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Objective To investigate the clinical features and risk factors of infections caused by cefepime- and ertapenem-heteroresistant Klebsiella pneumoniae (FEP-HR-KP and ETP-HR-KP, respectively). Methods We conducted a retrospective case-control study of 108 Klebsiella pneumoniae strains isolated from the body fluids of the inpatients in our hospital from January, 2014 to December, 2015. The heteroresistance of the isolated strains was detected using Kirby-Bauer disk diffusion test (K-B test) and E-test, and the results were further confirmed by population analysis profile (PAP) method. The risk factors for infections by FEP-HR-KP and ETP-HR-KP were analyzed using Chi-square test and logistic regression analysis. Results Of the total of 108 non-duplicate Klebsiella pneumoniae strains isolated, 41 (40.0%) were heteroresistant to cefepime, 63(58.3%) were heteroresistant to ertapenem, and 38 (35.2%) showed heteroresistance to both. The annual detection rate of FEP-HR-KP increased from 41.7% (20/48) in 2014 to 51.7% (31/60) in 2015, and that of ETP-HR-KP increased from 54.1% (26/48) in 2014 to 61.7% (37/60) in 2015. The strains were isolated mainly from blood specimens (25/66, 37.9%), and more than half (47/66, 71.2%) of the strains were isolated from the department of surgery. Multivariate logistic regression analysis revealed that soft tissue infection (OR=1.92, 95%CI: 0.91~3.91, P=0.049), mechanical ventilation (OR=2.45, 95%CI: 1.31~4.47, P=0.013), and use of cephalosporins (OR=2.10, 95%CI: 1.18~3.13, P=0.020) were independent risk factors for infections by FEP-HR-KP; use of cephalosporins (OR=2.08, 95%CI: 0.96~4.20, P=0.033), use of carbapenems (OR=2.52, 95%CI: 1.08~3.86, P=0.023) and drainage tube placement (OR=2.76, 95%CI: 1.49~4.90, P=0.018) were independent risk factors for ETP-HR-KP infections. Conclusion The Klebsiella pneumoniae strains isolated in our hospital show high rates of heteroresistance to cefepime and ertapenem. Avoiding unnecessary invasive operation and optimizing the use of antibiotics can help to reduce the generation of heteroresistant strains and improve the treatment efficacy for FEP-HR-KP and ETP-HR-KP 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. [ABSTRACT FROM AUTHOR]

• A high prevalence (57.3%) of cefepime heteroresistance (FEP-HR) was observed between 2011–2016. • Mechanistic analysis revealed that AmpC hyperproduction may have contributed to FEP-HR Pseudomonas aeruginosa bacteraemia. • Patients with advanced age, haematological malignancy, central venous catheter, and previous therapy with cephalosporins were identified as independent risk factors for acquiring FEP-HR P. aeruginosa bacteraemia. • Patients infected with FEP-HR were generally at greater risk of having an adverse prognosis than those with non-FEP-HR. • This study provides the first clinical evidence in vivo that cefepime heteroresistance in P. aeruginosa can be regarded as an intermediate stage for evolving from susceptibility to full resistance during antibiotic treatment. Heteroresistance to antibiotic agents can lead to diagnostic and therapeutic failures; however, to date, cefepime heteroresistance (FEP-HR) in Pseudomonas aeruginosa (P. aeruginosa) bacteraemia has not been characterised. The primary goal of this study was to investigate the molecular epidemiology, mechanisms and risk factors for cefepime-heteroresistant P. aeruginosa bacteraemia over approximately 6 years in Southwest China. A high prevalence (57.3%) of heteroresistance to cefepime was observed during the study period, and these FEP-HR isolates were not clonally related. Mechanistic studies revealed that AmpC hyperproduction contributed to the development of this phenomenon. In addition, patients with advanced age, haematological malignancies, central venous catheters, and previous cephalosporin therapy were identified as independent risk factors for acquiring FEP-HR P. aeruginosa bacteraemia. Furthermore, patients infected with FEP-HR were generally at a greater risk for an adverse prognosis compared with those with non-FEP-HR. More importantly, characterisation of three successive P. aeruginosa isolates recovered from the same patient revealed that heteroresistance can act as an intermediate stage during the evolution from susceptibility to full resistance in patients undergoing antibiotic therapy for prolonged periods. These findings emphasised the necessity of antimicrobial stewardship programs in clinical settings, as well as the need for some rapid screening methods for detecting this phenomenon. [ABSTRACT FROM AUTHOR]