Comparison of fitness of two isolates of Mycobacterium tuberculosis, one of which had developed multi-drug resistance during the course of treatment.
OBJECTIVE
We report the cases of two patients, brother and sister, both with pulmonary tuberculosis. Both patients complied poorly with treatment. One developed multi-drug resistant disease, whilst the other did not. We aimed to show that the two infecting strains were the same, and then to compare the fitness of the resistant strain to that of the sensitive strain.


METHODS
The isolates were typed by RFLP. The fitness of the multi-drug resistant tuberculosis strain was determined by calculating the ratio of generation produced by the drug-resistant and a drug-susceptible strain in a mixed culture. The number of bacteria present in this broth culture was estimated using the Miles and Misra technique. The number of drug-resistant bacteria present was determined by inoculating aliquots of broth onto Middlebrook 7H10 agar with 5mg/l rifampicin.


RESULTS
The infecting strain of Mycobacterium tuberculosis was shown to be the same on RFLP typing in both cases. It was found that the multi-drug resistant organism had decreased fitness compared to the sensitive organism.


CONCLUSIONS
The decreased relative fitness of the resistant strain implies a physiologic cal cost for the development of drug resistance.
Davies
A P
AP
Departments of Medical Microbiology, Royal Free Hospital, London, UK.
Billington
O J
OJ
Bannister
B A
BA
Weir
W R
WR
McHugh
T D
TD
Gillespie
S H
SH
D000995:Antitubercular Agents / Q000627:therapeutic use*; D015373:Bacterial Typing Techniques; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D008297:Male; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000187:drug effects / Q000302:isolation & purification / Q000502:physiology*; D010349:Patient Compliance; D012150:Polymorphism, Restriction Fragment Length; D018088:Tuberculosis, Multidrug-Resistant; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000382:microbiology*
D000995:Antitubercular Agents