Active tuberculosis, sequelae and COVID-19 co-infection: first cohort of 49 cases.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) pandemic has attracted interest because of its global rapid spread, clinical severity, high mortality rate, and capacity to overwhelm healthcare systems [1, 2]. SARS-CoV-2 transmission occurs mainly through droplets, although surface contamination contributes and debate continues on aerosol transmission [3\u20135]

Dried blood spots: A new tool for tuberculosis treatment optimization

Tuberculosis (TB) is a high-burden infectious disease, especially in low and middle-income countries. The efforts to eliminate this disease are challenged by the emergence of multidrug resistance and TB-HIV coinfection. The cumulative knowledge on pharmacokinetics/pharmacodynamics of antituberculosis agents has recently encouraged therapeutic drug monitoring (TDM) in patient care. However, logistical problems related to conventional sampling limit the application of TDM in research-oriented institutions. Dried blood spot (DBS) compared with conventional venous blood sampling has the advantages of easier sampling, storage and transportation, thus enabling the application of TDM even in remote areas. In addition, DBS with its lower biohazardous risk can be safely performed in a high HIV prevalence area, which also tends to have a high TB burden. Another benefit of DBS sampling is that it requires a smaller blood volume than conventional sampling and is highly recommended for application in pediatric TB. A limitation of DBS is that additional considerations are required for analysis, method development and validation. The accuracy of the DBS method is influenced by a number of factors that need to be thoroughly examined in method development and validation. Further, the agreement between DBS and plasma/serum concentrations is not always understood and further investigations are required

In vitro synergy between linezolid and clarithromycin against Mycobacterium tuberculosis

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Population pharmacokinetics and limited sampling strategy for first-line tuberculosis drugs and moxifloxacin

Item does not contain fulltextTherapeutic drug monitoring (TDM) of tuberculosis (TB) drugs currently focuses on peak plasma concentrations, yet total exposure [area under the 24-h concentration-time curve (AUC0-24)] is probably most relevant to the efficacy of these drugs. We therefore assessed population AUC0-24 data for all four first-line TB drugs (rifampicin, isoniazid, pyrazinamide and ethambutol) as well as moxifloxacin and developed limited sampling strategies to estimate AUC0-24 values conveniently. AUC0-24 and other pharmacokinetic (PK) parameters were determined following intensive PK sampling in two Dutch TB referral centres. Best subset selection multiple linear regression was performed to derive limited sampling equations. Median percentage prediction error and median absolute percentage prediction error were calculated via jackknife analysis to evaluate bias and imprecision of the predictions. Geometric mean AUC0-24 values for rifampicin, isoniazid, pyrazinamide, ethambutol and moxifloxacin were 41.1, 15.2, 380, 25.5 and 33.6hmg/L, respectively. Limited sampling at various fixed sampling points enabled an accurate and precise prediction of AUC0-24 values of all drugs separately and simultaneously. In the absence of clinically validated target values for AUC0-24, average AUC0-24 values can be used as reference values in TDM. Limited sampling of AUC0-24 is feasible in many settings and allows for TDM to be performed at a larger scale

Treatment correlates of successful outcomes in pulmonary multidrug-resistant tuberculosis: an individual patient data meta-analysis

Item does not contain fulltextBACKGROUND: Treatment outcomes for multidrug-resistant tuberculosis remain poor. We aimed to estimate the association of treatment success and death with the use of individual drugs, and the optimal number and duration of treatment with those drugs in patients with multidrug-resistant tuberculosis. METHODS: In this individual patient data meta-analysis, we searched MEDLINE, Embase, and the Cochrane Library to identify potentially eligible observational and experimental studies published between Jan 1, 2009, and April 30, 2016. We also searched reference lists from all systematic reviews of treatment of multidrug-resistant tuberculosis published since 2009. To be eligible, studies had to report original results, with end of treatment outcomes (treatment completion [success], failure, or relapse) in cohorts of at least 25 adults (aged >18 years). We used anonymised individual patient data from eligible studies, provided by study investigators, regarding clinical characteristics, treatment, and outcomes. Using propensity score-matched generalised mixed effects logistic, or linear regression, we calculated adjusted odds ratios and adjusted risk differences for success or death during treatment, for specific drugs currently used to treat multidrug-resistant tuberculosis, as well as the number of drugs used and treatment duration. FINDINGS: Of 12 030 patients from 25 countries in 50 studies, 7346 (61%) had treatment success, 1017 (8%) had failure or relapse, and 1729 (14%) died. Compared with failure or relapse, treatment success was positively associated with the use of linezolid (adjusted risk difference 0.15, 95% CI 0.11 to 0.18), levofloxacin (0.15, 0.13 to 0.18), carbapenems (0.14, 0.06 to 0.21), moxifloxacin (0.11, 0.08 to 0.14), bedaquiline (0.10, 0.05 to 0.14), and clofazimine (0.06, 0.01 to 0.10). There was a significant association between reduced mortality and use of linezolid (-0.20, -0.23 to -0.16), levofloxacin (-0.06, -0.09 to -0.04), moxifloxacin (-0.07, -0.10 to -0.04), or bedaquiline (-0.14, -0.19 to -0.10). Compared with regimens without any injectable drug, amikacin provided modest benefits, but kanamycin and capreomycin were associated with worse outcomes. The remaining drugs were associated with slight or no improvements in outcomes. Treatment outcomes were significantly worse for most drugs if they were used despite in-vitro resistance. The optimal number of effective drugs seemed to be five in the initial phase, and four in the continuation phase. In these adjusted analyses, heterogeneity, based on a simulated I(2) method, was high for approximately half the estimates for specific drugs, although relatively low for number of drugs and durations analyses. INTERPRETATION: Although inferences are limited by the observational nature of these data, treatment outcomes were significantly better with use of linezolid, later generation fluoroquinolones, bedaquiline, clofazimine, and carbapenems for treatment of multidrug-resistant tuberculosis. These findings emphasise the need for trials to ascertain the optimal combination and duration of these drugs for treatment of this condition. FUNDING: American Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America