Epidemiology and resistance mechanisms of tigecycline- and carbapenem-resistant Enterobacter cloacae in Southwest China: a 5-year retrospective study.

OBJECTIVES:The prevalence and molecular epidemiology of tigecycline resistance in carbapenem-resistant Enterobacter cloacae (CREC) in mainland China is unknown. We aimed to investigate the molecular characteristics and mechanisms of tigecycline-resistant CREC (TCREC) in Southwest China. METHODS:We conducted a 5-year retrospective study. TCREC isolates underwent antimicrobial susceptibility testing, PFGE and MLST. We determined the presence of genes, deficiency of outer membrane proteins (OMPs) and expression of efflux pumps using PCR, reverse transcription PCR and SDS-PAGE. RESULTS:A large proportion of CREC isolates (21.7%; 36/166) were TCREC. All isolates were resistant to ertapenem, whereas 67% remained susceptible to imipenem and meropenem. ST88 (10/36; 27.8%) was predominant and was associated with moderate resistance to tigecycline and high resistance to carbapenems, followed by ST256 (3/36; 8.3%), ST78 (2/36; 5.6%), ST557 (2/36; 5.6%) and ST102 (2/36; 5.6%). blaNDM-1 (6/36; 16.7%) was the most common carbapenemase gene, and ST88 (5/6; 83.3%) was the most common type, followed by blaIMP-8 (3/36; 8.3%). Coexistence of extended-spectrum β-lactamase (ESBL) genes and OmpF and/or OmpC loss was found in 27/36 isolates; additionally, increased co-expression of efflux pump genes acrB and oqxA was identified in 25/36 isolates, which may together contribute to co-resistance to carbapenems and tigecycline. CONCLUSION:Most ST88 strains carried carbapenemases, especially NDM-1. Overexpression of efflux pumps contributed to tigecycline resistance. The presence of carbapenemase and/or ESBL genes and lack of OMPs, but not efflux pump overexpression, may confer carbapenem resistance. Reasonable supervision and management of the epidemic of TCREC will help to stem the transmission of isolates.