Phenotypic and genotypic analysis of antimicrobial resistance in Nocardia species

Yizhak Hershko, Katia Levytskyi, Ella Rannon, Marc V. Assous, Shifra Ken-Dror, Sharon Amit, Haim Ben-Zvi, Orli Sagi, Orna Schwartz, Nadav Sorek, Moran Szwarcwort, Daniel Barkan, David Burstein, Amos Adler

Research output: Contribution to journalArticlepeer-review

Abstract

Background: 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. Methods: 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. Results: 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). Conclusions: 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.

Original languageAmerican English
Pages (from-to)2306-2314
Number of pages9
JournalJournal of Antimicrobial Chemotherapy
Volume78
Issue number9
DOIs
StatePublished - 1 Sep 2023

All Science Journal Classification (ASJC) codes

  • Microbiology (medical)
  • Pharmacology (medical)
  • Infectious Diseases
  • Pharmacology

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