Dataset Information

Multidrug-Resistant Tuberculosis Treatment Outcomes in Relation to Treatment and Initial Versus Acquired Second-Line Drug Resistance.

ABSTRACT: Resistance to second-line drugs develops during treatment of multidrug-resistant (MDR) tuberculosis, but the impact on treatment outcome has not been determined.Patients with MDR tuberculosis starting second-line drug treatment were enrolled in a prospective cohort study. Sputum cultures were analyzed at a central reference laboratory. We compared subjects with successful and poor treatment outcomes in terms of (1) initial and acquired resistance to fluoroquinolones and second-line injectable drugs (SLIs) and (2) treatment regimens.Of 1244 patients with MDR tuberculosis, 973 (78.2%) had known outcomes and 232 (18.6%) were lost to follow-up. Among those with known outcomes, treatment succeeded in 85.8% with plain MDR tuberculosis, 69.7% with initial resistance to either a fluoroquinolone or an SLI, 37.5% with acquired resistance to a fluoroquinolone or SLI, 29.3% with initial and 13.0% with acquired extensively drug-resistant tuberculosis (P < .001 for trend). In contrast, among those with known outcomes, treatment success increased stepwise from 41.6% to 92.3% as the number of drugs proven effective increased from ?1 to ?5 (P < .001 for trend), while acquired drug resistance decreased from 12% to 16% range, depending on the drug, down to 0%-2% (P < .001 for trend). In multivariable analysis, the adjusted odds of treatment success decreased 0.62-fold (95% confidence interval, .56-.69) for each increment in drug resistance and increased 2.1-fold (1.40-3.18) for each additional effective drug, controlling for differences between programs and patients. Specific treatment, patient, and program variables were also associated with treatment outcome.Increasing drug resistance was associated in a logical stepwise manner with poor treatment outcomes. Acquired resistance was worse than initial resistance to the same drugs. Increasing numbers of effective drugs, specific drugs, and specific program characteristics were associated with better outcomes and less acquired resistance.

SUBMITTER: Cegielski JP

PROVIDER: S-EPMC4725381 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Multidrug-Resistant Tuberculosis Treatment Outcomes in Relation to Treatment and Initial Versus Acquired Second-Line Drug Resistance.

Cegielski J Peter JP Kurbatova Ekaterina E van der Walt Martie M Brand Jeannette J Ershova Julia J Tupasi Thelma T Caoili Janice Campos JC Dalton Tracy T Contreras Carmen C Yagui Martin M Bayona Jaime J Kvasnovsky Charlotte C Leimane Vaira V Kuksa Liga L Chen Michael P MP Via Laura E LE Hwang Soo Hee SH Wolfgang Melanie M Volchenkov Grigory V GV Somova Tatiana T Smith Sarah E SE Akksilp Somsak S Wattanaamornkiet Wanpen W Kim Hee Jin HJ Kim Chang-Ki CK Kazennyy Boris Y BY Khorosheva Tatiana T Kliiman Kai K Viiklepp Piret P Jou Ruwen R Huang Angela Song-En AS Vasilyeva Irina A IA Demikhova Olga V OV Lancaster Joey J Odendaal Ronel R Diem Lois L Perez Therese C TC Gler Tarcela T Tan Kathrine K Bonilla Cesar C Jave Oswaldo O Asencios Luis L Yale Gloria G Suarez Carmen C Walker Allison Taylor AT Norvaisha Inga I Skenders Girts G Sture Ingrida I Riekstina Vija V Cirule Andra A Sigman Erika E Cho Sang-Nae SN Cai Ying Y Eum Seokyong S Lee Jongseok J Park Seungkyu S Jeon Doosoo D Shamputa Isdore C IC Metchock Beverly B Kuznetsova Tatiana T Akksilp Rattanawadee R Sitti Wanlaya W Inyapong Jirapan J Kiryanova Elena V EV Degtyareva Irina I Nemtsova Evgenia S ES Levina Klavdia K Danilovits Manfred M Kummik Tiina T Lei Yung-Chao YC Huang Wei-Lun WL Erokhin Vladislav V VV Chernousova Larisa N LN Andreevskaya Sofia N SN Larionova Elena E EE Smirnova Tatyana G TG

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20151027 4

<h4>Background</h4>Resistance to second-line drugs develops during treatment of multidrug-resistant (MDR) tuberculosis, but the impact on treatment outcome has not been determined.<h4>Methods</h4>Patients with MDR tuberculosis starting second-line drug treatment were enrolled in a prospective cohort study. Sputum cultures were analyzed at a central reference laboratory. We compared subjects with successful and poor treatment outcomes in terms of (1) initial and acquired resistance to fluoroquino ...[more]

PMID: 26508515

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Project description:IntroductionIndividualised treatment through therapeutic drug monitoring (TDM) may improve tuberculosis (TB) treatment outcomes but is not routinely implemented. Prospective clinical studies of drug exposure and minimum inhibitory concentrations (MICs) in multidrug-resistant TB (MDR-TB) are scarce. This translational study aims to characterise the area under the concentration-time curve of individual MDR-TB drugs, divided by the MIC for Mycobacterium tuberculosis isolates, to explore associations with markers of treatment progress and to develop useful strategies for clinical implementation of TDM in MDR-TB.Methods and analysisAdult patients with pulmonary MDR-TB treated in Xiamen, China, are included. Plasma samples for measure of drug exposure are obtained at 0, 1, 2, 4, 6, 8 and 10 hours after drug intake at week 2 and at 0, 4 and 6 hours during weeks 4 and 8. Sputum samples for evaluating time to culture positivity and MIC determination are collected at days 0, 2 and 7 and at weeks 2, 4, 8 and 12 after treatment initiation. Disease severity are assessed with a clinical scoring tool (TBscore II) and quality of life evaluated using EQ-5D-5L. Drug concentrations of pyrazinamide, ethambutol, levofloxacin, moxifloxacin, cycloserine, prothionamide and para-aminosalicylate are measured by liquid chromatography tandem-mass spectrometry and the levels of amikacin measured by immunoassay. Dried blood spot on filter paper, to facilitate blood sampling for analysis of drug concentrations, is also evaluated. The MICs of the drugs listed above are determined using custom-made broth microdilution plates and MYCOTB plates with Middlebrook 7H9 media. MIC determination of pyrazinamide is performed in BACTEC MGIT 960.Ethics and disseminationThis study has been approved by the ethical review boards of Karolinska Institutet, Sweden and Fudan University, China. Informed written consent is given by participants. The study results will be submitted to a peer-reviewed journal.Trial registration numberNCT02816931; Pre-results.

Dataset Information

Multidrug-Resistant Tuberculosis Treatment Outcomes in Relation to Treatment and Initial Versus Acquired Second-Line Drug Resistance.

Publications

Multidrug-Resistant Tuberculosis Treatment Outcomes in Relation to Treatment and Initial Versus Acquired Second-Line Drug Resistance.

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