9-12 months short treatment for patients with MDR-TB increases treatment success in Kyrgyzstan

Introduction: MDR/RR-TB is a growing problem in Kyrgyzstan. In 2005, the country introduced standard or individualized treatment for 20-24 months. Because of poor treatment outcomes, in 2017 a short treatment with strict eligibility criteria was introduced. The aim of this study was to compare characteristics and treatment outcomes of MDR/RR-TB patients receiving short (9-12 months) treatment in 2017 with those receiving standard or individualized (20-24 months) treatment in 2016/2017. Methodology: A comparative cohort study using routine programmatic data. Characteristics, sputum culture conversion and treatment outcomes were compared between those on short treatment with those on standard/individualized treatment using the chi-square test, crude and adjusted risk ratios (RR and aRR). Results: The study included 274, 82 and 132 patients on standard, individualized and short treatment, respectively. There were more females, fewer migrants/homeless and unemployed and more new TB patients on short treatment compared with the other two groups. A favorable outcome (cure and treatment completed) was significantly higher in short treatment patients (83%) compared with those on standard (50%) or individualized (59%) treatment (p < 0.001). There was higher 1-month sputum culture conversion with short treatment (35%) compared with the other two groups (19% and 24%, p < 0.05). Short treatment (aRR 1.6, 1.4-1.8), female gender (aRR 1.2, 1.1-1.4), not being homeless (aRR 12.9, 4.5-17.3) and having new TB (aRR 1.3, 1.0-1.5) were independently associated with a favorable outcome. Conclusions: The treatment success was higher in selected MDR-TB patients given short treatment in Kyrgyzstan: this regimen should be scaled-up to all MDR-TB patients.

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Treatment success using novel and adapted treatment regimens in registered DR-TB children in Dushanbe, Tajikistan, 2013-2019

The Journal of Infection in Developing Countries ◽

10.3855/jidc.14798 ◽

2021 ◽

Vol 15 (09.1) ◽

pp. 7S-16S

Author(s):

Bobojon Pirmahmadzoda ◽

Katrina Hann ◽

Kristina Akopyan ◽

Ruzanna Grigoryan ◽

Evgenia Geliukh ◽

...

Keyword(s):

Treatment Outcomes ◽

Treatment Success ◽

Short Treatment ◽

Female Ratio ◽

Treatment Regimens ◽

Tb Treatment ◽

National Tuberculosis ◽

Mdr Tb ◽

Pediatric Tb ◽

Culture Conversion

Introduction: Approximately 3% of all pediatric TB cases develop MDR-TB, with only 3–4% of such children receiving MDR-TB treatment. In Tajikistan, children as a proportion of all DR-TB in the country increased from 4.3 to 7.5% during 2013-2018. Despite limited evidence on the use of new anti-TB drugs in children, WHO has updated its guidelines for DR-TB treatment for children, and Tajikistan did so in 2013 and 2017. Novel and adapted regimens included individual regimens for RR/MDR, XDR (with and without Bedaquiline and Delamanid) and short treatment regimens with and without injectables. It is important to document the outcomes of the treatment regimens. Therefore, the aim of this study was to describe characteristics of children receiving different treatment regimens for DR-TB, the culture conversion and treatment outcomes. Methodology: Cohort study of children enrolled in DR-TB treatment by the National Tuberculosis Program in Dushanbe, Tajikistan, January 2013 to July 2019. Results: The study included 60 DR-TB children. The male to female ratio was 1:2 and mean age 13.6 years. Median time to culture conversion was 66 days [IQR:31-103; Range:2-232]. In children with treatment outcomes (N = 58), 93% had favorable outcomes. There were four children (7%) with unfavorable treatment outcomes, all of whom were female 15-17 years, on standard (RR/MDR) treatment during 2013-2015. Favorable outcomes by DR-TB type were 91%, 90%, and 100% in RR/MDR, PreXDR, and XDR-TB patients, respectively. Conclusions: All children enrolled after the introduction of modified guidelines for novel and adapted regimens for DR-TB showed positive TB treatment outcomes.

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Time to Sputum Culture Conversion and Treatment Outcomes Among Patients with Isoniazid-Resistant Tuberculosis in Atlanta, Georgia

Clinical Infectious Diseases ◽

10.1093/cid/cix686 ◽

2017 ◽

Vol 65 (11) ◽

pp. 1862-1871 ◽

Cited By ~ 6

Author(s):

Marcos C Schechter ◽

Destani Bizune ◽

Michelle Kagei ◽

Mamuka Machaidze ◽

David P Holland ◽

...

Keyword(s):

Treatment Outcomes ◽

Sputum Culture ◽

Sputum Culture Conversion ◽

Resistant Tuberculosis ◽

Culture Conversion

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Genotypic Resistance of Pyrazinamide but Not Minimum Inhibitory Concentration Is Associated With Longer Time to Sputum Culture Conversion in Patients With Multidrug-resistant Tuberculosis

Clinical Infectious Diseases ◽

10.1093/cid/ciaa1509 ◽

2020 ◽

Author(s):

Johanna Kuhlin ◽

Lina Davies Forsman ◽

Mikael Mansjö ◽

Michaela Jonsson Nordvall ◽

Maria Wijkander ◽

...

Keyword(s):

Treatment Outcome ◽

Minimum Inhibitory Concentration ◽

Inhibitory Concentration ◽

Multidrug Resistant ◽

Sputum Culture ◽

Sputum Culture Conversion ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb ◽

Culture Conversion

Abstract Background Pyrazinamide (PZA) resistance in multidrug-resistant tuberculosis (MDR-TB) is common; yet, it is not clear how it affects interim and treatment outcomes. Although rarely performed, phenotypic drug susceptibility testing (pDST) is used to define PZA resistance, but genotypic DST (gDST) and minimum inhibitory concentration (MIC) could be beneficial. We aimed to assess the impact of PZA gDST and MIC on time to sputum culture conversion (SCC) and treatment outcome in patients with MDR-TB. Methods Clinical, microbiological, and treatment data were collected in this cohort study for all patients diagnosed with MDR-TB in Sweden from 1992–2014. MIC, pDST, and whole-genome sequencing of the pncA, rpsA, and panD genes were used to define PZA resistance. A Cox regression model was used for statistical analyses. Results Of 157 patients with MDR-TB, 56.1% (n = 88) had PZA-resistant strains and 49.7% (n = 78) were treated with PZA. In crude and adjusted analysis (hazard ratio [HR], 0.49; 95% conficence interval [CI], .29-.82; P = .007), PZA gDST resistance was associated with a 29-day longer time to SCC. A 2-fold decrease in dilutions of PZA MIC for PZA-susceptible strains showed no association with SCC in crude or adjusted analyses (HR, 0.98; 95% CI, .73–1.31; P = .89). MIC and gDST for PZA were not associated with treatment outcome. Conclusions In patients with MDR-TB, gDST PZA resistance was associated with a longer time to SCC. Rapid PZA gDST is important to identify patients who may benefit from PZA treatment.

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Impact of smoking on sputum culture conversion and pulmonary tuberculosis treatment outcomes in Brazil: a retrospective cohort study

Jornal Brasileiro de Pneumologia ◽

10.1590/s1806-37562017000000161 ◽

2018 ◽

Vol 44 (2) ◽

pp. 99-105 ◽

Cited By ~ 3

Author(s):

Michelle Cailleaux-Cezar ◽

Carla Loredo ◽

José Roberto Lapa e Silva ◽

Marcus Barreto Conde

Keyword(s):

Cohort Study ◽

Relative Risk ◽

Pulmonary Tuberculosis ◽

Treatment Outcomes ◽

Retrospective Cohort ◽

Sputum Culture ◽

Sputum Culture Conversion ◽

Poor Treatment ◽

Never Smokers ◽

Culture Conversion

ABSTRACT Objective: To evaluate the impact of smoking on pulmonary tuberculosis (PTB) treatment outcomes and the two-month conversion rates for Mycobacterium tuberculosis sputum cultures among patients with culture-confirmed PTB in an area with a moderate incidence of tuberculosis in Brazil. Methods: This was a retrospective cohort study of PTB patients diagnosed and treated at the Thoracic Diseases Institute of the Federal University of Rio de Janeiro between 2004 and 2012. Results: Of the 298 patients diagnosed with PTB during the study period, 174 were included in the outcome analysis: 97 (55.7%) were never-smokers, 31 (17.8%) were former smokers, and 46 (26.5%) were current smokers. Smoking was associated with a delay in sputum culture conversion at the end of the second month of TB treatment (relative risk = 3.58 &091;95% CI: 1.3-9.86&093;; p = 0.01), as well as with poor treatment outcomes (relative risk = 6.29 &091;95% CI: 1.57-25.21&093;; p = 0.009). The association between smoking and a positive culture in the second month of treatment was statistically significant among the current smokers (p = 0.027). Conclusions: In our sample, the probability of a delay in sputum culture conversion was higher in current smokers than in never-smokers, as was the probability of a poor treatment outcome.

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Treatment Outcome of a Shorter Regimen Containing Clofazimine for Multidrug-resistant Tuberculosis: A Randomized Control Trial in China

Clinical Infectious Diseases ◽

10.1093/cid/ciz915 ◽

2019 ◽

Vol 71 (4) ◽

pp. 1047-1054 ◽

Cited By ~ 1

Author(s):

Yadong Du ◽

Chao Qiu ◽

Xiaohong Chen ◽

Jing Wang ◽

Wei Jing ◽

...

Keyword(s):

Multidrug Resistant ◽

Sputum Culture ◽

Control Group ◽

Sputum Culture Conversion ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Significant Difference ◽

Mdr Tb ◽

Experimental Group ◽

Culture Conversion

Abstract Background The emergence of multidrug-resistant tuberculosis (MDR-TB) poses a serious obstacle to global TB control programs. Methods We carried out a prospective, randomized, multicenter study in China that was focused on the potential of a shorter regimen containing clofazimine (CFZ) for the treatment of MDR-TB. There were 135 MDR-TB cases that met eligibility requirements and were randomly stratified into either the control group or experimental group. Patients in the control group received an 18-month treatment regimen, whereas patients in the experimental group received a 12-month treatment regimen containing CFZ. Results At the completion of the treatment period, the difference in sputum-culture conversion rates between the experimental group and the control group was not significant. Notably, by the end of 3 months of treatment, 68.7% patients receiving the experimental regimen had sputum-culture conversion, as compared with 55.9% of those receiving the control regimen; this was a significant difference, suggesting an early sputum conversion (P = .04). There were 67 adverse events reported in 56 patients in this study, including 32 in the control group and 35 in the experimental group. No significant difference in the overall incidences of adverse events was observed between the 2 groups. Conclusions The MDR-TB patients treated with the shorter regimen containing CFZ had a comparable successful outcome rate when compared to those with the standard regimen. The patients assigned to the experimental group achieved more rapid sputum-culture conversion, reflecting superior antimicrobial activity against MDR-TB. Clinical Trials Registration Chinese Clinical Trial Registry ChiCTR 1800020391.

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Artificial Intelligence and Amikacin Exposures Predictive of Outcomes in Multidrug-Resistant Tuberculosis Patients

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00962-16 ◽

2016 ◽

Vol 60 (10) ◽

pp. 5928-5932 ◽

Cited By ~ 25

Author(s):

Chawangwa Modongo ◽

Jotam G. Pasipanodya ◽

Beki T. Magazi ◽

Shashikant Srivastava ◽

Nicola M. Zetola ◽

...

Keyword(s):

Characteristic Curve ◽

Multidrug Resistant ◽

Sputum Culture ◽

Classification And Regression Tree ◽

Fiber System ◽

Sputum Culture Conversion ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb ◽

Culture Conversion

ABSTRACTAminoglycosides such as amikacin continue to be part of the backbone of treatment of multidrug-resistant tuberculosis (MDR-TB). We measured amikacin concentrations in 28 MDR-TB patients in Botswana receiving amikacin therapy together with oral levofloxacin, ethionamide, cycloserine, and pyrazinamide and calculated areas under the concentration-time curves from 0 to 24 h (AUC0–24). The patients were followed monthly for sputum culture conversion based on liquid cultures. The median duration of amikacin therapy was 184 (range, 28 to 866) days, at a median dose of 17.30 (range 11.11 to 19.23) mg/kg. Only 11 (39%) patients had sputum culture conversion during treatment; the rest failed. We utilized classification and regression tree analyses (CART) to examine all potential predictors of failure, including clinical and demographic features, comorbidities, and amikacin peak concentrations (Cmax), AUC0–24, and trough concentrations. The primary node for failure had two competing variables,Cmaxof <67 mg/liter and AUC0–24of <568.30 mg · h/L; weight of >41 kg was a secondary node with a score of 35% relative to the primary node. The area under the receiver operating characteristic curve for the CART model was an R2= 0.90 on posttest. In patients weighing >41 kg, sputum conversion was 3/3 (100%) in those with an amikacinCmaxof ≥67 mg/liter versus 3/15 (20%) in those with aCmaxof <67 mg/liter (relative risk [RR] = 5.00; 95% confidence interval [CI], 1.82 to 13.76). In all patients who had both amikacinCmaxand AUC0–24below the threshold, 7/7 (100%) failed, compared to 7/15 (47%) of those who had these parameters above threshold (RR = 2.14; 95% CI, 1.25 to 43.68). These amikacin dose-schedule patterns and exposures are virtually the same as those identified in the hollow-fiber system model.

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Polymorphisms in the vitamin D receptor gene are associated with reduced rate of sputum culture conversion in multidrug-resistant tuberculosis patients in South Africa

10.1101/132852 ◽

2017 ◽

Author(s):

Matthew J Magee ◽

Yan V. Sun ◽

James CM Brust ◽

N. Sarita Shah ◽

Yuming Ning ◽

...

Keyword(s):

South Africa ◽

Vitamin D ◽

Multidrug Resistant ◽

Sputum Culture ◽

Vdr Gene ◽

Sputum Culture Conversion ◽

Tb Treatment ◽

Genomic Analyses ◽

Mdr Tb ◽

Culture Conversion

AbstractBackgroundVitamin D modulates the inflammatory and immune response to tuberculosis (TB) and also mediates the induction of the antimicrobial peptide cathelicidin. Deficiency of 25-hydroxyvitamin D and single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene may increase the risk of TB disease and decrease culture conversion rates in drug susceptible TB. Whether these VDR SNPs are found in African populations or impact multidrug-resistant (MDR) TB treatment has not been established. We aimed to determine if SNPs in the VDR gene were associated with sputum culture conversion among a cohort of MDR TB patients in South Africa.MethodsWe conducted a prospective cohort study of adult MDR TB patients receiving second-line TB treatment in KwaZulu-Natal province. Subjects had monthly sputum cultures performed. In a subset of participants, whole blood samples were obtained for genomic analyses. Genomic DNA was extracted and genotyped with Affymetrix Axiom Pan-African Array. Cox proportional models were used to determine the association between VDR SNPs and rate of culture conversion.ResultsGenomic analyses were performed on 91 MDR TB subjects enrolled in the sub-study; 60% were female and median age was 35 years (interquartile range [IQR] 29-42). Smoking was reported by 21% of subjects and most subjects had HIV (80%), were smear negative (57%), and had cavitary disease (55%). Overall, 87 (96%) subjects initially converted cultures to negative, with median time to culture conversion of 57 days (IQR 17-114). Of 121 VDR SNPs examined, 10 were significantly associated (p<0.01) with rate of sputum conversion in multivariable analyses. Each additional risk allele on SNP rs74085240 delayed culture conversion significantly (adjusted hazard ratio 0.30, 95% confidence interval 0.14-0.67).ConclusionsPolymorphisms in the VDR gene were associated with rate of sputum culture conversion in MDR TB patients in this high HIV prevalence setting in South Africa.Author contributionsMJM, YVS, JCMB, SS, and NRG conceived and designed the study and drafted the initial manuscript. MJM, YVS, YN, and QH performed the data analyses. All authors contributed to interpretation of the data, revised the manuscript, and approved the final version.The findings and conclusions in this article are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention (CDC). The use of trade names and commercial sources is for identification only and does not imply endorsement by the CDC.

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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.

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Clinical Outcomes among Patients with Drug-resistant Tuberculosis receiving Bedaquiline or Delamanid Containing Regimens

Clinical Infectious Diseases ◽

10.1093/cid/ciz1107 ◽

2019 ◽

Cited By ~ 3

Author(s):

R R Kempker ◽

L Mikiashvili ◽

Y Zhao ◽

D Benkeser ◽

K Barbakadze ◽

...

Keyword(s):

Drug Resistance ◽

Clinical Outcomes ◽

Previous Treatment ◽

Sputum Culture ◽

Acquired Drug Resistance ◽

Sputum Culture Conversion ◽

Resistant Tuberculosis ◽

Conversion Rates ◽

Mdr Tb ◽

Culture Conversion

Abstract Background Bedaquiline and delamanid are newly available drugs for treating multidrug-resistant tuberculosis (MDR TB); however, there is limited data guiding their use and no comparison studies. Methods We conducted a prospective observational study among patients with MDR TB in Georgia receiving a bedaquiline or delamanid-based treatment regimen. Monthly sputum cultures, minimal inhibitory concentration testing, and adverse event monitoring were performed. Primary outcomes were culture conversion rates and clinical outcomes. Targeted maximum likelihood estimation (TMLE) and superlearning were utilized to produce a covariate-adjusted proportion of outcomes for each regimen. Results Among 156 patients with MDR TB, 100 were enrolled and 95 were receiving a bedaquiline (n=64) or delamanid (n=31) based regimen. Most were male (82%) and the median age was 38 years. Rates of previous treatment (56%) and cavitary disease (61%) were high. The most common companion drugs included linezolid, clofazimine, cycloserine and a fluoroquinolone. Median effective drugs received among patients on bedaquiline (4, IQR 4-4) and delamanid (4, IQR 3.5-5) based regimens were similar. Rates of acquired drug resistance were significantly higher among patients receiving delamanid versus bedaquiline (36% vs. 10%, p <0.01). Adjusted rates of sputum culture conversion at two months (67 vs. 47%, p=0.10) and six months (95 vs. 74%, p<0.01) and favorable clinical outcomes (96 vs. 72%, p<0.01) were higher among patients receiving bedaquiline versus delamanid. Conclusions Among patients with MDR TB, bedaquiline-based regimens were associated with higher rates of sputum culture conversion and favorable outcomes and a lower rate of acquired drug resistance versus delamanid-based regimens.

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Malnutrition is Associated with Delayed Sputum Culture Conversion Among Patients Treated for MDR-TB

Infection and Drug Resistance ◽

10.2147/idr.s293461 ◽

2021 ◽

Vol Volume 14 ◽

pp. 1659-1667

Author(s):

Asnake Balche Bade ◽

Teshale Ayele Mega ◽

Getandale Zeleke Negera

Keyword(s):

Sputum Culture ◽

Sputum Culture Conversion ◽

Mdr Tb ◽

Culture Conversion

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