Management Of Drug-resistant Tuberculosis Research Articles

Complete atrioventricular block due to overdose of pregabalin

Pregabalin, a synthetic derivate of the inhibitory neurotransmitter γ-aminobutyric acid, shows antiepileptic, analgesic, anticonvulsant, anxiolytic, and sleep-modulating activities. The major advantage of pregabalin is its relative reliability, easy use, high tolerance, and lack of negative interaction with other drugs. A 65-year-old woman with medical histories of diabetes mellitus, lumbar spondylosis, diabetic nephropathy, chronic renal failure, and anemia of chronic disease was admitted with the complaint of dizziness and syncope. She had been taking pregabalin 300 mg daily for 8 months. Electrocardiogram revealed complete atrioventricular (AV) block and right bundle-brunch block with a heart rate of 39 per minute. Her creatinine was 1.8 mg/dL, and creatinine clearance was 50 mL/min. Pregabalin treatment was discontinued. Four days later, the complete AV block resolved spontaneously to Mobitz type II block and to sinus rhythm with right bundle-brunch block on the seventh day. To our knowledge, this is the first case of complete AV block associated with pregabalin. We believe that AV block occurred as a result of pregabalin's effect on L-type Ca++ channels in the heart. Pregabalin's different effects on electrocardiogram and on the heart in different individuals may have an association with the patterns of distribution of the L-type calcium channels in myocardium.

Ethics, human rights and programmatic management of drug-resistant tuberculosis

Ethics, human rights and programmatic management of drug-resistant tuberculosis

Updated Guidelines for the Programmatic Management of Drug-Resistant TB

Target Population: Public health professionals involved in the prevention and control of drug-resistant tuberculosis (TB) Sponsoring Organization: WHO Type: Evidence-based consensus guidelines using a grading system Key Points: This document updates and expands guidelines for diagnosing and treating multidrug-resistant TB (MDR-TB — i.e., infection with Mycobacterium tuberculosis resistant to at least isoniazid and rifampicin) that were first released in 2006 and were updated on …

Ethionamide-induced hypothyroidism in children

Ethionamide is a second-line anti-tuberculosis drug used in the management of drug-resistant tuberculosis. Hypothyroidism is reported to be a rare adverse effect. A retrospective descriptive study was done of all children started on treatment for multidrug-resistant tuberculosis from 2006-2009, who received ethionamide as part of their drug regimen. Information collected included age, weight, human immunodefciency virus (HIV) status, ethionamide dose and thyroid function tests. Seven of 13 (54%) children developed hypothyroidism and received thyroxine for the duration of ethionamide treatment. Thyroid function returned to normal within two months of completion of tuberculosis treatment in six of the seven children (one lost to follow-up). Ethionamide-induced hypothyroidism is more common in this small number of patients than previously reported. The results warrant further studies to confrm these fndings and elucidate possible reasons.

Global Epidemiology of Tuberculosis: Prospects for Control

The burden of tuberculosis (TB) is now very slowly decreasing globally. However, the rate of decline is too slow to reach all the epidemiological impact targets set for 2015. The prospects for reaching the TB elimination target set for 2050 are even bleaker. Implementation of the World Health Organization's Stop TB Strategy is currently lagging behind the envisioned scale-up pace, particularly with regard to TB/HIV collaborative activities and management of drug resistant TB. To ensure long-term TB control there is, first, a need to ensure that all components of the Stop TB Strategy are scaled up according to plans, with special attention to improved access for the poor. However, this may not be enough. Recent analyses suggest that the impact of current efforts to reduce TB incidence is less than expected and that improved diagnostic and curative efforts need to be combined with additional preventive efforts. New and more effective vaccines and drugs for preventive treatment would revolutionize TB control. A stronger focus on prevention would also entail more concerted actions to limit the impact of TB risk factors, including HIV/AIDS, smoking, malnutrition, alcoholism, diabetes, crowded living conditions, and indoor air pollution, which may all contribute a considerable proportion of the global TB burden.

Treatment failure in a case of extensively drug-resistant tuberculosis associated with selection of a GyrB mutant causing fluoroquinolone resistance

Multidrug-resistant tuberculosis (MDR-TB), defined by resistance to both isoniazid and rifampin, is an increasing problem that accounts for 400,000 new cases worldwide each year [1]. The prognosis of individuals infected with MDR-TB remains poor, with 10–30% of cases resulting in failure and death [2]. Fluoroquinolones are some of the few potent antibiotics still active against most MDR strains of M. tuberculosis, and their use has been identified as a favorable prognostic factor in cases of MDR-TB [3]. Recently, the emergence of extensively drug-resistant strains (XDR) has been reported and these strains have been associated with a worse prognosis than MDR-TB strains [2]. XDR-TB is an infection with a MDR strain that is resistant to any fluoroquinolone and at least one of the three injectable drugs (capreomycin, kanamycin or amikacin) [4]. We describe here a clinical case of XDR-TB that illustrates the critical role fluoroquinolones play in the management of drugresistant tuberculosis. The case involved a 51-year-old man with no comorbid conditions who had been treated in Algeria for pulmonary tuberculosis since June 2001. The initial antibiotic susceptibility profile of the causative strain was unknown. His original treatment, which included isoniazid, rifampin, ethambutol and pyrazinamide for 3 months followed by isoniazid and ethambutol, had been taken irregularly. When hospitalized in Limoges, France, in June 2002, he suffered fever, anorexia, weight loss (15 kg), cough and hemoptysis. A computed tomography scan showed bilateral cavitations of the upper lobes (Fig. 1). Sputum-smear examination detected abundant acid-fast bacilli. Treatment with rifampin, isoniazid and pyrazinamide was initiated. Culture grew M. tuberculosis. Susceptibility testing of first-line drugs revealed resistance to rifampin, isoniazid, pyrazinamide and streptomycin. Treatment was consequently switched to amikacin (750 mg/day), ofloxacin (800 mg/day), ethionamide (500 mg/day) and ethambutol (1 g/day). Molecular studies performed at the National Reference Center revealed mutations in the katG gene (S315T), rpoB gene (H526D) and pncA gene (T100P), but no mutation in the gyrA gene [5, 6]. Further drug susceptibility tests showed resistance to isoniazid, rifampin, pyrazinamide, streptomycin, ethambutol, kanamycin, ethionamide, thiacetazone and cycloserine. The strain remained susceptible to amikacin, capreomycin, fluoroquinolones and para aminosalicylic acid. As a result, treatment was switched to amikacin (750 mg/day), ofloxacin (800 mg/day) and PAS (10 g/day) for 4 months. Under this treatment the patient’s general condition improved. In January 2003, treatment was continued with the combination of moxifloxacin (400 mg/day) and PAS and maintained for 12 more months. However, in May 2003 the patient returned to Algeria, where he again took his medication irregularly. In March 2004, he was readmitted Eur J Clin Microbiol Infect Dis (2007) 26:423–425 DOI 10.1007/s10096-007-0298-0

Musculoskeletal Tuberculosis

The overall goals of antituberculosis therapy are multifaceted and include achieving cure without relapse of disease, stopping transmission of Mycobacterium tuberculosis, and preventing the emergence of drug-resistant strains. In this article, we review the recommended patient-centered approach to successfully achieving these goals including details about current treatment regimens, methods to promote adherence and prevent relapse, management of drug-resistant tuberculosis and management of extrapulmonary tuberculosis. Detailed information on treatment of tuberculosis in special situations (patients with renal disease or hepatic disease, those of advanced age, etc.), the use of case management strategies (including DOT), regimen and dosing selection in adults and children (daily vs. intermittent), the role of therapeutic drug monitoring, treatment of tuberculosis in the presence of HIV infection (duration of tuberculosis treatment and timing of initiation of ART), treatment of tuberculosis in children, treatment of tuberculosis during pregnancy, and treatment of extrapulmonary tuberculosis, as well as key research priorities, are provided in recently published official guidelines developed by the newly published Official ATS/CDC/IDSATreatment of Drug-Susceptible Tuberculosis Guidelines available online.