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.

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 Diabetes Reduces the Rate of Sputum Culture Conversion in Patients With Primary Multidrug-Resistant Tuberculosis

2015 ◽  
Vol 2 (suppl_1) ◽  
Author(s):  
Argita Salindri ◽  
Maia Kipiani ◽  
Russell R Kempker ◽  
Neel Gandhi ◽  
Lasha Darchia ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Sputum Culture ◽  
Sputum Culture Conversion ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Culture Conversion

scholarly journals Evaluation of six months sputum culture conversion as a surrogate endpoint in a multidrug resistant-tuberculosis trial

PLoS ONE ◽  
2018 ◽  
Vol 13 (7) ◽  
pp. e0200539 ◽  
Author(s):  
Paul Meyvisch ◽  
Chrispin Kambili ◽  
Koen Andries ◽  
Nacer Lounis ◽  
Myriam Theeuwes ◽  
...  
Keyword(s):  
Surrogate Endpoint ◽  
Multidrug Resistant ◽  
Sputum Culture ◽  
Sputum Culture Conversion ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Culture Conversion
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