A simple and rapid method for classification of β-lactamases in bacterial cells into classes A, B, C and D was devised by utilizing three β-lactamase-inhibitors clavulanic acid, a carbapenem derivative (J-110, 441) and a monobactam derivative (Syn-2161). On the basis of the combined effects of ampicillin with the inhibitor on the MIC of ampicillin, the enzyme class in the test organisms was estimated. This method was evaluated according to its application in 14 bacterial strains, which consisted of seven gramnegative species. For routine assay, a liquid microdilution method for MIC determination was employed. However, the time required for assay was reduced to one-fifth by employing an ATP-bioluminescens method developed by Hattori N, et al.(Antimicrob. Agents Chemother., 42: 1406-1411, 1998).

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We examined 2, 202 central venous catheters (CVCs) inserted during the past 10 years to assess the severity of CVC-related infection (CRI) and to propose the proper treatment of CRI. Febrile catheterized patients (body temperature above 38°C) were diagnosed as having CRI when the cultures of CVC-tips were positive or when the fever dropped immediately (within 72 hours) after removal of the CVC. Cases were defined as ‘severe’ disease, when they showed hypotension (systolic blood pressure 5_90 mm Hg) and/or complication such as acute renal failure, heart failure, respiratory failure, or ophthalmitis. The rate of CRI was 10.6%(233/2, 202), and the rate of severe disease in CRI was 15.5%(36/233). There were no significant differences in the rate of severe disease according to age, sex, underlying disease, concurrent disease, or CVC indwelling time. The rate of severe disease was significantly higher (25.9%) among the patients whose CVCs were removed more than 72 hours after the initial febrile episode (P<0.05). The rate of severe disease was significantly higher (36.7%) in patients whose maximal body temperature was above 39°C and whose WBC counts were more than 10, 000/mm³. Of the 157 microorganisms isolated from CRI, 42.0% were gram-positive cocci (GPCs), 39.5% were fungi, and 16.6% were gram-negative rods (GNRs). Because more than a half of the GPCs and GNRs were resistant strains, blood and CVC-tips cultures were considered essential for proper choice of antimicrobials. The isolation rate of fungi decreased significantly in the final 3 years (P<0.001). The rate of severe disease in the cases in which GPCs were isolated (2.6%) was significantly lower (P<0.01) than in the cases in which GNRs (40.0%) or fungi (26.5%) were isolated. Early removal of infected CVCs was recognized as being important to prevention of deterioration of CRI. Patients whose body temperature is above 39°C and whose WBC count is more than 10, 000/mm³ were considered to have ‘moderate’ disease and should be treated in the same way as patients with severe disease. Patients with ‘mild’ disease (no complications and BT<39°C or WBC<10, 000/mm³) may be treated only by removal of infected CVC. In patients with moderate or severe disease, however empiric chemotherapy should be started along with removal of the CVC. The results of this study suggest that carbapenem is the agent of first choice for empiric chemotherapy of CRI. Azole should be added if serum β-D-glucan is positive, and vancomycin should be added when empiric chemotherapy with carbapenem with or without azole is not effective.

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As we have previously reported, clarithromycin (CAM), a 14-membered ring macrolide, is BRM active, and prolongs the survival time for patients with unresectable non-small cell lung cancer without impairing quality of life. In this study, we have evaluated retrospectively 119 patients with non-small cell lung cancer who were administered CAM, and compared the factors affecting survival between the responder group (11 patients who enjoyed longer survival and were administered CAM for more than 24 months) and the non-responder group (25 patients who were administered CAM for less than 6 months). The median survival time was 63 weeks in all patients, 78 weeks in patients with squamous cell carcinoma, 49 weeks in adenocarcinoma, and 68 weeks in large cell carcinoma. In the responder group, the number of patients with squamous cell carcinoma was 8 (73%), and that of patients with clinical stage IV was 3 (27%). Regarding the basic therapy, one patient received chemotherapy only, and 9 patients (82%) received basic therapy, including radiotherapy, in the responder group. In the non-responder group, however, 9 patients (36%) received chemotherapy only, and 12 patients (48%) received basic therapy, including radiotherapy. In the responder group, many patients had good performance status (PS), and significant increase in the body weight, and in the levels of hemoglobin, cholinesterase, and albumin. However, the non-responder group, showed no significant changes. The serum levels of IL-6 in the non-responder group were significantly higher than in the responder group even before CAM administration, and remained high at three months after administration. Our data suggest that patients with squamous cell carcinoma, patients with good PS, and patients with stage ifi who received basic therapy, including radiotherapy, are more likely to respond well to CAM, and to have long-term survival. The determination of body weight, and levels of serum IL-6, cholinesterase, and albumin at three months after CAM administration may be useful in predicting the prognosis of non-small cell lung cancer in patients treated with CAM.

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