test CARBA5 lateral flow immunoassay, Carba NP test, plasmid analysis and by whole-genome sequencing (WGS) for MLST, genetic relatedness and resistome characterization. Results Among the 263 Kp isolates collected, 101 (38.4%) were carbapenem resistant and 34 (12.9%) were carbapenem and colistin resistant. Twelve isolates exhibited an extremely drug-resistant phenotype, with in vitro activity retained only for eravacycline and aztreonam/avibactam, two agents that are currently unavailable for clinical use in Tunisia. Nine out of 10 patients who were treated with broad-spectrum antibiotics, including colistin and imipenem, died. WGS revealed OXA-48 and NDM-5 (12/12), CTX-M-15 (9/12) and the 16SRNA methylase ArmA (11/12) and identified ST 101 (n = 5), ST147 (n = 3) and ST 383 (n = 4), suggesting multi-clonal outbreak. While OXA-48 producing ST101 and ST147 were already present in a 2013 collection, ST383 has never been reported in the hospital nor in Tunisia. Conclusion Here we report double carbapenemase producing and colistin-resistant Kps with limited therapeutic options. Major efforts are needed in infection control and availability of novel molecules in Tunisia to restore safe conditions in hospitals.