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.

Evaluation of Six Phenotypic Methods for the Detection of Carbapenemases in Gram-Negative Bacteria With Characterized Resistance Mechanisms.

BACKGROUND: We compared the performance of the modified Hodge test (MHT), Triton Hodge test (THT), Carba NP test (CNPt), simplified Carba NP test (CNPt-direct), blue-Carba NP test (BCT), and carbapenem inactivation method (CIM) for rapid and accurate carbapenemase detection. METHODS: The methods were evaluated by using 256 gram-negative isolates, including 197 Enterobacteriaceae (79 Enterobacter spp., 74 Klebsiella spp., 33 Escherichia coli, 10 Citrobacter spp., and 1 Serratia marcescens), 51 Acinetobacter baumannii, and 8 Pseudomonas aeruginosa strains. The collection included 117 non-carbapenemase, 18 Klebsiella pneumoniae carbapenemases (KPC) producers, 46 New Delhi metallo-ß-lactamases (NDM) producers, 11 imipenemases (IMP) producers, and 51 oxacillinases (OXA) producers, and 13 strains harboring two different carbapenemase genes. RESULTS: The specificity of the THT (91.5%) was significantly lower than other methods, each of which had 100% specificity (P<0.003). This can be attributed to the false detection of Ampler class C ß-lactamases (AmpC) carriers. The CNPt-direct and CIM yielded the highest sensitivities (P<0.003), which were comparable (92.8% vs 93.5%, P>0.999). Because of improved detection of NDM carriers, THT showed significantly higher sensitivity than the MHT (84.9% vs 75.5%, P<0.001). However, poor performances in detecting OXA still influenced the sensitivities of the CNPt (66.2%) and BCT (82.0%), as well as the MHT and THT. CONCLUSIONS: CNPt-direct and CIM demonstrated the best performance for the efficient detection of carbapenemase among the six evaluated methods. Except the MHT and THT, the detection of carbapenemase-producing Enterobacteriaceae by all the other methods was acceptable, when the OXA-type carbapenemase was not prevalent.