Simultaneous Infection with Multiple Strains ofMycobacterium tuberculosis

Abstract

Drug-susceptible and drug-resistant isolates of Mycobacterium tuberculosis were recovered from 2 patients, 1 with isoniazid-resistant tuberculosis (patient 1) and another with multidrug-resistant tuberculosis (patient 2). An investigation included patient interviews, record reviews, and genotyping of isolates. Both patients worked in a medical-waste processing plant. Transmission from waste was responsible for at least the multidrug-resistant infection. We found no evidence that specimens were switched or that cross-contamination of cultures occurred. For patient 1, susceptible and isoniazid-resistant isolates, collected 15 days apart, had 21 and 19 restriction fragments containing IS6110, 18 of which were common to both. For patient 2, a single isolate contained both drug-susceptible and multidrug-resistant colonies, demonstrating 10 and 11 different restriction fragments, respectively. These observations indicate that simultaneous infections with multiple strains of M. tuberculosis occur in immunocompetent hosts and may be responsible for conflicting drug-susceptibility results, though the circumstances of infections in these cases may have been unusual.

Naturally occurring horizontal gene transfer and homologous recombination in Mycobacterium

“…If this isolate, containing a different resistance phenotype, incorporated the mutated allele into its genome through homologous recombination, one could obtain a multidrug-resistant strain. Simultaneous infection of patients by two different strains of M. tuberculosis (Braden et al, 2001) or M. avium (von Reyn et al, 1995) also creates the opportunity for such a DNA exchange.…”

Characterization of Clonal Complexity in Tuberculosis by Mycobacterial Interspersed Repetitive Unit-Variable-Number Tandem Repeat Typing

“…The complex situations found in tuberculosis include recurrences caused by exogenous reinfections (2,4,5,7,19); simultaneous coinfections by more than one M. tuberculosis strain (3,5,8,13,20); compartmentalization of the infection; with different strains infecting different tissues (3, 9, 12); and microevolution phenomena leading to the appearance of clonal variants within a host (6, 10). Unfortunately, the methodological approach to a search for clonal heterogenity or polyclonality is complex and/or laborious because it requires (i) a refined analysis of genotypic patterns to prove the existence of different clones or (ii) the analysis of multiple independent colonies from each specimen in order to detect the presence of clonal variants.…”

Co-infection with Pansensitive and Multidrug-Resistant Strains ofMycobacterium tuberculosis

“…In addition, exogenous reinfection should be considered as a possible reason for treatment failure or disease relapse (8)(9)(10)(11). However, an underrecognized cause of treatment failure is mixed infection with >2 strains of M. tuberculosis (12)(13)(14)(15). As reported previously (12), simultaneous infection with 2 competing strains should be considered when other common reasons are ruled out and a high index of suspicion is present.…”