Efficacy and safety of piperacillin/tazobactam versus biapenem in late elderly patients with nursing- and healthcare-associated pneumonia.

Pneumonia is associated with an extremely high mortality rate in patients of late elderly age. Piperacillin/tazobactam and carbapenems are drugs of first choice for hospitalized patients with potentially resistant bacteria. We compared the efficacy and safety of piperacillin/tazobactam and biapenem. Among elderly patients with nursing- and healthcare-associated pneumonia, we extracted 53 patients treated with piperacillin/tazobactam and 53 patients treated with biapenem who were matched for sex, age, and severity of pneumonia. The average age was more than 80 years; most of the patients were middle- to oldest old in age. Although clinical efficacy was equally good, patients in the piperacillin/tazobactam group achieved significantly faster improvements on chest X-ray and body temperature on day 7. However, in the piperacillin/tazobactam group, nephrotoxicity frequently led to a need for a reduction in the dose or complete discontinuation of treatment. The average age of patients who developed significant nephrotoxicity was high, at 83.2 years. The biapenem group exhibited significantly better continuation of treatment than the piperacillin/tazobactam group. Toxicity profiles were different between the two groups. Hepatic toxicity was significantly higher in the biapenem group, whereas nephrotoxicity was significantly more common in the piperacillin/tazobactam group. Rate of decrease in bacteria was equally good between the two groups. Providing careful follow-up and conducting more detailed examinations, including studies to determine optimal dose and timing of administration, are necessary for the treatment of late elderly patients with numerous underlying diseases and potential organ dysfunctions.

[The relationships between the peak inspiratory flow and the characteristics factors in the asthmatics with inhaled corticosteroid -a multicenter study in Chugoku Shikoku area].

BACKGROUND: Inhaled corticosteroid (ICS) will be effective if used properly. Inadequate intake may result in insufficiency, such as for elderly asthmatics, in particular, for use of dry powder inhalers. METHODS: 312 asthmatics treated with ICS for at least 6 months in the 6 facilities belonging to the Chugoku Shikoku Adult Asthma Research Forum were subject to investigation of the peak inspiratory flow (PIF) measured using In-check® and related factors. RESULTS: Nine (2.8%) patients were considered to have insufficient intake. By multivariate analysis, PIF (L/min) prediction formula was as follows: 79.0+0.19* peak expiratory flow (PEF: L/min)+22.9* FVC (L)-0.68* onset age (years)+34.7* gender (male, 1; female, 0)+16.1* V50/V25, [r^2=0.677, p<0.0001]. Using cluster analysis with Euclidean distance and Ward's method, the PIF without an adaptor was included in the same category as height and PEF, and the PIF with an adaptor was included in the same category as %FVC and %FEV1.0. CONCLUSION: The cases with insufficient PIF are few but present. Adequate device selection and inhalation guidance may be important. The meaning of PIF differs depending on whether or not an adaptor is present. Further investigation of intake is considered necessary.

[A case of miliary tuberculosis and esophageal perforation secondary to tuberculous mediastinal lymphadenitis].

An 80-year-old woman was admitted to a local hospital following transient disturbance of consciousness after a fall. High intermittent fever developed after hospitalization and she was diagnosed as having mediastinal abscess with esophageal perforation. She underwent mediastinal drainage and surgical repair of the esophagus. Acid-fast bacilli were detected in her sputum. Chest CT scanning showed a diffuse granular shadow. Then she was diagnosed as having miliary tuberculosis and treated with combination of INH, RFP, EB, and PZA. However, five days after treatment was initiated, fever and skin eruption appeared and treatment has to be stopped after one month. Then she was referred to our hospital. We gradually increased the dosages of INH and RFP, which resulted in pyrexia. Therefore, we changed EB to SM. Fever subsided and we were able to administer the full dose of drugs from the beginning of January 2007. Thereafter, the patient improved gradually. However, she died in February 2007. At autopsy, we identified tuberculous mediastinal lymphadenitis, inflammatory granuloma under the esophageal mucosa and miliary tuberculosis. We report this case as a rare case of miliary tuberculosis and esophageal perforation secondary to tuberculous mediastinal lymphadenitis.

[A case of axillary lymph node tuberculosis with paradoxical worsening in breast lesion].

A 80-year-old woman was admitted to our hospital because of left axillary swelling. Needle biopsy specimen showed negative results on a smear for acid-fast bacilli and PCR. The histological findings showed epithelioid cell granuloma with caseous necrosis. QFT TB-2G showed positivity of 1.9 IU/ml in ESAT-6. We diagnosed tuberculous lymphadenopathy and administered antituberculous drugs. After 3 weeks of treatment, in spite of the regression of lymphadenopathy, mammary swelling had progressed. We performed a biopsy of the mammary lesion, but did not detect any abnormal findings. As the mammary lesion had regressed by the continued treatment of antituberculous drugs, we thought the mammary swelling was paradoxical worsening.

[A case of Mycobacterium intracellulare pleurisy without active lung lesion].

Pleural effusion without occurrence of active pulmonary lesion due to nontuberculous mycobacteria is extremely rare. We report a case of Mycobacterium intracellulare pleurisy in an 84-year-old woman. The patient was admitted to a nearby hospital because of dyspnea. Massive right pleural effusion was observed on chest roentgenogram. Bacteriological examinations, smear and culture of the sputum or pleural effusion were negative. First we thought pleurisy was caused by M. tuberculosis as pleural effusion showed predominant lymphocyte count and high adenosine deaminase level. However, M. intracellulare was identified by the polymerase chain reaction method from pleural effusion. Based on clinical findings and laboratory data, we suspected pleurisy was due to M. intracellulare infection. Clarithromycin, kanamycin, rifampicin and ethambutol were administered. After four months of treatment pleural effusion disappeared without accompanying the active pulmonary lesion. Therefore, we diagnosed this case as pleurisy without pulmonary lesion due to M. intracellulare.

[A case of multi-drug resistant pulmonary tuberculosis after administration of standard anti-tuberculosis treatment for two times].

We reported a case in which multi-drug resistant tuberculosis was recognized after two courses of anti-tuberculosis treatment. A 41-year-old woman who had received two courses of anti-tuberculosis treatment for pulmonary tuberculosis was admitted to our hospital due to productive cough, high fever and positive sputum smear showing acid fast bacillus. In the past treatment, drug susceptibility was unknown because of culture-negative TB. Chest radiograph showed atelectasis of the right upper lobe. The pathological examination of surgically resected lung specimen revealed that atelectasis was formed by a granulation tissue with caseous necrosis progressed to the bronchus wall. We examined cultures three times using both solid and liquid media. Liquid culture of the first time specimen was positive for Mycobacterium tuberculosis after six weeks and multi-drug resistant tuberculosis was recognized on drug susceptibility test. Thereafter she was treated with KM, LVFX, PZA and PAS, and maintained sputum smear negative for 7 months after treatment. Physicians must consider possibility of MDR-TB despite findings showing smear-positive and culture-negative TB.

[Quantiferon TB-2G among nurses with a history of working in our tuberculosis ward].

PURPOSE: To investigate the infection rate of tuberculosis among nurses with a history of working in our hospital's tuberculosis ward (TW). METHODS: We measured interferon gamma levels in 50 nurses who had worked in our TW, and evaluated the infection rate among these nurses before (I) and after (II) the use of our hospital's tuberculosis infection control manual. RESULTS: The infection rate including probable infection was 6/50 (12.0%) in all TW nurses. The infection rate in the group I was 17.6%, but that in group II was 0%. CONCLUSION: Our hospital's tuberculosis infection control manual was effective for decreasing the infection rate, despite a high rate of infection in group I.

[A case of severe pulmonary hypertension associated with COPD treated with epoprostenol].

A rare case of chronic obstructive pulmonary disease (COPD) with severe pulmonary hypertension (PH) was found in a 68-year-old man. COPD was diagnosed in his 50s, from which time he received home oxygen therapy. In January 2007, he was admitted due to progression of dyspnea. On admission to our hospital, arterial blood gas analysis showed severe hypoxemia. Moreover, echocardiographic findings demonstrated severe deviation of the interventricular septum toward the left ventricle, with right ventricular dilatation. Cardiac catheterization data demonstrated pulmonary arterial hypertension with a low cardiac output. Because severe PH is uncommon in patients with COPD and there was no apparent etiology of PH other than COPD, we thought this case was predominantly a pulmonary vascular disease such as idiopathic pulmonary arterial hypertension. Though we first treated this patient with bosentan, it was not effective. Therefore, he was treated with continuous infusion of epoprostenol. Epoprostenol administration along with bosentan resulted in decrease of BNP and right ventricular function improvement. We report a case of severe PH due to severe COPD treated with continuous administration of epoprostenol.

[A suspected case of voriconazole-induced lung injury].

A 71-year-old man was initially given a diagnosis of pulmonary nontuberculous mycobacterial infection due to Mycobacterium intracellulare (M. intracellulare). The patient was admitted because chest roentgenogram and CT scanning showed a progression of infiltrating shadows in the bilateral upper lung fields. Aspergillus fumigatus was identified by bronchial lavage. The patient was found to have chronic necrotizing pulmonary aspergillosis with M. intracellulare and treated with voriconazole (VRCZ). After fifteen days of treatment, he complained of dyspnea and cough. A chest CT showed new diffuse ground glass opacity in the left lower lobe. Arterial blood gas analysis demonstrated severe hypoxemia. Due to concerns about drug-induced lung injury, voriconazole was discontinued and corticosteroid therapy was started. VRCZ was replaced by micafungin. Thereafter, symptoms and left lower shadows resolved. Although the lymphocyte stimulation test for voriconazole was negative, we considered that this pulmonary lesion may have been an adverse reaction to voriconazole.

Paradoxical worsening of pulmonary Mycobacterium abscessus.

Transient worsening of tuberculosis (TB) symptomatology and lesions in response to anti-TB therapy has previously been reported as paradoxical worsening. Recently, paradoxical worsening of TB following antiretroviral therapy in AIDS patients was reported. However, paradoxical worsening of nontuberculous mycobacterium, including Mycobacterium abscessus (M. abscessus), has not been reported previously. We reported the first case of paradoxical worsening of pulmonary M. abscessus.

[Use of QuantiFeron TB-2G test on high-risk groups for tuberculosis infection at our hospital].

PURPOSE: To investigate the infection rate of tuberculosis in high-risk employees at our hospital. METHODS: We measured interferon gamma levels in 40 employees and evaluated the infection rate in doctors working in the Tuberculosis Ward (D group), nurses in the Tuberculosis Ward (N group), and other high-risk employees (O group). RESULTS: The overall infection rate including probable infection was 6/40 (15.0%). The infection rate in the N group was 0%, while those in the D and O groups were 27.3% and 20.0% respectively. No new infection of tuberculosis was observed after the introduction of tuberculosis infection measure manual of our hospital. CONCLUSION: Our hospital's tuberculosis infection measure manual was effective in decreasing the new tuberculosis infection despite a high infection rate in high-risk employees at our hospital.

[Case of liver tuberculosis requiring differentiation from liver metastasis of cancer].

A 79-year-old woman was admitted to our hospital because of general fatigue. Chest radiograph and computed tomograph showed bronchiectasis and centrilobular nodules in the right middle lobe and lingula, which had not changed from previous examination. Intrahepatic nodular lesions and swelling of the left cervical lymph nodes, supraclavicular lymph node, abdominal paraaortic lymph nodes and inguinal lymph nodes was observed. Biopsy specimen of the liver lesion demonstrated epithelioid cell granulomas. Biopsy of the right inguinal lymph node demonstrated epithelioid cell granulomas with caseous necrosis and culture of the specimen showed Mycobacterium tuberculosis. The patient was diagnosed as having liver tuberculosis and multiple tuberculous lymphadenitis. Antituberculous treatment with isoniazid, rifampicin, ethambutol and pyrazinamide were started and continued for 6 months. All lesions improved after treatment. This was a rare case of liver tuberculosis that was difficult to distinguish from liver metastasis of cancer.

[Case of pulmonary tuberculosis with both a solitary nodule and enlarged lymph nodes showing intense uptake on 18f-fluoro-deoxy glucose positron emission tomography (18FDG-PET) requiring differentiation from lung cancer].

A 63-year-old man was admitted to our hospital for the evaluation of an abnormal nodule in lung. Chest CT demonstrated a smooth nodular shadow in the left S6 and enlarged left hilar and mediastinal lymph nodes. Local uptake in these nodes was demonstrated on 18FDG-PET. Although bronchoscopic study was performed, definitive diagnosis had not yet been determined. After one year, the nodular shadow increased in its size. To confirm the diagnosis, VATS was performed. The histological findings showed a caseating epithelioid-cell granuloma and culture of the specimen was positive for Mycobacterium tuberculosis. This case suggested the difficulty in distinguishing lung cancer from solitary tuberculous nodules by using 18FDG.

Clinical significance of the expression of tumor-associated antigen, RCAS1, and its soluble protein in pleural fluid in malignant mesothelioma.

RCAS1 is a type II membrane protein which is also secreted as a soluble protein. RCAS1 may play a role in evading immune surveillance by tumor cells and be responsible for the aggressive behavior of tumors. We examined the usefulness of RCAS1 in the follow-up of malignant mesothelioma. In addition, we examined the usefulness of its soluble protein (sRCAS1) in pleural effusion for the diagnosis of malignant mesothelioma. We studied 38 patients with pleural malignant mesothelioma and examined the correlation between RCAS1 expression, clinicopathologic variables and overall survival. We also determined the pleural fluid sRCAS1 concentration with an enzyme-linked immunosorbent assay (ELISA). We found that 34 out of 38 (89.5%) malignant mesothelioma cells stained for RCAS1. The positive rate was 90.9% in biphasic type, 78.6% in epithelioid type, and 100% in sarcomatoid type. No statistically significant correlation was observed between RCAS1 expression and gender, age, histology or clinical stage. Interestingly, survival of the malignant mesothelioma patients with RCAS1 expression was significantly increased compared with those without (median survival time: 13.0 vs. 4.3 months, p=0.011). Multivariate analysis of prognostic factors, using the Cox proportional hazards model, revealed that RCAS1 expression had a significantly positive effect on survival. sRCAS1 concentrations in pleural fluid in malignant mesothelioma were lower than those in lung cancer (2.18+/-2.20 vs. 46.3+/-129 U/ml; p=0.019). RCAS1 expression is informative for the follow-up of malignant mesothelioma patients. In addition, sRCAS1 in pleural fluid may be useful for the diagnosis of malignant mesothelioma.

Sudden onset of interstitial lung disease induced by gefitinib in a lung cancer patient with multiple drug allergy.

Gefitinib is an oral selective inhibitor of the epidermal growth factor receptor tyrosine kinase which is effective for patients with advanced non-small cell lung cancer. A 75-year-old man with advanced adenocarcinoma of the lung was treated with gefitinib. He had a history of allergy to several antibiotics and Welder's lung. Two days after initiation, he developed acute interstitial lung disease (ILD) and died of respiratory failure due to progression of ILD. Critical assessment pointed to gefitinib as the likely cause of this complication. This is the first report of rapid gefitinib-induced ILD. This case should alert physicians to the potential for dangerous pulmonary side-effects of gefitinib therapy, especially in patients with drug allergy.

Sedation for terminally ill patients with cancer with uncontrollable physical distress.

BACKGROUND: Relief of distressful symptoms in terminally ill patients with cancer is of prime importance. Use of sedation to accomplish this has been the focus of recent medical studies in countries other than Japan. We investigated the influence on consciousness of sedative drugs in a Japanese hospice. DESIGN AND SUBJECTS: We defined sedation as medical procedure to decrease level of consciousness in order to relieve severe physical distress refractory to standard interventions. We excluded increases in doses of morphine or other analgesic drugs resulting in secondary somnolence from the present study. We reviewed medical records of patients receiving sedation among 124 consecutive patients admitted to our palliative care unit between January and December in 1999. RESULTS: The 63 patients who received sedation (50.3%) died an average of 3.4 days after its initiation. Major symptoms requiring sedation were dyspnea, general malaise/restlessness, pain, agitation, and nausea/vomiting. The Palliative Performance Status (PPS) just before sedation was 20 or less in 83% of patients. Drugs administered for sedation were midazolam, haloperidol, scopolamine hydrobromide, and chlorpromazine. During the few days before death, sedated patients were significantly more drowsy and less responsive than that in those receiving non-sedative treatment. CONCLUSIONS: Our data suggest the effectiveness of sedation in relieving severe, refractory physical symptoms in terminally ill Japanese patients with cancer. Further investigation to confirm safety and effectiveness of sedation in this context is warranted.

Chronic lung abscess with Pasteurella multocida infection.

We report a patient with chronic lung abscess due to Pasteurella multocida infection that may be caused by the contact with cows in his workplace. Despite its apparent rarity, chronic abscess due to P. multocida should be considered in the differential diagnosis of solitary pulmonary masses. This case report suggests that P. multocida infection can be potentially caused from saliva of cows as well as dogs or cats.

Diagnostic significance of interferon-gamma in tuberculous pleural effusions.

STUDY OBJECTIVES: Tuberculosis (TB), the single most frequent infectious cause of death worldwide, also is a major cause of pleural effusion, which in TB usually has lymphocytic and exudative characteristics. Differential diagnosis between TB and nontuberculous pleural effusion can be sometimes difficult, representing a critically important clinical problem. METHODS: We studied 46 patients presenting with pleural effusion to the National Sanyo Hospital between April 2000 and January 2001 (34 men and 12 women; mean age, 64 years). Ten patients (22%) had tuberculous pleurisy, 19 patients (41%) had malignant pleuritis, and 17 patients (37%) had pleural effusion due to an etiology other than tuberculosis or cancer. Pleural fluid concentrations of four suggested markers were measured using commercially available kits. RESULTS: The pleural fluid levels (mean +/- SE) of adenosine deaminase (83.3 +/- 18.2 U/L vs 25.8 +/- 20.4 U/L, p < 0.0001), interferon-gamma (137 +/- 230 IU/mL vs 0.41 +/- 0.05 IU/mL, p < 0.0001), immunosuppressive acidic protein (741 +/- 213 micro g/mL vs 445 +/- 180 micro g/mL, p < 0.001) and soluble interleukin 2 receptor (7,618 +/- 3,662 U/mL vs 2,222 +/- 1,027 U/mL, p < 0.0001) were significantly higher for tuberculous pleuritis than for other causes of effusion. Receiver operating characteristic analysis demonstrated that pleural fluid content INF-gamma was the best indicator of tuberculous pleurisy among four relevant biological markers. CONCLUSIONS: INF-gamma in pleural fluid is the most sensitive and specific among four biological markers for tuberculous pleuritis. Thus, our results suggest that determination of INF-gamma at the onset of pleural effusion is informative for the diagnosis of tuberculous pleuritis. Further studies including larger numbers of patients are needed to verify this result.

Comparison of six biological markers for the diagnosis of tuberculous pleuritis.

STUDY OBJECTIVE: We sought a marker to differentiate tuberculous pleural effusions from nontuberculous pleural effusions, which otherwise can be difficult. PATIENTS: We studied 55 patients with pleural effusions, 20 (36%) with tuberculous pleuritis and 35 (64%) with a nontuberculous etiology. MEASUREMENTS AND RESULTS: Pleural fluid levels of adenosine deaminase, interferon (INF)-gamma, interleukin (IL)-12p40, IL-18, immunosuppressive acidic protein, and soluble IL-2 receptors were measured and were subjected to receiver operating characteristic analysis. INF-gamma had the greatest sensitivity and specificity for tuberculous pleuritis among the six biological markers studied. CONCLUSION: The determination of INF-gamma levels in pleural fluid is the most informative in the diagnosis of tuberculous effusion.

Soluble receptor-binding cancer antigen expressed on SiSo cells in pleural fluid: a potential diagnostic marker for malignant pleural effusion.

BACKGROUND: We sought a marker to differentiate malignant from nonmalignant pleural effusions. METHODS: We studied 41 patients presenting with pleural effusions to the National Sanyo Hospital between April 2000 and January 2002 (33 men and 8 women; mean age, 68 years). Twenty patients (49%) were proven to have malignant pleural effusions, while 21 patients (51%) had nonmalignant pleural effusions. Thoracentesis was performed. RESULTS: The mean (+/- SD) concentration of receptor-binding cancer antigen expressed on SiSo cells (RCAS1) in malignant pleural effusions, measured by enzyme-linked immunosorbent assay, was significantly higher than that in nonmalignant pleural effusions (15.1 +/- 33.6 vs 1.4 +/- 0.81 U/mL, respectively; p < 0.05). CONCLUSION: The determination of the RCAS1 concentration in pleural fluid is informative in the diagnosis of malignant pleural effusions.