The in vitro and in vivo antibacterial activities, and β-lactamase stability of FK 037 were compared with those of cefpirome (CPR), flomoxef (FMOX) and ceftazidime (CAZ) FK 037 demonstrated potent broad-spectrum activity against clinical isolates of gram-positive bacteria including staphylococci and gram-negative bacteria including Pseudomonas aeruginosa. In particular, was the most active of all the cephalosporins tested against highly methicillin-resistant Staphylococcus aureus (H-MRSA). Moreover, FK 037, like CPR, exhibited significant activity against Enterobacter cloacae and Citrobacter freundii, both of which were highly resistant to CAZ. FK 037 was highly stable to hydrolysis by various kinds of β-lactamases and showed an extremely low affinity for β-lactamases. FK 037 had potent therapeutic activity against lethal systemic infections due to a wide variety of gram-positive and gram-negative bacteria. The therapeutic activity of FK 037 correlated well with its MIC value. In particular, FK 037 was the most effective of the cephalosporins tested against MRSA systemic infection, although it was less active than vancomycin. Moreover, the therapeutic effect of FK 037 was only minimally influenced by challenge doses, while those of CPR, FMOX and imipenem/cilastatin were markedly reduced by high challenge doses. Against P.aeruginosa infection, FK 037 was more effective at triple divided doses than at a single dose.

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Aminoglycosides and β-lactams are frequently used in combination to enhance and widen the antibacterial spectrum. Typical side effects of aminoglycosides include ototoxicity and nephrotoxicity. Cefotaxime (CTX) or astromicin (ASTM), as representatives of β-lactams and aminoglycosides, respectively, were employed in this study. We administered either 4 g of CTX per day or 4g of CTX and 400 mg of ASTM per day and investigated the effects on creatinine (CRE), leucine aminopeptidase (LAP), N-acetyl-β-D-glucosaminidase (NAG) and β₂-microglobulin (BMG) levels in urine. An increasing tendency was found in the CRE, LAP/CRE, NAG/CRE and BMG/CRE levels, especially with the CTX-ASTM combination therapy. Based on these results, caution should be used when giving CTX and ASTM together. It is suggested that combination therapy with β-lactams and aminoglycosides should be utilized for the treatment of gynecol Ogic infections, and that β-lactam single therapy should be used as prophylaxis for post-operative infections.

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A dose-finding study was conducted to determine the optimal effective dosage of a cephem antebiotic, cefozopran (CZOP), administered for chronic respiratory tract infections, using acutely progressing cases as the study subjects, The daily dosage was set at 1 g of the study drug given in 2 divided doses (Group L) and 2 g given in 2 divided doses (Group H). This was contrasted with a daily dosage of 2 g of ceftazidime (CAZ) given in 2 divided doses as a control drug (Group C). The results of the study are summarized below.
1) Clinical efficacy: One case was judged to be “poor” and another case was designated “fair” in Group L and Group H. Group C also showed these results in 2 cases. The efficacy rate was 91.7%(11 cases of 12) for both Groups L and H, and 83.3%(10/12) for Control Group C.
2) Bacteriological effect: All of the 8 causative organisms completely disappeared in Group H, while the eradication rate was 90.9%(10/11) for Group L and 90.0%(9/10) for Group C.
3) Safety: As for side effects, one case in Group L developed rash, and fever was noted in one case in Group H. The appearance rate of abnormal laboratory findings was 23.1%(3/13) for Group L, 21.4%(3/14) for Group H, and 23.1%(3/13) for Group C. However, none of the symptoms or diagnose was serious.
4) Utility: Utility was rated to be 91.7%(11/12) for Group L, 100%(12/12) for Group H, and 83.3%(10/12) for Group C.
Based on the above findings, the authors judged that the optimal daily dose is 1-2 g of cefozopran (in 2 divided doses) and thought it appropriate to conduct the Phase III Comparative Study using a daily dose of 2 g (in 2 divided doses) of cefozopran to examine its effectiveness in respiratory tract infections.

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The effect of amphotericin B (AMPH) on the prevention of fungal infection in twentyeight patients with acute myeloblastic leukemia (AML) was studied. The patients received a BHAC-DP regimen as consolidation and intensification chemotherapy; Enocitabin (BH-AC) 250 mg/day for 7 days, Daunorubicin (DNR) 40 mg/day for 3 days, and Prednisolone (PSL) 30 mg/day for 7 days. Intravenous infusion (i. v.) of AMPH (0.15 mg/kg/day) was dosed, in addition to oral administration of AMPH (2, 400 mg/day), in 41 treatment periods in patients with AML (i. v. infusion group). Oral AMPH alone was administered, in 38 treatment periods, to patients with AML (oral administration group). The period of apyrexia, the period of fever, C reactive protein (CRP), erythrocyte sedimentation rate (ESR), culture data, incidence of adverse effects, and the quantity of endotoxin were compared between the two groups. The ENT. infusion group showed signififcantly better results than the oral administration group; the period of fever was significantly shorter (2.7 ± 3.5 days, p<0.05), and serious systemic fungal infection was less offen detected (0 cases) than in the oral administration group (3 cases). No serious adverse events were observed.

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The clinical usefulness of DQ-2556, a new parenteral cephem antibiotic, in the treatment of bacterial infections in the field of internal medicine and its optimal dosage in the treatment of pneumonia were investigated.
1. Open clinical studies
DQ-2556 was administered mainly at doses of 0.5 g b. i. d. and 1.0 g b. i. d. The clinical efficacy rates for lower respiratory tract infections were 76.5%(26/34) for pneumonia, 7/9 for secondary infections of chronic respiratory diseases, and 6/7 for bronchiectasis with infections, or 78.0%(46/59) overall. Efficacy rates classified by daily dosages were 73.7%(14/19) at 0.5 g b. i. d. and 83.3%(30/36) at 1.0 g b. i. d. The eradication rates of causative bacteria were 86.4%(19/22) for monomicrobial infections and 4/6 for polymicrobial infections, thus 82.1%(23/28) overall, The eradication rate for Staphylococcus aureus was 5/9, and five strains of Streptococcus pneumoniae, eight strains of Haemophilus influenzae and four strains of Moraxella catarrhalis were all eradicated. Three evaluable patients with urinary tract infections all showed bacterial eradication and good or excellent clinical efficacy. Side effects were observed in three patients (incidence 3.9%) with one each, showing eruption, angina pectoris and diarrhea, all three were treated at dosages of 1.0 g per time. Abnormal changes in laboratory test results, the most of which were abnormalities in liver function, were seen in 8.3%(2/24) at daily dosages of 0.5 g b. i. d. and in 23.9%(11/46) at daily dosages of 1.0 g b. i. d.
2. Dose-finding study
Clinical efficacies for pneumonia were compared among two groups treated with DQ-2556 at daily dosages of 0.5 g b. i. d.(DQ-1.0 group) and of 1.0 g b. i. d.(DQ-2.0 group) and the control group with treated with ceftazidime (CAZ) at daily dosages of 1.0 g b. i. d.(CAZ group) The overall clinical efficacy rates in the DQ-1.0 group, the DQ-2.0 group and the CAZ group were 94.4%(17/18), 82.4%(14/17) and 94.4%(17/18), respectively, without any significant differences among the three groups. The overall eradication rates of causative bactez in the DQ-1.0 group, the DQ-2.0 group and the CAZ group were 8/8, 8/8 and 5/6, respectively, without any significant differences among the three groups. The only side effect, eruption with fever, was observed in a patient in the DQ-2.0 group. Abnormal changes in laboratory test results were seen in 13.6%(3/22) of the DQ-1.0 group, 30.0%(6/20) of the DQ-2.0 group and 28.6%(6/21) of the CAZ group, the incidence was lower in the DQ-1.0 group than in the other two groups, but no significant differences were not noted among the three groups. Most of the abnormalities were seen in items of liver function. There were no significant differences among the three groups in the overall clinical utility rates. These results suggest that DQ-2556 is a useful antibiotic for treatment of lower respiratory tract infections, including pneumonia, and a dosage of 0.5 g b. i. d. is sufficient to exert good clinical effects on pneumonia. It is also considered that DQ-2556 may show almost the same degree of safety as CAZ, but an increased number of evaluable patients will required to clarify this.

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This study was carried out to evaluate the clinical efficacy of combination therapy with tobramycin (TOB) and ceftazidime (CAZ) as empiric treatment for infections in patients with hematological diseases. One hundred and thirty-five patients in 17 institutes with infections were treated with 120- 240mg TOB i. v. and 3-8g CAZ per day. Ninety-five patients (53 with acute leukemia, 6 with chronic leukemia, 4 with myelodysplastic syndrome, 6 with aplastic anemia, 20 with malignant lymphoma, 5 with dysproteinemia, 1 with megaloblastic anemia) who had severe infections (8 septicemia, 67 suspected septicemia, 15 pneumonia, 5 others) were evaluable in terms of clinical efficacy. Out of 95 patients, 71 including 6 with septicemia and 11 with pneumonia, responded to this combination chemotherapy. The overall efficacy rate was 74.7%(71/95). The efficacy rate in patients with peripheral blood granulocyte counts less than 100/μl at the initiation and end of treatment was 70.6%(12/17) Mild side effect, such as temporary skin rash, was noted in only one patient. These results suggest that combination therapy with TOB and CAZ is a useful empiric treatment for infections in patients with hematological diseases.

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It is very important to select effective antibiotic against a bacterial infection. Therefore, we studied annual changes in the susceptibility of various clinical isolates including Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, Serratia marcescens, Haemophilus influenzae, Pseudomonas aeruginosa and Proteus mirabilis from the sputum, urine and pus cefazolin (CEZ), cefotiam (CTM) and latamoxef (LMOX) to the cephems. Susceptibility testing was performed by the 1-dilution disc method, and we mainly studied the susceptibility ratings of (lll) and (-). CEZ still had moderate antibacterial activity against S. aureus, E. coli and K. pneumoniae after 20 years of clinical use. CTM had well-balanced high antibacterial activity against S. aureus, S. epidermidis, E. coli, K. pneumoniae, H. influenzae and P.mirabilis. LMOX had high antibacterial activity against E. coli, K. pneumoniae, H. influenzae and P. mirabilis, and moderate antibacterial activity against E. cloacae and S. marcescens.

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