Koret School of Veterinary Medicine, Robert H. Smith Faculty for Agriculture, The Hebrew University of Jerusalem, Rehovot, Israel.
Clinical Microbiology Laboratory, Tel-Aviv Sourasky Medical Center, Tel-Aviv University, Tel-Aviv, Israel.
J Antimicrob Chemother. 2023 Sep 5;78(9):2306-2314. doi: 10.1093/jac/dkad236.
Antimicrobial resistance is common in Nocardia species but data regarding the molecular mechanisms beyond their resistance traits are limited. Our study aimed to determine the species distribution, the antimicrobial susceptibility profiles, and investigate the associations between the resistance traits and their genotypic determinants.
The study included 138 clinical strains of Nocardia from nine Israeli microbiology laboratories. MIC values of 12 antimicrobial agents were determined using broth microdilution. WGS was performed on 129 isolates of the eight predominant species. Bioinformatic analysis included phylogeny and determination of antimicrobial resistance genes and mutations.
Among the isolates, Nocardia cyriacigeorgica was the most common species (36%), followed by Nocardia farcinica (16%), Nocardia wallacei (13%), Nocardia abscessus (9%) and Nocardia brasiliensis (8%). Linezolid was active against all isolates, followed by trimethoprim/sulfamethoxazole (93%) and amikacin (91%). Resistance to other antibiotics was species-specific, often associated with the presence of resistance genes or mutations: (1) aph(2″) in N. farcinica and N. wallacei (resistance to tobramycin); (ii) blaAST-1 in N. cyriacigeorgica and Nocardia neocaledoniensis (resistance to amoxicillin/clavulanate); (iii) blaFAR-1 in N. farcinica (resistance to ceftriaxone); (iv) Ser83Ala substitution in the gyrA gene in four species (resistance to ciprofloxacin); and (v) the 16S rRNA m1A1408 methyltransferase in N. wallacei isolates (correlating with amikacin resistance).
Our study provides a comprehensive understanding of Nocardia species diversity, antibiotic resistance patterns, and the molecular basis of antimicrobial resistance. Resistance appears to follow species-related patterns, suggesting a lesser role for de novo evolution or transmission of antimicrobial resistance.
诺卡氏菌属物种普遍存在抗药性，但有关其耐药特性以外的分子机制的数据有限。我们的研究旨在确定物种分布、抗菌药物敏感性谱，并研究耐药特性与其基因型决定因素之间的关联。
该研究纳入了来自以色列 9 个微生物学实验室的 138 株临床诺卡氏菌。采用肉汤微量稀释法测定 12 种抗菌药物的 MIC 值。对 8 个主要菌种的 129 株分离株进行 WGS。生物信息学分析包括系统发育和确定抗菌药物耐药基因和突变。
在所分离的菌株中，最常见的是中华诺卡氏菌（36%），其次是星形诺卡氏菌（16%）、巴西诺卡氏菌（13%）、脓肿诺卡氏菌（9%）和巴西诺卡氏菌（8%）。所有分离株均对利奈唑胺敏感，其次是甲氧苄啶/磺胺甲噁唑（93%）和阿米卡星（91%）。其他抗生素的耐药性具有种属特异性，通常与耐药基因或突变有关：（1）星形诺卡氏菌和巴西诺卡氏菌中的 aph(2″)（对妥布霉素耐药）；（2）中华诺卡氏菌和新喀里多尼亚诺卡氏菌中的 blaAST-1（对阿莫西林/克拉维酸耐药）；（3）星形诺卡氏菌中的 blaFAR-1（对头孢曲松耐药）；（4）四个菌种中的 gyrA 基因 Ser83Ala 取代（对环丙沙星耐药）；（5）在 Wallacei 诺卡氏菌分离株中的 16S rRNA m1A1408 甲基转移酶（与阿米卡星耐药相关）。
本研究全面了解了诺卡氏菌属的物种多样性、抗生素耐药模式以及抗菌药物耐药的分子基础。耐药性似乎遵循种属相关模式，表明新出现的耐药性或耐药性传播的作用较小。
