The results of clinical and laboratory studies on aspoxicillin (ASPC) are summarized in this paper.
1. ASPC possesses a broad antibacterial spectrum in vitro against Gram-positive and Gramnegative bacteria. ASPC shows more potent activity in vivo and stronger bactericidal action than expected from in vitro activity.
2. Peak blood levels of ASPC after intravenous injection or intravenous drip infusion are dose dependent and half-lives of ASPC in these cases are about 1.6 hours.
ASPC is excreted in active form mostly into urine via kidney.
ASPC is satisfactorily transferred into various tissues and body fluids, such as bile, sputum.
The binding rate of ASPC to serum protein is much lower than penicillin derivatives like piperacillin (PIPC), sulbenicillin (SBPC) and ampicillin (ABPC).
3. In an open clinical trial of ASPC, 1,845 cases were evaluated.
Clinical effects were excellent in 543 cases (29.4%) and good in 822 cases (44.6%), and the efficacy rate for cases judged as excellent and good comprised 74.0%.
4. Comparative studies in which the efficacy of ASPC was compared to efficacies of PIPC and SBPC were performed in patients with respiratory tract infections, postoperative wound infections and suppurative otitis media. ASPC showed satisfactory clinical effects in all trials.
5. In the above open and comparative clinical studies of ASPC, incidence of adverse side reaction was only 1.95% (45/2,304), and main side effects were skin rash and diarrhea.

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Latamoxef (LMOX) 1 g was administered twice daily for 5 days to patients undergoing operation for myoma uteri and the time course of tissue concentrations of the drug and the prophylactic effect of the treatment on postoperative infection were studied.
1. Area under concentration-time curve (AUC) of LMOX was the highest in the perimetrium (45.3%), followed by the cervix uteri (39.2%), endometrium (35.9%), oviduct (35.1%), myometrium (29.5%), and ovary (24.4%).
2. C_max was the highest in oviduct (46.9 μg/g), followed by C_max's in perimetrium (44.2 μg/g), cervix uteri (35.8 μg/g), myometrium (26.9 μg/g), endometrium (25.6 μg/g), and ovary (24.3 μg/g).
3. Serum half-lives were T 1/2 (α) =0.27 hour and T 1/2 (β) =1.81 hours.
4. Prophylactic efficacy against postoperative infections was 94.3%, and febrile morbidity was 5.7%. The preoperative and postoperative laboratory tests did not show appreciable changes, no adverse reaction was observed.
In the present study, LMOX showed good transfer into gynecological tissues, suggesting its very high usefulness in the treatment of infection and in the postoperative management.

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To prevent postoperative infection in obstetric gynecology, latamoxef (LMOX) and tobramycin (TOB) were intravenously administered to 81 patients at daily doses of 2 g and 120 mg, respectively, for 5 postoperative days, and the preventive effect of the combined drugs on postoperative infection were evaluated in terms of the clinical effects and safety.
1. The fever index was low as a whole; 3.38±2.30 degree hours in patients receiving simple panhysterectomy (n=61), 3.21±3.84 degree hours in those given cesarean section (n=12), and 3.53±2.78 degree hours in those given other surgical procedures (n=8).
2. There were no abnormalities in hematological findings or liver and kidney functions 14 days after the surgery. PIVKA-II was observed in 3 of 32 patients 14 days after the operation, at a rate of 9.4%.
3. Except mild diarrhea which was observed in 7 of the 81 patients (8.6%) in 4 to 6 days after the operation, no subjective or objective side effects or postoperative complications were observed.
The combined use of LMOX and TOB seems useful for preventing postoperative infection in obstetrics and gynecology in terms of its efficacy and safety.

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Ceftriaxone (CTRX) was studied regarding its penetration into the adnexa uteri and uterine tissues, as well as its utility and safety in the treatment of patients with obstetric and gynecologic infections.
The results obtained are summarized below.
1. When 1 g of CTRX was administered by intravenous bolus injection, C_max in tissues of adnexa uteri and uterus ranged from 42.2 to 80.5 μg/g, Tmax ranged from 0.42 to 0.81 hour, and the AUC ranged from 314.9 to 606.9 μg hr/g. Thus, drug penetration into these tissues was good.
2. Clinical efficacy of CTRX was evaluated in 29 obstetric and gynecological patients. The clinical efficacy was good in all cases.
3. Bacteriological effects of CTRX were very good, and 90% of the organisms isolated before treatment were eradicated.
4. Laboratory testing revealed an occurance of mild eosinophilia in 1 case.

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We conducted hemostatic studies with 1,043 adult patients with various diseases who were treated for their infection with cefotaxime (CTX) in 368 hospitals throughout Japan. Underlying diseases in 1,012 patients were nonhematological disorders and those in 31 were hematological diseases.
Thirteen (1.2%) out of 1,043 patients showed some abnormal results in blood coagulation tests following the administration of CTX. All the 13 cases with abnormal blood coagulation tests had poor dietary intake, and appeared to have liver damage before or during the drug administra tion, but in none of the cases which had abnormal laboratory findings were clinical bleeding symptoms observed.
Consequently, we have concluded that the incidence of abnormal hemostatic tests following CTX administration is low, and that the appearance of abnormal tests is most likely dependent upon the condition of the patient.

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The disulfiram-like reaction due to cephems with methyltetrazolethiol (tetrazole) moiety was studied in biotransformation of these drugs.
The serum tetrazole concentration was determined following intravenous administration of cefoperazone (CPZ) 1 g, latamoxef (LMOX) 1 g, or cefmetazole (CMZ) 2 g to patients suffering infections without liver dysfunction, and of CPZ 1 g to patients with liver cirrhosis. Tetrazole concentrations in normal patients were 0.5-2.0 μg/ml after 3 hours, and 0.14-0.26 μg/ml after 12 hours, and undetectable after 24 hours. On the other hand, the tetrazole concentration in cirrhotic patients was 0.143±0.07 μg/ml (Mean±S.D.) even after 24 hours. Therefore, it is concluded that the disulfiram-like reaction due to cephems with tetrazole moiety closely related to the metabolism of these drugs in liver, and probably be caused by the inhibition of acetaldehyde dehydrogenase activity in liver by the free tetrazole group produced by the metabolism of these drugs in liver.

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Astromicin (ASTM) was administered by intravenous drip infusion (i.v.d.) to 22 patients with chronic complicated urinary tract infections and the clinical efficacy and safety of this drug were evaluated. The overall clinical efficacy rate obtained was 71.4% (excellent 6; moderate 9) of 21 evaluable cases by the UTI committee's criteria. Concerning the response on clinical isolates, the drug was highly effective especially against strains of Escherichia coli, indole positive Proteus and Serratia marcescens. It was not effective, however, against 2 strains of Pseudomonas aeruginosa.
As for adverse reactions, there was one case which complained of headache on the 3rd day after starting treatment. In this case the drug administration was discontinued at the 5th day. The symptom disappeared within 24 hours without any treatment. No any other adverse reactions were noted. With regard to clinical test values for peripheral blood, liver and renal functions, no abnormality was observed in any of the cases treated with the drug.
In conclusion, ASTM was found to be a highly effective and safe drug when administered by intravenous drip infusion in the treatment of chronic complicated urinary tract infections.

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Piperacillin sodium (PIPC) is a semisynthetic penicillin displaying high antibacterial activities against Gram-positive and Gram-negative bacteria including Pseudomonas sp., Proteus sp., etc. It acts bactericidally and is stable against β-lactamases. The usefulness of PIPC in the treatment of infections in mature and premature neonates was investigated and the following results were obtained.
The pharmacokinetics (half-life, distribution volume, total body clearance) of PIPC after 50 mg/kg intravenous drip infusion in 10 cases of neonates were examined: Relationship between T 1/2 and hours after birth was clearely determined.
Adverse effects and abnormality in laboratory test values were not observed.
It is considered from the above results that PIPC may be an useful antibacterial agent for the treatment of infections in neonates.

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Aztreonam (AZT), which has a newly developed and synthetic structure belonging to the group of monobactams, possesses excellent antibacterial activity against a broad range of Gramnegative bacteria (including the β-lactamaseproducing strains). Antibacterial activities of AZT were examined and compared with those of 5 antibiotics (cefoperazone (CPZ), latamoxef (LMOX), cefotaxime (CTX), cefmetazole (CMZ) and cefsulodin (CFS)) against 296 strains of clinical isolates. The evaluation of antibacterial activities was determined with the inhibition zone diameter obtained by the single disc method. The results can be summarized by three categories as follows:
1. Susceptibility of clinical isolates to AZT and other antibiotics
AZT and other 3rd-generation antibiotics (CPZ, LMOX, CTX) showed excellent antibacterial activities against most strains. Especially AZT was more active against Enterobacter cloacae and Serratia marcescens than reference drugs.
Against Pseudomonas aeruginosa, the activity of AZT was similar to that of CFS. AZT showed as excellent activity against P. aeruginosa as CFS.
2. Susceptibility of strains isolated from different clinical materials and different clinics
AZT showed the highest antibacterial activity against the clinical isolates from sputum, pharynx, urine, pus, bile, puncture fluid, blood and others. AZT exhibited the most potent activity against isolates in the 7 clinics we tested.
3. Susceptibility of strains isolated from inpatients and outpatients
AZT demonstrated the highest antibacterial activity (the rate of susceptibility: 87.0%) against strains obtained from inpatients (except for P. aeruginosa). The activity of AZT (81.4%) against P. aeruginosa was as active as that of CFS (81.4%), and it was the highest in all drugs. Antibacterial activity of these antibiotics against bacteria was rated as follows:
AZT > LMOX > CPZ > CTX > CMZ
AZT showed the highest antibacterial activity (100%) against strains isolated in all the materials and at all the clinics tested of outpatients. Antibacterial activity of these antibiotics against isolates from outpatients was rated as follows:
AZT > CPZ > LMOX > CTX > CMZ

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