Qu Junyan, Yu Rujia, Wang Qujue, Feng Chunlu, Lv Xiaoju
Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.
Department of Infectious Diseases, Renshou County People's Hospital, Renshou, China.
Front Microbiol. 2020 Oct 15;11:541423. doi: 10.3389/fmicb.2020.541423. eCollection 2020.
This study aimed to explore the activity of combined antimicrobials , and the relationship among resistance mechanisms, antimicrobial regimens, and the clinical outcome of patients with carbapenem-resistant (CRAB) infections in western China. A total of 89 CRAB strains were collected from patients with CRAB infection from January 2018 to June 2018. The checkerboard assay was used to study the combined effects . Carbapenemase-encoding genes were detected by polymerase chain reaction (PCR) or multiplex PCR technique. The clinical data of 86 patients were collected. CRAB showed high susceptibility to tigecycline (91.01% inhibition) and polymyxin (83.15% inhibition). Polymyxin plus sulbactam exhibited the highest synergistic effect at a rate of 82.35%. Production of carbapenemase ( ) was the main resistance mechanism of CRAB to carbapenem (95.35%). Excessive expression of active efflux pump genes (, , and ) and deletion of the CarO protein accounted for 13.95% (12/86) and 84.88% (73/86), respectively. The synergistic effect of the sulbactam-based combination was higher than that of the polymyxin B-tigecycline combination for carbapenemase-producing CRAB ( < 0.05). The clinical outcome was not affected by the resistance mechanisms ( > 0.05). Advanced age, multiple organ dysfunction syndromes (MODS), and admission to the intensive care unit (ICU) were associated with treatment failure ( < 0.05). Appropriate antibiotic therapy did not improve the clinical outcome of critically ill patients. Higher minimum inhibitory concentrations (MICs) of tigecycline were associated with treatment failure ( < 0.05). A multivariate analysis showed that ICU stay (OR = 15.123, 95% CI: 2.600-87.951, = 0.002) and procalcitonin ≥2 ng/ml (OR = 2.636, 95% CI: 1.173-5.924, = 0.019) were the risk factors for treatment failure. In conclusion, this study demonstrated that the sulbactam-based combination exhibited a synergistic effect . The clinical outcome of patients was not associated with resistance mechanisms. This indicates that the early control of the progression from infection to severe disease may be important.
本研究旨在探讨联合抗菌药物的活性，以及中国西部耐碳青霉烯类鲍曼不动杆菌（CRAB）感染患者的耐药机制、抗菌治疗方案与临床结局之间的关系。2018年1月至2018年6月，共收集了89株来自CRAB感染患者的菌株。采用棋盘法研究联合效应。通过聚合酶链反应（PCR）或多重PCR技术检测碳青霉烯酶编码基因。收集了86例患者的临床资料。CRAB对替加环素（抑菌率91.01%）和多粘菌素（抑菌率83.15%）表现出高敏感性。多粘菌素加舒巴坦的协同效应最高，协同率为82.35%。碳青霉烯酶的产生是CRAB对碳青霉烯耐药的主要机制（95.35%）。主动外排泵基因（、和）的过度表达以及CarO蛋白的缺失分别占13.95%（12/86）和84.88%（73/86）。对于产碳青霉烯酶的CRAB，基于舒巴坦的联合治疗的协同效应高于多粘菌素B-替加环素联合治疗（<0.05）。临床结局不受耐药机制的影响（>0.05）。高龄、多器官功能障碍综合征（MODS）和入住重症监护病房（ICU）与治疗失败相关（<0.05）。恰当的抗生素治疗并未改善重症患者的临床结局。替加环素较高的最低抑菌浓度（MIC）与治疗失败相关（<0.05）。多因素分析显示，入住ICU（OR = 15.123，95%CI：2.600 - 87.951，= 0.002）和降钙素原≥2 ng/ml（OR = 2.636，95%CI：1.173 - 5.924，= 0.019）是治疗失败的危险因素。总之，本研究表明基于舒巴坦的联合治疗具有协同效应。患者的临床结局与耐药机制无关。这表明早期控制感染向重症疾病的进展可能很重要。
