Resistance to fluoroquinolones and second-line injectable drugs: Impact on multidrug-resistant TB outcomes

Dennis Falzon, Neel Gandhi, Giovanni B. Migliori, Giovanni Sotgiu, Helen S. Cox, Timothy H. Holtz, Maria Graciela Hollm-Delgado, Salmaan Keshavjee, Kathryn DeRiemer, Rosella Centis, Lia D'Ambrosio, Christoph G. Lange, Melissa Bauer, Dick Menzies, S. D. Ahuja, D. Ashkin, M. Avendaño, R. Banerjee, M. Bauer, M. C. BecerraA. Benedetti, M. Burgos, R. Centis, E. D. Chan, C. Y. Chiang, F. Cobelens, H. Cox, L. D'Ambrosio, W. C M De Lange, D. Enarson, D. Falzon, K. L. Flanagan, J. Flood, N. Gandhi, M. L. Garcia-Garcia, R. M. Granich, M. G. Hollm-Delgado, T. H. Holtz, P. Hopewell, M. D. Iseman, L. G. Jarlsberg, S. Keshavjee, H. R. Kim, W. J. Koh, J. L. Lancaster, C. Lange, V. Leimane, C. C. Leung, J. Li, D. Menzies, G. B. Migliori, C. D. Mitnick, M. Narita, E. Nathanson, R. Odendaal, P. O'Riordan, M. Pai, D. Palmero, S. K. Park, G. Pasvol, J. M. Pena, C. Pérez-Guzmán, A. Ponce-De-Leon, M. I D Quelapio, H. T. Quy, V. Riekstina, J. Robert, S. Royce, M. Salim, H. S. Schaaf, K. J. Seung, L. Shah, K. Shean, T. S. Shim, S. S. Shin, Y. Shiraishi, J. Sifuentes-Osornio, G. Sotgiu, M. J. Strand, S. W. Sung, P. Tabarsi, T. E. Tupasi, M. H. Vargas, R. Van Altena, M. L. Van Der Walt, T. S. Van Der Werf, P. Viiklepp, J. Westenhouse, W. W. Yew, J. J. Yim

Research output: Contribution to journalArticle

258 Citations (Scopus)

Abstract

A meta-analysis for response to treatment was undertaken using individual data of multidrug-resistant tuberculosis (MDR-TB) (resistance to isoniazid and rifampicin) patients from 26 centres. The analysis assessed the impact of additional resistance to fluoroquinolones and/or second-line injectable drugs on treatment outcome. Compared with treatment failure, relapse and death, treatment success was higher in MDR-TB patients infected with strains without additional resistance (n=4763; 64%, 95%CI 57-72%) or with resistance to second-line injectable drugs only (n=1130; 56%, 95%CI 45-66%), than in those having resistance to fluoroquinolones alone (n=426; 48%, 95%CI 36-60%) or to fluoroquinolones plus second-line injectable drugs (extensively drug resistant (XDR)-TB) (n=405; 40%, 95%CI 27-53%). In XDR-TB patients, treatment success was highest if at least six drugs were used in the intensive phase (adjusted OR 4.9, 95%CI 1.4-16.6; reference fewer than three drugs) and four in the continuation phase (OR 6.1, 95%CI 1.4-26.3). The odds of success in XDR-TB patients was maximised when the intensive phase reached 6.6-9.0 months duration and the total duration of treatment 20.1-25.0 months. In XDR-TB patients, regimens containing more drugs than those recommended in MDR-TB but given for a similar duration were associated with the highest odds of success. All data were from observational studies and methodologies varied between centres, therefore, the bias may be substantial. Better quality evidence is needed to optimise regimens.

Original languageEnglish (US)
Pages (from-to)156-168
Number of pages13
JournalEuropean Respiratory Journal
Volume42
Issue number1
DOIs
StatePublished - Jul 1 2013
Externally publishedYes

Fingerprint

Fluoroquinolones
Extensively Drug-Resistant Tuberculosis
Injections
Multidrug-Resistant Tuberculosis
Pharmaceutical Preparations
Isoniazid
Therapeutics
Rifampin
Treatment Failure
Observational Studies
Meta-Analysis
Recurrence

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Falzon, D., Gandhi, N., Migliori, G. B., Sotgiu, G., Cox, H. S., Holtz, T. H., ... Yim, J. J. (2013). Resistance to fluoroquinolones and second-line injectable drugs: Impact on multidrug-resistant TB outcomes. European Respiratory Journal, 42(1), 156-168. https://doi.org/10.1183/09031936.00134712

Resistance to fluoroquinolones and second-line injectable drugs : Impact on multidrug-resistant TB outcomes. / Falzon, Dennis; Gandhi, Neel; Migliori, Giovanni B.; Sotgiu, Giovanni; Cox, Helen S.; Holtz, Timothy H.; Hollm-Delgado, Maria Graciela; Keshavjee, Salmaan; DeRiemer, Kathryn; Centis, Rosella; D'Ambrosio, Lia; Lange, Christoph G.; Bauer, Melissa; Menzies, Dick; Ahuja, S. D.; Ashkin, D.; Avendaño, M.; Banerjee, R.; Bauer, M.; Becerra, M. C.; Benedetti, A.; Burgos, M.; Centis, R.; Chan, E. D.; Chiang, C. Y.; Cobelens, F.; Cox, H.; D'Ambrosio, L.; De Lange, W. C M; Enarson, D.; Falzon, D.; Flanagan, K. L.; Flood, J.; Gandhi, N.; Garcia-Garcia, M. L.; Granich, R. M.; Hollm-Delgado, M. G.; Holtz, T. H.; Hopewell, P.; Iseman, M. D.; Jarlsberg, L. G.; Keshavjee, S.; Kim, H. R.; Koh, W. J.; Lancaster, J. L.; Lange, C.; Leimane, V.; Leung, C. C.; Li, J.; Menzies, D.; Migliori, G. B.; Mitnick, C. D.; Narita, M.; Nathanson, E.; Odendaal, R.; O'Riordan, P.; Pai, M.; Palmero, D.; Park, S. K.; Pasvol, G.; Pena, J. M.; Pérez-Guzmán, C.; Ponce-De-Leon, A.; Quelapio, M. I D; Quy, H. T.; Riekstina, V.; Robert, J.; Royce, S.; Salim, M.; Schaaf, H. S.; Seung, K. J.; Shah, L.; Shean, K.; Shim, T. S.; Shin, S. S.; Shiraishi, Y.; Sifuentes-Osornio, J.; Sotgiu, G.; Strand, M. J.; Sung, S. W.; Tabarsi, P.; Tupasi, T. E.; Vargas, M. H.; Van Altena, R.; Van Der Walt, M. L.; Van Der Werf, T. S.; Viiklepp, P.; Westenhouse, J.; Yew, W. W.; Yim, J. J.

In: European Respiratory Journal, Vol. 42, No. 1, 01.07.2013, p. 156-168.

Research output: Contribution to journalArticle

Falzon, D, Gandhi, N, Migliori, GB, Sotgiu, G, Cox, HS, Holtz, TH, Hollm-Delgado, MG, Keshavjee, S, DeRiemer, K, Centis, R, D'Ambrosio, L, Lange, CG, Bauer, M, Menzies, D, Ahuja, SD, Ashkin, D, Avendaño, M, Banerjee, R, Bauer, M, Becerra, MC, Benedetti, A, Burgos, M, Centis, R, Chan, ED, Chiang, CY, Cobelens, F, Cox, H, D'Ambrosio, L, De Lange, WCM, Enarson, D, Falzon, D, Flanagan, KL, Flood, J, Gandhi, N, Garcia-Garcia, ML, Granich, RM, Hollm-Delgado, MG, Holtz, TH, Hopewell, P, Iseman, MD, Jarlsberg, LG, Keshavjee, S, Kim, HR, Koh, WJ, Lancaster, JL, Lange, C, Leimane, V, Leung, CC, Li, J, Menzies, D, Migliori, GB, Mitnick, CD, Narita, M, Nathanson, E, Odendaal, R, O'Riordan, P, Pai, M, Palmero, D, Park, SK, Pasvol, G, Pena, JM, Pérez-Guzmán, C, Ponce-De-Leon, A, Quelapio, MID, Quy, HT, Riekstina, V, Robert, J, Royce, S, Salim, M, Schaaf, HS, Seung, KJ, Shah, L, Shean, K, Shim, TS, Shin, SS, Shiraishi, Y, Sifuentes-Osornio, J, Sotgiu, G, Strand, MJ, Sung, SW, Tabarsi, P, Tupasi, TE, Vargas, MH, Van Altena, R, Van Der Walt, ML, Van Der Werf, TS, Viiklepp, P, Westenhouse, J, Yew, WW & Yim, JJ 2013, 'Resistance to fluoroquinolones and second-line injectable drugs: Impact on multidrug-resistant TB outcomes', European Respiratory Journal, vol. 42, no. 1, pp. 156-168. https://doi.org/10.1183/09031936.00134712
Falzon, Dennis ; Gandhi, Neel ; Migliori, Giovanni B. ; Sotgiu, Giovanni ; Cox, Helen S. ; Holtz, Timothy H. ; Hollm-Delgado, Maria Graciela ; Keshavjee, Salmaan ; DeRiemer, Kathryn ; Centis, Rosella ; D'Ambrosio, Lia ; Lange, Christoph G. ; Bauer, Melissa ; Menzies, Dick ; Ahuja, S. D. ; Ashkin, D. ; Avendaño, M. ; Banerjee, R. ; Bauer, M. ; Becerra, M. C. ; Benedetti, A. ; Burgos, M. ; Centis, R. ; Chan, E. D. ; Chiang, C. Y. ; Cobelens, F. ; Cox, H. ; D'Ambrosio, L. ; De Lange, W. C M ; Enarson, D. ; Falzon, D. ; Flanagan, K. L. ; Flood, J. ; Gandhi, N. ; Garcia-Garcia, M. L. ; Granich, R. M. ; Hollm-Delgado, M. G. ; Holtz, T. H. ; Hopewell, P. ; Iseman, M. D. ; Jarlsberg, L. G. ; Keshavjee, S. ; Kim, H. R. ; Koh, W. J. ; Lancaster, J. L. ; Lange, C. ; Leimane, V. ; Leung, C. C. ; Li, J. ; Menzies, D. ; Migliori, G. B. ; Mitnick, C. D. ; Narita, M. ; Nathanson, E. ; Odendaal, R. ; O'Riordan, P. ; Pai, M. ; Palmero, D. ; Park, S. K. ; Pasvol, G. ; Pena, J. M. ; Pérez-Guzmán, C. ; Ponce-De-Leon, A. ; Quelapio, M. I D ; Quy, H. T. ; Riekstina, V. ; Robert, J. ; Royce, S. ; Salim, M. ; Schaaf, H. S. ; Seung, K. J. ; Shah, L. ; Shean, K. ; Shim, T. S. ; Shin, S. S. ; Shiraishi, Y. ; Sifuentes-Osornio, J. ; Sotgiu, G. ; Strand, M. J. ; Sung, S. W. ; Tabarsi, P. ; Tupasi, T. E. ; Vargas, M. H. ; Van Altena, R. ; Van Der Walt, M. L. ; Van Der Werf, T. S. ; Viiklepp, P. ; Westenhouse, J. ; Yew, W. W. ; Yim, J. J. / Resistance to fluoroquinolones and second-line injectable drugs : Impact on multidrug-resistant TB outcomes. In: European Respiratory Journal. 2013 ; Vol. 42, No. 1. pp. 156-168.
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abstract = "A meta-analysis for response to treatment was undertaken using individual data of multidrug-resistant tuberculosis (MDR-TB) (resistance to isoniazid and rifampicin) patients from 26 centres. The analysis assessed the impact of additional resistance to fluoroquinolones and/or second-line injectable drugs on treatment outcome. Compared with treatment failure, relapse and death, treatment success was higher in MDR-TB patients infected with strains without additional resistance (n=4763; 64{\%}, 95{\%}CI 57-72{\%}) or with resistance to second-line injectable drugs only (n=1130; 56{\%}, 95{\%}CI 45-66{\%}), than in those having resistance to fluoroquinolones alone (n=426; 48{\%}, 95{\%}CI 36-60{\%}) or to fluoroquinolones plus second-line injectable drugs (extensively drug resistant (XDR)-TB) (n=405; 40{\%}, 95{\%}CI 27-53{\%}). In XDR-TB patients, treatment success was highest if at least six drugs were used in the intensive phase (adjusted OR 4.9, 95{\%}CI 1.4-16.6; reference fewer than three drugs) and four in the continuation phase (OR 6.1, 95{\%}CI 1.4-26.3). The odds of success in XDR-TB patients was maximised when the intensive phase reached 6.6-9.0 months duration and the total duration of treatment 20.1-25.0 months. In XDR-TB patients, regimens containing more drugs than those recommended in MDR-TB but given for a similar duration were associated with the highest odds of success. All data were from observational studies and methodologies varied between centres, therefore, the bias may be substantial. Better quality evidence is needed to optimise regimens.",
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TY - JOUR

T1 - Resistance to fluoroquinolones and second-line injectable drugs

T2 - Impact on multidrug-resistant TB outcomes

AU - Falzon, Dennis

AU - Gandhi, Neel

AU - Migliori, Giovanni B.

AU - Sotgiu, Giovanni

AU - Cox, Helen S.

AU - Holtz, Timothy H.

AU - Hollm-Delgado, Maria Graciela

AU - Keshavjee, Salmaan

AU - DeRiemer, Kathryn

AU - Centis, Rosella

AU - D'Ambrosio, Lia

AU - Lange, Christoph G.

AU - Bauer, Melissa

AU - Menzies, Dick

AU - Ahuja, S. D.

AU - Ashkin, D.

AU - Avendaño, M.

AU - Banerjee, R.

AU - Bauer, M.

AU - Becerra, M. C.

AU - Benedetti, A.

AU - Burgos, M.

AU - Centis, R.

AU - Chan, E. D.

AU - Chiang, C. Y.

AU - Cobelens, F.

AU - Cox, H.

AU - D'Ambrosio, L.

AU - De Lange, W. C M

AU - Enarson, D.

AU - Falzon, D.

AU - Flanagan, K. L.

AU - Flood, J.

AU - Gandhi, N.

AU - Garcia-Garcia, M. L.

AU - Granich, R. M.

AU - Hollm-Delgado, M. G.

AU - Holtz, T. H.

AU - Hopewell, P.

AU - Iseman, M. D.

AU - Jarlsberg, L. G.

AU - Keshavjee, S.

AU - Kim, H. R.

AU - Koh, W. J.

AU - Lancaster, J. L.

AU - Lange, C.

AU - Leimane, V.

AU - Leung, C. C.

AU - Li, J.

AU - Menzies, D.

AU - Migliori, G. B.

AU - Mitnick, C. D.

AU - Narita, M.

AU - Nathanson, E.

AU - Odendaal, R.

AU - O'Riordan, P.

AU - Pai, M.

AU - Palmero, D.

AU - Park, S. K.

AU - Pasvol, G.

AU - Pena, J. M.

AU - Pérez-Guzmán, C.

AU - Ponce-De-Leon, A.

AU - Quelapio, M. I D

AU - Quy, H. T.

AU - Riekstina, V.

AU - Robert, J.

AU - Royce, S.

AU - Salim, M.

AU - Schaaf, H. S.

AU - Seung, K. J.

AU - Shah, L.

AU - Shean, K.

AU - Shim, T. S.

AU - Shin, S. S.

AU - Shiraishi, Y.

AU - Sifuentes-Osornio, J.

AU - Sotgiu, G.

AU - Strand, M. J.

AU - Sung, S. W.

AU - Tabarsi, P.

AU - Tupasi, T. E.

AU - Vargas, M. H.

AU - Van Altena, R.

AU - Van Der Walt, M. L.

AU - Van Der Werf, T. S.

AU - Viiklepp, P.

AU - Westenhouse, J.

AU - Yew, W. W.

AU - Yim, J. J.

PY - 2013/7/1

Y1 - 2013/7/1

N2 - A meta-analysis for response to treatment was undertaken using individual data of multidrug-resistant tuberculosis (MDR-TB) (resistance to isoniazid and rifampicin) patients from 26 centres. The analysis assessed the impact of additional resistance to fluoroquinolones and/or second-line injectable drugs on treatment outcome. Compared with treatment failure, relapse and death, treatment success was higher in MDR-TB patients infected with strains without additional resistance (n=4763; 64%, 95%CI 57-72%) or with resistance to second-line injectable drugs only (n=1130; 56%, 95%CI 45-66%), than in those having resistance to fluoroquinolones alone (n=426; 48%, 95%CI 36-60%) or to fluoroquinolones plus second-line injectable drugs (extensively drug resistant (XDR)-TB) (n=405; 40%, 95%CI 27-53%). In XDR-TB patients, treatment success was highest if at least six drugs were used in the intensive phase (adjusted OR 4.9, 95%CI 1.4-16.6; reference fewer than three drugs) and four in the continuation phase (OR 6.1, 95%CI 1.4-26.3). The odds of success in XDR-TB patients was maximised when the intensive phase reached 6.6-9.0 months duration and the total duration of treatment 20.1-25.0 months. In XDR-TB patients, regimens containing more drugs than those recommended in MDR-TB but given for a similar duration were associated with the highest odds of success. All data were from observational studies and methodologies varied between centres, therefore, the bias may be substantial. Better quality evidence is needed to optimise regimens.

AB - A meta-analysis for response to treatment was undertaken using individual data of multidrug-resistant tuberculosis (MDR-TB) (resistance to isoniazid and rifampicin) patients from 26 centres. The analysis assessed the impact of additional resistance to fluoroquinolones and/or second-line injectable drugs on treatment outcome. Compared with treatment failure, relapse and death, treatment success was higher in MDR-TB patients infected with strains without additional resistance (n=4763; 64%, 95%CI 57-72%) or with resistance to second-line injectable drugs only (n=1130; 56%, 95%CI 45-66%), than in those having resistance to fluoroquinolones alone (n=426; 48%, 95%CI 36-60%) or to fluoroquinolones plus second-line injectable drugs (extensively drug resistant (XDR)-TB) (n=405; 40%, 95%CI 27-53%). In XDR-TB patients, treatment success was highest if at least six drugs were used in the intensive phase (adjusted OR 4.9, 95%CI 1.4-16.6; reference fewer than three drugs) and four in the continuation phase (OR 6.1, 95%CI 1.4-26.3). The odds of success in XDR-TB patients was maximised when the intensive phase reached 6.6-9.0 months duration and the total duration of treatment 20.1-25.0 months. In XDR-TB patients, regimens containing more drugs than those recommended in MDR-TB but given for a similar duration were associated with the highest odds of success. All data were from observational studies and methodologies varied between centres, therefore, the bias may be substantial. Better quality evidence is needed to optimise regimens.

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U2 - 10.1183/09031936.00134712

DO - 10.1183/09031936.00134712

M3 - Article

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VL - 42

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EP - 168

JO - European Respiratory Journal

JF - European Respiratory Journal

SN - 0903-1936

IS - 1

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