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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 C2 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 C2 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.

Background and Objective: Antimicrobial resistance is a global problem and the prevalence is high in many Asian countries., Methods: A prospective observational study of the prevalence of bacterial pathogens and their antimicrobial susceptibilities in patients with acute exacerbations of chronic bronchitis (AECB) was conducted in Indonesia, Philippines, Korea, Thailand, Malaysia, Taiwan and Hong Kong from August 2006 to April 2008. The diagnosis of AECB was based on increased cough and worsening of two of following: dyspnoea, increased sputum volume or purulence. Patients who had taken antibiotics within 72 h of presentation were excluded. All bacterial strains were submitted to a central laboratory for re-identification and antimicrobial susceptibility testing to 16 antimicrobial agents according to Clinical and Laboratory Standards Institute., Results: Four hundred and seven isolates were identified among 447 patients of AECB. The most frequent organisms isolated were Klebsiella pneumoniae and associated species (n = 91 + 17), Haemophilus influenzae (n = 71), Pseudomonas aeruginosa (n = 63), Streptococcus pneumoniae (n = 32), Acinetobacter baumannii (n = 22) and Moraxella catarrhalis (n = 21). According to Clinical and Laboratory Standards Institute susceptibility breakpoints, 85.7% and >90% of these pathogens were susceptible to levofloxacin and cefepime respectively. Other options with overall lower susceptibilities include imipenem, ceftazidime, ceftriaxone and amoxicillin/clavulanate., Conclusions: Gram-negative bacteria including Klebsiella spp., P. aeruginosa and Acinetobacter spp. constitute a large proportion of pathogens identified in patients with AECB in some Asian countries. Surveillance on the local prevalence and antibiotic resistance of these organisms is important in guiding appropriate choice of antimicrobials in the management of AECB., (© 2011 The Authors. Respirology © 2011 Asian Pacific Society of Respirology.)

Background: Limited understanding of the presentation and course of influenza A(H5N1) infection in humans hinders evidence-based management., Methods: We reviewed the case records of patients admitted to the Persahabatan Hospital (RSP), Jakarta, Indonesia, with influenza A(H5N1) confirmed by real-time polymerase chain reaction., Results: Twenty-two previously well patients, aged 3 to 47 years (median 24.5 years), were identified. All attended a clinic or hospital after a median of 2 days of illness (range 0-7). Times to first dose of oseltamivir (three died before receiving oseltamivir) were 2 to 12 days (median 7 days), administered mostly (n = 15) at RSP. Nineteen patients required mechanical ventilation. Deaths numbered 18 (case fatality = 82%) occurring within hours to 6 days of RSP admission, corresponding to 6 to 16 days of illness. Admission hyperglycemia ( >or= 140 mg/dL), unrelated to steroids or known underlying diabetes mellitus, and elevated D-dimer levels (0.81-5.2 mg/L, upper limit of normal < 0.5 mg/L) were present in 14/21 (67%) and 20/21 (95%) patients, respectively. Fibrinogen concentrations were mostly low/normal at 129.9 to 517.9 mg/dL (median 241.1, normal 200-400 mg/dL), whereas C-reactive protein (9/11) and ferritin (6/8) levels were increased. Risk factors for death (univariate analysis) included: (1) increased D-dimers, (2) hyperglycema, (3) increased urea, (4) more extensive chest radiograph shadowing, and (5) lower admission oxygen saturation., Conclusions: 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.

Background and Objective: The growing burden of COPD in the Asia-Pacific region supports the need for more intensive research and analysis of the epidemiology of COPD to raise awareness of the disease and its causes, to ensure the development of effective national health policies and to facilitate equitable deployment of finite health-care resources in the prevention and management of COPD. This study estimated and compared COPD mortality and hospital morbidity rates and trends in these rates over time across countries and regions of Asia-Pacific., Methods: Data consistent with standard definitions of COPD (ICD-9/ICD-10) for the period 1991-2004 were obtained from national health statistics agencies. For countries/regions with complete national mortality and hospitalization data (Australia, Pacific Canada (British Columbia, Hong Kong, South Korea and Taiwan), annual age-standardized mortality and hospitalization rates were calculated for men and women aged >or= 40 years. Negative binomial regression modelling was used to estimate rate ratios for country/region, gender and age differences and general trends over time., Results: Mortality rates per 10,000 population ranged 6.4-9.2 in men, 2.1-3.5 in women and 3.7-5.3 overall in 2003. Corresponding ranges for morbidity were 32.6-334.7, 21.2-129 and 28.1-207.3 per 10 000. Trend analysis of data since 1997 produced annual percentage changes in mortality versus hospitalization of -4.4% versus -0.7% in Australia, -3.6% versus 7.5% in Pacific Canada (British Columbia), -7.15% versus -5.6% in Hong Kong and -2.9% versus -4.2% in Taiwan., Conclusions: 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.

There is growing concern, even among developed countries, about the increasing incidence of tuberculosis that is resistant to both isoniazid and rifampicin. Results are reported herein from a study investigating ofloxacin in the treatment of 58 patients with multidrug-resistant tuberculosis (MDR-TB). Patients received ofloxacin 400 mg/day accompanied by three other anti-TB drugs to which there was in vitro susceptibility. Treatment duration was nine months. Of 50 evaluable patients, our results showed that bacterial conversion as assessed by sputum microscopy occurred in 23 patients (46%) at three months of therapy, in 36 (72%) at six months, and in 39 (78%) at the end of nine months of therapy. Culture negativity was found in 36 patients (72%) at nine months of therapy. Relapses occurred in four of 36 patients (11%) who achieved culture negativity at the end of the treatment period. Ofloxacin 400 mg in combination with other active anti-TB medications shows promising results in the treatment of MDR-TB in Indonesian patients.

Lower respiratory tract infection (LRTI) is one of the major health problems in developing countries such as Indonesia. According to the National Household Health Survey conducted by the Ministry of Health in 1992, LRTIs still rank fourth as the main cause of death in Indonesia. The problem of LRTIs could be simply managed as long as the causative organism can be identified and the proper antibiotic known. In some occasions, it is not quite so easy to identify the causative micro-organism, especially in lower tract infections. There are several methods of obtaining specimens from LRTIs for cultures. The easiest, most simple way is to collect expectorated sputum. Unfortunately, because of the high rate of contamination by upper respiratory tract flora, this method is not reliable. Recognizing the difficulties with routine expectorated sputum cultures, two alternative approaches have been suggested. One approach is to bypass potential expectorated sputum 'contaminants' in the oropharynx by transtracheal aspiration or transthoracic aspiration. The second approach is to modify the usual technique of processing expectorated sputum by either washing techniques or by quantitative cultures. Azithromycin and clarithromycin are chemically related to macrolide erithromycin. Both antibiotics retain the traditional macrolide spectrum of activity against gram-positive and atypical pneumonia pathogens, while demonstrating improved activity against gram-negative bacteria. The American Thoracic Society (ATS) recommended the use of macrolide for outpatients with community-acquired pneumonia, without comorbidity and 60 years of age or younger. A total of 34 outpatients with acute LRTIs were open-comparative, randomly allocated to treatment with the new macrolide in Persahabatan Hospital, Jakarta, 1996. The purposes of this study were: (i) to identify the causative micro-organisms; and (ii) to evaluate the clinical efficacy of the new macrolide in these infections. Azithromycin 500 mg was given orally once a day for 3 days and was administered 1 h before or 2 h after every meal. Clarithromycin 500 mg was given orally every 12 h for 10 days. The diagnosis of the patients were: 16 with pneumonia, 10 with acute bronchitis and 8 with acute exacerbation of chronic bronchitis. In this study of 34 patients, the sputum specimens were washed with N acetylcysteine before culture and we could only detect micro-organisms in one patient. Before treatment, we found 47 strains in 33 (97.05%) patients and after treatment we found five strains. From serological examination, only four (11.76%) atypical bacterial were detected. The most frequently found microorganisms were 23 strains of Klebsiella pneumoniae (40.42%), 10 of Streptococcus alpha haemolyticus (21.26%), five of Streptococcus pneumoniae (10.63%) and five of Staphylococcus aureus (10.63%). The atypical bacterial were: two Legionella pneumophila, one Mycoplasma pneumoniae and one Chlamydia pneumoniae. The clinical efficacy of new macrolides were 100% and the bacteriological responses with eradication of 94.12% vs 70.59% of isolates in the azithromycin and clarithromycin groups are shown in Table 1. There were no adverse reactions detected in the two treatment groups until the end of the study.

Indonesia as a developing country has air pollution which is mainly caused by motor vehicle emissions and industrial smoke. The most important indoor air pollution is cigarette smoke. The prevalence of smoking among Indonesian men is 45.7%. Of the population, 10.8% are ex-smokers and 43.5% are non-smokers. Among the female population, only 1.8% smoke. There are some important factors that influence the air pollution in Indonesia; this paper identifies the real problems and their impact. The paper reviews various studies that have been carried out in Indonesia which were related to ambient air quality, industrial air pollutants levels (SO2, NOx, Ox, Pb, CO, HC) in large cities in Indonesia have exceeded the acceptable level, especially in industrial trade and heavy traffic areas. The more cigarettes inhaled and the deeper the inhalation, especially the kretek cigarettes, the risk of ling function abnormality becomes greater. Smoking high dose kretek cigarettes, that is > or = 116 cigarettes/day x years, the risk of abnormal lung function is 13-fold that of a non-smoker; if added with the deep inhalation of smoke, the risk becomes 20-fold. Smoking increases the risk of occupational lung disease. The level of dust in some industrial areas exceeded the standard level and correlated with respiratory problems. The existence of industry caused by air pollution in the environment increased the incidence of obstructive airway diseases. We conclude that the main cause of air pollution in Indonesia is motor vehicle emissions, followed by industrial smoke. Cigarette smoke is also related to abnormal lung function.