Introduction The crucial therapeutic issue in 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 and to prevent the emergency of additional drug resistance. Aim of the study was 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 (82.5%) was observed 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 (66%) out of 12 patients: 6 (75%) out of 8 patients, treated with UCD, underwent positive outcome vs 2 (50%) out 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 small sample size can justify the lack of statistical significance in these two groups. Of the 62 (56%) 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 CTB). Conclusion 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. Previous data reported 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 casistry ever reported. s the difficulty of identifying at least 4 available “active” anti-TB drugs, to ensure treatment success and to prevent the emergency of additional drug resistance. Aim of the study was 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 (82.5%) was observed 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 (66%) out of 12 patients: 6 (75%) out of 8 patients, treated with UCD, underwent positive outcome vs 2 (50%) out 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 small sample size can justify the lack of statistical significance in these two groups. Of the 62 (56%) 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 CTB). Conclusion 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. Previous data reported 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.

EVALUATION OF UNCONVENTIONAL ANTI-TB DRUGS EFFICACY IN TREATING MDR-TB AND XDR-TB. EPIDEMIOLOGICAL AND CLINICAL REMARKS

Maritati, Martina
Conceptualization
;
Contini, Carlo
Writing – Review & Editing
2015

Abstract

Introduction The crucial therapeutic issue in 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 and to prevent the emergency of additional drug resistance. Aim of the study was 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 (82.5%) was observed 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 (66%) out of 12 patients: 6 (75%) out of 8 patients, treated with UCD, underwent positive outcome vs 2 (50%) out 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 small sample size can justify the lack of statistical significance in these two groups. Of the 62 (56%) 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 CTB). Conclusion 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. Previous data reported 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 casistry ever reported. s the difficulty of identifying at least 4 available “active” anti-TB drugs, to ensure treatment success and to prevent the emergency of additional drug resistance. Aim of the study was 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 (82.5%) was observed 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 (66%) out of 12 patients: 6 (75%) out of 8 patients, treated with UCD, underwent positive outcome vs 2 (50%) out 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 small sample size can justify the lack of statistical significance in these two groups. Of the 62 (56%) 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 CTB). Conclusion 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. Previous data reported 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.
Tuberculosis, MDR, XDR-TB, Unconventional TB drugs, UCD, Meropenem-clavulanate, linezolid, conventional anti-TB drugs, CTB
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2378946
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