Treatment correlates of successful outcomes in pulmonary multidrug-resistant tuberculosis: an individual patient data meta-analysis

Treatment outcomes for multidrug-resistant tuberculosis remain poor. We aimed to estimate the association of treatment success and death with the use of individual drugs, and the optimal number and duration of treatment with those drugs in patients with multidrug-resistant tuberculosis. In this indi...

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Vydáno v:	The Lancet (British edition) Ročník 392; číslo 10150; s. 821 - 834
Hlavní autoři:	Ahmad, Nafees, Ahuja, Shama D, Akkerman, Onno W, Alffenaar, Jan-Willem C, Anderson, Laura F, Bang, Didi, Barry, Pennan M, Bastos, Mayara L, Behera, Digamber, Benedetti, Andrea, Bisson, Gregory P, Boeree, Martin J, Bonnet, Maryline, Brode, Sarah K, Brust, James C M, Cai, Ying, Caumes, Eric, Cegielski, J Peter, Centis, Rosella, Chan, Pei-Chun, Chang, Kwok-Chiu, Charles, Macarthur, Cirule, Andra, Dalcolmo, Margareth Pretti, D'Ambrosio, Lia, de Vries, Gerard, Dheda, Keertan, Esmail, Aliasgar, Flood, Jennifer, Fox, Gregory J, Fréchet-Jachym, Mathilde, Fregona, Geisa, Gayoso, Regina, Gegia, Medea, Gler, Maria Tarcela, Gu, Sue, Guglielmetti, Lorenzo, Holtz, Timothy H, Hughes, Jennifer, Jarlsberg, Leah, Kempker, Russell R, Keshavjee, Salmaan, Kipiani, Maia, Koenig, Serena P, Koh, Won-Jung, Kritski, Afranio, Kuksa, Liga, Kvasnovsky, Charlotte L, Lan, Zhiyi, Lange, Christoph, Laniado-Laborín, Rafael, Lee, Myungsun, Leung, Chi-Chiu, Leung, Eric Chung-Ching, Li, Pei Zhi, Lowenthal, Phil, Maciel, Ethel L, Marks, Suzanne M, Mase, Sundari, Mbuagbaw, Lawrence, Migliori, Giovanni B, Milanov, Vladimir, Miller, Ann C, Mitnick, Carole D, Modongo, Chawangwa, Mohr, Erika, Monedero, Ignacio, Nahid, Payam, Ndjeka, Norbert, O'Donnell, Max R, Padayatchi, Nesri, Palmero, Domingo, Pape, Jean William, Podewils, Laura J, Reynolds, Ian, Riekstina, Vija, Robert, Jérôme, Rodriguez, Maria, Seung, Kwonjune J, Schnippel, Kathryn, Shim, Tae Sun, Singla, Rupak, Smith, Sarah E, Sotgiu, Giovanni, Sukhbaatar, Ganzaya, Tabarsi, Payam, Tiberi, Simon, Trieu, Lisa, Udwadia, Zarir F, van der Werf, Tjip S, Veziris, Nicolas, Viiklepp, Piret, Vilbrun, Stalz Charles, Walsh, Kathleen, Westenhouse, Janice, Yew, Wing-Wai, Yim, Jae-Joon, Zetola, Nicola M, Zignol, Matteo, Menzies, Dick
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	England Elsevier Ltd 08.09.2018 Elsevier Limited Elsevier
Témata:	Adults Amikacin Amikacin - therapeutic use Antibiotics Antitubercular Agents - administration & dosage Antitubercular Agents - therapeutic use Bacteriology Capreomycin Capreomycin - therapeutic use Carbapenems Carbapenems - therapeutic use Clinical outcomes Clinical trials Clofazimine Clofazimine - therapeutic use Data analysis Data processing Diarylquinolines - therapeutic use Disease control Drug resistance Drug Therapy, Combination Drugs Fluoroquinolones Fluoroquinolones - therapeutic use Heterogeneity Humans Infectious diseases Kanamycin Kanamycin - therapeutic use Levofloxacin Levofloxacin - therapeutic use Life Sciences Linezolid Linezolid - therapeutic use Literature reviews Meta-analysis Microbiology and Parasitology Mortality Moxifloxacin Multidrug resistance Multidrug resistant organisms Patients Recurrence Regression analysis Respiration Success Systematic review Thorax Treatment Failure Tuberculosis Tuberculosis, Multidrug-Resistant - drug therapy Tuberculosis, Multidrug-Resistant - mortality Tuberculosis, Pulmonary - drug therapy Tuberculosis, Pulmonary - mortality
ISSN:	0140-6736, 1474-547X, 1474-547X
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Popis
Shrnutí:	Treatment outcomes for multidrug-resistant tuberculosis remain poor. We aimed to estimate the association of treatment success and death with the use of individual drugs, and the optimal number and duration of treatment with those drugs in patients with multidrug-resistant tuberculosis. In this individual patient data meta-analysis, we searched MEDLINE, Embase, and the Cochrane Library to identify potentially eligible observational and experimental studies published between Jan 1, 2009, and April 30, 2016. We also searched reference lists from all systematic reviews of treatment of multidrug-resistant tuberculosis published since 2009. To be eligible, studies had to report original results, with end of treatment outcomes (treatment completion [success], failure, or relapse) in cohorts of at least 25 adults (aged >18 years). We used anonymised individual patient data from eligible studies, provided by study investigators, regarding clinical characteristics, treatment, and outcomes. Using propensity score-matched generalised mixed effects logistic, or linear regression, we calculated adjusted odds ratios and adjusted risk differences for success or death during treatment, for specific drugs currently used to treat multidrug-resistant tuberculosis, as well as the number of drugs used and treatment duration. Of 12 030 patients from 25 countries in 50 studies, 7346 (61%) had treatment success, 1017 (8%) had failure or relapse, and 1729 (14%) died. Compared with failure or relapse, treatment success was positively associated with the use of linezolid (adjusted risk difference 0·15, 95% CI 0·11 to 0·18), levofloxacin (0·15, 0·13 to 0·18), carbapenems (0·14, 0·06 to 0·21), moxifloxacin (0·11, 0·08 to 0·14), bedaquiline (0·10, 0·05 to 0·14), and clofazimine (0·06, 0·01 to 0·10). There was a significant association between reduced mortality and use of linezolid (–0·20, –0·23 to –0·16), levofloxacin (–0·06, –0·09 to –0·04), moxifloxacin (–0·07, –0·10 to –0·04), or bedaquiline (–0·14, –0·19 to –0·10). Compared with regimens without any injectable drug, amikacin provided modest benefits, but kanamycin and capreomycin were associated with worse outcomes. The remaining drugs were associated with slight or no improvements in outcomes. Treatment outcomes were significantly worse for most drugs if they were used despite in-vitro resistance. The optimal number of effective drugs seemed to be five in the initial phase, and four in the continuation phase. In these adjusted analyses, heterogeneity, based on a simulated I2 method, was high for approximately half the estimates for specific drugs, although relatively low for number of drugs and durations analyses. Although inferences are limited by the observational nature of these data, treatment outcomes were significantly better with use of linezolid, later generation fluoroquinolones, bedaquiline, clofazimine, and carbapenems for treatment of multidrug-resistant tuberculosis. These findings emphasise the need for trials to ascertain the optimal combination and duration of these drugs for treatment of this condition. American Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America.
Bibliografie:	ObjectType-Article-2 SourceType-Scholarly Journals-1 content type line 14 ObjectType-Feature-3 ObjectType-Evidence Based Healthcare-1 ObjectType-Article-1 ObjectType-Feature-2 ObjectType-Review-3 content type line 23 DM, PN, BS, GBM, and SM designed the study and protocol. NA, SDA, OWA, J-WCA, LFA, PB, DBa, PMB, MLB, DBe, GPB, MJB, MB, SKB, JCMB, YC, GFF, EC, JPC, RC, P-CC, EDC, K-CC, MC, AC, MPD, LD’A, GdV, KD, AE, JF, GF, RG, MG, MTG, SG, LG, THH, JH, PI, MF-J, LJ, RRK, SK, MK, SPK, W-JK, AK, LK, CLK, NK, CL, RL-L, ML, VL, C-CL, EC-CL, PZL, ELM, SMM, LM, GBM, VM, ACM, CDM, CM, EM, IM, NN, MRO’D, NP, DP, JWP, LJP, IR, VR, JR, MR, KJS, KS, TSS, RS, SES, GSo, GSu, PT, ST, AT, LT, ZFU, TSvdW, NV, PV, SCV, KW, JW, W-WY, J-JY, NMZ, and MZ contributed data to the meta-analysis. ZL, DM, PL, AB, and FAK did the data analysis. DM wrote the initial draft of the manuscript, and all authors provided critical input and revisions to the draft manuscripts, and approved the final manuscript. Contributors
ISSN:	0140-6736 1474-547X 1474-547X
DOI:	10.1016/S0140-6736(18)31644-1