Abstract
The role of so-called "group 5" second-line drugs as a part of antibiotic therapy for multidrug-resistant tuberculosis (MDR-TB) is widely debated. We performed an individual patient data meta-analysis to evaluate the effectiveness of several group 5 drugs including amoxicillin/clavulanic acid, thioacetazone, the macrolide antibiotics, linezolid, clofazimine and terizidone for treatment of patients with MDR-TB. Detailed individual patient data were obtained from 31 published cohort studies of MDR-TB therapy. Pooled treatment outcomes for each group 5 drug were calculated using a random effects meta-analysis. Primary analyses compared treatment success to a combined outcome of failure, relapse or death. Among 9282 included patients, 2191 received at least one group 5 drug. We found no improvement in treatment success among patients taking clofazimine, amoxicillin/clavulanic acid or macrolide antibiotics, despite applying a number of statistical approaches to control confounding. Thioacetazone was associated with increased treatment success (OR 2.6, 95% CI 1.1-6.1) when matched controls were selected from studies in which the group 5 drugs were not used at all, although this result was heavily influenced by a single study. The development of more effective antibiotics to treat drug-resistant TB remains an urgent priority.
| Original language | English |
|---|---|
| Article number | 1600993 |
| Journal | European Respiratory Journal |
| Volume | 49 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 1 2017 |
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ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
Cite this
Group 5 drugs for multidrug-resistant tuberculosis : Individual patient data meta-analysis. / Fox, Greg J.; Benedetti, Andrea; Cox, Helen; Koh, Won Jung; Viiklepp, Piret; Ahuja, Shama; Pasvol, Geoffrey; Menzies, Dick; Ahuja, S.; Ashkin, D.; Avendaño, M.; Banerjee, R.; Bauer, M.; Hollm-Delgado, M. G.; Pai, M.; Shah, L.; Bayona, J. N.; Becerra, M.; Burgos, M.; Centis, R.; D'Ambrosio, L.; Migliori, G. B.; Chan, E. D.; Chiang, C. Y.; De Lange, W. C M; Van Altena, R.; Van Der Werf, T. S.; De Riemer, K.; Dung, N. H.; Enarson, D.; Falzon, D.; Granich, R. M.; Flanagan, K.; Flood, J.; Gandhi, N.; Garcia-Garcia, L.; Holtz, T. H.; Iseman, M.; Strand, M. J.; Jarlsberg, L. G.; Royce, S.; Keshavjee, S.; Kim, H. R.; Mitnick, C. D.; Lancaster, J.; Van Der Walt, M.; Lange, C.; Leimane, V.; Riekstina, V.; Leung, C. C.; Li, J.; Narita, M.; O'Riordan, P.; Palmero, D.; Park, S. K.; Pena, J.; Pérez-Guzmán, C.; Ponce-De-Leon, A.; Sifuentes-Osornio, J.; Quelapio, M. I D; Tupasi, T. E.; Robert, J.; Schaaf, H. S.; Seung, K. J.; Shin, S. S.; Shim, T. S.; Shiraishi, Y.; Sotgiu, G.; Tabarsi, P.; Vargas, M. H.; Westenhouse, J.; Yew, W. W.; Yim, J. J.
In: European Respiratory Journal, Vol. 49, No. 1, 1600993, 01.01.2017.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Group 5 drugs for multidrug-resistant tuberculosis
T2 - Individual patient data meta-analysis
AU - Fox, Greg J.
AU - Benedetti, Andrea
AU - Cox, Helen
AU - Koh, Won Jung
AU - Viiklepp, Piret
AU - Ahuja, Shama
AU - Pasvol, Geoffrey
AU - Menzies, Dick
AU - Ahuja, S.
AU - Ashkin, D.
AU - Avendaño, M.
AU - Banerjee, R.
AU - Bauer, M.
AU - Hollm-Delgado, M. G.
AU - Pai, M.
AU - Shah, L.
AU - Bayona, J. N.
AU - Becerra, M.
AU - Burgos, M.
AU - Centis, R.
AU - D'Ambrosio, L.
AU - Migliori, G. B.
AU - Chan, E. D.
AU - Chiang, C. Y.
AU - De Lange, W. C M
AU - Van Altena, R.
AU - Van Der Werf, T. S.
AU - De Riemer, K.
AU - Dung, N. H.
AU - Enarson, D.
AU - Falzon, D.
AU - Granich, R. M.
AU - Flanagan, K.
AU - Flood, J.
AU - Gandhi, N.
AU - Garcia-Garcia, L.
AU - Holtz, T. H.
AU - Iseman, M.
AU - Strand, M. J.
AU - Jarlsberg, L. G.
AU - Royce, S.
AU - Keshavjee, S.
AU - Kim, H. R.
AU - Mitnick, C. D.
AU - Lancaster, J.
AU - Van Der Walt, M.
AU - Lange, C.
AU - Leimane, V.
AU - Riekstina, V.
AU - Leung, C. C.
AU - Li, J.
AU - Narita, M.
AU - O'Riordan, P.
AU - Palmero, D.
AU - Park, S. K.
AU - Pena, J.
AU - Pérez-Guzmán, C.
AU - Ponce-De-Leon, A.
AU - Sifuentes-Osornio, J.
AU - Quelapio, M. I D
AU - Tupasi, T. E.
AU - Robert, J.
AU - Schaaf, H. S.
AU - Seung, K. J.
AU - Shin, S. S.
AU - Shim, T. S.
AU - Shiraishi, Y.
AU - Sotgiu, G.
AU - Tabarsi, P.
AU - Vargas, M. H.
AU - Westenhouse, J.
AU - Yew, W. W.
AU - Yim, J. J.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - The role of so-called "group 5" second-line drugs as a part of antibiotic therapy for multidrug-resistant tuberculosis (MDR-TB) is widely debated. We performed an individual patient data meta-analysis to evaluate the effectiveness of several group 5 drugs including amoxicillin/clavulanic acid, thioacetazone, the macrolide antibiotics, linezolid, clofazimine and terizidone for treatment of patients with MDR-TB. Detailed individual patient data were obtained from 31 published cohort studies of MDR-TB therapy. Pooled treatment outcomes for each group 5 drug were calculated using a random effects meta-analysis. Primary analyses compared treatment success to a combined outcome of failure, relapse or death. Among 9282 included patients, 2191 received at least one group 5 drug. We found no improvement in treatment success among patients taking clofazimine, amoxicillin/clavulanic acid or macrolide antibiotics, despite applying a number of statistical approaches to control confounding. Thioacetazone was associated with increased treatment success (OR 2.6, 95% CI 1.1-6.1) when matched controls were selected from studies in which the group 5 drugs were not used at all, although this result was heavily influenced by a single study. The development of more effective antibiotics to treat drug-resistant TB remains an urgent priority.
AB - The role of so-called "group 5" second-line drugs as a part of antibiotic therapy for multidrug-resistant tuberculosis (MDR-TB) is widely debated. We performed an individual patient data meta-analysis to evaluate the effectiveness of several group 5 drugs including amoxicillin/clavulanic acid, thioacetazone, the macrolide antibiotics, linezolid, clofazimine and terizidone for treatment of patients with MDR-TB. Detailed individual patient data were obtained from 31 published cohort studies of MDR-TB therapy. Pooled treatment outcomes for each group 5 drug were calculated using a random effects meta-analysis. Primary analyses compared treatment success to a combined outcome of failure, relapse or death. Among 9282 included patients, 2191 received at least one group 5 drug. We found no improvement in treatment success among patients taking clofazimine, amoxicillin/clavulanic acid or macrolide antibiotics, despite applying a number of statistical approaches to control confounding. Thioacetazone was associated with increased treatment success (OR 2.6, 95% CI 1.1-6.1) when matched controls were selected from studies in which the group 5 drugs were not used at all, although this result was heavily influenced by a single study. The development of more effective antibiotics to treat drug-resistant TB remains an urgent priority.
UR - http://www.scopus.com/inward/record.url?scp=85008474067&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85008474067&partnerID=8YFLogxK
U2 - 10.1183/13993003.00993-2016
DO - 10.1183/13993003.00993-2016
M3 - Article
C2 - 28049171
AN - SCOPUS:85008474067
VL - 49
JO - European Respiratory Journal
JF - European Respiratory Journal
SN - 0903-1936
IS - 1
M1 - 1600993
ER -