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

ABSTRACTIt 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 thegyrAgene 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.

Download Full-text

Treatment outcomes in multidrug-resistant tuberculosis according to pyrazinamide susceptibility

The International Journal of Tuberculosis and Lung Disease ◽

10.5588/ijtld.19.0314 ◽

2020 ◽

Vol 24 (2) ◽

pp. 233-239

Author(s):

S. Park ◽

K-W. Jo ◽

T. S. Shim

Keyword(s):

Success Rate ◽

Treatment Outcomes ◽

Treatment Success ◽

Multidrug Resistant ◽

Treatment Success Rate ◽

Aminosalicylic Acid ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb ◽

Effective Drugs

BACKGROUND: Pyrazinamide (PZA) is an important anti-tuberculosis drug for multidrug-resistant tuberculosis (MDR-TB). However, PZA has recently been demoted within the hierarchy of TB drugs used for MDR-TB.METHODS: We conducted a retrospective cohort study to investigate treatment outcomes for simple MDR-TB (susceptible to both second-line injectable drugs and fluoroquinolones) according to PZA susceptibility.RESULTS: Among 216 pulmonary MDR-TB patients included in the study, 68 (31.5%) were PZA-resistant (PZA-R). The mean age was 41.8 years, and 63.4% were male. Baseline characteristics such as comorbidity, previous TB history, acid-fast bacilli (AFB) smear positivity and cavitation were similar in PZA-susceptible (PZA-S) and PZA-R patients. The number of potentially effective drugs was slightly higher among PZA-S patients than among the PZA-R (5.1 vs. 4.8, respectively; P = 0.003). PZA was more frequently used in PZA-S patients (73.0%) than in the PZA-R (14.7%), while para-aminosalicylic acid was more frequently used in PZA-R than in PZA-S patients (76.5% vs. 50.7%). The treatment success rate was similar in PZA-S (77.7%) and PZA-R (75.0%) patients. PZA resistance was not associated with treatment success in multivariate analysis.CONCLUSIONS: PZA-resistant simple MDR-TB patients had the same treatment success rate as the PZA-susceptible group even without using novel anti-TB drugs.

Download Full-text

Prevalence and Factors Associated with Multidrug-Resistant Tuberculosis (MDR-TB) among Presumptive MDR-TB Patients in Tigray Region, Northern Ethiopia

Canadian Journal of Infectious Diseases and Medical Microbiology ◽

10.1155/2019/2923549 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

Kibriti Mehari ◽

Tsehaye Asmelash ◽

Haftamu Hailekiros ◽

Tewolde Wubayehu ◽

Hagos Godefay ◽

...

Keyword(s):

Odds Ratio ◽

Multidrug Resistant ◽

Sputum Smear ◽

Northern Ethiopia ◽

Crude Odds Ratio ◽

Factors Associated ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Regional State ◽

Mdr Tb

Background. Tuberculosis (TB) is one of the major public health problems. There are alarming reports of increasing multidrug-resistant tuberculosis (MTR-TB) from various parts of the globe, including Ethiopia. This study was designed to determine the prevalence and factors associated with MDR-TB among presumptive MDR-TB cases in Tigray Regional State, Ethiopia. Methods. A cross-sectional study was conducted in Tigray Regional State from 2015 to 2016. Two hundred sputum samples were collected, transported, processed using 2% N-acetyl-L-cysteine-sodium hydroxide, and cultured in LJ medium. Besides, the microscopic examination was performed after ZN staining. Moreover, drug susceptibility test was done using molecular line probe assay. Descriptive statistics and binary and multivariable logistic regression were done. A statistical test was regarded as significant when the P value was <0.05. Results. The prevalence of MDR-TB was found to be 18.5%. About one-fourth (26.5%) of the study participants had sputum smear positive for acid-fast bacilli (AFB). TB culture was positive in 37% of the samples, and rifampicin mono-resistant cases accounted for 3.5% of the presumptive MDR-TB cases. Three (1.5%) were new MDR-TB cases, while the rest had been treated previously for TB. Most (63.5%) of the MDR-TB cases were from 15 to 44 years of age. Age was associated with MDR-TB with a crude odds ratio of 1.06 (CI: 1.02–1.10) and adjusted odds ratio of 1.06 (CI: 1.00–1.11). Conclusions. The prevalence of MDR-TB was found to be high. Preventive measures should be taken to prevent the transmission of MDR-TB in the community.

Download Full-text

Epidemiology of drug-resistant tuberculosis in Chongqing, China: a retrospective observational study from 2010 to 2017

10.1101/610048 ◽

2019 ◽

Author(s):

Bo Wu ◽

Ya Yu ◽

Changting Du ◽

Ying Liu ◽

Daiyu Hu

Keyword(s):

Observational Study ◽

Treatment Success ◽

Multidrug Resistant ◽

Policy Support ◽

Retrospective Observational Study ◽

Drug Resistant ◽

Notification Rate ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb

AbstractChina is one of the top 30 countries with high multidrug-resistant tuberculosis (MDR-TB) and rifampin-resistant tuberculosis (RR-TB) burden. Chongqing is a southwest city of China with a large rural population. A retrospective observational study has been performed based on routine tuberculosis (TB) surveillance data in Chongqing from 2010 to 2017. The MDR/RR-TB notification rate increased from 0.03 cases per 100,000 population in 2010 to 2.09 cases per 100,000 population in 2017. The extensively drug-resistant TB (XDR-TB) notification rate has increased to 0.09 cases per 100,000 population in 2017. There was a decreasing detection gap between the number of notified MDR/RR-TB cases and the estimate number of MDR/RR-TB cases among all notified TB cases. The treatment success rate of MDR/RR-TB was 50.66% in this period. The rate of MDR/RR-TB in new TB cases was 6.23%, and this rate in previously treated TB cases was 32.7%. Despite the progress achieved, the prevalence of MDR/RR-TB was still high facing challenges including detection gaps, the regional disparity, and the high risk for MDR/RR-TB in elderly people and farmers. Sustained government financing and policy support should be guaranteed in the future.

Download Full-text

Effectiveness of Shorter Treatment Regimen in Multidrug-Resistant Tuberculosis Patients in Pakistan: A Multicenter Retrospective Record Review

American Journal of Tropical Medicine and Hygiene ◽

10.4269/ajtmh.20-1134 ◽

2021 ◽

Author(s):

Abudl Wahid ◽

Nafees Ahmad ◽

Abdul Ghafoor ◽

Abdullah Latif ◽

Fahad Saleem ◽

...

Keyword(s):

Treatment Failure ◽

Success Rate ◽

Treatment Success ◽

Multidrug Resistant ◽

Retrospective Record Review ◽

Tb Treatment ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb ◽

Record Review

In Pakistan, the treatment of multidrug-resistant tuberculosis (MDR-TB) with a shorter treatment regimen (STR), that is, 4–6 months of amikacin, moxifloxacin (Mfx), ethionamide, clofazimine (Cfz), pyrazinamide (Z), ethambutol (E), and high-dose isoniazid, followed by 5 months of Mfx, Cfz, Z, and E, was initiated in 2018. However, there is a lack of information about its effectiveness in Pakistani healthcare settings. Therefore, this retrospective record review of MDR-TB patients treated with STR at eight treatment sites in Pakistan aimed to fill this gap. Data were analyzed using SPSS 23. Multivariate binary logistic regression (MVBLR) analysis was conducted to find factors associated with death and treatment failure, and lost to follow-up (LTFU). A P-value < 0.05 was considered statistically significant. Of 912 MDR-TB patients enrolled at the study sites, only 313 (34.3%) eligible patients were treated with STR and included in the current study. Of them, a total of 250 (79.9%) were cured, 12 (3.8%) completed treated, 31 (9.9%) died, 16 (5.1%) were LTFU, and four (1.3%) were declared as treatment failures. The overall treatment success rate was 83.7%. In MVBLR analysis, patients’ age of 41–60 (odds ratio [OR] = 4.9, P-value = 0.020) and > 60 years (OR = 3.6, P-value = 0.035), being underweight (OR = 2.7, P-value = 0.042), and previous TB treatment (OR = 0.4, P-value = 0.042) had statistically significant association with death and treatment failure, whereas patients’ age of > 60 years (OR = 5.4, P-value = 0.040) and previous TB treatment (OR = 0.2, P-value = 0.008) had statistically significant association with LTFU. The treatment success rate of STR was encouraging. However, to further improve the treatment outcomes, special attention should be paid to the patients with identified risk factors.

Download Full-text

Survival of patients with multidrug-resistant tuberculosis in Central China: a retrospective cohort study

Epidemiology and Infection ◽

10.1017/s0950268820000485 ◽

2020 ◽

Vol 148 ◽

Author(s):

Jianjie Wang ◽

Meilan Zhou ◽

Zi Chen ◽

Cong Chen ◽

Gang Wu ◽

...

Keyword(s):

Risk Factors ◽

Regression Analysis ◽

Patient Survival ◽

Multidrug Resistant ◽

Central China ◽

Risk Of Death ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb

Abstract The aim of this study was to evaluate long-term survival and risk factors associated with multidrug-resistant tuberculosis (MDR-TB) patient survival in Central China. Between December 2006 and June 2011, incident and retreatment adult MDR-TB patients were enrolled in the present study. Cox proportional hazard regression analysis was used to evaluate the risk factors affecting survival. The total follow-up period was 270 person-years (PY) for 356 MDR-TB cases in Wuhan. Of the 356 cases, 103 patients died, yielding an average case fatality rate of 381.2 per 1000 TB patients per year. Using adjusted Cox regression analysis, older age (adjusted hazard ratio (aHR) >3.0 starting from 30 years) and low education level (primary and middle school; aHR 1.67 (95% CI 1.01–2.77)) were independently associated with lower survival. Diabetes mellitus profoundly affected the survival of MDR-TB patients (aHR 1.95 (95% CI 1.30–2.93)). Our data demonstrate that coexistent diabetes significantly and negatively impacted MDR-TB patient survival. In addition, MDR-TB patients aged 60 years or older exhibited a greater risk of mortality during follow-up. Our findings emphasise that MDR-TB patients with comorbidities that increase their risk of death require additional medical interventions to reduce mortality.

Download Full-text

Adverse treatment outcomes in multidrug resistant tuberculosis go beyond the microbe-drug interaction: Results of a multiple correspondence analysis.

Biomédica ◽

10.7705/biomedica.5072 ◽

2020 ◽

Vol 40 (4) ◽

pp. 616-625

Author(s):

Ángela Tobón ◽

Johana Rueda ◽

Diego H. Cáceres ◽

Gloria I. Mejía ◽

Elsa M. Zapata ◽

...

Keyword(s):

Treatment Outcomes ◽

Treatment Success ◽

Multidrug Resistant ◽

Chronic Obstructive ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb ◽

Poor Outcomes ◽

Lost To Follow Up

Introduction: Multidrug-resistant tuberculosis treatment is effective in 50% of patients due to several factors including antibiotic susceptibility of the microorganism, adverse treatment reactions, social factors, and associated comorbidities.Objectives: In this study, we describe the demographics, clinical characteristics, and factors associated with treatment outcomes in multidrug-resistant tuberculosis (MDR-TB) patients in Medellín, Colombia.Materials and methods: We conducted a retrospective analysis using data from patients diagnosed with MDR-TB attending Hospital La María in Medellín, Colombia, for treatment between 2010 and 2015. Patients were categorized as having successful (cured) or poor (failure, lost to follow-up, and death) treatment outcomes. Associations between demographic, clinical factors, laboratory results, treatment outcomes, and follow-up information were evaluated by univariate, multivariate, and multiple correspondence analyses.Results: Of the 128 patients with MDR-TB, 77 (60%) had successful outcomes. Of those with poor outcomes, 26 were lost to follow-up, 15 died, and 10 were treatment failures. Irregular treatment, the presence of comorbidities, and positive cultures after more than two months of treatment were associated with poor outcomes compared to successful ones (p<0.05 for all). The multiple correspondence analyses grouped patients who were lost to follow-up, had HIV, and drug addiction, as well as patients with treatment failure, irregular treatment, and chronic obstructive pulmonary disease.Conclusion: The recognition of factors affecting treatment is essential and was associated with treatment outcomes in this series of patients. Early identification of these factors should increase the rates of treatment success and contribute to MDR-TB control.

Download Full-text

Effectiveness and Safety of Bedaquiline-containing Regimens for Treatment on Patients With Refractory Rifampicin/multidrug-resistant Tuberculosis: A Retrospective Cohort Study in East China

10.21203/rs.3.rs-833736/v1 ◽

2021 ◽

Author(s):

Shao-Jun Zhang ◽

Yan Yang ◽

Wen-Wen Sun ◽

Zhong-Shun Zhang ◽

He-ping Xiao ◽

...

Keyword(s):

Treatment Outcomes ◽

Treatment Success ◽

Multidrug Resistant ◽

East China ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Conversion Rates ◽

Mdr Tb ◽

Culture Conversion ◽

Closing Rate

Abstract Objective: To compare the effectiveness and safety of bedaquiline-containing and bedaquiline-free regimens for treatment of patients with refractory rifampicin-resistant/multidrug-resistant tuberculosis (RR/MDR-TB).Methods: Patients with refractory RR/MDR-TB receiving bedaquiline-containing regimens (bedaquiline group, n=102) and bedaquiline-free regimens (non-bedaquiline group, n=100) were included in this retrospective historical control study across East China. The culture conversion, end-of-treatment outcomes, cavity closing rate, and adverse events (AEs) were compared between the two groups. Univariate and multivariate analyses were performed to identify independent predictors of treatment success and culture reversion.Results: The baseline characteristics of the patients were well balanced between the two groups. The culture conversion rates in the bedaquiline group at month 3 (89.2% vs. 66.0%), month 6 (90.2% vs. 72.0%), month 9 (91.2% vs. 66.0%), and month 12 (94.1% vs. 65.0%) were all significantly higher than those in the non-bedaquiline group (all p<0.001). Similar results were observed in the cavity closing rate at month 9 (19.6% vs. 8.0%, p=0.017) and month 12 (39.2% vs. 15.0%, p<0.001). Patients receiving bedaquiline-containing regimens had more treatment success than those receiving bedaquiline-free regimens (p<0.001; cure rate, 69.6% vs. 45.0%; complete the treatment, 22.5% vs. 18.0%; treatment success, 92.2% vs. 63.0%). The use of bedaquiline was identified as an independent predictor of both treatment success (OR=7.356, 95% CI: 2.920–18.530, p<0.001) and culture reversion (OR=0.124, 95% CI: 0.035–0.452, p<0.001). AEs were similarly reported in 26.5% of patients in the bedaquiline group and 19.0% in the non-bedaquiline group (p=0.206).Conclusions: Bedaquiline-containing regimens resulted in better treatment outcomes and similar safety relative to bedaquiline-free regimens for patients with refractory pulmonary RR/MDR-TB.

Download Full-text

Group 5 drugs for multidrug-resistant tuberculosis: individual patient data meta-analysis

European Respiratory Journal ◽

10.1183/13993003.00993-2016 ◽

2016 ◽

Vol 49 (1) ◽

pp. 1600993 ◽

Cited By ~ 14

Author(s):

Greg J. Fox ◽

Andrea Benedetti ◽

Helen Cox ◽

Won-Jung Koh ◽

Piret Viiklepp ◽

...

Keyword(s):

Individual Patient Data ◽

Meta Analysis ◽

Treatment Success ◽

Multidrug Resistant ◽

Patient Data ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb ◽

Amoxicillin Clavulanic Acid ◽

Group 5

The role of so-called “group 5” second-line drugs as a part of antibiotic therapy for multidrug-resistant tuberculosis (MDR-TB) is widely debated. We performed an individual patient data meta-analysis to evaluate the effectiveness of several group 5 drugs including amoxicillin/clavulanic acid, thioacetazone, the macrolide antibiotics, linezolid, clofazimine and terizidone for treatment of patients with MDR-TB.Detailed individual patient data were obtained from 31 published cohort studies of MDR-TB therapy. Pooled treatment outcomes for each group 5 drug were calculated using a random effects meta-analysis. Primary analyses compared treatment success to a combined outcome of failure, relapse or death.Among 9282 included patients, 2191 received at least one group 5 drug. We found no improvement in treatment success among patients taking clofazimine, amoxicillin/clavulanic acid or macrolide antibiotics, despite applying a number of statistical approaches to control confounding. Thioacetazone was associated with increased treatment success (OR 2.6, 95% CI 1.1–6.1) when matched controls were selected from studies in which the group 5 drugs were not used at all, although this result was heavily influenced by a single study.The development of more effective antibiotics to treat drug-resistant TB remains an urgent priority.

Download Full-text

Multidrug-resistant tuberculosis around the world: what progress has been made?

European Respiratory Journal ◽

10.1183/09031936.00101814 ◽

2014 ◽

Vol 45 (1) ◽

pp. 150-160 ◽

Cited By ~ 68

Author(s):

Dennis Falzon ◽

Fuad Mirzayev ◽

Fraser Wares ◽

Inés Garcia Baena ◽

Matteo Zignol ◽

...

Keyword(s):

Treatment Success ◽

Multidrug Resistant ◽

Outcome Data ◽

Interquartile Range ◽

World Health ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Number Of Patients ◽

The World ◽

Mdr Tb

Multidrug-resistant tuberculosis (MDR-TB) (resistance to at least isoniazid and rifampicin) will influence the future of global TB control. 88% of estimated MDR-TB cases occur in middle- or high-income countries, and 60% occur in Brazil, China, India, the Russian Federation and South Africa.The World Health Organization collects country data annually to monitor the response to MDR-TB. Notification, treatment enrolment and outcome data were summarised for 30 countries, accounting for >90% of the estimated MDR-TB cases among notified TB cases worldwide.In 2012, a median of 14% (interquartile range 6–50%) of estimated MDR-TB cases were notified in the 30 countries studied. In 15 of the 30 countries, the number of patients treated for MDR-TB in 2012 (71 681) was >50% higher than in 2011. Median treatment success was 53% (interquartile range 40–70%) in the 25 countries reporting data for 30 021 MDR-TB cases who started treatment in 2010.Although progress has been noted in the expansion of MDR-TB care, urgent efforts are required in order to provide wider access to diagnosis and treatment in most countries with the highest burden of MDR-TB.

Download Full-text

Immunomodulatory agents combat multidrug-resistant tuberculosis by improving antimicrobial immunity

The Journal of Infectious Diseases ◽

10.1093/infdis/jiab100 ◽

2021 ◽

Author(s):

Jagadeeswara Rao Muvva ◽

Sultan Ahmed ◽

Rokeya Sultana Rekha ◽

Sadaf Kalsum ◽

Ramona Groenheit ◽

...

Keyword(s):

Treatment Options ◽

Treatment Success ◽

Treatment Strategies ◽

Multidrug Resistant ◽

Success Rates ◽

Immunomodulatory Agents ◽

Human Macrophages ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb

Abstract Background Multidrug-resistant tuberculosis (MDR-TB) has low treatment success rates and new treatment strategies are needed. We explored if treatment with vitamin D (vitD) and phenylbutyrate (PBA) could improve conventional chemotherapy by enhancing immune-mediated eradication of Mycobacterium tuberculosis. Methods A clinically relevant model was used consisting of human macrophages infected with M. tuberculosis-isolates (n=15) with different antibiotic-resistance profiles. The antimicrobial effect of vitD+PBA, was tested together with rifampicin or isoniazid. Methods included colony-forming units (intracellular bacterial growth), mRNA expression analyses (LL-37, β-defensin, nitric oxide synthase, and dual oxidase-2), RNA interference (LL-37-silencing in primary macrophages), western blot and confocal microscopy (LL-37 and LC3 protein expression). Results VitD+PBA inhibited growth of clinical MDR-TB strains in human macrophages and strengthened intracellular growth inhibition of rifampicin and isoniazid via induction of the antimicrobial peptide LL-37 and LC3-dependent autophagy. Gene-silencing of LL-37 expression enhanced MDR-TB growth in vitD+PBA-treated macrophages. The combination of vitD+PBA and isoniazid were equally effective to reduce intracellular MDR-TB growth as compared to a >125-fold higher dose of isoniazid alone, suggesting potent additive effects of vitD+PBA with isoniazid. Conclusions Immunomodulatory agents that trigger multiple immune pathways can strengthen standard MDR-TB treatment and contribute to next-generation individualized treatment options for difficult-to-treat pulmonary TB patients.

Download Full-text