Table_5_Epidemiological characteristics, virulence potential, antimicrobial resistance profiles, and phylogenetic analysis of Aeromonas caviae isolated from extra-intestinal infections.xlsx

ObjectiveAeromonas caviae (A. caviae) is one of the major etiological agents in human intestinal infections reported to be associated with a broad spectrum of extra-intestinal infections with increasing incidence over recent years. Although previous studies have established its significance as a causative agent of both bloodstream and gastrointestinal infections, the characteristics of A. caviae that cause extra-intestinal infections remain unilluminated.In this single-center retrospective study, we investigated epidemiological characteristics, antimicrobial resistance genes and phenotypes, virulence genes, and phyloevolution of 47 clinical A. caviae isolated from patients with extra-intestinal infections from 2017 to 2020.
MethodsA. caviae strains were identified by biochemical tests and matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF/MS), ultimately confirmed to species level by whole-genome sequencing (WGS). Antimicrobial resistance and virulence genes were identified using the Comprehensive Antibiotic Resistance Database (CARD) and the virulence factor database (VFDB), respectively. Phylogenetic analysis of 47 clinical strains was performed by combining with 521 A. caviae strains from NCBI database.
ResultsA. caviae was an opportunistic pathogen in immunocompromised patients, especially those with underlying hepatobiliary diseases and malignancies. 19 out of 47 isolates were identified as multidrug resistance (MDR) strains. Piperacillin-tazobactam, levofloxacin, gentamicin, amikacin with a resistance rate of less than 10% remained as options to treat extra-intestinal infections. 24 out of 47 isolates exhibited non-susceptibility to cephalosporins and cephamycins, all of which carried β-lactamase gene, including blaMOX, blaPER-3, blaOXA, blaNDM, and blaCphA. Most stains (98%, 46/47) carried at least one of the virulence genes, but extra-intestinal infections had a low mortality rate. Phylogenetic analysis indicated the risk of nosocomial transmission but revealed no outbreak. However, the emergence of MDR and β-lactamase resistance genes in extra-intestinal isolates of A. caviae is becoming an increasing risk to public health and requires attention.
ConclusionsThis study strengthen our understanding of A.caviae isolated from extra-intestinal infections. It may contribute to the management of extra-intestinal infections as well as the prevention and control of drug resistance.

研究背景：嗜水气单胞菌（Aeromonas caviae, A. caviae）是人类肠道感染的主要病原体之一，近年来其关联的多种肠外感染病例发生率呈逐年上升趋势。尽管既往研究已明确其可引发血流感染与胃肠道感染，但导致肠外感染的嗜水气单胞菌的致病特征仍未被阐明。本研究为单中心回顾性研究，纳入2017年至2020年期间从肠外感染患者体内分离的47株临床嗜水气单胞菌，对其流行病学特征、抗菌耐药基因与表型、毒力基因及系统发育演化特征进行分析。

研究方法：本研究通过生化鉴定试验与基质辅助激光解吸电离飞行时间质谱（matrix-assisted laser desorption/ionization-time of flight mass spectrometry, MALDI-TOF/MS）对嗜水气单胞菌菌株进行初步鉴定，最终通过全基因组测序（whole-genome sequencing, WGS）确认菌种分型。分别采用综合抗生素耐药数据库（Comprehensive Antibiotic Resistance Database, CARD）与毒力因子数据库（virulence factor database, VFDB）对抗菌耐药基因及毒力基因进行注释鉴定。结合NCBI数据库中收录的521株嗜水气单胞菌菌株，对本研究纳入的47株临床菌株进行系统发育分析。

研究结果：嗜水气单胞菌为免疫功能低下患者的机会致病菌，尤其易感染合并肝胆基础疾病或恶性肿瘤的人群。47株分离株中共有19株被鉴定为多重耐药（multidrug resistance, MDR）菌株。哌拉西林他唑巴坦、左氧氟沙星、庆大霉素与阿米卡星的耐药率均低于10%，可作为肠外感染的临床治疗备选药物。47株分离株中有24株对头孢菌素类与头孢霉素类药物表现为不敏感，上述菌株均携带β-内酰胺酶基因，包括blaMOX、blaPER-3、blaOXA、blaNDM及blaCphA。绝大多数菌株（98%，46/47）携带至少一种毒力基因，但肠外感染患者的总体病死率较低。系统发育分析提示存在医院内传播风险，但未发现明确的暴发流行。然而，肠外感染分离的嗜水气单胞菌中多重耐药菌株与β-内酰胺酶耐药基因的检出率不断上升，已对公共卫生安全构成日益严峻的威胁，亟需引起重视。

结论：本研究加深了学界对肠外感染分离嗜水气单胞菌的认知，可为肠外感染的临床诊疗以及耐药菌防控工作提供参考依据。