Treatment Outcomes among Patients with Extensively Drug‐Resistant Tuberculosis: Systematic Review and Meta‐Analysis

Abstract

Background The treatment of extensively drug-resistant tuberculosis (XDR TB) presents a major challenge. Second-line antimycobacterial drugs are less effective, more toxic, and more costly than first-line agents, and XDR TB strains are, by definition, resistant to the most potent second-line options: the injectable agents and fluoroquinolones. We conducted a meta-analysis to assess XDR TB treatment outcomes and to identify therapeutic approaches associated with favorable responses. Methods We searched PubMed and EMBASE databases to identify studies conducted through May 2009 that report XDR TB treatment outcomes. Results The search yielded 13 observational studies covering 560 patients, of whom 43.7% (95% confidence interval, 32.8%–54.5%) experienced favorable outcomes, defined as either cure or treatment completion, and 20.8% (95% confidence interval, 14.2%–27.3%) died. Random effects meta-analysis and meta-regression showed that studies in which a higher proportion of patients received a later-generation fluoroquinolone reported a higher proportion of favorable treatment outcomes (P = .012). Conclusions This meta-analysis provides the first empirical evidence that the use of later-generation fluoroquinolones for the treatment of XDR TB significantly improves treatment outcomes, even though drug-susceptibility testing demonstrates resistance to a representative fluoroquinolone. These results suggest that the addition of later-generation fluoroquinolones to XDR TB regimens may improve treatment outcomes and should be systematically evaluated in well-designed clinical studies.

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis

“…• Regimens should be constructed on the basis of prevailing patterns of drug resistance and on similar principles to those outlined for MDR tuberculosis (use of ≥4 drugs is likely to be effective) • We recommend a backbone of bedaquiline or delamanid, or both, plus linezolid, inclusion of a later-generation fluoroquinolone, and addition of other drugs such as clofazimine, para-aminosalicylic acid, pyrazinamide, high-dose isoniazid, and other drugs depending on the likelihood of susceptibility • Bedaquiline and delamanid can be used in combination (with careful monitoring for corrected QT prolongationeg, every 2 weeks for the first 12 weeks) • Adverse events such as renal failure, hypokalaemia, hypomagnesaemia, and hearing loss are associated with capreomycin, which has high levels of cross-resistance with aminoglycosides 275 • Differential susceptibility to fluoroquinolones might occur 276 • Group D3 drugs such as meropenem plus clavulanate can be used, but their clinical effectiveness is uncertain …”

Tuberculosis: A Literature Review

“…The patient with MDR-TB and HIV infection mortality rate is more than 98%. Various new drugs in the trial stage show the effectiveness against multidrugresistant tuberculosis and extensively drug-resistant tuberculosis [52][53][54][55] . Daily dose of isoniazid (300 -mg) for 6 months or either 9-month therapy preferred 9-month therapy for HIV-infected persons, daily dose for 6 months also preferred with lower efficacy and it also extended to 36 months for decreased the risk of HIV-positive patients Weekly dose of isoniazid (900 -mg) with rifapentine (900 -mg) for 3 months administration under directly observed therapy Higher completion rate with HIV-uninfected persons & shows the equal efficacy, as compared to 9 months isoniazid therapy Daily dose of rifampin (600 -mg) for 4-month therapy Effective therapy for persons infected with silicosis Daily dose of isoniazid (300 -mg) with rifampin (600 -mg) for 3 months therapy Effective therapy for HIV-infected persons Twice weekly dose of isoniazid (900 -mg) with rifampin (600-mg) for 3-month therapy Effective therapy for HIV-infected persons …”

Knowledge and Attitude about Multidrug-Resistant Tuberculosis among Healthcare Workers in Public Health Centres

“…Furthermore, it may take more than two years for MDR-TB treatment which leads to social isolation, loss of employment, socioeconomic crisis and psychosocial burden. 6 In 2015, at least 504 new MDR-TB cases were identified in Indonesia. Based on this alarming condition, it is crucial that healthcare providers in Indonesia are knowledgeable about MDR-TB and certain measures to control its transmission.…”