Imipenem, in combination with cefazolin and ceftizoxime, showed good activity in vitro against 25 methicillin-resistant Staphylococcus aureus (MRSA) strains. A combination of these drugs showed synergy for more than 80% of MRSA strains. Mutation-and selection-experiments showed a synergistic effect for the isolation of high MRSA from intermediate MRSA. The combination resulted in a greater decrease in mutation frequency of high MRSA when compared with the frequency of either drug alone.

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To gain a better understanding of how the hydroxyl and N⁴-methyl-D-asparaginyl groups in aspoxicillin (ASPC) effectively contribute to its penetration into infected lesion, the concentration of ASPC in cerebrospinal fluid (CSF) in rats with pneumococcal meningitis was compared with that of dehydroxyaspoxicillin (AB-ASPC), amoxicillin (AMPC), ampicillin (ABPC), mezlocillin (MZPC) and piperacillin (PIPC).
By an intravenous bolus injection of each penicillin 24 hours after infection, ASPC and AB-ASPC, with a side chain of N⁴-methyl-D-asparagine, gave the highest maximum concentrations and AUC values in CSF among the penicillins tested. The AUC values in CSF/AUC values in serum ratios of ASPC and AB-ASPC were also superior to those of AMPC, ABPC, MZPC and PIPC. From the above results, we hypothesize that the side chain of N⁴-methyl-D-asparagine of ASPC plays an important role in the penetration of the penicillins into CSF and that the hydroxyl group introduced in to the phenyl group of ASPC is also helpful in maintaining the CSF levels.

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A clinical isolate of Streptococcus pneumoniae from an infant with otitis media was used to prepare an experimental otitis media model in guinea pigs. Aspoxicillin (ASPC), mezlocillin (MZPC) and piperacillin (PIPC) were administered to the models at a dose of 40 mg/kg by intravenous injection. On the basis of the pharmacokinetic parameters thus obtained, the penetration of ASPC into the infected lesions was compared with those of MZPC and PIPC.
In order to examine the substitution effect of a hydroxy-and N⁴-methyl-D-asparagine moiety to the phenyl and amino groups of ampicillin on the penetration into the infected lesions, ASPC and other structure-related penicillins were administered intravenously at a dose of 40 mg/kg via the ear
Analysis of the results revealed that the N⁴-methyl-D-asparaginyl and hydroxyl groups introduced into the amino and phenyl groups of ampicillin increased the drug penetration into the infected lesions.
Good correlations between the AUC values of penicillins in the infected lesions and those in the serum were observed.

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We carried out this study to clarify the immunological characteristics of cefaclor (CCL). We also performed experiments on the immunogenic reactivity to cephalexin (CEX) and benzylpenicillin (PCG). The results obtained were as follows.
As an immunogen, CCL was used alone or coupled with ascaris suum extract (Ase). In various schedules of immunization of mice and guinea pigs, CCL showed only weak antibody forming activity.
The highest antibody titers were observed in the sera of guinea pigs immunized with CCL-Ase with Al(OH)₃. No antigenic cross-reactivity to and PCG-Ase antibody was observed. Also, no antibody formation was detected in mice and guinea pigs sensitized with CCL alone or Al(OH)₃.
In guinea pigs sensitized with CCL-Ase, no signs of anaphylactic shock were observed.
From these results, we propose that CCL in experimental animals has weak antigenic potency as compared with PCG and CEX.

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Recently, a tendency to bleed as a side effect of antibiotics has been given attention.
We studied the effect of imipenem/cilastatin sodium (IPM/CS), a carbapenem antibiotic which belongs to a new class of beta-lactam agents, on platelet function and blood coagulation.
The subjects were 11 patients with respiratory infections: 10 with pneumonia and 1 with pulmonary suppuration.
IPM/CS was administered by i. v. drip at a dose of 1 g/day for 7 days, and the following parameters measured before and after treatment: platelet count, bleeding time, platelet adhesiveness, platelet aggregation, platelet ATP release, prothrombin time, active partial thromboplastin time, serum fibrinogen, fibrin degradation products, thrombo test and clotting factors II·VII·IV·V. There was no deterioration in the platelet function or blood coagulation tests after administrations of IPM/CS.
We therefore concluded that IPM/CS is a safe antibiotic in regard to platelet function and blood coagulation.

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Transient and drastic decreases in blood pressure were observed when DNR was alternately or simultaneously injected with OTC, CMX, CMZ, PCG, LM or PL into cats at clinical doses. The same phenomena were observed when MINO and OTC were alternately or simultaneously injected.
The percentage decrease against histamine standard was 170% for the third alternate administration of DNR and OTC.
The maximum percentage decrease against histamine standard was 90, 77, 190, 100 and 180% for simultaneous administration of DNR and CMX, CMZ, PCG, LM and FL, respectively. The percent decrease against histamine standard was 100-350% when MINO and OTC were simultaneously injected into cats.

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To prepare an experimental otitis media animal model, guinea pigs were inoculated with a strain of Streptococcus pneumoniae isolated from an infant with otitis media.
To evaluate the therapeutic efficacy of aspoxicillin (ASPC), mezlocillin (MZPC) and sulbenicillin (SBPC) in this model, each penicillin was administered by intramuscular injection and time course changes in the number of bacterial cells and concentrations of each penicillin in middle ear effusion were studied. The therapeutic effect of ASPC after intramuscular injection at a dose of 40 mg/kg was also histopathologically examined, indicating that ASPC exhibits a clear therapeutic effect with time. Furthermore, the time above MIC (TAM) value of each penicillin was determined based on the time course changes of penicillin concentrations in middle ear effusion. The TAM values of ASPC and MZPC after 40 mg/kg of each drug by intramuscular injection were found to be 6.2 and 2.8 hours.
Since the therapeutic efficacy of ASPC at a dose of 4 mg/kg was comparable to that of 40 mg/kg of MZPC, it was considered that the TAM value against a pathogen plays an important role in treating bacterial infections with antibiotics. Hence the TAM value is a useful parameter when predicting the therapeutic efficacy of antibiotics.

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We performed basic and clinical studies on cefodizime (CDZM), a newly developed cephem antibiotic agent, in obstetrics and gynecology and obtained the following results.
1) The cubital vein blood level of CDZM was approximately 40μg/ml at 45 min after initiation of i. v. drip infusion of 1 g, then declined and remained at 10-18μg/ml for 180 min. The concentration of CDZM in genital organ tissues ranged from 15-24μg/g at 45 min after i. v. drip infusion of 1 g, then declined and remained at 7.4-11.7μg/g for 190 min.
The transfer of CDZM into retroperitoneal fluid was 3.26±2.42μg/ml at 30 min after i. v. administration of 1 g, then increased gradually and reached 7.87±1.93μg/ml at 120 min.
2) In the clinical study, CDZM was administered to 5 patients with obstetric and gynecological infections (3 with pelvic peritonitis, 1 with Douglas' and subcutaneous abscess and 1 with retroperitoneal abscess).
The clinical results were excellent in 1 case and good in 4, the efficacy rate being 100%. No side effects were observed in any cases treated.

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To evaluate the clinical efficacy, side effects and utility of a new oral antimicrobial agent, T-3262 (tosufloxacin tosilate), in the treatment of obstetric and gynecological infections, we performed a comparative study with bacampicillin (BAPC) as a control drug, using a double-blind method.
The target diseases were intra-uterine infection and adnexitis (A-group) and bartholinitis and Bartholin's abscess (B-group). T-3262 was administered for 7 days at a daily dose of450 mg (divided into three portions) and BAPC for 7 days at a daily dose of 1, 000 mg (divided into four portions).
Of 230 patients given the test compounds, 168 (80 with T-3262 and 88 with BAPC) were accepted by the committee for the evaluation of efficacy. The efficacy rate of T-3262 and BAPC was 90.0% and 68.2%, indicating significant superiority of T-3262 to BAPC. In the A-group, the efficacy rate of 52 patients with T-3262 and 59 with BAPC was 90.4% and 71.2%. In the B-group, the efficacy rate of 28 patients with T-3262 and 29 with BAPC was 89.3% and 62.1%. In both groups, T-3262 was significantly superior to BAPC.
The rate of clinical improvement (judged by the attending doctor) was 97.5% in the T-3262 group and 73.9% in the BAPC group, the same as assessed by the committee.
As for bacteriological efficacy, 42 patients given T-3262 and 53 given BAPC were evaluable. The eradication rate in the T-3262 and BAPC groups was 94.9% and 72.0% again indicating significant superiority of T-3262.
Side effects were noted in 8 of 108 patients given T-3262 and 12 of 116 given BAPC, and abnormal laboratory findings were noted in 2 of 103 patients in the T-3262 group and 1 of 108 in the BAPC group. There was no significant difference between the T-3262 and BAPC groups.

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We evaluated the efficacy, safety and utility of lomefloxacin (NY-198), a new quinolone antibacterial agent, in the treatment of intrauterine infection or adnexitis (A-group), bartholinitis or Bartholin gland abscess (B-group) by a comparative double-blind method, using bacampicillin (BAPC) as a reference drug.
NY-198 was administered for 7 days at a daily dose of 600 mg (divided into 3 portions) and BAPC for 7 days at a daily dose of 1, 000 mg (divided into 4 portions).
1) Of 219 patients included in this study, 112 received NY-198 and the remaining 107 BAPC.
Sixty-nine patients (NY-198, 34: BAPC, 35) were excluded from the efficacy evaluation and 11 (NY-198, 6: BAPC, 5) from the analysis of adverse reactions. No statistically significant difference was observed between the two groups.
2) The clinical efficacy rate (excellent and good) on the basis of committee judgement was 83.6%(61/73) in the NY-198 group and 81.7%(58/71) in the BAPC group. No statisticallysignificant difference was observed between the two groups.
3) The bacteriological efficacy, evaluated in terms of the eradication rate of isolated organisms, was 88.6%(39/44) for the NY-198 group and 71.9%(23/32) for the BAPC group. Thedifference between the groups was not significant.
4) The overall clinical efficacy rate (excellent and good) for NY-198 and BAPC was 83.6%(61/73) and 81.7%(58/71). No statistically significant difference was observed between the two groups.
5) The clinical improvement rate (markedly improved and improved) according to the doctors in charge was 83.3%(65/78) in the NY-198 group and 87.5%(63/72) in the BAPC group.
As to the A-group diseases, the clinical improvement rate of the NY-198 and BAPC groups was 76.6%(36/47) and 89.1%(41/46).
As to the B-group diseases, the clinical improvement rate of the NY-198 and BAPC groups was 93.5%(29/31) and 84.6%(22/26). There was no statistically significant difference between the two groups.
6) Undesirable symptoms were observed in 5 patients (4.7%) and abnormal changes in laboratory findings in 1 patient (1.0%) in the NY-198 group. Thus no statistically significant difference was observed between the two groups.
7) The utility rate (markedly satisfactory and moderately satisfactory) according to the doctors in c harge was 85.9%(67/78) in the NY-198 group and 87.5%(63/72) in the BAPC group. No statistically significant difference was observed between the two groups.
From these results, we conclude that NY-198 in a daily dose of 600 mg is as effective and useful s BAPC in a daily dose of 1, 000 mg for the treatment of female genital organ infections.

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