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


OBJECTIVE
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.


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.
van Rie
Annelies
A
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
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
D000995:Antitubercular Agents / Q000627:therapeutic use; D016172:DNA Fingerprinting; D004252:DNA Mutational Analysis; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D006801:Humans; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000302:isolation & purification; D012008:Recurrence; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000235:genetics* / Q000382:microbiology*
D000995:Antitubercular Agents