We studied synergy of bactericidal effect onE. coli between CBPZ and fresh serum of guinea pigs, and compared with those of 9 cephem antibiotics.
Bactericidal effects of the fresh serum in the presence of sub-MICs of cephem antibiotics were determined by counting survival bacterial cells at various incubation periods. Synergy of bactericidal effect on E. coli NIHJ JC-2 cells was observed between 1% fresh serum and cefmetazole, cefmenoxime at 1/2 MIC and cefbuperazone up to 1/4 MIC, whereas latamoxef, cefotetan, cefoperazone and cefotaxi-me didn't kill all the cells at 1/2 MIC in 1% fresh serum. Synergy of bactericidal effect on E. coli KC-14 cells was observed between 10% fresh serum and cefotamixe at 1/2 MIC and cefbuperazone up to 1/4 MIC, whereas cefoperazone didn't kill all the cells at 1/2 MIC in 10% fresh serum.
Sensitivity of E. coli NIHJ JC-2 to the fresh serum was found to be increased by pretreatment with sub-MICs of cefbuperazone and cefotaxime for various periods from 0.5 to 2 hours. This effect of cefbuperazone was stronger than that of cefotaxime. Growing cells of E. coli KC-14 treated with cefbuperazone at sub-MICs were capable of greater complement activation than the normal cells.
Synergy of bactericidal activity of the any cephem antibiotics with the inactivated serum was in-ferior than with the fresh serum, suggesting that relevancy of the complement etc. is important.

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The antiviral effect of carboxyethylgermanium sesquioxide (Ge-132) was examined in mice infected with mouse-adapted influenza A₂ (H₂N₂) virus. A multiple administration of the compound at doses of 300-33mg/kg protected mice from virus infection. When a 100mg/kg dose of Ge-132 was administered orally, the protective effect was demonstrated on the basis of 1) survival of infected mice, 2) reduction of virus growth in lungs, 3) inhibition of the development of lung consolidations, and 4) response for HAI antibodies. When mice were treated with the agent prophylactically, no clear antiviral effect was obtained. However, when mice were treated with Ge-132 chemotherapeutically in the early time after virus infection, survival rate of the infected mice was increased significantly. Although the antiviral effect was displayed when Ge-132 was administered ip, sc, and im, oral treatment of the compound resulted in the greatest protection. Since Ge-132 itself have no direct action on virus perticles and virus infected cells in vitro, these antiviral effects of the agent against influenza diseases in vivo may be expressed through a potentiation of host's defense functions including an interferon gamma (IFN-γ) production and an augmentation of natural killer (NK) cell activity. The IFN-γ inducing-and NK cell stimulating-activities of Ge-132 have been already demonstrated in animals and in man.

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The therapeutic effect of granulocyte transfusion was evaluated in pseudomonal infections in cyclophosphamide-induced granulocytopenic mice, an immunosuppressed model.
When granulocytes from normal mice were transfused to the granulocytopenic mice, host defense of the mice against pseudomonal infections was slightly enhanced.
However, therapeutic efficacy of granulocyte transfusion (10⁷ cells/mouse) against pseudomonal infections in the granulocytopenic mice was enhanced makedly by combined use with the some antipseudomonal antibiotics in the comparison with the use of those antibiotics alone.

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Influence of imipenem/cilastatin sodium on the human fecal microflora was studied, employing 4 volunteer (healthy adult males, A, B, C and D) to whom 500mg/500mg of imipenem/cilastatin sodium was intravenously administered twice a day for 5 days.
1) The total counts of fecal aerobic and anaerobic organisms were slightly decreased in all of the subjects by administration of imipenem/cilastatin sodium. Imipenem/cilastatin sodium, at least, caused the reduction of the number of aerobic and anaerobic bacteria belonging to Enterobacteriaceae and Bacteroidaceae during the administration period.
2) A period of 1 week after withdrawal of imipenem/cilastatin sodium was sufficient for recovery of fecal microflora to normal levels.
3) Clostridium difficile strains, which produce D-1 toxin, were isolated from 2 out of 4 subjects. No diarrhoea was, however, observed in any subjects during the period of study.

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Cefmenoxime (CMX), a cephem antibiotic with a methyltetrazole group, was evaluated for its effects on the bleeding tendency. Subjects without hemorrhagic dispositions were selected from surgical in-patients in the field of gynecology and obstetrics. They were given 1 or 2g of CMX by intravenous drip infusion twice daily for 7 days beginning on the day of surgery. Some of the patients given a daily dose of 4g CMX received a single dose of 30mg of vitamin K₂, too, by i. v. drip on the day of surgery. Tests on the bleeding tendency were carried out before and after the 7-days administration with CMX.
The examined items were as follows: thromboelastogram (r, k, and ma values), coagulation time (prothrombin time, PT; thrombotest, TT; hepaplastintest [normotest], HPT), quantity of coagulation factors (prothrombin, fibrinogen), bleeding time (BT), platelet count, platelet aggregation activity (aggregation reagents: ADP, collagen, epinephrine), and fibrinolytic activity (fibrin and fibrinogen degradation products, FDP; plasmin value; streptokinase-activated plasmin value).
Results: 2g/day of CMX caused no statistically significant changes of the data in the direction of increased bleeding tendency, while in the group given 4g daily, PT, TT, and BT were slightly but significantly prolonged, although no significant changes were found in other parameters. Single injection of vitamin K₂ could prevent the prolongation of coagulation time (PT, TT). Clinical hemorrhage did not occur in any patient.
These results obtained should suggest that 4g CMX/day can be safely given for a week or so to patients in fairly good condition without vitamin K deficiency, but, when the drug is given to patients on parenteral alimentation, to the aged, or to those in poor conditions, vitamin K should be given as well to ensure safety.

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By means of applying leucocyte migration inhibition test (LMIT) that demonstrates delayed type hypersensitivity (DTH), causative drugs were detected in patients with antibacterial drug allergy (ADA).
Water-insoluble antibacterial drugs could be applied in LMIT by dissolving them in three kinds of solvents (0.1 M Phosphoric acid, 0.1 M Sodium hydroxide, Propylene glycol). Antigen solutions were prepared subtoxic concentrations of drugs and made polyvalent antigens by means of adding patient's serum of the same volume.
LMIT was performed in 61 cases suspected of ADA and found to be positive drugs in 41 cases (67%). According to symptom, it was found to be positive in 33 (65%) of 51 cases suspected of drug eruption and in 14 (93%) of 15 cases suspected of drug fever and in 8 (89%) of 9 cases suspected of drug induced hepatic injury. These results suggest that DTH may play an important role in ADA and that LMIT may be useful for the detection of causative drugs in patients with ADA.
Females aged from their fifties to their seventies formed 41% of LMIT-positive cases and beta-Lactam antibiotics formed 69% of LMIT-positive antibacterial drugs. This study indicates that ADA tends to appear frequently in old-age female and that beta-Lactam antibiotics has a high immuno-genicity in DTH.

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The concentration of cefoperazone (CPZ) in serum and various tissues of the genitourinary tract was measured after the intravenous administration of 1 g of CPZ. The results were as follows.
1) The mean serum concentrations ranged from 55.3 μg/ml at 90 minutes to 32.3μg/ml at 150 minutes following injection, decreasing gradually.
2) Renal tissues were obtained between 120 and 240 minutes after administration of CPZ in 6 cases. CPZ concentration ranged from 2.4μg/g to 142.1μg/ml (mean value 37.7μg).
3) CPZ concentration in the tissue of prostatic adenomas ranged 4.9μg to 23.9μg/g, testes, from 12.8μg/g to 30.0μg/g, urethral caruncles, from 0.9μg/g to 39.8μg.
The high CPZ concentrations found in the serum and genitourinary tract tissues lead us to expect successful therapy when CPZ is used to treat bacterial infections with sensitive pathogens in the urogenital tract.

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A well-controlled comparison of MK-0787/MK-0791 (MK), combination of N-formimidoyl thienamycin (imipenem) and dehydropeptidase inhibitor (cilastatin), and cefoperazone (CPZ) was carried out in the treatment of complicated urinary tract infections. Patients were randomly assigned to receive 1g of either MK (0.5g as MK-0787) or CPZ twice a day for 5 days by intravenous drip infusion.
All patients had pyuria of at least 5 WBCs per high power field, bacteriuria of at least 10⁴ bacteriaper ml of urine and identifiable underlying urinary tract disease. The overall clinical efficacy of the treatment was evaluated by the criteria proposed by the UTI Committee in Japan as excellent, moderate or poor based on the combination of changes in pyuria and bacteriuria.
Of the 223 patients evaluated for the clinical efficacy, 108 patients received MK and 115 received CPZ. No significant difference in background characteristics was observed between the two treatment groups. Excellent and moderate responses were obtained in 74.1% of the patients receiving MK and in 55.7% of the patients receiving CPZ. This difference was statistically significant (P<0.01). The overall bacteriological eradication rates obtained were 86.9% of 160 strains in the MK group and 74.1% of 174 strains in the CPZ group. This difference was also significant (P<0.01). Significantly higher eradication rates for S. aureus and C. freundii were achieved in the MK group.
Clinical adverse reactions were observed in one patient (0.7%) in the MK group an I in 3 patients (2.1%) in the CPZ group. Drug related laboratory adverse reactions were observed in 10 patients in the MK group and in 15 patients in the CPZ group. There were no significant difference between the two treatment groups regarding the incidence of clinical and laboratory adverse reactions and MK appeared to be as well tolerated as CPZ.
From the results obtained in this study, we concluded that MK was more useful than CPZ in the treatment of complicated urinary tract infections.

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