Between January 1992 and June 1993, serotype identification was carried out against Pseudomonas aeruginosa isolated in the microbiology laboratory of Osaka University Hospital, and the isolation rate of serotypes was evaluated according to materials and department clinics. The MICs of fifteen antibiotics, piperacillin (PIPC), cefsulodin (CFS). ceftazidime (CAZ), cefoperazone (CPZ), cefclidin (CFCL), aztreonam (AZT), carumonam (CRMN), imipenem (IPM), tobramycin (TOB), amikacin (AMK), gentamicin (GM), minocycline (MINO), ofloxacin (OFLX), ciprofloxacin (CPFX) and fosfomycin (FOM), were measured by the micro-broth dilution method in about 100 strains that indicated a high incidence of serotype, and we evaluated the MIC₈₀, materials, clinics and serotypes individually.
1. Isolation rates of serotypes were in the order of G, E, B, I, A, non-type, M, F, H, D, C and K. P. aeruginosa was isolated most often from sputum and throat samples of inpatients, and from pus, secretion and wound of outpatients. Among department clinics, P.aeruginosa was most often isolated from inpatients of the department of abdominal surgery, and from outpatients of the department of otorhinolaryngology.
2. MIC₈₀ s of antibiotics against P. aeruginosa 100 strains were in the order of CPFX > CFCL, IPM, TOB>GM, OFLX, CAZ>CFS>CRMN, MINO, AZT, PIPC, AMK>CPZ > FOM, The MIC₈₀ of CPFX was 2μg/ml, and that of CFCL, IPM and TOB was 4μg/ml.
3. Susceptibility rate of each antibiotic that based on interpretative standards by NCCLS was in the order of CFCL 97.0%, IPM 91.0%, TOB 90.0%, followed by PIPC, CAZ, CPFX, GM, AMK, CPZ, CRMN, AZT, OFLX, CFS, MINO and FOM.

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This report concerns the fact that the postmortem level of histamine in blood was unchanged in guinea pigs (GP) that they died of antibody reaction the cefaclor (CCL)-human serum albumin (HSA) conjugates or cephalexin (CEX)-HSA during anaphylactic shock. In order to analyze this result, we studied how antibiotics affect platelets activated by platelet activating factor (PAF), as platelets are major source of histamine in GP blood. When PAF (1.5×10^-7M) reacts to platelets histamine is released and platelet aggregation is induced, CCL and CEX (1mM or 10mM) blocked histamine release but did not block platelet aggregation. From these results, it was suggested that the release of histamine from platelets was blocked by CCL and CEX, and therefore, the level of histamine did not increase during anaphylactic shock.

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The anti-chlamydial activities of rokitamycin (RKM), an oral 16-member macrolide antibiotic, were investigated in vitro (MICs) and in terms of therapeutic effect of mice experimental Chlamydia psittaci pneumonia. MICs of RKM against standard strains of Chlamydia sp. were excellent 0.063-0.125μ/ml and were superior to MICs of erythromycin and roxithromycin. However, a therapeutic effect of RKM in the animal model was inferior to those of other macrolides. The study of pharmacokinetics of RKM in mice plasma showed rapid metabolism of RKM to metabolites with low anti-chlamydial activities. According to the above results, we conclude thatthe discrepancy between the in vitro and in vivo antichlamydial activities of RKM was caused by the pharmacokinetic characteristics of the drug in mice plasma. In human plasma, RKM was found to be stable. Therefore, we can expect good clinical effects of RKM against chlamydial respiratory tract infection.

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In the present study, the therapeutic effect of primaquine and clindamycin against Pneumocystis carinii pneumonia was evaluated using a rat model. Both primaquine and clindamycin showed no significant effect in reducing the cyst count in the lung when each drug was administered separately at a dose of 1mg/kg/day and 100mg/kg/day, respectively. The combined use of these drugs, however, significantly reduced the cyst count and inflamation in the lung. Furthermore, clindamycin showed a dose-dependent therapeutic effect when used concomitantly with primaquine. It is estimated that the number of patients infected with human immunodeficiency virus will increase in the near future in Japan, necessitating new therapies for P. carinii pneumonia, because of the occasional serious side effects of sulfamethoxazole/trimethoprim and pentamidine, which are commonly used at present. The data in this study indicate the effectiveness of the combined use of primaquine and clindamycin in the treatment of P. carinii pneumonia in an animal model, and indicate the necessity for clinical trials in Japan.

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The serum protein-binding of representative oral cephems (cefdinir, cefixirne and ceftibuten) was assessed, using sera from young healthy subjects (mean age, 28, 3 years old) and elderly healthy subjects (mean age, 73.3 years old), applying equilibrium dialysis under the same conditions in vitro. The protein binding capacity of oral cephems in elderly subjects was significantly less than that in young subjects, and a marked increase in free drug concentration was observed in elderly subjects. The addition of palmitic acid (PA)/oleic acid (OA), a common non-esterified fatty acid (NEFA), to pooled sera from young healty subjects caused the binding capacity of oral cephems to decrease, accompanied by an increase in the PA/OA concentration. This decrease in the protein binding capacity of oral cephems in elderly subjects was possibly caused by decreased serum albumin and age-related change in NEFA. As the free-drug concentration participates in the appearance of effects and adverse reactions, the possibility of enhanced pharmacological effects and increased adverse reactions of oral cephems due to decreased protein binding in elderly subjects should be considered.

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Fundamental and clinical studies of ofloxacin (OFLX), a new oral quinolon antibiotic, were carried out on oral infections of 60 patients. The concentration of OFLX in the gingiva and serum was determined 3 hours after it was administered orally (100mg). In addition, the clinical efficacy of OFLX was evaluated and bacterial sensitivity tests in patients with oral maxillofacial infection were carried out. OFLX was administered orally at a dose of 600 mg for three days to eight days.
1) Gingiva and serum concentrations of OFLX (100mg administered) were 0.82±0.4μg/g and 1.02±0.5μg/ml, respectively. In 91%(21) of the bacterial strains isolated the MIC was less than 1.56μg/ml, which means the sensitivity to OFLX was quite favorable.
2) OFLX (100mg), lomefloxacin (100mg) and tosufloxacin (150mg) were administered orally at the same time 3 hours before surgery. The tissue and serum concentrations of OFLX were 0.74±0.4μg (gingiva), 0.99±0.5μg/ml (serum), which was higher than those of lomefloxacin and tosufloxacin.
3) The clinical response to OFLX was excellent in 2 cases, good in 17 cases, fair in no cases and poor in 1 case. Thus the clinical efficacy was 95% overall. The efficacy rate on day 3 (n=13) was 76.9%; on day 5 (n=5), 80%, and there were no safety problems.
It was concluded that OFLX is a useful drug for treating oro-maxillofacial infections.

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A double-blind comparison of biapenem (BIPM), a new parenteral carbapenem, and imipenem/cilastatin (IPM/CS) was carried out in the treatment of complicated urinary tract infection. Patients were randomly assigned to receive either 300 mg b. i. d. of BIPM or 500mg/500mg b.i.d. of IPM/CS for 5 days by intravenous drip infusion. All patients were shown to have pyuria of at least 5 WBC per high power field, bacteriuria of at least 10⁴ CFU per ml of urine and identifiable underlying urinary tract disease. Overall chinical efficacy was evaluated on the basis of criteria proposed by the Japanese UTI Committee as “excellent, ” “moderate” or “poor.” Of the 200 patients evaluated for clinical efficacy, 98 patients received BIPM and 102 received IPM/CS. No significant differences were observed in the background characteristics between the two treatment groups except that the age distribution in the BIPM group was higher than that in the IPM/CS group (p<0.1). The overall efficacy rate was 82.7% in the BIPM group and 77.5% in the IPM/CS group. The difference was not statistically significant. The bacteriological eradication rate was 90.2% of 163 strains in the BIPM group and 86.3% of 161 strains in the IPM/CS group, the difference being not statistically significant. Clinical adverse reactions were experienced in 1.9% of 107 patients in the BIPM group and in 1.8% of 112 patients in the IPM/CS group. Laboratory adverse reactions were observed in 9.5% of 105 patients in the BIPM group and in 7.3% of 109 patients in the IPM/CS group, with no significant differences regarding the incidences of either clinical or laboratory adverse reactions. Global safety and clinical value were not significantly different between the two treatment groups. From the results obtained in this study, we concluded that treatment of complicated urinary tract infection with 300mg b.i.d. of BIPM is as effective and well tolerated as that with 500 mg/500mg b.i.d. of IPM/CS.

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We reviewed the charts of 7 patients (mean age: 29.9 years old) with human immunodeficiency virus (HIV) infection complicated with adverse reaction to sulfamethoxazole-trimethoprim (ST). Six of the 7 patients were male hemophiliacs and one patient was the wife of a hemophiliac. We administrated ST (initial dose: 2-12 tablets per day) to 4 patients for the treatment of Pneumocystis carinii (PC) pneumonia and 3 patients for prophylaxis of PC pneumonia. The adverse reaction occurred in 4 patients between 9 to 16 days after beginning of the treatment and consisted of skin eruption, fever and general fatigue. Abnormal changes in laboratory data developed in all 7 patients between 7 to 22 days after administration of ST, and consisted of liver disorder, leukopenia, thrombocytopenia, renal disorder, elevation of serum level of amylase and disseminated intravascular coagulation. We continued administration of ST in 6 patients and stopped it in 1 patient. In patients with HIV infection, ST has a high incidence of adverse reaction, especially within one month after the beginning of ST treatment.

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I studied the transfer of aspoxicillin (ASPC) to the bronchoalveolar system, using bronchoalveolar lavage (BAL), and compared the findings with my previous results for cefmenoxime (CMX), astromicin (ASTM), ofloxacin (OFLX) and aztreonam (AZT). The subjects were 22 patients with various respiratory diseases: 14 with chronic respiratory infection and 4 each with interstitial pneumonia and lung cancer. 1g of ASPC was given intravenously in group I, and with 1g of CMX in group II. BAL was performed 60 minutes after a single intravenous injection of ASPC. The concentrations of ASPC, CMX total protein and albumin were measured in serum and bronchoalveolar lavage fluid (BALF), and the following results were obtained.
1) The concentration of ASPC was 11.2-69.8μg/ml in serum, and 0.071-1.420μg/ml in BALF, the mean values±standard deviation being 37.53±17.3μg/ml and 0.307±0.409mg/ml, respectively.
2) The concentration of CMX was 24.7-61.8μg/ml in serum, and 0-0.77μg/ml in BALF, the mean values±standard deviation being 41.4±14.9μg/ml and 0.209±0.241μg/ml, respectively.
3) Thus, transfer of ASPC was superior to that of CMX, and next to those of OFLX and ASTM in my previous study.

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