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Reinfection and mixed infection cause changing Mycobacterium tuberculosis drug-resistance patterns.


ABSTRACT:

Rationale

Multiple infections with different strains of Mycobacterium tuberculosis may occur in settings where the infection pressure is high. The relevance of mixed infections for the patient, clinician, and control program remains unclear.

Objectives

This study aimed to describe reinfection and mixed infection as underlying mechanisms of changing drug-susceptibility patterns in serial sputum cultures.

Methods

Serial M. tuberculosis sputum cultures from patients diagnosed with multi-drug-resistant (MDR) tuberculosis were evaluated by phenotypic drug-susceptibility testing and mutation detection methods. Genotypic analysis was done by IS6110 DNA fingerprinting and a novel strain-specific polymerase chain reaction amplification method.

Measurements and main results

DNA fingerprinting analysis of serial sputum cultures from 48 patients with MDR tuberculosis attributed 10 cases to reinfection and 1 case to mixed infection. In contrast, strain-specific polymerase chain reaction amplification analysis in 9 of the 11 cases demonstrated mixed infection in 5 cases, reinfection in 3 cases, and laboratory contamination in 1 case. Analysis of clinical data suggests that first-line therapy can select for a resistant subpopulation, whereas poor adherence or second-line therapy resulted in the reemergence of the drug-susceptible subpopulations.

Conclusions

We have shown that, in some patients with MDR tuberculosis, mixed infection may be responsible for observations attributed to reinfection by DNA fingerprinting. We conclude that treatment and adherence determines which strain is dominant. We hypothesize that treatment with second-line drugs may lead to reemergence of the drug-susceptible strain in patients with mixed infection.

SUBMITTER: van Rie A 

PROVIDER: S-EPMC2718533 | biostudies-literature | 2005 Sep

REPOSITORIES: biostudies-literature

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Publications

Reinfection and mixed infection cause changing Mycobacterium tuberculosis drug-resistance patterns.

van Rie Annelies A   Victor Thomas C TC   Richardson Madalene M   Johnson Rabia R   van der Spuy Gian D GD   Murray Emma J EJ   Beyers Nulda N   Gey van Pittius Nico C NC   van Helden Paul D PD   Warren Robin M RM  

American journal of respiratory and critical care medicine 20050609 5


<h4>Rationale</h4>Multiple infections with different strains of Mycobacterium tuberculosis may occur in settings where the infection pressure is high. The relevance of mixed infections for the patient, clinician, and control program remains unclear.<h4>Objectives</h4>This study aimed to describe reinfection and mixed infection as underlying mechanisms of changing drug-susceptibility patterns in serial sputum cultures.<h4>Methods</h4>Serial M. tuberculosis sputum cultures from patients diagnosed  ...[more]

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