Attributable factors to the emergence of multidrug-resistant Mycobacterium tuberculosis based on the observation of consecutive drug resistance test results

Thirty six cases with multidrug-resistant tuberculosis were retrospectively studied to define the causes attributable to the emergence of multidrug-resistant M. tuberculosis. All these tuberculosis cases were microbiologically confirmed and resistant to at least isoniazid and rifampicin. Data analysis using matched-pair sampling methods (1:3) demonstrated that the followings are the significant risk factors for the emergence of multidrug-resistant tuberculosis; incompliance to treatment (Odds ratio 21.0: 95% CI 4.10-107.63), alcohol abuse (Odds ratio 15.0: 95% CI 2.34-96.1) and the history of previous treatment (Odds ratio 5.0: 95% CI 2.04-12.21), while diabetes mellitus is not statistically significant. The incompliance to treatment which is primarily thought to be patient's responsibility results in non-optimal administration of antituberculous agents, leading to the multidrug-resistant tuberculosis. Other factors that may have contributed to the emergence of resistance included 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 with ethambutol 3-months after the initiation of regimen including SM, INH and RFP because of abnormal elevation of GOT and GPT without any supporting evidence that RFP was causative. 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. This case suggests unnecessary interruption of RFP could lead to the emergence of resistance to INH as well as RFP. One known mechanism of drug resistance is random mutation and the selection by drugs administered during the course of chemotherapy. The cases with advanced cavitary lesions would have a higher probability of the occurrence of mutation. The more the number of mutant bacilli, the higher the probability of emergence of multidrug resistance. Those cases in which longer period of time is needed for the negative conversion of M. tuberculosis should be treated with potent chemotherapy regimens under the intense supervision. Since both INH and RFP are the most potent among currently available antituberculous agents. It is crucial to preserve the potency of these essential agents before novel antituberculous are developed.