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.
Department of Laboratory Medicine, Chongqing Traditional Chinese Medicine Hospital, Chongqing, China.
Int J Antimicrob Agents. 2020 Mar;55(3):105832. doi: 10.1016/j.ijantimicag.2019.10.013. Epub 2020 Feb 1.
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.
抗生素耐药性会导致诊断和治疗失败；然而，迄今为止，铜绿假单胞菌（P. aeruginosa）菌血症中的头孢吡肟异质性耐药（FEP-HR）尚未得到明确。本研究的主要目的是在中国西南地区约 6 年内调查头孢吡肟异质性耐药铜绿假单胞菌菌血症的分子流行病学、机制和危险因素。
在研究期间，观察到头孢吡肟异质性耐药率较高（57.3%），且这些 FEP-HR 分离株无克隆相关性。机制研究表明 AmpC 过度产生导致了这种现象的发生。此外，年龄较大、血液恶性肿瘤、中心静脉导管和以前使用头孢菌素治疗的患者是获得 FEP-HR 铜绿假单胞菌菌血症的独立危险因素。此外，与非 FEP-HR 患者相比，感染 FEP-HR 的患者通常预后较差的风险更大。更重要的是，对同一患者中连续三个分离的铜绿假单胞菌的特征分析表明，在接受抗生素治疗的患者中，异质性耐药可作为从敏感性向完全耐药演变的中间阶段。
这些发现强调了临床环境中抗菌药物管理计划的必要性，以及需要一些快速的筛选方法来检测这种现象。
