Colistin-heteroresistance in carbapenemase-producing Enterobacter species causing hospital-acquired infections among Egyptian patients

Objectives: Colistin is the last resort for treating carbapenemase-producing Enterobacter. Colistin-heteroresistance is a new concern as it may cause treatment failure. Our study aimed to detect colistin-heteroresistance among carbapenemase-producing Enterobacter species causing hospital-acquired infections in patients at Mansoura University Hospitals (MUHs). Methods: Sensitivity of recovered Enterobacter species to imipenem, meropenem and colistin was estimated by the broth dilution method. Carbapenemase production was detected with the Carba NP test and confirmed with multiplex PCR. Population analysis profile (PAP) was performed to assess colistin-heteroresistance. Enterobacter isolates with colistin MIC ≤ 2 μg/mL had subpopulations growing at colistin concentration > 2 μg/mL were considered heteroresistant. Isolates with subpopulations growing at colistin concentrations two times higher than MIC but ≤ 2 μg/mLwere considered heterogeneous. Results: Of 115 Enterobacter isolates collected during the period of the study, 61 (53%) were cabapenem-resistant. Of these, 49 isolates (42.6%) were carbapenemase-producers, including Enterobacter cloacae complex (37; 75.5%) and Enterobacter aerogenes (12; 24.5%). The most prevalent carbapenemase gene was blaNDM (20 isolates; 40.8%). Seven isolates were colistin-resistant (7/115; 6.1%). Seventeen isolates (34.7% of carbapenemase-producers) were colistin-heteroresistant and two isolates had heterogeneous profiles. Most of these isolates were E. cloacae complex (12/17) and from bloodstream infection (10/17). The frequency of heteroresistant subpopulations ranged from 1 × 10−5 to 5.5 × 10−4. Conclusion: Carbapenem-resistant Enterobacter is a common resistant pathogen in the hospital setting. Colistin-heteroresistance among carbapenemase-producing Enterobacter is a growing serious medical problem as colistin is considered the last hope for treating infections caused by these multidrug-resistant pathogens