f Numerous studies have reported low concentrations of antituberculosis drugs in tuberculosis (TB) patients, but few studies have examined whether low drug concentrations affect TB treatment response. We examined steady-state plasma concentrations of isoniazid, rifampin, and pyrazinamide at 2 h after the administration of drugs (C 2 h ) among 181 patients with pulmonary tuberculosis in Indonesia and related these to bacteriological response during treatment. C 2 h values below reference values for either isoniazid, rifampin, or pyrazinamide were found in 91% of patients; 60% had at least two low C 2 h concentrations. The isoniazid C 2 h was noticeably lower in fast versus slow acetylators (0.9 mg/liter versus 2.2 mg/liter, P < 0.001). At the end of treatment, 82% of the patients were cured, whereas 30 patients (17%) had dropped out during the study, and 2 patients (1%) failed treatment. No association was found between C 2 h concentrations and sputum culture results at 8 weeks of treatment. Post hoc analysis showed that patients with low pyrazinamide C 2 h (P ؍ 0.01) and patients with large extensive lung lesions (P ؍ 0.01) were at risk of at least one positive culture at week 4, 8, or 24/32. Antituberculosis drug concentrations were often low, but treatment response was nevertheless good. No association was found between drug concentrations and 8 weeks culture conversion, but low pyrazinamide drug concentrations may be associated with a less favorable bacteriological response. The use of higher doses of pyrazinamide may warrant further investigation. G enerally, first-line treatment of drug-susceptible tuberculosis (TB) is highly effective. However, a number of patients do not respond adequately to treatment, develop drug resistance or experience a relapse of TB after completion of treatment. Inadequate exposure to anti-TB drugs may constitute one of the factors underlying suboptimal treatment response (1, 2). Among adults, low plasma concentrations of anti-TB drugs have been found in patients with HIV infection, gastrointestinal tract disorders, high body weight, male gender, or diabetes mellitus (DM) (3-11) and in fast acetylators for isoniazid (12). Low plasma concentrations can also result from interindividual variability in drug absorption, metabolism, or excretion (3, 13). Some studies have reported associations between low concentrations of anti-TB drugs and poor treatment response (1-3, 14), although this was not found in other studies (7,15). In a recent study performed in a preclinical model, pharmacokinetic variability appeared to be more important in the emergence of multidrug-resistant tuberculosis (MDR-TB) than nonadherence (16). Furthermore, a systematic review showed that pharmacokinetic variability to isoniazid in multi-drug TB regimens is significantly associated with therapy failure and acquired drug resistance (17).Nevertheless, the number of studies examining the relation between plasma concentrations of anti-TB drugs and treatment response remains limited and the majority of them inves...
These data reflect the overall high prevalence of these atypical pathogens among Asian patients with CAP.
In Asia-Pacific, overall mortality and morbidity rates are high and trends in mortality and morbidity vary between countries/regions. Differences in rates and trends for men and women most likely reflect the different trends in historical and prevalent smoking profiles for COPD in the different countries and regions.
Chronic obstructive pulmonary disease (COPD) is a major public health problem and its prevalence and mortality are increasing throughout the world, including the Asia-Pacific region. To arrest these worldwide trends, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Expert Panel's global strategy for the diagnosis, management, and prevention of COPD was published in 2001. Based on recently published clinical trials, the GOLD statement was updated in 2003. The Asia-Pacific COPD Roundtable Group, a taskforce of expert respirologists from the Asia-Pacific region, has recently formulated a consensus statement on implementation of the GOLD strategy for COPD in the Asia-Pacific region. The key issues identified by the COPD Roundtable Group for comment are: (i) where there is no access to spirometry, diagnosis of COPD could be suspected on the basis of history, symptoms and physical signs; (ii) inhaled bronchodilators are the preferred regular treatment for COPD in the region, but oral bronchodilators may be considered if the cost of inhaled bronchodilators is a barrier to treatment; (iii) the use of a Metered Dose Inhaler with spacer in place of a nebulizer is recommended in the treatment of acute airflow obstruction in patients with COPD; (iv) influenza vaccination is recommended for all patients with COPD in communities where there is a high likelihood of Severe Acute Respiratory Syndrome; and (v) simplified pulmonary rehabilitation programmes should be established in areas where comprehensive programmes are unavailable. Physical exercise training and education on smoking cessation should be core elements of any rehabilitation program. In summary, the COPD Roundtable Group supports implementation of the GOLD strategy for the diagnosis, management and prevention of COPD in the Asia-Pacific region, subject to the additions and modifications to the guidelines suggested above.
Early diagnosis and effective treatment of human influenza A(H5N1) infection remains challenging. Most patients were referred late with advanced disease. Oseltamivir had limited clinical impact. Elevated D-dimer levels, consistent with fibrinolysis, and hyperglycemia warrant more research to determine their underlying mechanisms and optimal treatment.
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