Multidrug-resistant tuberculosis treatment failure detection depends on monitoring interval and microbiological method

Carole D. Mitnick, Richard A. White, Chunling Lu, Carly A. Rodriguez, Jaime Bayona, Mercedes C. Becerra, Marcos Burgos, Rosella Centis, Theodore Cohen, Helen Cox, Lia D'Ambrosio, Manfred Danilovitz, Dennis Falzon, Irina Y. Gelmanova, Maria T. Gler, Jennifer A. Grinsdale, Timothy H. Holtz, Salmaan Keshavjee, Vaira Leimane, Dick MenziesGiovanni Battista Migliori, Meredith B. Milstein, Sergey P. Mishustin, Marcello Pagano, Maria I. Quelapio, Karen Shean, Sonya S. Shin, Arielle W. Tolman, Martha L. Van Der Walt, Armand Van Deun, Piret Viiklepp, Shama D. Ahuja, Yevgeny G. Andreev, David Ashkin, Monika Avendano, Rita Banerjee, Melissa Bauer, Andrea Benedetti, Jeannette Brand, Edward D. Chan, Chen Yuan Chiang, Kathy DeRiemer, Nguyen Huy Dung, Donald Enarson, Katherine Flanagan, Jennifer Flood, Lourdes García-García, Neel Gandhi, Reuben M. Granich, Maria G. Hollm-Delgado, Michael D. Iseman, Leah G. Jarlsberg, Hye Ryoun Kim, Won Jung Koh, Joey Lancaster, Christophe Lange, Wiel C.M. De Lange, Chi Chiu Leung, Jiehui Li, Aung Kya Jai Maug, Masa Narita, Ronel Odendaal, Philly O'Riordan, Madhukar Pai, Domingo Palmero, Seung-Kyu, Geoffrey Pasvol, Jose Peña, Carlos Pérez-Guzmán, Alfredo Ponce-De-Leon, Vija Riekstina, Jerome Robert, Sarah Royce, H. Simon Schaaf, Kwonjune J. Seung, Lena Shah, Tae Sun Shim, Yuji Shiraishi, José Sifuentes-Osornio, Matthew J. Strand, Payam Tabarsi Shaheed, Thelma E. Tupasi, Robert Van Altena, Tjip S. Van Der Werf, Mario H. Vargas, Janice Westenhouse, Wing Wai Yew, Jae Joon Yim

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Debate persists about monitoring method (culture or smear) and interval (monthly or less frequently) during treatment for multidrug-resistant tuberculosis (MDR-TB). We analysed existing data and estimated the effect of monitoring strategies on timing of failure detection. We identified studies reporting microbiological response to MDR-TB treatment and solicited individual patient data from authors. Frailty survival models were used to estimate pooled relative risk of failure detection in the last 12 months of treatment; hazard of failure using monthly culture was the reference. Data were obtained for 5410 patients across 12 observational studies. During the last 12 months of treatment, failure detection occurred in a median of 3 months by monthly culture; failure detection was delayed by 2, 7, and 9 months relying on bimonthly culture, monthly smear and bimonthly smear, respectively. Risk (95% CI) of failure detection delay resulting from monthly smear relative to culture is 0.38 (0.34-0.42) for all patients and 0.33 (0.25-0.42) for HIV-co-infected patients. Failure detection is delayed by reducing the sensitivity and frequency of the monitoring method. Monthly monitoring of sputum cultures from patients receiving MDR-TB treatment is recommended. Expanded laboratory capacity is needed for high-quality culture, and for smear microscopy and rapid molecular tests.

Original languageEnglish (US)
Pages (from-to)1160-1170
Number of pages11
JournalEuropean Respiratory Journal
Issue number4
StatePublished - Oct 1 2016

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine


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