Perfis de susceptibilidade aos agentes antimicrobianos de estirpes de Corynebacterium diphtheriae e Corynebacterium ulcerans isoladas no Brasil entre 1980 e 2024

Abstract

Corynebacterium diphtheriae and Corynebacterium ulcerans are species of the C. diphtheriae complex, which includes phylogenetically related species capable of producing diphtheria toxin (DT). These speciesare considered the main etiological agents of diphtheria, a disease that can affect the respiratory tract and skin. Although preventable by vaccination, outbreaks and isolated cases of diphtheria are still reported, including Brazil. The treatment of diphtheria is based on the use of diphtheria antitoxin and antimicrobials. Besides to diphtheria, C. diphtheriae and C. ulcerans strains, especially non-DT-producing strains, have been associated with various infections. Although the resistance of C. diphtheriae and C. ulcerans strains to several antimicrobials has already been described in the literature, specific clinical breakpoints for these species were only defined for the first time in 2023 by the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Therefore, the present work aimed to determine the antimicrobial susceptibility profiles of C. diphtheriae and C. ulcerans strains isolated in various Brazilian states, between 1980 and 2024, according to the new cutoff points. For this, the strainswere recovered from the bacteria collection of the Laboratory of Diphtheria and Corynebacteria of Clinical Importance at the State University of Rio de Janeiro and had their identification in the species level confirmed by mass spectrometry and genotypic analysis. Additionally, the presence of the tox gene, that encodes the DT. The antimicrobial susceptibility profiles were obtained through the disk-diffusion method and by determining the minimum inhibitory concentration, using strip impregnated with gradient concentrations of antimicrobials. A total of 62 strains were recovered with the majority (92%) belonging to C. diphtheriae species. The tox gene was identified in 32% of the strains. All studied strains were sensitive to meropenem and linezolid; they also presented the susceptible with increasing exposure profile to benzylpenicillin, cefotaxime and ciprofloxacin. Strains resistant to tetracycline, rifampicin, trimethoprim-sulfamethoxazole, and clindamycin were found. Regarding the studied period, the years that had the highest numbers of resistant strains isolated were 2010 and 2015 and the Federative Unit were Rio de Janeiro, followed by Pernambuco and Maranhão. The results obtained demonstrate the diversity of susceptibility profiles to antimicrobial agents among Brazilian strains of C. diphtheriae and C. ulcerans and emphasize the importance of performing susceptibility testing to antimicrobial agents. Not only to guide therapeutic choice, but for the global understanding of resistance mechanisms in the species tested.