Genetic characterization of multidrug-resistant Mycobacterium bovis strains from a hospital outbreak involving human immunodeficiency virus-positive patients

Abstract

Nineteen multidrug-resistant (MDR) Mycobacterium complex strains isolated in a nosocomial outbreak were characterized at the molecular level. The strains were microbiologically characterized as Mycobacterium bovis. The mpt40 sequence was not present in chromosomal DNA from these strains, supporting the fact that they were M. bovis. All of the isolates were resistant to isoniazid, rifampin, pyrazinamide, ethambutol, streptomycin, para-aminosalicylic acid, clarithromycin, cycloserine, ethionamide, ofloxacin, capreomycin, and amikacin. By performing the standardized IS6110 fingerprinting by restriction fragment length polymorphism (RFLP) analysis, we were able to differentiate two groups (groups A and B) containing two (16 isolates) and three (3 isolates) IS6110 copies, respectively. These strains were typed by spoligotyping, developed to distinguish M. bovis strains and also to distinguish them from M. tuberculosis strains (J. Kamerbeek et al., J. Clin. Microbiol. 35:907-914, 1997). All the strains were confirmed to be M. bovis. In addition, spoligotyping showed a difference in only 1 of 43 spacers between RFLP groups A and B. The rpo␤ region of several strains representative of each identified group was cloned and sequenced, and identical mutations (Ser-531 to Leu) responsible for the rifampin resistance phenotype were found. To our knowledge, this is the first characterization at the molecular level of an MDR M. bovis strain responsible for a nosocomial outbreak.

Molecular genetic basis of antimicrobial agent resistance inMycobacterium tuberculosis: 1998 update

“…222 MDR-TB organisms also have been documented to be the cause of a nosocomial outbreak in Argentina. 223 Similarly, clonally-related strains of M. bovis resistant to INH, RIF, PZA, ETH, STR, AMI, CAP, para-aminosalicylic acid, clarithromycin, ethionamide, and ofloxacin caused 16 cases of tuberculosis in a nosocomial outbreak involving HIV-positive patients in Spain, 207,224,225 and transmission of this organism to an immunocompetent patient also has been documented. 226 These MDR isolates arise because random mutations in genes that encode targets for the individual antimicrobial agents are selected by subtherapeutic drug levels that can occur due to processes such as treatment errors, poor adherence to treatment protocols, or other factors.…”

Molecular epidemiology of tuberculosis and other mycobacterial infections: main methodologies and achievements

“…Middlebrook and Cohn [230] showed that some INH‐resistant strains were less pathogenic in guinea pigs and this was attributed to the reduction of the catalase activity in these bacteria. Despite this apparently reduced virulence of some INH‐resistant M. tuberculosis strains, many outbreaks of (multidrug) resistant strains were recorded with DNA fingerprinting methods [32, 138, 207, 208, 231–233]. The susceptibility of HIV‐positive patients to tuberculosis infections and the accelerated breakdown to disease often result in more rapid transmission of the disease, as indicated in many outbreaks investigated with DNA fingerprinting [31, 33–37, 234, 235].…”

Prevalence of Multidrug Resistance Mycobacterium Bovis in Human: A Systematic Review and Meta-Analysis

“…MDR-TB cases have been reported in many regions of the World [12]. Although MDR-TB is mainly developed from infection with mycobacterium tuberculosis, MDR-M.bovis outbreaks have been reported [13,14]. In Spain, M.bovis strains resistant to both rifampin and isoniazid were isolated from tuberculosis patients [8].…”