Evaluation of Unconventional anti TB-Drugs Efficacy in Treating MDR and XDR-Tuberculosis (TB). Epidemiological and Clinical Remarks.

Introduction: The crucial therapeutic issue in MDR and XDR-TB is the difficulty of identifying at least 4 available “active” anti-TB drugs, to ensure treatment success as well as to prevent the emergency of additional drug resistance. Aim of the study: to retrospectively analyze the clinical and epidemiological characteristics of patients with MDR and XDR-TB, untreatable with 4 active drugs, in relation to treatment with unconventional drugs [UCD] (meropenem-clavulanate and linezolid), outcome and follow-up. Material and Methods: Adult and HIV-negative patients with confirmed culture MDR and XDR-TB were selected and enrolled in Morelli Hospital (Sondalo, Italy), a specialised centre in the management of complicated TB cases. Resistance to first and second line anti-TB drugs was assessed in accordance with WHO directives. Results: A total of 127 patients was enrolled (103 MDR-TB, 12 pre-XDR-TB and 12 XDR-TB). Of these, 58 were treated with UCD, 69 with conventional anti-TB drugs (CTB). Sputum culture conversion was obtained in 109 of them (86%). A 100% sputum culture conversion, administrating CTB only, was found in group A (21 patients with MDR-TB associated to another resistance to a first line drug), whilst the worst outcome was observed (82.5%) in group B (40 patients with M. tuberculosis strains resistant to all first line drugs). Of these last, 8 were treated with CTB (sputum culture conversion was obtained in 2 cases only, 25%); in the remaining 32 patients treated by UCD, this occurred in 31(96%). The outcome of this subgroup, compared to group A, did not differ statistically (p=0.76). The lack of statistical significance between the 2 groups, predictable in relation to increased severity of patients treated with unconventional regimens, confirm the potential association between UCD used in our study and CTB. With regard to pre-XDR-TB cases, a positive outcome was obtained in 8 out (75%) of 12 patients: 6 out (75%) of 8 patients, treated with UCD, underwent positive outcome vs 2 out (50%) of 4 treated with CTB (p=0.33). Referring to XDR-TB group, 8 patients were treated with CTB (positive outcome in 3 patients, 38%); whereas in the resting 4 patients, treated with UCD, a positive outcome was achieved in 3 (75%) (p=0.24). The lack of statistical significance in these two groups is probably due to small sample representativeness. Of the 62 out (%?) of 109 patients joined after follow-up, 2 patients only did relapse (both presented a resistance pattern involving all first line drugs and were treated with UCD. Conclusions: The presence of M. tuberculosis strains resistant to all first line drugs worsens outcome. However, the use of UCB in group B resulted in resetting the statistical significance in terms of outcome compared with group A. Literature data, report a positive outcome of 65% and 60% for MDR and XDR-TB respectively, far lower than the one achieved in our study. Finally, the mentioned follow-up is to our knowledge the largest Italian casuistry ever reported