[Trends in antibiotic susceptibility and genetic beta-lactam resistance patterns among Haemophilus influenzae cases isolated from adult patients with respiratory tract infection].

Haemophilus influenzae, a major respiratory tract pathogen, is becoming increasingly resistant to beta-lactam antibiotics. Studying annual trends in antibiotic susceptibility and genetic patterns of H. influenzae beta-lactam resistance, we isolated 122 strains from the adult respiratory tract in 2007, determined MIC for different antibiotics, and analyzed TEM-1 beta-lactamase resistant genes and ftsI encoding PBP3 mutation compared to results in 2005 and 2007. We found that ABPC-susceptible strains with MIC <1 microg/mL (BLNAS) accounted for 71.0%, ABPC-resistant strains with MIC exceeding 2 microg/mL without beta-lactamase activity (BLNAR) for 25.3%, and beta-lactamase-positive strains (BLP) for 3.7%. The BLNAS ratio showed no significant change from 2002 and 2005. The BLP ratio decreased from those in 2002 and 2005. Genetic studies of resistant genes showed that gBLNAS with no resistant genes had increased in the last five years. The ratio of all strains with PBP3 mutation (gBLNAR and gLow-BLNAR) remained constant from 2002 to 2007. The proportion of gBLNAR with two PBP3 mutations had increased, however, while gLow-BLNAR with one mutation had decreased. LVFX showed constant strong antimicrobial potency for all mutation groups. Among beta-lactam antibiotics, the lowest MIC90 was observed in parenteral CTRX and oral CDTR-PI use. Although a new MIC peak generated by gBLNAR became obvious in the ABPC and CDTR-PI MIC distribution, the MIC of the new peak was still low enough to treat with high doses of those two antibiotics.

[A case of pulmonary Mycobacterium avium infection presenting multiple nodules with substantial difference in 18F-fluorodeoxyglucose uptake].

A 56-year-old man presented with a chief complaint of chronic cough due to bronchial asthma and pulmonary emphysema in 2001, without any abnormal findings on chest CT. His symptoms improved with high-dose inhaled corticosteroid. In February 2004, multiple nodules without bronchiectasis appeared in the chest CT. Pulmonary Mycobacterium avium infection was diagnosed by bronchial lavage and sputum culture. After multiple nodules appeared and disappeared repeatedly without medication, most nodules vanished after administration of antituberculous drugs. In Feburary 2007, a rapidly growing mass appeared in the right upper lobe, and a new nodule emerged in the left upper lobe the following month. On 18F-fluorodeoxyglucose positron emission tomography (18 FDG-PET), a substantial difference in 18FDG uptake was observed although both lesions were shown to be caused by Mycobacterium avium infection by needle biopsy. The lung specimen of the lesion with high 18FDG uptake demonstrated neutrophil infiltrates, suggesting acute inflammation. On the other hand, neutrophil infiltrates were not observed in the lesion with low uptake. We conclude that the degree of 18FDG uptake is not useful to decide when to initiate therapy and evaluate the efficacy of treatment.

[Usefulness of monitoring plasma voriconazole concentration in patients with chronic necrotizing pulmonary aspergillosis].

We investigated the significance and the usefulness of monitoring plasma voriconazole levels in patients with chronic necrotizing pulmonary aspergillosis associated with underlying chronic respiratory diseases. The average trough level was 2.2 microg/ml and there was no correlation between trough levels and voriconazole doses. Orally administered drug showed no significant difference in trough or peak levels compared with parenteral injection. Six cases with visual adverse events had significantly higher nadirs compared to those without visual disturbance. All three cases who discontinued the drug due to liver dysfunction had plasma trough levels higher than 4.0 microg/ml. Those who failed to respond to the treatment had trough levels lower than 1.4 microg/ml or peak levels lower than 2.8 microg/ml, while some cases with plasma level lower than those levels responded well. Since plasma voriconazole level has a large inter-patient variability, drug monitoring may be beneficial to evaluate the drug efficacy and safety in each individual.

[Clinical features of pulmonary disease caused by Mycobacterium fortuitum].

We analyzed clinical and microbiological features of six cases involving Mycobacterium fortuitum isolated from sputum or surgical lung specimen. Patients were five men and one woman with an average age of 59. Four cases had a history of pulmonary tuberculosis and three had nontuberculous mycobacterial lung disease. Three out of six cases had underlying chronic obstructive pulmonary disease. Diabetes mellitus was complicated in five cases. All diseases were in the upper lobes of either lung. Clinical symptoms were mainly cough and sputum, while two cases developed pneumothorax. Although all strains showed low sensitivity to standard anti-tuberculous agents, chemotherapy including those drugs or fluoroquinolones and macrolides were successful in all treated cases.

[Clinical features of chronic necrotizing pulmonary aspergillosis treated with voriconazole in patients with chronic respiratory disease].

We analyzed clinical features of chronic necrotizing pulmonary aspergillosis (CNPA) in patients with underlying chronic respiratory disease, and evaluated the efficacy and tolerability of voriconazole against CNPA in those patients. Voriconazole therapy was indicated in 45 CNPA patients between October 2005 and September 2007, in 23 patients as first-line treatment and in 22 after lack of response to or intolerance of prior antifungal agent. The most common underlying respiratory disease was sequelae of tuberculosis (n = 23) followed by COPD (n = 13). Cavitary lesions were found in 32 patients. Galactomannan antigen test was positive in 29 patients while 28 patients out of 36 were positive for anti-Aspergillus serum antibody. The antibody-negative group had significantly higher levels of galactomannan antigen than the antibody-positive group. Mycological culture or hyphae were positive in 15 patients. Beta-D glucan level was within the normal limit in 27 patients. Clinical, radiological improvement, or both was obtained in 30 patients after an average voriconazole treatment of 4.8 months, with the main adverse effects being visual disturbance and hepatotoxicity. During the observation period 14 patients died due to CNPA or other causes. Although voriconazole demonstrated good efficacy against CNPA, the outcome is still unsatisfactory.

[Four cases of pulmonary infection due to Mycobacterium szulgai with a review of previous case reports in Japan].

We report 4 cases of pulmonary infection due to Mycobacterium szulgai with review of 23 cases previously reported in Japan. All 4 patients were male and two of them in their 20's were found to have abnormal chest X-ray findings recognized on a health checkup without any symptoms. One case had no previous history of illness and had never smoked. Radiographic study showed thick-walled cavities in 3 cases and multiple small nodules in 2, indicating the difficulty of distinguishing M. szulgai infection from pulmonary tuberculosis or M. kansasii infection. Three cases were treated as pulmonary tuberculosis at first, and later we changed the medication referring to the drug susceptibility. In most cases, rifampicin, ethionamide and ethanbutol were used and the medication regimen was successfully completed in all cases. Considering that the detected M. szulgai could be regarded as pathogen in almost all cases, it is important to evaluate the risk factor of patients and not to delay diagnosis and treatment with adhering to usual diagnostic criteria.

[A case of lung adenocarcinoma with gradual enlargement of thin-walled cavity causing pneumothorax].

A 71-year-old man presented with a thin-walled cavity in his left lung in November 2006. A previous chest CT in 2003 showed a small thin-walled cavity in his left lingula. Although no obvious change was observed in 2004, the cavity increased its size from 11mm to 14mm in diameter and the wall became thicker in June 2006. On the first visit to our hospital in November 2006, the diameter of the cavity was 30mm and some part of the wall was thinner than on the previous CT. The patient developed pneumothorax one month later and underwent segmentectomy of the left lingula after unsuccessful thoracic drainage. Poorly differentiated adenocarcinoma was identified in both the pleura and the inner wall around the cavity. Lung adenocarcinoma with gradual enlargement of a thin-walled cavity causing pneumothorax has never been reported before. We report here the natural course of lung adenocarcinoma with a thin-walled cavity.

[Case of pneumothorax associated with pulmonary Mycobacterium fortuitum infection].

A 39-year-old man with dyspnea was revealed to have severe pneumothorax and received partial resection of the left upper lobe after unsuccessful drainage. Necrotizing epitheloid granuloma was found in the resected lung and Mycobacterium fortuitum was detected from the lesion. Chemotherapy with levofloxacin and clarithromycin was started one year after surgery because of the newly found nodular shadow near the lesion. The case experienced pyothorax due to pulmonary tuberculosis three years before and Mycobacterium avium pleuritis one year before this episode. Three-time mycobacterial pleural infection in three years seems to be uncommon. Furthermore this is the first report of pneumothorax associated with pulmonary Mycobacterium fortuitum infection.

[An autopsy case of invasive thymoma extending to the right atrium with superior vena cava syndrome as the initial manifestation].

We report a case of invasive thymoma presenting with superior vena caval obstruction and intracardiac extension. A 74-year-old man was admitted in July 2002 with swelling of the face and right upper extremity. Computed tomography of the chest revealed a small anterior mediastinal mass, which infiltrated the lumen of the superior vena cava extending into the right atrium. Invasive thymoma was strongly suspected, but he refused any medical treatment. His health declined steadily, with repeated right-sided heart failure. He died due to cardiac tamponade 50 months after his first visit. On autopsy, the tumor was diagnosed as a thymoma classified as type B3 according to the WHO histological classification. Formation of a tumor thrombus in the superior vena cava and the right atrium is a rare mode of extension of thymoma. In this respect, our case may be valuable for improving the understanding of the natural course of invasive thymoma.

[Chronic summer-type hypersensitivity pneumonitis presenting with acute exacerbation].

A 77-year-old man was admitted to our hospital. He had first noticed a cough, sputum production, and low-grade fever during the summer of 1988. He was diagnosed as having summer-type hypersensitivity pneumonitis (HP) in 1989 on the basis of positive findings of anti-Trichosporon antibodies in the serum and bronchoalveolar lavage (BAL) fluid and and in environmental provocation tests. Thereafter, he presented with re-exacerbation of his disease in summer every year. In 1995, he retired from his work at a moldy hotel and moved to another house to avoid the causative antigen completely. There was no recurrence for the following 5 years. He suffered from cough, sputum production, and dyspnea 4 months after returning to his previous moldy house in October, 2000. A chest CT scan showed peribronchial and subpleural honeycombing, ground glass opacities, and traction bronchiectasis. BAL demonstrated that the lymphocyte count had changed from 78.9% to 42.9% and the CD4/CD8 ratio from 0.39 to 4.07 in 12 years. Antigen avoidance and steroid therapy have improved his condition. However, he stayed repeatedly in his moldy house, and finally died from acute exacerbation in March, 2002. Postmortem examination demonstrated diffuse alveolar damage (DAD) superimposed on honeycombing in the lungs.