The activities of three carbapenems, imipenem, meropenem, and panipenam, as well as that of tosufloxacin, against 88 strains of Pseudomonas aeruginosa, 48 strains of Staphylococcus aureus and 37 strains of Enterococcus faecalis were examined. In P.aeruginosa, the activities of piperacillin, ceftazidime, amikacin, tobramycin, ofloxacin, and carumonam were also evaluated. To compare activities the ratios of the minimum inhibitory concentration (MIC) of imipenem to the respective MICs of meropenem, panipenem, and tosufloxacin were calculated. In P.aeruginosa, meropenem had the lowest MICs among the carbapenems. In S.aureus as well as E.faecalis, imipenem had the lowest MICs among the carbapenems. To evaluate the cross-antimicrobial activity between imipenem and the other antimicrobial agents, we introduced a parameter called the MIC ratios distribution index. In P.aeruginosa, MIC ratios distribution indexes between meropenem and imipenem, panipenem and imipenem, tosufloxacin and imipenem, piperacillin and imipenem, ceftazidime and imipenem, amikacin and imipenem, tobramycin and imipenem, ofloxacin and imipenem, and carumonam and imipenem were 1.01, 0.41, 1.86, 1.47, 1.26, 1.66, 1.82, 1.82, and 1.41, respectively, indicating cross-antimicrobial activity between imipenem and panipenem. In S.aureus, the MIC ratios distribution indexes between meropenem and imipenem, panipenem and imipenem, and tosufloxacin and imipenem were 0.35, 0.42, and 0.75, respectively, indecating cross-antimicrobial activity between carbapenems. In E. faecalis, the MIC ratios distribution indexes between meropenem and imipenem, panipenem and imipenem, and tosufloxacin and imipenem were 0.65, 0.19, and 2.57, respectively, indicating crossantimicrobial activity between carbapenems, but no cross-antimicrobial activity between imipenem and tosufloxacin. These results seem helpful in providing useful guidelines for choosing an effective treatment against clinical isolates of P. aeruginosa, S.aureus, and E.faecalis.

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Methicillin-resistant Staphylococcus aureus (MRSA) N 133 was intranasally inoculated to mice. Three hours after inoculation with 10⁶ CFU of S.aureus N 133, 10⁵CFU of the bacteria was detected in the caecum. The viable cell count in the caecum decreased to 10²CFU three days after inoculation but increased again to approximately 10³CFU five days after inoculation. And the cell level was maintained for at least ten days. Ampicillin increased the viable cell count slightly when administered subcutaneously at a dose of 10 or 20mg/kg twice a day for four days starting on the day before inoculation, whereas cefotiam suppressed growth slightly, and cefozopran inhibited it completely. When mice underwent abdominal surgery to provide stress or were administered 200mg/kg of cyclophosphamide or dexamethasone in order to supress immunity, the growth of MRSA in the caecum was enhanced significantly. On the other hand, oral administration of Enterococcus faecium before inoculation suppressed the excessive growth of MRSA induced by abdominal surgery. These results suggest that immunosuppression and stress by abdominal surgery play more important roles than antibiotics in the growth of MRSA in the caecum.

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The protective effect of piperacillin against the nephrotoxicity of vancomycin and arbekacin was examined in rats. Nephrotoxicities were induced by the intravenous administration of vancomycin (160mg/kg) or by the intramuscular administration of arbekacin (16mg/kg) for 4 days. Rats receiving vancomycin (160mg/kg) showed slight elevation of urinary NAG in comparison with the control, and showed some histological changes including mild renal tubular dilatation. Rats receiving arbekacin (16 mg/kg) showed slight hyaline droplet degeneration of proximal tubular epithelia. Piperacillin (320mg/kg) reduced these toxicological parameters. Rats receiving vancomycin (160mg/kg) plus arbekacin (16mg/kg) showed elevation of blood urea nitrogen, creatinine concentration, urinary NAG, protein and β₂-microglo-bulin, showed increased kidney weight, and showed some histological changes including tubular necrosis. Nephrotoxicity was remarkably enhanced by combined treatment with vancomycin and arbekacin. However, piperacillin (320mg/kg) significantly reduced these toxicological parameters.

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We performed a comparative study between norfloxacin (NFLX) and polymyxin B (PMB) to determine the prevention of infection during the granulocytopenic period after anti-leukemic chemotherapy for acute leukemia. Twelve patients with acute leukemia were orally administered NFLX at 800mg/day or PMB at 600×10⁴U/day accompanied by amphotericin B at 2, 400mg/day, for 23 courses while their peripheral neutrophil count was less than 1, 000/ul. Background factors before administration, average age, leukemic state, complications, peripheral leukocyte count and body temperature, were not significantly different between the two groups. Since febrile episodes during administration occurred at the same frequency (6 of 11 courses in the NFLX group, and 7 of 12 courses in the PMB group), the effect of NFLX did not seem to be different from that of PMB. The serum level of endospecies were decreased by the administration of each antibiotic in 3 of 4 NFLX courses and in 4 of 7 PMB courses, without any findings of infection. The serum level of beta -D-glucan, an indicator of fungal infection, did not increase in any patients except one in the NFLX group who had no clinical manifestation of any infection. In conclusion, the oral administration of NFLX for the prevention of infection showed the same effectiveness as that of PMB, and was safe without any side-effects in patients with acute leukemia.

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A clinical trial of a combination therapy with aztreonam (AZT) and clindamycin (CLDM) was carried at the First Department of Medicine, Hokkaido University School of Medicine, and its 17 affiliated hospitals to evaluate current usefulness of the therapy. The daily dose was, in general, 2.0g of AZT and 1.2g of CLDM, or 4.0g of AZT and 2.4g of CLDM (divided into two doses). The antibiotics were administered via drip infusion for 3 to 14 days.
1) The study subjects included 84 patients with bacterial pneumonia, 18 patients with mycoplasmal pneumonia, and 17 patients with miscellaneous respiratory infections. Side effects and abnormal laboratory findings were evaluated in all subjects, and clinical efficacy and usefulness in 114.
2) The clinical efficacy rates (excellent+good) in bacterial and mycoplasmal pneumonia were similar, 84.2% and 76.4%, respectively. The rate was 53.3% in other miscellaneous respiratory infections. The rate of excellent and good efficacy in all subjects were 20.2%(23/114) and 58.8%(67/114), respectively, and the overall efficacy rate was 79.0%.
3) Side effects were observed in 4.2%(5/119) of patients. There were 1 case of pseudomembranous colitis and 4 cases of eruption. Abnormal laboratory findings were observed in 20.2%(24/119) of patients. There were 2 cases of eosinophilia and 22 cases of mild to moderate abnormal hepatic enzyme values (14 cases of increased GOT, 20 cases of increased GPT).
4) The usefulness rates (very useful+useful) in bacterial pneumonia, mycoplasmal pneumonia, and other miscellaneous respiratory infections were 76.8%, 64.7%, and 53.3%, respectively. The overall usefulness rate was 71.9%.
These findings demonstrated that combination therapy with AZT and CLDM for respiratory infections is still an effective therapeutic modality long after the development of these agents.

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The efficacy and safety of combined therapy including azithromycin (AZM) and ofloxacin (OFLX) and single therapy with OFLX were compared in patients with rafractory complicated urinary tract infection (UTI) caused by catheters, to assess these methods of treating biofilm infection of the urinary tract. The subjects were patients with UTI who were treated with urethral catheter (including cystostomy). Seven days before the start of administration, the indwelling catheter was changed, and the course was observed without administration of any antimicrobial drug. Patients were registered at the time of this observation. The combined therapy group was given AZM at a single daily dose of 500 mg for 3 days and OFLX at a dose of 200mg three times a day for 7 days. The single therapy group was given OFLX at a dose of 200mg three times a day for 7 days. Eight days after the start of administration, the catheter was changed again. Urinary sediment and culture, and clinical tests were performed before and after the administration of drugs, and the surface of the catheter was observed by electron microscopy. Fifteen of the 37 patients were assigned to the combined therapy group and 17 to the single therapy group. The efficacy rates were 66.7% and 47.1% in the respective groups, as evaluated by the attending doctor. According to the criteria of the Japanease UTI committee, overall clinical efficacy was 60.0% in the combined therapy group and 41.2% in the single therapy group. The urine became negative for bacteria in 53.3% of the patients in the combined therapy group and 35.3% of those in the single therapy group. The bacteriological eradication rate was 91.2% in the combined therapy group and 68.8% in the single therapy group. There were no associated side effects or abnormal changes in clinical laboratory test values except for discomfort in the stomach of one patient in the combined therapy group. The inhibitory effect on biofilm formation as determined by electron microscopy tended to be superior in the combined therapy group. These results suggest that combined therapy with AZM and OFLX is an effective method of treating refractory complicated UTI in patients with a catheter.

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