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A Review of Moxifloxacin for the Treatment of Drug-Susceptible Tuberculosis.

ABSTRACT: Moxifloxacin, an 8-methoxy quinolone, is an important drug in the treatment of multidrug-resistant tuberculosis and is being investigated in novel drug regimens with pretomanid, bedaquiline, and pyrazinamide, or rifapentine, for the treatment of drug-susceptible tuberculosis. Early results of these studies are promising. Although current evidence does not support the use of moxifloxacin in treatment-shortening regimens for drug-susceptible tuberculosis, it may be recommended in patients unable to tolerate standard first-line drug regimens or for isoniazid monoresistance. Evidence suggests that the standard 400-mg dose of moxifloxacin used in the treatment of tuberculosis may be suboptimal in some patients, leading to worse tuberculosis treatment outcomes and emergence of drug resistance. Furthermore, a drug interaction with the rifamycins results in up to 31% reduced plasma concentrations of moxifloxacin when these are combined for treatment of drug-susceptible tuberculosis, although the clinical relevance of this interaction is unclear. Moxifloxacin exhibits extensive interindividual pharmacokinetic variability. Higher doses of moxifloxacin may be needed to achieve drug exposures required for improved clinical outcomes. Further study is, however, needed to determine the safety of proposed higher doses and clinically validated targets for drug exposure to moxifloxacin associated with improved tuberculosis treatment outcomes. We discuss in this review the evidence for the use of moxifloxacin in drug-susceptible tuberculosis and explore the role of moxifloxacin pharmacokinetics, pharmacodynamics, and drug interactions with rifamycins, on tuberculosis treatment outcomes when used in first-line tuberculosis drug regimens.

SUBMITTER: Naidoo A

PROVIDER: S-EPMC5663285 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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A Review of Moxifloxacin for the Treatment of Drug-Susceptible Tuberculosis.

Naidoo Anushka A Naidoo Kogieleum K McIlleron Helen H Essack Sabiha S Padayatchi Nesri N

Journal of clinical pharmacology 20170724 11

Moxifloxacin, an 8-methoxy quinolone, is an important drug in the treatment of multidrug-resistant tuberculosis and is being investigated in novel drug regimens with pretomanid, bedaquiline, and pyrazinamide, or rifapentine, for the treatment of drug-susceptible tuberculosis. Early results of these studies are promising. Although current evidence does not support the use of moxifloxacin in treatment-shortening regimens for drug-susceptible tuberculosis, it may be recommended in patients unable t ...[more]

PMID: 28741299

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Project description:BackgroundEarly-phase and preclinical studies suggest that moxifloxacin-containing regimens could allow for effective 4-month treatment of uncomplicated, smear-positive pulmonary tuberculosis.MethodsWe conducted a randomized, double-blind, placebo-controlled, phase 3 trial to test the noninferiority of two moxifloxacin-containing regimens as compared with a control regimen. One group of patients received isoniazid, rifampin, pyrazinamide, and ethambutol for 8 weeks, followed by 18 weeks of isoniazid and rifampin (control group). In the second group, we replaced ethambutol with moxifloxacin for 17 weeks, followed by 9 weeks of placebo (isoniazid group), and in the third group, we replaced isoniazid with moxifloxacin for 17 weeks, followed by 9 weeks of placebo (ethambutol group). The primary end point was treatment failure or relapse within 18 months after randomization.ResultsOf the 1931 patients who underwent randomization, in the per-protocol analysis, a favorable outcome was reported in fewer patients in the isoniazid group (85%) and the ethambutol group (80%) than in the control group (92%), for a difference favoring the control group of 6.1 percentage points (97.5% confidence interval [CI], 1.7 to 10.5) versus the isoniazid group and 11.4 percentage points (97.5% CI, 6.7 to 16.1) versus the ethambutol group. Results were consistent in the modified intention-to-treat analysis and all sensitivity analyses. The hazard ratios for the time to culture negativity in both solid and liquid mediums for the isoniazid and ethambutol groups, as compared with the control group, ranged from 1.17 to 1.25, indicating a shorter duration, with the lower bounds of the 95% confidence intervals exceeding 1.00 in all cases. There was no significant difference in the incidence of grade 3 or 4 adverse events, with events reported in 127 patients (19%) in the isoniazid group, 111 (17%) in the ethambutol group, and 123 (19%) in the control group.ConclusionsThe two moxifloxacin-containing regimens produced a more rapid initial decline in bacterial load, as compared with the control group. However, noninferiority for these regimens was not shown, which indicates that shortening treatment to 4 months was not effective in this setting. (Funded by the Global Alliance for TB Drug Development and others; REMoxTB ClinicalTrials.gov number, NCT00864383.).

Project description:BackgroundThe Lagos State Tuberculosis, Buruli Ulcer, and Leprosy Control Program (LSTBLCP) started engaging private hospitals under the Public-Private Mix (PPM) Program in 2008. The study aimed to evaluate the trend and predictors of successful Tuberculosis (TB) treatment outcomes of patients managed across these private health facilities between 2010-2016 in Lagos, Nigeria.MethodsRetrospective review of TB treatment register and treatment cards of patients commenced on TB treatment between January 2010 and December 2016 in 36 private health facilities engaged by the LSTBLCP. Between December 2016 and February 2017, data were collected and entered into Microsoft Excel by trained data entry clerks. The analysis was done using SPSS software. Independent predictors of successful treatment outcomes were determined using multivariate analysis at the statistical significance of p<0.05 and 95% confidence interval.ResultsA total of 1660 records of TB patients were reviewed. 1535 (92.47%) commenced treatment, while 1337 (87.10%) of all records had documented treatment outcomes. Of the 1337 patients with outcomes, 1044 (78.09%) had a successful treatment outcome, and 293 (21.91%) had an unsuccessful outcome. Majority were male, 980 (59.04%), Human Immunodeficiency Virus (HIV) negative status, 1295 (80.24%), diagnosed with smear, 1141 (73.14%), treated in private not-for-profit (PNFP) hospital, 1097 (66.08%), treated for TB between 2014-2016 (18.96%-19.52%). In multivariate analysis, age>20years (aOR = 0.26, p = 0.001), receiving TB treatment in 2013 (aOR = 0.39, p = 0.001), having genexpert for TB diagnosis (aOR = 0.26, p = 0.031) and being HIV positive (aOR = 0.37, p = 0.001) significantly reduced likelihood of successful treatment outcome. The site of TB, being on ART or CPT, were confounding determinants of successful treatment outcomes as they became non-significant at the multivariate analysis level.ConclusionTreatment outcome among Lagos private hospitals was low compared with NTBLCP and World Health Organization (WHO) target. We urge the government and TB stakeholders to strengthen the PPM interventions to improve adherence, particularly among People Living with HIV (PLHIV) and older TB patients. Hence, promotion of early care-seeking, improving diagnostic and case holding efficiencies of health facilities, and TB/HIV collaborative interventions can reduce the risk of an unsuccessful outcome.

Project description:PurposeNon-adherence to tuberculosis therapy can lead to drug resistance, prolonged infectiousness, and death; therefore, understanding what causes treatment default is important. Pakistan has one of the highest burdens of tuberculosis in the world, yet there have been no qualitative studies in Pakistan that have specifically examined why default occurs. We conducted a mixed methods study at a tuberculosis clinic in Karachi to understand why patients with drug-susceptible tuberculosis default from treatment, and to identify factors associated with default. Patients attending this clinic pick up medications weekly and undergo family-supported directly observed therapy.MethodsIn-depth interviews were administered to 21 patients who had defaulted. We also compared patients who defaulted with those who were cured, had completed, or had failed treatment in 2013.ResultsQualitative analyses showed the most common reasons for default were the financial burden of treatment, and medication side effects and beliefs. The influence of finances on other causes of default was also prominent, as was concern about the effect of treatment on family members. In quantitative analysis, of 2120 patients, 301 (14.2%) defaulted. Univariate analysis found that male gender (OR: 1.34, 95% CI: 1.04-1.71), being 35-59 years of age (OR: 1.54, 95% CI: 1.14-2.08), or being 60 years of age or older (OR: 1.84, 95% CI: 1.17-2.88) were associated with default. After adjusting for gender, disease site, and patient category, being 35-59 years of age (aOR: 1.49, 95% CI: 1.10-2.03) or 60 years of age or older (aOR: 1.76, 95% CI: 1.12-2.77) were associated with default.ConclusionsIn multivariate analysis age was the only variable associated with default. This lack of identifiable risk factors and our qualitative findings imply that default is complex and often due to extrinsic and medication-related factors. More tolerable medications, improved side effect management, and innovative cost-reduction measures are needed to reduce default from tuberculosis treatment.

Dataset Information

A Review of Moxifloxacin for the Treatment of Drug-Susceptible Tuberculosis.

Publications

A Review of Moxifloxacin for the Treatment of Drug-Susceptible Tuberculosis.

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