Thirty six cases with multidrug-resistant tuberculosis were retrospectively studied todefine the causes attributable to the emergence of multidrug-resistant M. tuberculosis.
All these tuberculosis cases were microbiologically confirmed and resistant to at leastisoniazid and rifampicin.
Data analysis using matched-pair sampling methods (1: 3) demonstrated that the followingsare the significant risk factors for the emergence of multidrug-resistant tuberculosis; incompliance to treatment (Odds ratio 21.0: 95%Cl 4.10-107.63), alcohol abuse (Odds ratio 15.0: 95%Cl 2.34-96. 1) and the history of previous treatment (Odds ratio 5.0: 95%Cl 2.04-12.21), while diabetes mellitus is not statistically significant.
The incompliance to treatment which is primarily thought to be patient's responsibilityresults in non-optimal administration of antituberculous agents, leading to the multidrugresistant tuberculosis. Other factors that may have contributed to the emergence of resistanceincluded the unnecessary change of regimen before completion of chemotherapy.This is patient-unrelated situation where responsibility lies in the medical side.
A clinical case presented here is an example. In this case RFP was replaced withethambutol 3-months after the initiation of regimen including SM, INH and RFP becauseof abnormal elevation of GOT and GPT without any supporting evidence that RFP wascausative. The readministration of RFP after 1-year cessation did not induce liver dysfunction, while the drug resistance was observed not only to RFP but also to INH. Thiscase suggests unnecessary interruption of RFP could lead to the emergence of resistanceto INH as well as RFP.
One known mechanism of drug resistance is random mutation and the selection bydrugs administered during the course of chemotherapy. The cases with advanced cavitarylesions would have a higher probability of the occurrence of mutation. The more thenumber of mutant bacilli, the higher the probability of emergence of multidrugresistance. Those cases in which longer period of time is needed for the negative conversionof M. tuberculosis should be treated with potent chemotherapy regimens under theintensive supervision.
Since both INH and RFP are the most potent among currently available antituberculousagents. It is crucial to preserve the potency of these essential agents before novel antituberculousare developed.