Deciphering the Genetic Mechanisms Driving Carbapenem Resistance: A Multicenter Study from Seven Egyptian...

Carbapenem-resistant Enterobacterales (CRE) causing healthcare-associated infections (HAI) represent a growing public health threat. We conducted a large-scale multicenter study to characterize CRE isolates from ICU patients in Egypt. Non-repetitive CRE clinical isolates were collected from infected ICU patients in 10 tertiary hospitals across 7 governorates over one year. Identification and susceptibility testing were performed using VITEK-2. Carbapenemase genes were detected by multiplex PCR for bla_NDM, bla_OXA-48, bla_VIM, bla_SPM, bla_GIM, bla_IMP, bla_KPC, bla_DIM, bla_SIM, and bla_AIM, and whole genome sequencing (WGS) was conducted on 40 selected isolates. Of 646 CRE isolates, K. pneumoniae (86%) and E. coli (12%) predominated. High resistance rates were observed, with tigecycline showing the highest activity (78.7% susceptible). Ceftazidime-avibactam activity varied widely (2-74.2%) among hospitals. The most prevalent carbapenemase genes were bla_NDM (77%) and bla_OXA-48 (64%), while bla_KPC was found in 4.6%. Fourteen isolates (2.2%) lacked the screened carbapenemase genes. WGS revealed four ST types among 14 E. coli isolates, mainly ST2 and ST650, while 26 K. pneumoniae isolates were dominated by ST147 (27%) and ST11 (23%). Genes linked to hypermucoviscosity (rmpA, rmpA2) were present in 31% of K. pneumoniae, alongside other carbapenem resistance mechanisms (absence of outer membrane porins, and efflux pump activation). Carbapenemase production is the main driver of CRE among ICU-HAIs in Egypt. WGS showed diverse sequence types suggesting limited local spread, frequent hypermucoviscosity, porin loss, and efflux-mediated resistance among CRE isolates.