In this study, the drug resistance patterns of MTBC and associated factors were evaluated. The overall resistance to one or more first line drug(s) was 58.6 %. This was in agreement with the previous study in Addis Ababa in which 58 % of isolates were resistant to one or more drugs [13]. However, any drug resistance rate in the present study was lower than the rate observed in recent study in Addis Ababa where 72.9 % isolates were resistant to one or more drugs [14]. This difference in findings might be due to difference in proportion of retreatment sub-categories since majority of the cases in that study were referral cases and most referral cases were treatment failure.
The current WHO treatment guideline recommends the combined treatment of two months rifampicin, isoniazid, pyrazinamide, ethambutol and streptomycin, one-month rifampicin, isonaizid, pyrazinamide, ethambutol and, five months rifampicin, isonaizid, and ethambutol (2RHZES/RHZE/5RHE) for previously treated TB patients by simply adding streptomycin to the regimen for new cases. This repeated treatment practice can amplify resistance in these patients who are likely to have developed resistance to some or all of the previously used first line anti- TB drugs [15]. The situation is further complicated in developing countries where there are inadequate laboratories that have capacity for culture and DST. This challenge could be surmounted by giving priority for previously treated TB cases for culture and DST.
The highest proportion of any drug resistance was observed to isoniazid (51.4 %). This is comparable with the study done in India (52 %) [16] and recent report from study in Addis Ababa (56.1 %) [14]. However, our finding was higher than that of previous studies in Ethiopia 44 % [13] and 42.7 %) [17]. The higher prevalence of isoniazid resistance has also important implications. Isoniazid is the cornerstone drug used throughout the course of non-MDR-TB treatment. It is also the drug of choice for chemoprophylaxis of TB in developing countries for treating latent TB infection. Loss of the effectiveness of this drug compromises both the preventive therapy and treatment of TB disease. Moreover, it is predictor for MDR-TB in the future since MDR-TB often develops from initial isoniazid mono-resistant strains [18].
The second highest any resistance was against streptomycin (42.9 %). The figure is high when compared with earlier studies in Ethiopia where streptomycin resistance accounted for 21 % [17] and 28 % [13]. However, the result is lower than that of recent study in Addis Ababa (67.3 %) [14]. The high any resistance to streptomycin may be due to its early introduction, its common use for treatment of other bacterial infections and inadequate treatment due to poor compliance by patients [19].
The rate of rifampicin resistance was 32.9 %. This is in agreement with the study in Addis Ababa (33.3 %) [13]. The higher rate of rifampicin resistance might be due to its adverse effects such as nausea, vomiting, rashes, hepatitis, GIT upset, flu-like symptoms, fever and jaundice, which could result in patient non-adherence and hence may lead to the selection of resistant strains [19]. In this study, there was only one case with rifampicin mono resistance. The low proportion (1.4 %) of non-MDR rifampicin resistance in this study supports the use of rifampicin resistance as surrogate marker for MDR-TB. It is also in line with WHO recommendation of non MDR-TB rifampicin resistance less than 3 % as good quality performance indicator [20].
The proportion of any ethambutol resistance was 28.6 %. Ethambutol is the first-line drug included in the regimen of second-line drugs to treat MDR-TB cases. The high rate of ethambutol resistance would challenge its inclusion in MDR-TB therapy as this may lead to unintentional incorrect therapy [21]. Thus, further study is recommended to know the level of ethambutol resistance specifically in MDR-TB isolates. This can help in developing national or regional standardized second-line treatment regimen for MDR-TB cases.
In this study the prevalence of MDR-TB (31.4 %) was more than twice the Ethiopian national prevalence of 12 % for retreatment cases [3]. The rate of MDR-TB in retreatment cases in this study is higher than other studies conducted in Uganda (17.8 %) [22] and Ethiopia (28 %) [13]. However, our finding is lower than the recent report from Addis Ababa (46.3 %) [14], India (47.1 %) [16] and Philippines (76.4 %) [23]. The discrepancy in findings between the present study and that of recent study in Addis Ababa can be explained by the differences in the nature of the populations included in the studies. The study in Addis Ababa was conducted retrospectively on data from national TB diagnosis and treatment centers. Most of the cases were referral cases. Most of the referral cases for DST and culture in Ethiopia are treatment failures. However, our study included both referral patients and smear positive previously treated cases diagnosed at Jimma University MRC. In addition there may also be geographical variation in the level of drug resistance.
In the present study, majority (90.9 %) of the MDR-TB cases were in the age between 15 and 44 years. This is in agreement with the report from Iran [24]. The high frequency of MDR-TB among young age groups may indicate the likelihood of propagation of MDR-TB in the community because of high mobility of youth from place to place. This also suggests the occurrence of recent transmission of TB infection because the rate of TB in the older age group mostly suggests the infection has been acquired in the past [25].
The origin drug resistant TB is mostly due to chromosomal alterations such as mutations or deletions. However, TB service related factors have a significant impact on the amplification and transmission [26]. Other mechanisms like efflux pumps have their own contribution in drug resistant TB [11]. In the current study, place of residence, duration of illness and frequency of treatments before this episode showed significant association with any drug resistance. In this study, the history of category I and category II treatment failures were identified as the strongest predictors for either rifampicin resistance or MDR-TB. This is consistent with previous studies in Addis Ababa, Ethiopia [13, 14] and China [25]. Our result showed that more than half of treatment failures were identified as MDR-TB. Majority of these cases were from category I treatment failures (75.6 %). This suggests the importance of early request for culture and DST than awaiting the outcome of extended category II treatment among patients for whom category I failed.
High rates of MDR-TB among treatment failures (72.7 %) can be influenced by the acquisition of resistance in the intensive and continuation phases of treatment or the rate of primary MDR-TB infection [27]. However, the rate of MDR-TB among newly diagnosed TB patients in Jimma was low (1.5 %) [28]. Therefore, the most possible reason for higher rate of MDR-TB in our study is acquisition of drug resistance during the intensive or/and continuation phases of treatment. This may provide clue for the importance of evaluation of currently available TB control programs on proper usage of the drugs. Moreover, it supports the necessity of looking in to the adherence of patients to full course of chemotherapy.
Our study suggests that patients from urban area were more likely to harbor drug resistant TB bacilli. The slumps in urban areas are the favorable environment for the TB transmission including the drug resistant strains. Moreover, relatively high access to unregulated antibiotics in urban area may contribute to the development and selection of drug resistant MTB strains. There was high frequency of MDR-TB cases among patients with the history of alcohol drinking and HIV infection. We did not find statistically significant association between MDR-TB and alcohol consumption and HIV positivity. However, alcohol consumption and HIV treatment can cause concomitant hepatotoxicity that may lead to inadequate adherence to the anti-TB treatment.
This study has its own limitations. Frist, it is institution-based study and hence there could have been significant referral bias involved in patient selection. Second, since DST was not recorded in the previous disease episode, we were unable to determine the extent of amplification in the acquired drug resistance in study population. Finally, data about people’s contact with MDR-TB cases were not available. Despite this limitation, this study provided the first information on TB drug resistance among previously treated cases in the study setting. This can be used for better planning of TB management and tackling further increase in the level of MDR-TB.
