Isoniazid, rifampin, and pyrazinamide plasma concentrations in relation to treatment response in Indonesian pulmonary tuberculosis patients.

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.

Spectrum and antimicrobial resistance of common pathogenic bacteria isolated from patients with acute exacerbation of chronic obstructive pulmonary disease in mainland of China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Bacteria-induced respiratory infection has been long considered to be the major cause of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Therefore, a clear picture about the distribution and drug-resistance of pathogenic bacteria in the lower airways should be helpful for treatment of the disease. So far, data on this topic among Chinese are lacking.</p><p><b>METHODS</b>A surveillance study was performed in consecutive patients with AECOPD at five areas in China between October 2006 and April 2008. The sputum from these patients was cultured and isolated for bacteria. Agar dilution method was used to determine the minimal inhibitory concentrations (MICs) of levofoxacin and other 15 antibiotics against these strains.</p><p><b>RESULTS</b>Three hundred and fifty-nine pathogenic bacterial strains were isolated among 884 patients with AECOPD. The predominant bacteria were Pseudomonas aeruginosa (21.7%), Klebsiella pneumoniae (12.3%), Haemophilus influenzae (14.2%) and Streptococcus pneumoniae (11.7%), followed by Haemophilus parainfluenzae (9.5%), Acinetobacter baumannii (7.8%), Moraxella catarrhalis (6.4%) and Escherichia coli (3.6%). The majority of bacterial pathogens isolated in this study were susceptible to fuoroquinolones, ceftazidime, cefepime and imipenem.</p><p><b>CONCLUSIONS</b>Gram-negative bacilli are the leading pathogens in patients with AECOPD in China. Haemophilus parainfluenzae may be one of the most important pathogens in AECOPD. This study provides evidence for local surveillance of AECOPD pathogens and appropriate choice of antimicrobials in China.</p>

A multicentre surveillance study on the characteristics, bacterial aetiologies and in vitro antibiotic susceptibilities in patients with acute exacerbations of chronic bronchitis.

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.

Clinical course of avian influenza A(H5N1) in patients at the Persahabatan Hospital, Jakarta, Indonesia, 2005-2008.

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.