Methicillin-resistant Staphylococcus aureus (MRSA) isolated from clinical materials at the Chiba University Hospital during 5 years from 1981 to 1985 were examined to study susceptibility against various antibiotics and coagulase types. The isolation frequency of MRSA from Staphylococcus aureus increased from 16.6%(51 strains) in 1981 to 33.2%(144 strains) in 1985. MRSA from the inpatient increased significantlyfrom 17.8%(29 strains) in 1981 to 40.0%(106 strains) in 1985. However, MRSA from the outpatient were constantly about 20% during these periods. MRSA were most frequently isolated from pus and otorrhea. Particularly, the isolation of MRSA from the inpatient increased in sputum, urine and blood. The isolation frequency of MRSA were higher at the surgical departments than at the internal departments. The coagulase type of most strains of MRSA was classified into type II and type IV. Type IV strains were mostly isolated from the outpatients and type II strains from the inpatients increased after 1984.
Many strains of MRSA were resistant to PCG, ABPC, MPIPC, CET, GM, EM, CLDM, and MINO, respectively. Methicillin-sensitive Staphylococcus aureus (MSSA) were much more sensitive to these antibiotics. Coagulase type II strains were sensitive to MINO and relatively resistant to MCIPC and cephems. On the contrary, coagulase type IV strains were sensitive to MCIPC and relatively resistant to MINO. All strains of MRSA were sensitive to VCM and only 2 strains were resistant to RFP. We examined effects of incubation temperature and time on susceptibility using microdilution method. The MICs against DMPPC obtained after 18 hr of incubation at 30°C were generally 2-to 8-fold higher than those obtained at 37°C. The MICs of most MRSA against DMPPC obtained after 48 hr of incubation at 37°C were distributed between those obtained after 18 hr of incubation at 37°C and 30°C.

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The antibiotic activities of 9 aminoglycoside antibiotics (AGs)[arbekacin (HBK), dibekacin (DKB), gentamicin (GM), amikacin (AMK), tobramycin (TOB), netilmicin (NTL), sisomicin (SISO), micronomicin (MCR) and astromicin (ASTM)] and 2 beta-lactam antibiotics [methicillin (DMPPC) and cefaaolin (CEZ)] were examined against 50 MRSA strains isolated from blood, sputum or exudates from patients with septicemia or respiratory tract infections.
1) Antibiotic activities of various AGs against MRSA The antibiotic activities of HBK and NTL were excellent, i. e., their MIC80 values were 0.78μg/ml and 1.56μg/ml, respectively. The MIC₈₀ of AMK was 25μg/ml although there were a few strains which were resistant to more than 100 μg/ml.
The other AGs showed inferior antibiotic activity; the MIC50 values of DKB, GM and SISO were 100μg/ml, and those of TOB, MCR and ASTM were more than 100μg/ml.
The MIC distributions of GM, SISO, MCR and ASTM showed the same pattern, while highlyresistant strains occupied a high percentage of the MIC distribution of TOB. The antibiotic activities of these AGs were thus diverse.
2) MIC distributions of DMPPC and CEZ The MIC distribution of DMPPC was almost the same as that of CEZ; strains which were resistant to DMPPC were also resistant to CEZ.
The MIC distribution of DMPPC against MRSA varied somewhat with the temperature, 32°C and 37°C, Some strains showed a low MIC at 37°C, while most of the other strains showed a very high MIC even at 37°C. These results suggest that some MRSA strains' susceptibility to beta-lactam antibiotics is temperature-dependent while others do not show temperature-dependent susceptibility and are highly resistant to multiple drugs.

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A new reversed phase ion-pair high-performance liquid chromatographic method for the assay of cefmetazole (CMZ) and gentamlcin (GM) in human serum which were administered in combination therapy was developed, The condition of HPLC system was as follows: Mobile phase was prepared to contain 0.1 M disodium 1, 2-ethanedisulfonate and 0.005 M sodium octanesulfonate in 16% acetonitrile solution adjusted to pH 3.2-3.3 with acetic acid.Counter-ion reagent was prepared to contain 0.2 M disodium 1, 2-ethanedisulfonate and 0.01M octanesulfonate adjusted to pH 2.5 with acetic acid. Flow rate of mobile phase and fluorescent phase (o-phthalaldehyde) was 1.2 and 0.3ml/min respectively. After detection of CMZ by UV absorption (254nm), three major components of GM (C_1a, C₂, C₁) were measured with the fluorescent detection method (EM 452nm, EX 357nm). Deproteinization was performed by adding 99.7% methanol (100μl) to a mixture of serum sample (50μl) and internal standard (tobramycin;20μl).After centrifugation, 200μl of counter-ion reagent was added to asupematant.After being centrifuged, a supernatant of 100 μl was injecled on a revered phase column (Zorbax ODS).The results were as follows: Retention time of CMZ was 5 min and those of C_1a, C₂ and C₁ of GM were 15, 18 and 22 min respectively. Peak height of CMZ and peak height ratio of GM to the internal standard were proportional to the concentmtions in the range of therapeutic concentrations.Minimum detectable concentration of GM by this method was 1μg/ml.Favorable within-day repeatability from low to high concentrations (CMZ;2.2-4.6%, GM;6.4-7.9%) and dayto-day reproducibility (CMZ; 8.2-9.1%, GM; 2.2-13.3%) (CV) were obtained.Serum concentrations of CMZ and GM were measured in 9 gynecologic patients with normal renal function who had been given 2g of CMZ by intravenous drip infusion for 1 hour combined with 40mg of GM by intramuscular injection. Thus, this method proved useful for the rapid monitoring of CMZ and GM in the comblnation therapy.

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Fosfomycin (FOM), 100mg/kg, was injected intramuscularly in normal and pneumonic rats.After 0.5hr, 1 hr and 2 hr bronchoalveolar lavage (BAL) was carried out 10 times and the concentration of FOM recovered in the BAL fluids was measured.
The following results were obtained:
1) The concentration of FOM in BAL fluid at 0.5 hr after administration decreased rapidly with each lavage and FOM in BAL fluids after 7th-8th lavage is not detectable.
2) In the pneumonic rats (20 ml solution containing P. aeruginosa IFO 3445 10⁹/ml was sprayed), the total recovery of FOM following ten BAL procedures was 46.4±14.6μg in 0.5 hr and 36.2 ± 11.1μg in 1 hr and these were much greater than those in the normal group (21.7± 3.9μg in 0.5 hr and 14.1±5.4 μg in 1 hr), and those difference were significant (P<0.02, P<0.01).There is no difference of the recovery in 2 hr between the normal rats and the pneumonic rats.
3) There are no difference of serum concentration in 0.5 hr, 1 hr and 2 hr between the normal rats and the pneumonic rats.
4) There is no difference of amount of FOM in lungs in 0.5 hr between the normal rats and the pneumonic rats.
5) The increased FOM concentration in the BAL fluid of the pneumonic rats were thought to be due to the augmented permeability of the capillary vessels and alveolar layer caused by inflammation.

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A double blind comparison of carumonam, a new parenteral monobactam antibiotic, and cefoperazone was carried out in the treatment of complicated urinary tract infections due to gram-negative bacilli. Patients received 1g of either carumonam or cefoperasone twice a day for 5 days by intravenous drip infusion.
All patients had pyuria of at least 5 WBCs per high power field, gram-negative bacilluria of at least 10⁴ bacilli per ml of urine and identifiable underlying urinary tract disease. The overall clinical efficacy of the treatment was evaluated by the criteria proposed by the UTI Committee in Japan as excellent, moderate or poor based on the combination of changes in pyuria and bacteriuria.
Of the 213 patients evaluated for the clinical efficacy, 113 patients received carumonam and 100 received cefoperazone. No significant difference in background charecteristics was observed between the two treatment groups. Excellent and moderate responses were obtained in 70.8% of the patient. receiving carumonam and in 61.0% of the patients receiving cefoperazone. This difference was not statistically significant. The overall bacteriological eradication rates obtained were 90.3% of 175 strains in the carumonam group and 80.1% of 151 strains in the cefoperazone group. This difference was statistically significant (P<0.05). Significantly higher eradication rate for S. marcescens was achieved in the carumonam group (P<0.05).
Clinical adverse reactions were observed in two patients (1.1%) in the carumonam group and in one patient (0.6%) in the cefoperasone group. The incidences of patients with elevated S-GOT and S-GPT were significantly lower in the carumonam group (P<0.05).
From the results obtained in this study, we concluded that carumonam was as useful as cefoperasone in the treatment of complicated urinary tract infections due to gram-negative bacilli.

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