The susceptibility of 260 strains of Pseudomonas aeruginosa to several antibiotics and the mechanism ofresistance to carbapenems were investigated. The number of strains of P. aeruginosa moderately resistant orresistant to ofloxacin, ceftazidime and imipenem (IPM) were 76 (29.2%), 31 (11.9%) and 30 (11.5%), respectively. There was no clear relationship between the drug resistance of P.aeruginosa and serum type.Fourteen strains (46.6%) out of 30 IPM-resistant strains were susceptible to meropenem (MEPM). Twenty seven (90.0%) IPM-resistant strains showed cross resistant to panipenem (PAPM), and 12 strains (44.4%) out of the 27strains showed high susceptibility to MEPM. P aeruginosa becomes resistant to IPM and PAPM only by thedecrease in the outer membrane permeability of these carbapenems. In contrast, P.aeruginosa becomes equallyresistant to MEPM by concurrent occurrence of the increase in the efflux of the antibiotics and the decreasein the outer membrane permeability of the antibiotics. The possibility that both mechanisms are taken placeconcurrently in P. aeruginosa is considered to be low, and it was also supported by the results of the present study.

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The ability of antibiotics to penetrate the target organs is an important factor for the clinical effects and sideeffects in the treatment of infection. In the present study the comparative tissue distribution of 4 kinds ofmacrolide antibiotics was determined in rats.
After oral administration of 20 mg/kg, roxithromycin (RXM) had the highest plasma concentration, andclarithromycin (CAM) has the second highest. The C_max of RXM and CAM were 2.7 and 1.0 μg/ml, respectively.On the other hand, both levels of erythromycin-stearate (EM-S) and azithrorrycin (AZM) were extremely low, with a C_max of 0.1 μg/ml.
Concentration of the 4 compounds were measurable in the liver, kidney, spleen, lung and heart. The concentrationin all tissues for each compound were significantly higher than those in the plasma. AZM had the mostsustained and the highest tissue levels. The distribution patterns of RXM and AZM were almost similar to thecase of EM-S, in that the highest tissue concentration was observed in the liver, followed in descending order byconcentration in the kidney, spleen, lung and heart. On the other hand, CAM had the highest concentration in thelung, and was moderated in the liver.
Major clinical indications are infections of the respiratory tracts, and commonly reported side-effects arehepatotoxity. Therefore, it is worth noting that the lung levels of CAM were significantly higher than in the liver, as the separation of clinical effects and side-effects.

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The clinical effect of faropenem was evaluated in 165 ambulatory patients with various infections in thefield of obstetrics and gynecology at 10 institutions in Yamagata Prefecture. The results obtained are summarizedbelow.
1. The rate of efficacy, as determined from the clinical effect following 3- to 7-day repeated administrationat a dose of 600 mg/day, was 97.9% (46/47) for intrauterine infections, 92.0% (23/25) for adnexitis, 93.8% (15/16) for external genital infections, 88.9% (8/9) for mastitis, 94.0% (63/67) for cystitis, and 100% (1/1) forcervicitis. The overall efficacy rate was estimated to be 94.5% (156/165).
2. The rate of clinical efficacy, as classified by isolate, was high, 95.1% for Gram-positive bacteria, 100%for Gram-negative bacteria, and 100% for anaerobes. As for bacteriological response classified by isolate, theeradication rate was high, 91.4% (74/81) for Gram-positive bacteria, 98.4% (62/63) for Gram-negative bacteria, 89.5% (17/19) for anaerobes, and 93.9% (153/163) in all.
3. No adverse reactions or laboratory abnormalities were observed in any patient.
The results presented suggest that faropenem is a highly safe and effective antibiotic for the treatment of obstetric or gynecological infections of various kinds in an ambulatory setting.

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An investigation was carried out to determine the therapeutic effect of levofloxacin (LVFX) once-a-day oral therapy at the dose of 200 mg/day for 7 days on uterine cervicitis, in comparison with LVFX twice-a-day oral therapy at the dose of 200 mg/day for 7 days. Of the 102 patients enrolled in the study, 90 were subjected to the analysis. The efficacy rate on uterine cervicitis of the once-a-day therapy and twice-a-day therapy groups according to the evaluation of the Drug Efficacy Evaluation Committee were 72.0% (36/50) and 82.5% (33/40), respectively. The efficacy rate on uterine chlamydial cervicitis of the once-a-day therapy and twice-a-day therapy groups according to the evaluation of the Drug Efficacy Evaluation Committee were 88.0% (22/25) and 85.7% (18/21), respectively. Safety was evaluated as “safe” in 88 of the 90 assessable patients (97.8%). Side effects were seen in two cases, which belong to the once-a-day therapy group; mild candidiasis and mild breast distension sense. As the antimicrobial treatment started, the levels of the inflammtory cytokines, interleukin-6 (IL-6) and interleukin-8 (IL-8) in the cervical mucus, decreased. It is suggested that IL-6 and IL-8 can be useful indicators of the antimicrobial treatment in the uterine cervicitis. These results suggested that the LVFX once-a-day therapy can be useful on uterine cervicitis.

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The subjects were 531 patients who underwent orthopedic surgery. Flomoxef was administered, and liverfunction was examined before and after administration.
Abnormal liver function after administration of flomoxef was found in 14.3% of patients. In male patients, ahigh rate of 18.8% was observed. A particularly high rate of 37.0% was obtained among patients who showed GOT values of more than 40U/L before treatment with flomoxef.
The prevalence of abnormal GOT and GPT values after administration of flomoxef was 3.6% and 13.2%, respectively. These values were significantly higher than those obtained with other cephem antibiotics. Theserates of occurrence of abnormally high GOT and GPT are obviously higher than those submitted at the time ofapproval and reported in the drug use investigation.
The prevalence of abnormal liver function values was high in patients receiving flomoxef, and particularlyhigh in male patients and patients whose GOT was high before administration of flomoxef. Therefore, sufficient check of liver function appears important when administration of flomoxef to these types of patients is intended.

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