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

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

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

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.

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 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.

Body mass index predictive of sputum culture conversion among MDR-TB patients in Indonesia

2014 ◽  
Vol 18 (5) ◽  
pp. 564-570 ◽  
Author(s):  
F. A. Putri ◽  
E. Burhan ◽  
A. Nawas ◽  
P. Z. Soepandi ◽  
D. K. Sutoyo ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Sputum Culture ◽  
Sputum Culture Conversion ◽  
Mdr Tb ◽  
Culture Conversion

scholarly journals Diabetes Reduces the Rate of Sputum Culture Conversion in Patients With Newly Diagnosed Multidrug-Resistant Tuberculosis

2016 ◽  
Vol 3 (3) ◽  
Author(s):  
Argita D. Salindri ◽  
Maia Kipiani ◽  
Russell R. Kempker ◽  
Neel R. Gandhi ◽  
Lasha Darchia ◽  
...  
Keyword(s):  
Cox Regression ◽  
Glycosylated Hemoglobin ◽  
Patient Characteristics ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Sputum Culture ◽  
Sputum Culture Conversion ◽  
Increased Risk ◽  
Mdr Tb ◽  
Culture Conversion

Abstract Background.  Diabetes is a risk factor for active tuberculosis (TB), but little is known about the relationship between diabetes and multidrug-resistant (MDR) TB. We aimed to assess risk factors for primary MDR TB, including diabetes, and determine whether diabetes reduced the rate of sputum culture conversion among patients with MDR TB. Methods.  From 2011 to 2014, we conducted a cohort study at the National Center for Tuberculosis and Lung Diseases in Tbilisi, Georgia. Adult (≥35 years) patients with primary TB were eligible. Multidrug-resistant TB was defined as resistance to at least rifampicin and isoniazid. Patients with capillary glycosylated hemoglobin (HbA1c) ≥ 6.5% or previous diagnosis were defined to have diabetes. Polytomous regression was used to estimate the association of patient characteristics with drug resistance. Cox regression was used to compare rates of sputum culture conversion in patients with and without diabetes. Results.  Among 318 patients with TB, 268 had drug-susceptibility test (DST) results. Among patients with DST results, 19.4% (52 of 268) had primary MDR TB and 13.4% (36 of 268) had diabetes. In multivariable analyses, diabetes (adjusted odds ratio [aOR], 2.51; 95% confidence interval [CI], 1.00–6.31) and lower socioeconomic status (aOR, 3.51; 95% CI, 1.56–8.20) were associated with primary MDR TB. Among patients with primary MDR TB, 44 (84.6%) converted sputum cultures to negative. The rate of sputum culture conversion was lower among patients with diabetes (adjusted hazard ratio [aHR], 0.34; 95% CI, .13–.87) and among smokers (aHR, 0.16; 95% CI, .04–.61). Conclusions.  We found diabetes was associated with an increased risk of primary MDR TB; both diabetes and smoking were associated with a longer time to sputum culture conversion.

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

2021 ◽  
Vol 15 (09.1) ◽  
pp. 66S-74S
Author(s):  
Elena Zhdanova ◽  
Olga Goncharova ◽  
Hayk Davtyan ◽  
Sevak Alaverdyan ◽  
Aelita Sargsyan ◽  
...  
Keyword(s):  
Treatment Outcomes ◽  
Treatment Success ◽  
Individualized Treatment ◽  
Sputum Culture ◽  
The Other ◽  
Favorable Outcome ◽  
Short Treatment ◽  
Sputum Culture Conversion ◽  
Mdr Tb ◽  
Culture Conversion

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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