Predictors of pulmonary tuberculosis treatment outcomes in South Korea: a prospective cohort study, 2005-2012

Choi, Hong-Jo; Lee, Myungsun; Chen, Ray Y.; Kim, Youngran; Yoon, So-Young; Joh, Joon Sung; Park, Seung Kyu; Dodd, Lori E.; Lee, Jong-Seok; Song, Taeksun; Cai, Ying; Goldfeder, Lisa C.; Via, Laura E.; Carroll, Matthew; Barry, Clifton E.; Cho, Sung Rae

doi:10.1186/1471-2334-14-360

Cited by 58 publications

(48 citation statements)

References 19 publications

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“…In univariate logistic regression analysis, patients with diabetes were more likely to experience an unfavourable outcome than patients without diabetes (OR=2.6, 95% CI 1.48 to 4.56, p=0.001). Other studies conducted in Taiwan and South Korea have also reported an increased risk of unfavourable treatment outcome among patients with diabetes and PTB as compared to patients without diabetes and PTB, that is, an OR of 1.46 (95% CI of 1.03 to 2.08)28 and 1.78 (95% CI 1.07 to 2.95),29 respectively.…”

Section: Findings To Datementioning

confidence: 86%

Cohort profile: the diabetes-tuberculosis treatment outcome (DITTO) study in Pakistan

Mukhtar

Butt

2016

BMJ Open

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PurposePakistan is faced with an increasing prevalence of diabetes in addition to its existing high burden of tuberculosis (TB). Diabetes has a detrimental effect on treatment outcomes of patients with TB, which may hinder achieving the goals of the End-TB strategy by 2030. We conducted a prospective cohort study to determine difference between treatment outcomes among patients with diabetes and new pulmonary tuberculosis (PTB) and patients without diabetes and new PTB. This would help generate contextual and valid scientific evidence from a developing country like Pakistan with its unique interplay of sociocultural, economic and health system factors to inform policy and practice.ParticipantsThis paper outlines the baseline characteristics of 614 new cases of PTB, aged 15 years and older, which were followed up prospectively at 2nd, 5th and 6th months while on antituberculosis treatment and at 6 months after treatment completion.Findings to dateWe ascertained patients' diabetic status by conducting random and fasting blood glucose tests and their glycaemic control by determining glycosylated haemoglobin. Treatment outcomes were established using standardised definitions provided by WHO. The assessment of 614 respondents' diabetic status revealed that 113 (18%) were diabetic and 501 (82%) were non-diabetic. A greater proportion of patients with diabetes and PTB were illiterate (n=74/113, 65.5%) as compared to patients without diabetes and PTB (n=249/501, 50%) (p=0.035). More patients with diabetes and PTB gave a history of heart disease (n=14/113, 12%) and hypertension (n=26/113, 23%) as compared to patients without diabetes and PTB (n=2/501, 0.4% (heart disease) and n=13 501, 3% (hypertension)) (p<0.001). Unfavourable treatment outcome was more likely among patients with diabetes and PTB (n=23/93, 25%) as opposed to patients without diabetes and PTB (n=46/410, 11%) (p=0.001).Future plansWe are negotiating with the government regarding funding for a further 2-year follow-up of the cohort to ascertain death and relapse in the post-treatment period and also differentiate between re-infection and recurrence among these patients with respect to their diabetic status.

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Section: Findings To Datementioning

confidence: 86%

Cohort profile: the diabetes-tuberculosis treatment outcome (DITTO) study in Pakistan

Mukhtar

Butt

2016

BMJ Open

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“…The relationship between the previous TB treatment and poor treatment outcome had been confirmed already in a meta-analysis (2). Additionally, indicators of disease severity, such as cavity and severe pulmonary disease on CXR, increase the risk of poor treatment outcome by inadequate penetration of the drug into the most diseased tissue due to the damaged lung parenchyma (30)(31)(32)(33). These factors might also need to be taken into account when predicting treatment outcomes of MDR-TB.…”

Section: Discussionmentioning

confidence: 99%

Determination of MIC Breakpoints for Second-Line Drugs Associated with Clinical Outcomes in Multidrug-Resistant Tuberculosis Treatment in China

Zheng

et al. 2016

Antimicrob Agents Chemother

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f Our study aims to identify the clinical breakpoints (CBPs) of second-line drugs (SLDs) above which standard therapy fails in order to improve multidrug-resistant tuberculosis (MDR-TB) treatment. MICs of SLDs were determined for M. tuberculosis isolates cultured from 207 MDR-TB patients in a prospective cohort study in China between January 2010 and December 2012. Classification and regression tree (CART) analysis was used to identify the CBPs predictive of treatment outcome. Of the 207 MDR-TB isolates included in the present study, the proportion of isolates above the critical concentration recommended by WHO ranged from 5.3% in pyrazinamide to 62.8% in amikacin. By selecting pyrazinamide as the primary node (CBP, 18.75 mg/ liter), 72.1% of sputum culture conversions at month four could be predicted. As for treatment outcome, pyrazinamide (CBP, 37.5 mg/liter) was selected as the primary node to predict 89% of the treatment success, followed by ofloxacin (CBP, 3 mg/liter), improving the predictive capacity of the primary node by 10.6%. Adjusted by identified confounders, the CART-derived pyrazinamide CBP remained the strongest predictor in the model of treatment outcome. Our findings indicate that the critical breakpoints of some second-line drugs and PZA need to be reconsidered in order to better indicate MDR-TB treatment outcome.M ycobacterium tuberculosis is a major public health problem worldwide (1). The emergence of multidrug-resistant (MDR) M. tuberculosis strains has complicated treatment and is associated with increased treatment failure (2). A reduction in the efficacy of second-line drugs (SLDs) against MDR tuberculosis (MDR-TB) strains with resistance to SLDs has been described in observational studies (2, 3). Subtle changes in drug susceptibility may be predictive of clinical failures, especially when the drug susceptibility testing (DST) result is at the borderline of the susceptibility range.Susceptibility testing for M. tuberculosis is increasingly being utilized in diagnostic laboratories to guide TB treatment. However, there has been considerable debate regarding the critical concentrations used to define resistance of antituberculosis drugs (4, 5). Until now, the standard approach for identifying antibiotic susceptibility breakpoints has been the epidemiological cutoff method. This method is based on the MIC distribution of a drug, which identifies the upper 95% cutoff point on the Gaussian curve of wild-type susceptible M. tuberculosis isolates (6-8). However, Gumbo, using Monte Carlo simulations, concluded that current critical concentrations of first-line drugs were overoptimistic, and new susceptibility breakpoints should be defined considering microbiologic and clinical outcomes (4). Therefore, clinical outcome studies including MIC results are needed. The aim of this study was to identify the clinical breakpoints (CBPs) in a cohort of MDR-TB patients in China and to develop a decision tree to better predict treatment outcomes of MDR-TB patients. MATERIALS AND METHODS Study design.We con...

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“…Up to this point, most data have been acquired at an endpoint-removal of the granuloma as part of a necropsy. Newer technologies, including 18 F-fluorodeoxyglucose (FDG)-positron emission tomography-computed tomography (PET/CT) imaging of humans (113,114) and macaques (109,115) with TB, has given us a new appreciation for the dynamic process of inflammation in the granuloma. Our in silico model complements these technologies by allowing us to test mechanistic hypotheses at the individual-granuloma level, including our hypothesis that distinct macrophage polarization and granuloma polarization trajectories are associated with differential control of bacterium and granuloma outcomes.…”

Section: Discussionmentioning

confidence: 99%

Macrophage Polarization Drives Granuloma Outcome during Mycobacterium tuberculosis Infection

et al. 2015

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c Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), induces formation of granulomas, structures in which immune cells and bacteria colocalize. Macrophages are among the most abundant cell types in granulomas and have been shown to serve as both critical bactericidal cells and targets for M. tuberculosis infection and proliferation throughout the course of infection. Very little is known about how these processes are regulated, what controls macrophage microenvironment-specific polarization and plasticity, or why some granulomas control bacteria and others permit bacterial dissemination. We take a computational-biology approach to investigate mechanisms that drive macrophage polarization, function, and bacterial control in granulomas. We define a "macrophage polarization ratio" as a metric to understand how cytokine signaling translates into polarization of single macrophages in a granuloma, which in turn modulates cellular functions, including antimicrobial activity and cytokine production. Ultimately, we extend this macrophage ratio to the tissue scale and define a "granuloma polarization ratio" describing mean polarization measures for entire granulomas. Here we coupled experimental data from nonhuman primate TB granulomas to our computational model, and we predict two novel and testable hypotheses regarding macrophage profiles in TB outcomes. First, the temporal dynamics of granuloma polarization ratios are predictive of granuloma outcome. Second, stable necrotic granulomas with low CFU counts and limited inflammation are characterized by short NF-B signal activation intervals. These results suggest that the dynamics of NF-B signaling is a viable therapeutic target to promote M 1 polarization early during infection and to improve outcome.

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Predictors of pulmonary tuberculosis treatment outcomes in South Korea: a prospective cohort study, 2005-2012

Cited by 58 publications

References 19 publications

Cohort profile: the diabetes-tuberculosis treatment outcome (DITTO) study in Pakistan

Cohort profile: the diabetes-tuberculosis treatment outcome (DITTO) study in Pakistan

Determination of MIC Breakpoints for Second-Line Drugs Associated with Clinical Outcomes in Multidrug-Resistant Tuberculosis Treatment in China

Macrophage Polarization Drives Granuloma Outcome during Mycobacterium tuberculosis Infection

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