Xiaojiong Jia1, Weijia Ma2, Jianchun He3, Xiaolang Tian4, Hang Liu5, Hua Zou5, Si Cheng6. 1. Key Laboratory of Molecular Biology of Infectious Diseases Designated by the Chinese Ministry of Education, Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China. 2. Department of Laboratory Medicine, Chongqing Traditional Chinese Medicine Hospital, Chongqing, China. 3. Department of Laboratory Medicine, Chongqing Dazu District People's Hospital, Chongqing, China. 4. Department of Clinical Laboratory, University of Chinese Academy of Sciences Chongqing Renji Hospital, Fifth People's Hospital of Chongqing, Chongqing, China. 5. Department of Laboratory Medicine, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China. 6. Department of Orthopaedics, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address: 304238@cqmu.edu.cn304238@cqmu.edu.cn.
Abstract
INTRODUCTION: 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. RESULTS: 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. CONCLUSION: 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.
INTRODUCTION: 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. RESULTS: 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. CONCLUSION: 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.
Authors: Mohammad Abavisani; Mansoor Kodori; Fariba Akrami; Ali Radfar; Ali Hashemi Journal: Can J Infect Dis Med Microbiol Date: 2022-09-19 Impact factor: 2.585