Molecular characterization of colistin resistance in Gram negative isolates

Background: The increasing prevalence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria (GNB) presents a critical global health challenge. Colistin and polymyxin B have regained prominence as last-resort antibiotics against MDR/XDR infections. However, the overuse and misuse of colistin have led to rising resistance. Colistin resistance (COR) is primarily driven by chromosomal mutations and, more concerningly, by the emergence of plasmid-mediated mcr genes. Here, we attempted to screen mcr genes (mcr-1 through mcr-9) prevalence in COR isolates. Methods: This study, conducted at Cairo University hospitals, aimed to investigate the prevalence of mcr genes (mcr-1 to mcr-9) in colistin-resistant isolates. Out of 380 collected clinical samples, 100 MDR/XDR and PDR isolates were selected for analysis. Phenotypic (COR) was determined using the broth microdilution (BMD) method, while genotypic detection of mcr genes were performed by multiplex PCR. Results: Among the 100 isolates, 68% exhibited colistin resistance, predominantly found in ICU patients (75%). Klebsiella pneumoniae was the most common resistant organism (57.4%), followed by Pseudomonas species (23.5%) and Acinetobacter species (17.6%). Notably, mcr-4 was detected in 5.8% (4/68) of colistin-resistant isolates, with no detection of other mcr genes. The mcr-4 positive isolates were predominantly Acinetobacter species (75%) and Klebsiella pneumonia (25%), all from ICU patients with bloodstream infections (75%) and urinary tract infections (25%). Conclusions: The findings highlight the alarming prevalence of colistin resistance and the emergence of mcr-4 mediated resistance. These results underscore the urgent need for enhanced antimicrobial stewardship and ongoing surveillance to monitor resistance patterns and guide treatment strategies.