Dataset Information

Moxifloxacin Improves Treatment Outcomes in Patients with Ofloxacin-Resistant Multidrug-Resistant Tuberculosis.

ABSTRACT: It is unclear whether the use of moxifloxacin (MFX), a newer synthetic fluoroquinolone, results in better outcomes in patients with ofloxacin (OFX)-resistant multidrug-resistant tuberculosis (MDR-TB). During the period from April 2006 to December 2013, a total of 2,511 patients with culture-confirmed tuberculosis (TB) were treated at a TB referral hospital in southern Taiwan. Of the 2,511 patients, 325 (12.9%) had MDR-TB, and of those 325 patients, 81 (24.9%) had OFX-resistant MDR-TB and were included in the study. Among the 81 patients with OFX-resistant MDR-TB, 50 (61.7%) were successfully treated and 31 (38.3%) had unfavorable outcomes, including treatment failure (n = 25; 30.9%), loss to follow-up (n = 2; 2.5%), and death (n = 4; 4.9%). Patients treated with MFX had a significantly higher rate of treatment success (77.3% versus 43.2%; odds ratio [OR] = 4.46, 95% confidence interval [CI] = 1.710 to 11.646, P = 0.002) than patients not treated with MFX, especially among those infected with MFX-susceptible isolates (40.7%) or isolates with low-level resistance to MFX (28.4%). Multivariate logistic regression analysis showed that treatment with MFX (adjusted odds ratio = 6.54, 95% CI = 1.44 to 29.59, P = 0.015) was the only independent factor associated with treatment success. Mutation at codon 94 in the gyrA gene was the most frequent mutation (68.0%) associated with high-level MFX resistance. Multivariate Cox proportional hazards regression analysis showed that treatment with MFX was also an independent factor associated with early culture conversion (hazard ratio = 3.12, 95% CI = 1.48 to 6.54, P = 0.003). Our results show that a significant proportion of OFX-resistant MDR-TB isolates were susceptible or had low-level resistance to MFX, indicating that patients with OFX-resistant MDR-TB benefit from treatment with MFX.

SUBMITTER: Chien JY

PROVIDER: S-EPMC4958188 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Moxifloxacin Improves Treatment Outcomes in Patients with Ofloxacin-Resistant Multidrug-Resistant Tuberculosis.

Chien Jung-Yien JY Chien Shun-Tien ST Chiu Wei-Yih WY Yu Chong-Jen CJ Hsueh Po-Ren PR

Antimicrobial agents and chemotherapy 20160722 8

It is unclear whether the use of moxifloxacin (MFX), a newer synthetic fluoroquinolone, results in better outcomes in patients with ofloxacin (OFX)-resistant multidrug-resistant tuberculosis (MDR-TB). During the period from April 2006 to December 2013, a total of 2,511 patients with culture-confirmed tuberculosis (TB) were treated at a TB referral hospital in southern Taiwan. Of the 2,511 patients, 325 (12.9%) had MDR-TB, and of those 325 patients, 81 (24.9%) had OFX-resistant MDR-TB and were in ...[more]

PMID: 27216062

Similar Datasets

Project description:BackgroundInterim treatment outcomes at 6-months for multidrug-resistant tuberculosis (MDR-TB) treatment are among the most basic performance monitoring and key evaluation indicators in the Stop and End TB strategy of the World Health Organization (WHO). Therefore, this study was conducted to evaluate the interim treatment outcomes of MDR-TB patients in Pakistan.MethodsThis study was conducted at the Programmatic Management Unit for Drug-resistance TB (PMDT) site of the National Tuberculosis Program (NTP), Pakistan. It is located in the Chest Disease Unit (CDU) of the Bahawal Victoria Hospital (BVH), Bahawalpur, Punjab, Pakistan. Data was collected between April 1, 2014 and December 31, 2015. The medical records, Electronic Nominal Recording Reporting System (ENRS) data and MRD-TB notification forms of the MDR-TB patients registered at the PMDT site were reviewed to obtain data. For reporting and calculation of interim treatment outcomes, standardized WHO methodology was adopted. Simple logistic regression analysis was used to examine the possible association between the dependent variable (i.e. unsuccessful interim treatment outcome) and selected socio-demographic and clinical variables.ResultsA total of 100 drug-resistant TB (DR-TB) patients (all types) were registered during the study period. Out of these, 80 were MDR-TB patients for whom interim results were available. Out of the 80 MDR-TB cases, 48 (60%) were classified under the successful interim treatment outcome category. The remaining 40% had unsuccessful 6-month treatment outcomes and 12 (15%) patients died, while nine (11.3%) were lost to follow-up by six months. The final predictors of unsuccessful interim treatment outcomes were; being resistant to ofloxacin (AOR 3.23, 95% CI 0.96-10.89; p-value = 0.04), having above normal baseline serum creatinine levels (AOR 6.49, 95% CI 1.39-30.27; p-value = 0.02), and being culture positive at the second month of treatment (AOR 6.94, 95% CI 2-24.12; p-value = 0.01).ConclusionsDespite free treatment and programmatic efforts to ensure patient adherence, the high rate of unsuccessful interim treatment outcomes is concerning. The identified risk factors for unsuccessful interim treatment outcomes in the current study provides clinicians an opportunity to identify high-risk patients and ensure enhanced clinical management and greater treatment success rates.

Project description:The worldwide emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) has posed additional challenges for global tuberculosis (TB) control efforts, as limited treatment options are available and treatment outcomes are often sub-optimal. This study determined treatment outcomes among a cohort of MDR-TB and XDR-TB patients in Hunan Province, China, and identified factors associated with poor treatment outcomes.We conducted a retrospective study using data obtained from medical records of TB patients in Hunan Chest Hospital, and from the internet-based TB management information system managed by the Tuberculosis Control Institute of Hunan Province, for the period 2011 to 2014. Treatment outcomes were assessed for patients diagnosed with MDR-TB (TB resistant to at least isoniazid and rifampicin) and XDR-TB (MDR-TB plus resistance to any fluoroquinolone and at least 1 second-line injectable drug). Cumulative incidence functions were used to estimate time to events (i.e. poor treatment outcomes, loss to follow-up, and unfavourable treatment outcomes); and a competing-risks survival regression model was used to identify predictors of treatment outcomes.Of 481 bacteriologically-confirmed patients, with a mean age of 40 years (standard deviation SD ± 13 years), 10 (2%) had XDR-TB and the remainder (471; 98%) had MDR-TB. For the entire cohort, treatment success was 57% (n = 275); 58% (n = 272) for MDR-TB and 30% (n = 3) for XDR-TB. Overall, 27% were lost to follow-up (n = 130), 27% (n = 126) for MDR-TB and 40% (n = 4) for XDR-TB; and 16% had a poor treatment outcome (n = 76), 15% for MDR-TB and 30% (n = 3) for XDR-TB. Of the 10 XDR-TB patients, 3 (30%) completed treatment, 3 (30%) died and 4 (40%) were lost to follow-up. Of the 471 MDR-TB patients, 258 (57%) were cured, 16 (3%) completed treatment, 13 (3%) died, 60 (13%) experienced treatment failure, and 126 (27%) were lost to follow-up. Resistance to ofloxacin was an independent predictor of poor (AHR = 3.1; 95%CI = 1.5, 6.3), and unfavourable (AHR = 1.7; 95%CI = 1.07, 2.9) treatment outcomes. Patients who started treatment during 2011-2012 (AHR = 2.8; 95% CI = 1.5, 5.3) and 2013 (AHR = 2.1; 95% CI = 1.2, 3.9) had poorer treatment outcomes compared to patients who started treatment during 2014.Patients with MDR-TB and XDR-TB had low rates of treatment success in Hunan Province, especially among patients who started treatment during 2011 to 2013, with evidence of improved treatment outcomes in 2014. Resistance to ofloxacin was an independent predictor of poor treatment outcomes.

Project description:BackgroundMoxifloxacin is currently recommended at a dose of 7.5-10 mg/kg for children with multidrug-resistant (MDR) tuberculosis, but pharmacokinetic and long-term safety data of moxifloxacin in children with tuberculosis are lacking. An area under the curve (AUC) of 40-60 µg × h/mL following an oral moxifloxacin dose of 400 mg has been reported in adults.MethodsIn a prospective pharmacokinetic and safety study, children 7-15 years of age routinely receiving moxifloxacin 10 mg/kg daily as part of multidrug treatment for MDR tuberculosis in Cape Town, South Africa, for at least 2 weeks, underwent intensive pharmacokinetic sampling (predose and 1, 2, 4, 8, and either 6 or 11 hours) and were followed for safety. Assays were performed using liquid chromatography-tandem mass spectrometry, and pharmacokinetic measures calculated using noncompartmental analysis.ResultsTwenty-three children were included (median age, 11.1 years; interquartile range [IQR], 9.2-12.0 years); 6 of 23 (26.1%) were human immunodeficiency virus (HIV)-infected. The median maximum serum concentration (Cmax), area under the curve from 0-8 hours (AUC0-8), time until Cmax (Tmax), and half-life for moxifloxacin were 3.08 (IQR, 2.85-3.82) µg/mL, 17.24 (IQR, 14.47-21.99) µg × h/mL, 2.0 (IQR, 1.0-8.0) h, and 4.14 (IQR, 3.45-6.11), respectively. Three children, all HIV-infected, were underweight for age. AUC0-8 was reduced by 6.85 µg × h/mL (95% confidence interval, -11.15 to -2.56) in HIV-infected children. Tmax was shorter with crushed vs whole tablets (P = .047). Except in 1 child with hepatotoxicity, all adverse effects were mild and nonpersistent. Mean corrected QT interval was 403 (standard deviation, 30) ms, and no prolongation >450 ms occurred.ConclusionsChildren 7-15 years of age receiving moxifloxacin 10 mg/kg/day as part of MDR tuberculosis treatment have low serum concentrations compared with adults receiving 400 mg moxifloxacin daily. Higher moxifloxacin dosages may be required in children. Moxifloxacin was well tolerated in children treated for MDR tuberculosis.

Project description:ImportanceThe management of multidrug-resistant tuberculosis (MDR-TB) during pregnancy is challenging, yet no systematic synthesis of evidence has accurately measured treatment outcomes.ObjectiveTo systematically synthesize treatment outcomes and adverse events among pregnant patients with MDR-TB.Data sourcesPubMed, Scopus, Web of Science, and ProQuest were searched from the inception of each database through August 31, 2021.Study selectionStudies containing cohorts of pregnant patients with a defined treatment outcome were eligible.Data extraction and synthesisIndependent reviewers screened studies and assessed the risk of bias. The study followed the Preferring Reporting Items for Systematic Review and Meta-analyses reporting guideline. Meta-analysis was performed using random-effects models. The sources of heterogeneity were explored through metaregression.Main outcomes and measuresThe primary outcome was the proportion of patients with each treatment outcome (including treatment success, death, loss to follow-up, and treatment failure), and the secondary outcomes included the proportion of patients experiencing adverse events during pregnancy.ResultsIn this systematic review and meta-analysis, 10 studies containing 275 pregnant patients with available data on treatment outcomes were included. The pooled estimate was 72.5% (95% CI, 63.3%-81.0%) for treatment success, 6.8% (95% CI, 2.6%-12.4%) for death, 18.4% (95% CI, 13.1%-24.2%) for loss to follow-up, and 0.6% (95% CI, 0.0%-2.9%) for treatment failure. Treatment success was significantly higher in studies in which the proportion of patients taking linezolid was greater than the median (20.1%) compared with studies in which this proportion was lower than the median (odds ratio, 1.22; 95% CI, 1.05-1.42). More than half of the pregnant patients (54.7%; 95% CI, 43.5%-65.4%) experienced at least 1 type of adverse event, most commonly liver function impairment (30.4%; 95% CI, 17.7%-45.7%), kidney function impairment (14.9%; 95% CI, 6.2%-28.3%), hypokalemia (11.9%; 95% CI, 3.9%-25.6%), hearing loss (11.8%; 95% CI, 5.5%-21.3%), gastrointestinal disorders (11.8%; 95% CI, 5.2%-21.8%), psychiatric disorders (9.1%; 95% CI, 2.5%-21.6%), or anemia (8.9%; 95% CI, 3.6%-17.4%). The pooled proportion of favorable pregnancy outcomes was 73.2% (95% CI, 49.4%-92.1%). The most common types of adverse pregnancy outcomes were preterm birth (9.5%; 95% CI, 0.0%-29.0%), pregnancy loss (6.0%; 95% CI, 1.3%-12.9%), low birth weight (3.9%; 95% CI, 0.0%-18.7%), and stillbirth (1.9%; 95% CI, 0.1%-5.1%). Most of the studies had low-quality (3 studies) or medium-quality (4 studies) scores.Conclusions and relevanceIn this systematic review and meta-analysis, high treatment success and favorable pregnancy outcomes were reported among pregnant patients with MDR-TB. Further research is needed to design shorter, more effective, and safer treatment regimens for pregnant patients with MDR-TB.

Dataset Information

Moxifloxacin Improves Treatment Outcomes in Patients with Ofloxacin-Resistant Multidrug-Resistant Tuberculosis.

Publications

Moxifloxacin Improves Treatment Outcomes in Patients with Ofloxacin-Resistant Multidrug-Resistant Tuberculosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets