Real-time PCR is more specific than conventional PCR for induced sputum diagnosis of Pneumocystis pneumonia in immunocompromised patients without HIV infection.

BACKGROUND AND OBJECTIVE: The diagnosis of Pneumocystis pneumonia (PCP) is based on microscopic examination of respiratory specimens. PCP patients without AIDS have a lower burden of P. jiroveci than those with AIDS, which leads to difficulty in detecting the organisms. Although conventional PCR (c-PCR) has been used to detect the DNA, it is frequently positive in patients with colonization. Real-time PCR (r-PCR), a method to detect the DNA quantitatively, might be helpful in distinguishing between infection and colonization. We investigated the utility of real-time PCR in the diagnosis of PCP in non-AIDS patients. METHODS: Induced sputum samples obtained from 86 non-HIV immunocompromized patients with clinical symptoms of pulmonary infection were evaluated for the presence of Pneumocystis jiroveci-specific DNA using c-PCR and r-PCR. The diagnosis of PCP was confirmed by typical clinical and radiological findings and response to treatment. RESULTS: Of the 86 patients, 17 were diagnosed as having PCP. Twenty-eight samples were positive for c-PCR, but the false-positive rate was high (46.4%). Sensitivity, specificity and positive predictive values (PPV) of c-PCR were 88.2%, 81.2% and 53.6%, respectively. Concentrations of the DNA detected by r-PCR were significantly higher in PCP patients than in non-PCP patients. Using 30 copies per tube as a cut-off value for the diagnosis of PCP, the sensitivity (82.4%) of r-PCR was almost equal to c-PCR. Notably, its specificity and PPV were higher than c-PCR (98.6% and 93.3%, respectively). CONCLUSIONS: r-PCR on induced sputum is more useful for diagnosing PCP than c-PCR in non-HIV immunocompromized patients, especially in terms of distinguishing between colonization and infection.

Intravenous immunoglobulin therapy for refractory interstitial lung disease associated with polymyositis/dermatomyositis.

Interstitial lung disease (ILD) associated with polymyositis/dermatomyositis (ILD-PM/DM), including amyopathic dermatomyositis (ADM), is recognized as an important condition because it frequently causes death, despite intensive therapy with high-dose corticosteroid and immunosuppressive agents, such as cyclosporine A and cyclophosphamide. Intravenous immunoglobulin therapy (IVIG) has shown efficacy for myopathy associated with PM/DM, but its usefulness for ILD-PM/DM is unclear. This study was designed to investigate the efficacy of IVIG for refractory ILD-PM/DM. A review was made of medical charts of five patients (2 men and 3 women) who were treated with IVIG for refractory ILD-PM/DM resistant to high-dose corticosteroid and cyclosporine A and/or cyclophosphamide. One patient had acute ILD-PM and four patients had acute ILD-ADM. Of the five patients, one patient with ILD-PM and one patient with ILD-ADM survived. No adverse reactions were seen due to IVIG treatment. There were no critical differences in the clinical parameters and clinical courses between survivors and nonsurvivors. IVIG treatment is safe and could be an effective salvage therapy for refractory ILD-PM/DM in certain cases, suggesting that further controlled trials are worthwhile.

[An autopsy case of fulminant community-acquired pneumonia due to Acinetobacter baumannii].

A 73-year-old man with underlying chronic renal failure, angina pectoris, chronic heart failure, and respiratory failure reporting three-day appetite loss, fever, and drowsiness was admitted for lower right lung pneumonia. Despite antibiotic administration, infiltration progressed to the entire right lung and upper left lung after 12 hours, and he developed acute respiratory distress syndrome (ARDS) and multiple organ failure. Respirator ventilation and continuous hemodiafiltration (CHDF) failed to halt this progression and he died on hospital day 3. Acinetobacter baumannii was cultured from bronchoalveolar lavage fluid and the postmortem lung specimen, indicating that his severe community-acquired pneumonia was due to A. baumannii. Microscopically, the lung specimen showed prominent cellular alveolar exudate and partial hyaline membrane with suppurative pneumonia. Although A. baumannii is considered the causative agent in nosocomical pneumonia, community-acquired pneumonia due to A. baumannii is very rare. This is, to our knowledge, the first report in Japan. In the subtropical zone, A. baumannii is recognized as an important cause of severe community-acquired pneumonia. Given the apparent progress of global warming, physicians in Japan would do well to familiarize themselves with subtropical disease causes such A. baumannii when managing severe community-acquired pneumonia.

Alterations in smoking habits are associated with acute eosinophilic pneumonia.

BACKGROUND: Acute eosinophilic pneumonia (AEP) is characterized by a febrile illness, diffuse pulmonary infiltrates, and pulmonary eosinophilia. The etiology of AEP remains unknown, but several studies have proposed a relationship between cigarette smoking and AEP. However, most studies showing this possibility are single-case reports, and cigarette smoke has not been fully validated as a causative agent of AEP in a large series of patients. The present study was conducted to clarify the etiologic role of cigarette smoking in AEP, with special reference to alterations in smoking habits. METHODS: We took a detailed history of smoking habits before AEP onset in 33 patients with AEP, and performed a cigarette smoke provocation test. RESULTS: Of our AEP patients, all but one (97%) were current smokers. Interestingly, 21 of these were new-onset smokers, and 2 had restarted smoking after a 1- to 2-year cessation of smoking. The duration between starting smoking and AEP onset was within 1 month (0.67 +/- 0.53 months). Additionally, six of the remaining smokers had increased the quantity of cigarettes smoked daily, fourfold to fivefold, mostly within the month before AEP onset (0.81 +/- 0.58 months). Only three smokers had not changed their smoking habits before AEP onset. Cigarette smoke provocation tests revealed positive results in all nine patients tested. CONCLUSION: These data suggest that recent alterations in smoking habits, not only beginning to smoke, but also restarting to smoke and increasing daily smoking doses, are associated with the development of AEP.

[Clinical feature of 23 cases of combined influenza virus and bacterial pneumonia].

We investigated 23 patients with combined influenza virus and bacterial pneumonia of whom 10 patients were men, 13 were women and the mean age was 78.0 years old. The causative virus of 12 patients was type A, that of 10 patients was type B, and 1 patient was unclassified. S. pneumonia was isolated from 12 patients, S. aureus and H. influenza was isolated from 2 patients. B. Catarrhalis and Milleri spp was isolated from one patient each. The mean interval between onset of influenza and influenza pneumonia was 2.09 days. Fourteen cases developed pneumonia within 2 days after influenza infection. In particular, all nine cases with chronic respiratory disease developed pneumonia within 2 days. All cases except one were treated with oseltamivir and antibiotics, resulting in cure. These data suggest that patients with chronic respiratory disease might develop influenza pneumonia earlier than past reported cases.

Nonspecific interstitial pneumonia in collagen vascular diseases: comparison of the clinical characteristics and prognostic significance with usual interstitial pneumonia.

BACKGROUND: Nonspecific interstitial pneumonia (NSIP) has recently been described as a distinct clinicopathological entity among idiopathic interstitial pneumonias (IIP), having more favorable prognosis than usual interstitial pneumonia (UIP). Although NSIP was initially reported to also occur in patients with interstitial pneumonia associated with collagen vascular diseases (IP-CVD), the prevalence of NSIP and its prognostic significance in IP-CVD remains to be determined. Thus, we attempted to clarify clinical characteristics and prognostic significance of NSIP in IP-CVD. METHODS: We histologically examined surgical lung biopsies from 43 patients with IP-CVD based on a current classification of interstitial pneumonias, and compared the clinical characteristics and prognostic significance of NSIP with UIP in IP-CVD. We also studied 98 patients with biopsy-proven NSIP and UIP in IIP, and compared the prognostic significance of histopathologic subclassification in IIP with that in IP-CVD. RESULTS: In IP-CVD, twenty-six patients (60%) were classified as NSIP, 17 (40%) as UIP. In contrast, 76 (77%) were categorized into UIP and 22 (23%) into NSIP of the patients with IIP. No significant difference in survival rates was observed between UIP and NSIP in IP-CVD (p = 0.3863), while, in IIP, NSIP has a significant better survival than UIP (p = 0.022). CONCLUSIONS: These results suggest that NSIP is more common histologic pattern than UIP in IP-CVD and, unlike in IIP, the prognosis of NSIP patients may not be different from that of UIP patients in IP-CVD.

[Hypersensitivity pneumonitis induced by Pleurotus eryngii spores--a case report].

A 52-year-old man was hospitalized because of recurrent fever, dyspnea and cough in February 2002. He had worked in a Eringi (Pleurotus eryngii) mushroom factory since 1996. Chest radiography showed diffuse fine nodular shadows. Chest computed tomography demonstrated centrilobular nodules and increased attenuation in both lungs. The patient suffered from hypoxemia (PaO2 = 65 torr) while breathing room air. The lymphocyte count in the bronchoalveolar lavage fluid was increased, and transbronchial lung biopsy specimens showed lymphocyte alveolitis with epithelioid cell granulomas in the alveolar spaces. After admission, the patient's symptoms improved rapidly without medication. However, on his return to work, fever and hypoxemia appeared again. The lymphocyte stimulating test was positive against extracts of Eringi spores. Precipitins against the extracts of Eringi spores were detected by the double immunodiffusion test. Our diagnosis was hypersensitivity pneumonitis (HP) caused by Eringi spores. In Japan, more than 30 cases of HP induced by mushroom spores have been reported. It is a matter of great urgency to prevent the occurrence of occupational HP in mushroom factories.

[Hypersensitivity pneumonitis induced by Aspergillus niger--a case report].

A 52-year-old woman was hospitalized because of severe cough in August 1994. She had engaged in culturing roses in greenhouses since 1968, and had developed a cough during the summer of 1990. Chest radiography showed diffuse ground-glass opacity in both lung fields, and she suffered from hypoxemia (PaO2 = 45.6 torr) while breathing room air. The lymphocyte count in the bronchoalveolar lavage fluid was increased, and transbronchial lung biopsy specimens showed lymphocyte alveolitis in the alveolar spaces. After admission, the patient's symptoms improved rapidly without medication. However, on her return to work, the cough and hypoxemia reappeared. In her rose culture, she had used Rockwool, and Aspergillus niger was detected predominantly in the Rockwool. Precipitins against the extracts of Aspergillus niger were detected with the double immunodiffusion test and the inhalation provocation test yielded clinical symptoms. Our diagnosis was hypersensitivity pneumonitis caused by Aspergillus niger.

[Two cases of intralobar pulmonary sequestration associated with nontuberculous mycobacterial infection in a young patient].

We report two cases of intralobar pulmonary sequestration associated with nontuberculous mycobacterial infection. Case 1: A 28-year-old woman was hospitalized because of cough. Chest CT demonstrated multi-cystic lesions with an air-fluid level in the right lower lobe. Case 2: A 25-year-old woman was hospitalized because of fever. Chest CT demonstrated homogeneous consolidation in the right lower lobe. In both cases, aortography showed an anomalous artery supplying the right basal segment, and pulmonary sequestration was diagnosed. Furthermore, Mycobacterium avium was detected in the bronchial lavage, and a right lower lung lobectomy was performed after chemotherapy. Mycobacterium avium was cultured from the fluid in the sequestrated lung, and histological findings of the resected lobe showed epithelioid cell granulomas. We diagnosed these cases as having pulmonary sequestrations associated with nontuberculous mycobacterial infection. We concluded that pulmonary sequestration should be considered an underlying disease of secondary nontuberculous mycobacterial infections in young patients.

Recommended initial loading dose of teicoplanin, established by therapeutic drug monitoring, and outcome in terms of optimal trough level.

Teicoplanin has a long serum half-life, and therefore it takes time to reach a steady-state concentration. An initial loading procedure has been recommended for teicoplanin to enable prompt reaching of the optimal serum trough level (10-15 microg/ml). However, the dose of teicoplanin that should be administered to patients with varying renal function levels remains inconclusive. In this study, we monitored the serum concentrations of teicoplanin in patients with methicillin-resistant Staphylococcus aureus (MRSA) pneumonia and compared different teicoplanin serum concentrations and their clinical efficacy, investigating the significance of the mean dose administered during the initial 3 days. The study included 48 patients with MRSA pneumonia. The peak and trough concentrations of teicoplanin were determined utilizing a fluorescence polarization immunoassay and a two-compartment Bayesian population model. Teicoplanin was given at a loading dose of 400 or 800 mg on the first day, followed by maintenance doses of 200 or 400 mg. The mean initial dose (MID) over the first 3 days was calculated as: (loading dose + dose on 2nd day + dose on 3rd day)/3. Patients with an MID of 266.7 mg or less (400 mg for loading, 200 mg over the 2nd and 3rd days) did not have a trough level that exceeded 10 microg/ml at the point before the injection on the 4th day. Even in patients with hemodialysis (HD), an MID of 266.7 mg was not enough to provide a trough level of 10 microg/ml. Patients with an MID than 533.3 mg had significantly elevated trough levels, showing better outcomes. A multiple regression formula for predicting trough level before the fourth day of administration is given as: 0.034 + 0.030 x (MID; mg) - 0.057 x creatinine clearance (Ccr; ml/min). These findings suggest that 800 mg as an initial dose, followed by 400 mg maintenance doses over the following 2 days, makes it possible to safely attain an optimal trough level, even in the patients with HD.