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

2019 ◽  
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.

scholarly journals 1884. Clinical Outcomes Among Patients with Drug-Resistant Tuberculosis Receiving Bedaquiline or Delamanid Containing Regimens

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S52-S52
Author(s):  
Russell R Kempker ◽  
Lali Mikiashvili ◽  
Yuan Zhao ◽  
David Benkeser ◽  
Ketino Barbakadze ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Clinical Outcomes ◽  
Treatment Options ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Acquired Drug Resistance ◽  
Treatment Regimens ◽  
Resistant Tuberculosis ◽  
Conversion Rates ◽  
Culture Conversion

Abstract Background Bedaquiline and delamanid are new and much-needed treatment options for drug-resistant tuberculosis (TB); however, there are limited data guiding their use and no direct comparison of the two drugs. We thus sought to compare the clinical outcomes of patients with drug-resistant tuberculosis receiving either a bedaquiline- or delamanid-based treatment regimen. Methods This is a prospective observational study among patients with drug-resistant pulmonary TB in the country of Georgia from 2015 to 2017. Patients receiving bedaquiline or delamanid were eligible to be enrolled. Monthly sputum cultures and MIC testing on Mycobacterium tuberculosis isolates were performed. Clinical outcomes included time to culture conversion, rate of acquired drug resistance and treatment outcomes. Results Among 156 patients with MDR-TB who were approached, 100 were enrolled, and 95 were receiving a bedaquiline (n = 64) or delamanid (n = 31) based regimen and included in the study. Patients receiving bedaquiline or delamanid were similar with regards to age, BMI, substance use, comorbidities, rate of cavitary disease, and extensively drug-resistant (XDR) TB. Rates of additional Class A drug use including linezolid (78 vs. 81%) and a fluoroquinolone (39 vs. 36%) were similar and the mean effective drugs received per group was 4 (IQR 3–4, P = 0.33). Median drug duration was 171 days for bedaquiline and 182 days for delamanid; no patient discontinued due to QTC prolongation. Adjusted cumulative culture conversion rates at 60 days (64% vs. 48%, P = 0.14) and 180 days (95% vs. 77%, P = 0.02) were higher in patients receiving bedaquiline compared with delamanid (see figure). Rates of acquired drug resistance were higher in patients receiving delamanid compared with bedaquiline (35 vs. 12%, P < 0.01). Lastly, patients receiving a bedaquiline-based regimen had higher rates of favorable outcomes as compared with patients receiving delamanid (94% vs. 67%, P < 0.01). Conclusion Patients receiving bedaquiline- and delamanid-based treatment regimens for drug-resistant TB had similar characteristics and those receiving bedaquiline had better clinical outcomes. Our results provide an important first comparison of bedaquiline vs. delamanid containing regimens. Disclosures All Authors: No reported Disclosures.

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

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.

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

2019 ◽  
Vol 71 (4) ◽  
pp. 1047-1054 ◽  
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.

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

2016 ◽  
Vol 60 (10) ◽  
pp. 5928-5932 ◽  
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.

scholarly journals Predictors of time to sputum culture conversion in multi-drug-resistant tuberculosis and extensively drug-resistant tuberculosis in patients at Tshepong-Klerksdorp Hospital

2019 ◽  
Vol 34 (1) ◽  
Author(s):  
Relebohile Ncha ◽  
Ebrahim Variava ◽  
Kennedy Otwombe ◽  
Mary Kawonga ◽  
Neil A. Martinson
Keyword(s):  
Sputum Culture ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
North West ◽  
Sputum Culture Conversion ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Multi Drug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Culture Conversion

Setting: Klerksdorp-Tshepong Hospital Complex MDR-TB Unit, North-West Province, South Africa.Background: To determine the time to sputum culture conversion (TTSCC) and factors predictive of TTSCC in patients with multi-drug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) in the North-West Province.Methods: A retrospective cohort study, abstracting patient demographic and clinical data, laboratory results, dates of sputum testing and sputum culture conversion results, from medical records of 526 MDR-TB and 47 XDR-TB patients started on TB treatment between 01 January 2012 and 31 December 2014. Predictors of TTSCC were determined by Cox proportional hazards regression.Results: The median age was 38 years (interquartile range 31–47) with 64% being male. Overall, 79% (449) were Human Immunodeficiency Virus (HIV)-infected. The median TTSCC was 56.5 days and 162.5 days for MDR-TB and XDR-TB patients, respectively. In the multivariate analysis, age [hazard ratio (HR): 0.89, 95% confidence interval (CI): 0.96–0.99], being underweight (HR: 0.631.61, 95% CI: 0.451.03–0.882.51), Acid Fast Bacilli (AFB) positivity (HR: 0.72, 95% CI: 0.51–1.01) and having XDR-TB (HR: 0.36. 95% CI: 0.19–0.69) were predictive of longer TTSCC.Conclusion: Predictors of TTSC allow for MDR-TB- and XDR-TB-diagnosed patients to be identified early for effective management. Those with risk factors for delayed sputum culture conversion which are being underweight and having XDR-TB should be monitored carefully during treatment so that they can achieve sputum culture conversion early.

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

2017 ◽  
Vol 65 (11) ◽  
pp. 1862-1871 ◽  
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

scholarly journals Predictors of Time to Sputum Culture Conversion Among Drug-Resistant Tuberculosis Patients in Oromia Region Hospitals, Ethiopia

2020 ◽  
Vol Volume 13 ◽  
pp. 2547-2556
Author(s):  
Yohannes Tekalegn ◽  
Demelash Woldeyohannes ◽  
Tesfaye Assefa ◽  
Rameto Aman ◽  
Biniyam Sahiledengle
Keyword(s):  
Sputum Culture ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Tuberculosis Patients ◽  
Sputum Culture Conversion ◽  
Resistant Tuberculosis ◽  
Culture Conversion

Culture Conversion at 6 Months in Patients Receiving Delamanid-containing Regimens for the Treatment of Multidrug-resistant Tuberculosis

2019 ◽  
Vol 71 (2) ◽  
pp. 415-418 ◽  
Author(s):  
Kwonjune J Seung ◽  
Palwasha Khan ◽  
Molly F Franke ◽  
Saman Ahmed ◽  
Stalbek Aiylchiev ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Observational Study ◽  
Multidrug Resistant ◽  
Sputum Culture ◽  
Drug Markets ◽  
Sputum Culture Conversion ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Resistant Strains ◽  
Culture Conversion

Abstract Delamanid should be effective against highly resistant strains of Mycobacteriumtuberculosis, but uptake has been slow globally. In the endTB (expand new drug markets for TB) Observational Study, which enrolled a large, heterogeneous cohorts of patients receiving delamanid as part of a multidrug regimen, 80% of participants experienced sputum culture conversion within 6 months. Clinical Trials Registration. NCT02754765.

scholarly journals Treatment Outcomes and Adverse Drug Effects of Ethambutol, Cycloserine, and Terizidone for the Treatment of Multidrug-Resistant Tuberculosis in South Africa

2020 ◽  
Vol 65 (1) ◽  
pp. e00744-20
Author(s):  
Martha L. van der Walt ◽  
Karen Shean ◽  
Piet Becker ◽  
Karen H. Keddy ◽  
Joey Lancaster
Keyword(s):  
Treatment Outcomes ◽  
Adverse Drug Events ◽  
Drug Effects ◽  
Multidrug Resistant ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Default Rates ◽  
Conversion Rates ◽  
Mdr Tb ◽  
Culture Conversion

ABSTRACTTreatment outcomes among multidrug-resistant tuberculosis (MDR-TB) patients receiving ethambutol, cycloserine, or terizidone as part of a standardized regimen were compared, determining occurrence of serious adverse drug events (SADEs). Newly diagnosed adult MDR-TB patients were enrolled between 2000 and 2004, receiving a standardized multidrug regimen for 18 to 24 months, including ethambutol, cycloserine, or terizidone. Cycloserine and terizidone were recorded individually. SADEs and factors associated with culture conversion and unfavorable treatment outcomes (default, death, treatment failure) were determined. Of 858 patients, 435 (51%) received ethambutol, 278 (32%) received cycloserine, and 145 (17%) received terizidone. Demographic and baseline clinical data were comparable. Successful treatment occurred in 56%, significantly more in patients receiving cycloserine (60%) and terizidone (62%) than in those receiving ethambutol (52% [P = 0.03]). Defaults rates were 30% in ethambutol patients versus 15% and 11% for cycloserine and terizidone patients, respectively. Terizidone was associated with fewer unfavorable outcomes (adjusted odds ratio [AOR], 0.4; P = 0.008; 95% confidence interval [CI], 0.2 to 0.8). Patients receiving cycloserine were more likely to achieve culture conversion than those receiving ethambutol or terizidone (AOR, 2.2; P = 0.02; 95% CI, 1.12 to 4.38). Failure to convert increased the odds of unfavorable outcomes (AOR, 23.7; P < 0.001; 95% CI, 13 to 44). SADEs were reported in two patients receiving ethambutol, seven patients receiving cycloserine, and three receiving terizidone (P = 0.05). Ethambutol was associated with high culture conversion and default rates. Cycloserine achieved higher culture conversion rates than terizidone. Fewer patients on terizidone experienced SADEs, with lower default rates. The differences that we observed between cycloserine and terizidone require further elucidation.

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