Heteroresistance to carbapenems in invasive Pseudomonas aeruginosa infections.

Heteroresistance is common in a variety of microbes, however carbapenem heteroresistance among invasive Pseudomonas aeruginosa infections has not been thoroughly characterised to date. The objective of this study was to investigate the mechanisms, molecular epidemiology and risk factors for invasive carbapenem-heteroresistant P. aeruginosa (CHPA) infections between 2011 and 2015 in Chongqing, China. A significant increase in the rates of heteroresistance to imipenem and meropenem was observed during the study period. Mechanistic analysis revealed that efflux system overexpression and decreased OprD could have contributed to carbapenem heteroresistance in P. aeruginosa. It was also observed that all of the subpopulations produced enhanced levels of biofilm compared with their native strains. Moreover, previous carbapenem exposure was identified as a common independent risk factor for imipenem-heteroresistant (IPM-HR) and meropenem-heteroresistant (MEM-HR) isolates, but patients infected with MEM-HR isolates were at higher risk of poor outcomes than those with IPM-HR isolates. Most importantly, there was a remarkable increase in the prescription of carbapenems during the study period, which was demonstrated to correlate significantly with the quarterly increasing prevalence of IPM-HR and MEM-HR isolates, respectively. These findings show the necessity of routine detection of carbapenem-heteroresistant strains and that strict control of carbapenem use is critical to reduce CHPA infections in hospitalised patients.