[Successful macrolide therapy for recurrent pneumococcal pneumonia in a man with X-linked agammaglobulinemia].

A 55-year-old man, who had not suffered from any severe or recurrent bacterial infections previously, visited our hospital because of symptoms of fever, cough, sputum, and otorrhea. Chest X-ray and computed tomography demonstrated infiltrates in the right middle lobe and lingula. Pneumococcal pneumonia and tympanitis were diagnosed based on the isolation of Streptococcus pneumoniae from sputum and otorrhea specimens. A peripheral blood analysis showed a remarkable reduction in serum IgG level and the flow cytometric analysis of his peripheral monocytes indicated a significant reduction in Bruton's tyrosine kinase expression. Thus, we diagnosed his illness as X-linked agammaglobulinemia (XLA). Although immunoglobulin replacement therapy was performed, he developed recurrent lower respiratory tract infections. Low-dose long-term erythromycin treatment resulted in decreased frequency of respiratory tract infections. These results suggest that erythromycin therapy may be useful for the control of lower respiratory tract infections in patients with XLA. Even in adults with recurrent bacterial respiratory tract infections, the presence of XLA as an underlying disease should be considered. The effect of macrolide therapy for chronic lower respiratory tract infection associated with humoral immunodeficiency has rarely been reported. This case study may provide valuable information about macrolide therapy for such an infection in patients with humoral immunodeficiency.

Pharmacokinetic study of pleural fluid penetration of carbapenem antibiotic agents in chemical pleurisy.

STUDY OBJECTIVES: We investigated pleural fluid penetration of carbapenem antibiotic agents [imipenem (IPM), panipenem (PAPM), meropenem (MEPM), and biapenem (BIPM)] using an experimental rabbit pleuritis model to clarify the usefulness of the carbapenem agents for the treatment of bacterial pleurisy or pyothorax. MEASUREMENTS AND RESULTS: Serum and pleural fluid specimens were serially collected at 5, 10, 15, 30, 60, 90, 120, 180, 240, 300, and 360 min after antibiotic administration for measurement of antibiotic levels. We investigated each agent alone as well as drug solutions containing each agent and a dehydropeptidase-I-specific inhibitor, cilastatin (CS), to remove the influence of dehydropeptidase-I-related hydrolysis. Groups of animals (n=3) received each carbapenem agent with or without CS. Serum and pleural fluid antibiotic levels were measured by high-performance liquid chromatography (HPLC). Because Cmax is not useful for evaluating the antimicrobial effects of carbapenem antibiotic agents due to their dose-dependent antimicrobial activity, we also investigated the AUC, which is correlated with the total drug levels in vivo. Among the drug solutions containing CS, MEPM/CS had the highest pleural fluid AUC0-360 (1594.8+/-510.3 microg min/ml), and the highest pleural fluid AUC0-360/plasma AUC0-360 ratio (0.79+/-0.04). BIPM/CS had the highest plasma AUC0-360 (3040.1+/-1525.9 microg min/ml). In pleural fluid AUC0-360/plasma AUC0-360 ratio MEPM/CS was significantly higher than those for the remaining agents. In pleural fluid AUC0-360 and plasma AUC0-360 there were no significant differences among these mixed solutions. CONCLUSIONS: MEPM had the most favorable pleural fluid penetration. Pleural fluid penetration should be examined in infection models and in clinical trials.

Combined effects of panipenem and aminoglycosides on methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa in vitro.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa are the main causes of refractory infections that are often resistant to antimicrobial agents. In these cases, combination of agents with antimicrobial activity is being examined. However, few studies have investigated combined effects with antimicrobial agents including carbapenem and aminoglycosides. METHODS: We evaluated the effects of panipenem (PAPM) combined with 3 aminoglycosides, arbekacin, amikacin, and netilmicin, and vancomicin (VCM) with an agar dilution checkerboard technique and the fractional inhibitory concentration index against 47 strains of MRSA and 56 strains of P. aeruginosa. RESULTS: PAPM combined with VCM achieved a synergic effect against MRSA in 80.9%. PAPM combined with aminoglycosides showed only additive effects against MRSA and P. aeruginosa. When comparing the activity of Mueller-Hinton agar (MHA) medium with MHA medium diluted 40-fold (1/40 MHA) against P. aeruginosa, the mean minimum inhibitory concentration of PAPM was decreased to 1/16. CONCLUSIONS: Combination of PAPM and VCM is effective against MRSA. Combinations of PAPM and aminoglycosides showed additive effects against MRSA and P. aeruginosa.

Isolation of nontuberculous mycobacteria from patients with pneumoconiosis.

This study aimed to confirm the isolation of nontuberculous mycobacteria (NTM) from patients with pneumoconiosis. Monthly sputum examinations in 155 patients were performed from April 1998 to December 2002. When NTM were isolated, species were identified and the frequency of isolation was reviewed. We then identified the patients who satisfied the bacteriologic criteria for the diagnosis of nontuberculous mycobacterial pulmonary disease (NTM pulmonary disease) recommended by the American Thoracic Society (ATS). Symptoms and findings on computed tomography (CT) scans were evaluated. NTM were isolated from 60 patients (39%): common etiologic species defined by the ATS, i.e., Mycobacterium avium, M. intracellulare, M. abscessus, and M. kansasii, were identified in 21 patients; unusual etiologic species, i.e., M. fortuitum, M. simiae, and M. szulgai, were identified in 11 patients; and undefined species, which appeared to be nonpathogenic, were identified in 41 patients. The bacteriologic criteria were satisfied in 8 patients. NTM species isolated in conformity with the bacteriologic criteria were: M. avium in 4 patients, M. intracellulare in 2, a combination of M. intracellulare and M. kansasii in 1, and M. gordonae in 1 patient. Two patients, from whom M. avium were repeatedly isolated, satisfied the ATS diagnostic criteria for NTM pulmonary disease. It is important to note that NTM, including both pathogenic species and nonpathogenic species, were isolated from patients with pneumoconiosis.