Association of indicators of extensive disease and rifampin-resistant tuberculosis treatment outcomes: an individual participant data meta-analysis.

Background: Indicators of extensive disease-acid fast bacilli (AFB) smear positivity and lung cavitation-have been inconsistently associated with clinical rifampin-resistant/multidrug-resistant tuberculosis (RR/MDR-TB) outcomes. We evaluated the association of these indicators with end-of-treatment outcomes.

Methods: We did an individual participant data meta-analysis of people treated for RR/MDR-TB with longer regimens with documented AFB smear and chest radiography findings.

Voriconazole exposure is influenced by inflammation: A population pharmacokinetic model.

Background: Voriconazole is an antifungal drug used for the treatment of invasive fungal infections. Due to highly variable drug exposure, therapeutic drug monitoring (TDM) has been recommended. TDM may be helpful to predict exposure accurately, but covariates, such as severe inflammation, that influence the metabolism of voriconazole have not been included in the population pharmacokinetic (popPK) models suitable for routine TDM.

Exposure of anti-infective drugs and the dynamic changes of the gut microbiota during gastrointestinal mucositis in autologous stem cell transplant patients: a pilot study.

Gastrointestinal mucositis could potentially compromise drug absorption due to functional loss of mucosa and other pathophysiological changes in the gastrointestinal microenvironment. Little is known about this effect on commonly used anti-infectives. This study aimed to explore the association between different stages of gastrointestinal mucositis, drug exposure, and gut microbiota.

Therapeutic drug monitoring-guided treatment versus standard dosing of voriconazole for invasive aspergillosis in haematological patients: a multicentre, prospective, cluster randomised, crossover clinical trial.

Objectives: Voriconazole therapeutic drug monitoring (TDM) is recommended based on retrospective data and limited prospective studies. This study aimed to investigate whether TDM-guided voriconazole treatment is superior to standard treatment for invasive aspergillosis.

Methods: A multicentre (n = 10), prospective, cluster randomised, crossover clinical trial was performed in haematological patients aged ≥18 years treated with voriconazole.

Relationship between biomarkers and findings on low-dose computed tomography in hospitalised patients with acute exacerbation of COPD.

Background: Acute exacerbations of COPD (AECOPD) and community acquired pneumonia (CAP) often coexist. Although chest radiographs may differentiate between these diagnoses, chest radiography is known to underestimate the incidence of CAP in AECOPD. In this exploratory study, we prospectively investigated the incidence of infiltrative changes using low-dose computed tomography (LDCT).

Population Pharmacokinetic Modelling and Limited Sampling Strategies for Therapeutic Drug Monitoring of Pyrazinamide in Patients with Tuberculosis.

Pyrazinamide is one of the first-line antituberculosis drugs. The efficacy of pyrazinamide is associated with the ratio of 24-h area under the concentration-time curve (AUC) to MIC. The objective of this study was to develop and validate a limited sampling strategy (LSS) based on a population pharmacokinetic (popPK) model to predict AUC.

Malnutrition assessment methods in adult patients with tuberculosis: a systematic review.

Objectives: Malnutrition is associated with a twofold higher risk of dying in patients with tuberculosis (TB) and considered an important potentially reversible risk factor for failure of TB treatment. The construct of malnutrition has three domains: intake or uptake of nutrition; body composition and physical and cognitive function. The objectives of this systematic review are to identify malnutrition assessment methods, and to quantify how malnutrition assessment methods capture the international consensus definition for malnutrition, in patients with TB.

Standard ganciclovir dosing results in slow decline of cytomegalovirus viral loads.

Background: Cytomegalovirus (CMV) can cause severe disease, including rejection in transplant recipients. Ganciclovir and its oral prodrug valganciclovir have been used as first-line therapy for CMV disease in transplant recipients. The exposure targets of ganciclovir are not exactly known, and toxicity and resistance have interfered with ganciclovir therapy.

Clinical Relevance of Rifampicin-Moxifloxacin Interaction in Isoniazid-Resistant/Intolerant Tuberculosis Patients.

Moxifloxacin is an attractive drug for the treatment of isoniazid-resistant rifampicin-susceptible tuberculosis (TB) or drug-susceptible TB complicated by isoniazid intolerance. However, co-administration with rifampicin decreases moxifloxacin exposure. It remains unclear whether this drug-drug interaction has clinical implications.

Sarcoidosis presenting with glazy mucoid sputum and dyspnea: a case report.

Background: Patients with pulmonary sarcoidosis commonly present with a dry cough; a productive cough suggests a complicating airway infection or an alternative diagnosis such as tuberculosis or bronchiectasis.

Case Presentation: A 36-year-old European (Frisian) woman recently diagnosed with pulmonary sarcoidosis presented with debilitating exertional dyspnea and cough productive of glazy mucoid sputum. Several different attempts including video-assisted thoracoscopic biopsies failed to reach a second or alternative diagnosis including an infectious, autoimmune or collagen-vascular condition.

COPD-Lower Respiratory Tract Infection Visual Analogue Score (c-LRTI-VAS) validation in stable and exacerbated patients with COPD.

Background: We developed the chronic obstructive pulmonary disease (COPD)-Lower Respiratory Tract Infection-Visual Analogue Score (c-LRTI-VAS) in order to easily quantify symptoms during exacerbations in patients with COPD. This study aimed to validate this score.

Methods: In our study, patients with stable COPD as well as those with an acute exacerbations of COPD (AECOPD) were included.

Treatment outcomes of patients with MDR-TB in Nepal on a current programmatic standardised regimen: retrospective single-centre study.

Objectives: The objectives of this study were to evaluate treatment in patients on current programmatic multidrug-resistant tuberculosis (MDR-TB) regimen and verify eligibility for the 9-month regimen and therapeutic drug monitoring (TDM).

Methods: We performed a retrospective chart review of patients with MDR-TB receiving standardised regimen at the German Nepal TB Project Clinic, Nepal, between 2014 and 2016. Eligibility for the 9-month regimen and indications for TDM were evaluated.

Caspofungin Weight-Based Dosing Supported by a Population Pharmacokinetic Model in Critically Ill Patients.

The objective of this study was to develop a population pharmacokinetic model and to determine a dosing regimen for caspofungin in critically ill patients. Nine blood samples were drawn per dosing occasion. Fifteen patients with (suspected) invasive candidiasis had one dosing occasion and five had two dosing occasions, measured on day 3 (±1) of treatment.

Retraction Note: Infection of great apes and a zoo keeper with the same Mycobacterium tuberculosis spoligotype.

The original article can be found online.

Prospective evaluation of improving fluoroquinolone exposure using centralised therapeutic drug monitoring (TDM) in patients with tuberculosis (PERFECT): a study protocol of a prospective multicentre cohort study.

Introduction: Global multidrug-resistant tuberculosis (MDR-TB) treatment success rates remain suboptimal. Highly active WHO group A drugs moxifloxacin and levofloxacin show intraindividual and interindividual pharmacokinetic variability which can cause low drug exposure. Therefore, therapeutic drug monitoring (TDM) of fluoroquinolones is recommended to personalise the drug dosage, aiming to prevent the development of drug resistance and optimise treatment.

Towards elimination of childhood and adolescent tuberculosis in the Netherlands: an epidemiological time-series analysis of national surveillance data.

Background: Tuberculosis (TB) in children and adolescents is a sentinel event for ongoing transmission. In the Netherlands, epidemiological characteristics of childhood and adolescent TB have not been fully evaluated. Therefore, we aimed to assess TB epidemiology within this population to provide guidance for TB elimination.

Corticosteroid therapy for the management of paradoxical inflammatory reaction in patients with pulmonary tuberculosis.

Background: Paradoxical reaction after the initiation of tuberculosis treatment is defined as increased inflammation following effective antimycobacterial treatment. This is a phenomenon that can severely complicate a patient's recovery, potentially leading to further morbidity and residual deficits. Paradoxical reaction remains poorly understood regarding its pathophysiology and management.

Pharmacologic management of infection.

Introduction: Pharmacological treatment of Buruli ulcer ( infection; BU) is highly effective, as shown in two randomized trials in Africa.

Areas Covered: We review BU drug treatment - in vitro, in vivo and clinical trials (PubMed: '(Buruli OR (Mycobacterium AND ulcerans)) AND (treatment OR therapy).' We also highlight the pathogenesis of infection that is dominated by mycolactone, a secreted exotoxin, that causes skin and soft tissue necrosis, and impaired immune response and tissue repair.

Rifampicin and clarithromycin (extended release) versus rifampicin and streptomycin for limited Buruli ulcer lesions: a randomised, open-label, non-inferiority phase 3 trial.

Background: Buruli ulcer is a neglected tropical disease caused by Mycobacterium ulcerans infection that damages the skin and subcutis. It is most prevalent in western and central Africa and Australia. Standard antimicrobial treatment with oral rifampicin 10 mg/kg plus intramuscular streptomycin 15 mg/kg once daily for 8 weeks (RS8) is highly effective, but streptomycin injections are painful and potentially harmful.