The frequency of isolation of Providencia stuartii from various clinical sources was examined from 1981-1986. Sixty-nine strains were isolated from otorrhea and 4 from sputum or pus. This indicates that P. stuartii is clinically important as a causative microorganism of chronic otitis media.
Twenty strains, isolated from 1984-1985, were tested for their susceptibility to various chemotherapeutics. The majority of the strains were resistant to chloramphenicol, tetracyclineand sulfamethoxazole.
Many were resistant to fosfomycin, ampicillin, cefazolin and several aminoglycoside antibiotics, namely, streptomycin, kanamycin, gentamicin, dibekacin, sisomicin and tobramycin. In contrast, the majority of the strains were susceptible to cefmenoxime, cefotiam, amikacin, fortimicin, norfloxacin, trimethoprim and sulfamethoxazole-trimethoprim.
Profiles of plasmid DNA of the 20 isolates were analyzed, and plasmid DNA was found in 14. Conjugation and transformation were carried out for the detection of R plasmid. One of the 14 donors transferred resistance markers by conjugation.

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We examined 526 strains of S. aureus isolated from infectious skin lesions for coagulase-type, exfoliative toxin (ET) production and susceptibility to various antimicrobial agents. As to coagulase, type IV was most frequently isolated, followed by non-typable forms, types III, I and V. In deep seated pyoderma such as furuncle, furunculosis, sweat gland abscess and others, type IV S. aureus strains were the most frequently isolated. In superficial pyoderma such as impetigo and staphylococcal scalded skin syndrome (SSSS), types I and V were most frequently isolated. As to the secondary infection, eczema and dermatitis groups, there was no specific increase in coagulase types: 84.0% of S. aureus from impetigo and 88.9% from SSSS were ET (+); 41.1% from other skin infections were ET (+). The rate of methicillin-resistant S. aureus (MRSA) was about 20%. Most strains were susceptible to CER, MINO and new quinolones. About 10% of S. aureus were resistant to MDIPC and MCIPC. Type I and V strains were very susceptible, but type IV strains were multiply resistant. In 1987, 87.5% of coagulase type IV strains were MRSA.

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The therapeutic effect of aspoxicillin (ASPC) on experimental pneumonia induced with Klebsiella pneumoniae B-54 in mice was compared with those of piperacillin (PIPC) and mezlocillin (MZPC) under various administration schedules. A 50 mg/kg/dose of each drug was subcutaneously injected to the mice 10 times at 1, 2, 3 or 6-hourly intervals and the survival rates were determined. Under the 1, 2 and 3-hourly regimens, the survival rates with ASPC were nearly equal, but at 6-h intervals decreased slightly. The survival rates with PIPC and MZPC decreased with an increase in interval.
Mice were given 50 mg/kg/dose of each drug by single injection, 10 times at 1-hourly or 15 times at 2-hourly intervals, and the bacterial counts in the lung measured. The decrease in viable bacterial count after injection of ASPC occured more rapidly than with the other drugs under all administration schedules. On the other hand, treatment with PIPC or MZPC exerted only a slow decrease during the injection period.
Mice were given 50 mg/kg of each drug and concentrations in the lung were determined. The concentrations of ASPC were higher than those of others and the time above MIC value of ASPC was about 2.3 times longer.

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We performed pharmacokinetic studies on carboplatin, one of the new platinum analogues, and compared it with cisplatin. Both drugs were administered by intravenous short term (30 min) drip infusion. The doses of carboplatin and cisplatin were 450mg/m² and 80mg/m², respectively. Platinum Pt) concentrations were determined in whole plasma and plasma ultrafiltrate by atomic absorption spectrometry. Following the end of the infusion, plasma concentration of total platinum of carboplatin and cisplatin decayed biphasically. Ultrafilterable platinum in plasma decreased in a biexponential mode with carboplatin, whereas the free platinum of cisplatin showed monoexponential disappearance. Peak plasma concentrations and AUCs of the drugs were 19.90μg/ml and 3446μg/min/ml with carboplatin and 3.09 μg/ml and 208 μg/min/ml with cisplatin, respectively. The higher peak plasma concentration and longer retention time of active and non protein-bound platinum of carboplatin in plasma than of cisplatin suggest promising anticancer activity of this agent against a variety of tumor types.

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We studied the cross-reactivity of penams and cephems in delayed-type hypersensitivity (DTH) by leucocyte migration inhibition test (LMIT) to test the cross-reactivity of 10 patients displaying hypersensitivity to penams and 20 with hypersensitivity to cephems.
The cross-reaction rate in the LMIT of penam-sensitive patients was 56%(10/18) to penams, 71%(10/14) to penams with similar structures to the causative drugs in the C-6 side chain, and 0%(0/4) to penams without such similarities. On the other hand, 8%(3/38) to cephems, 16%(3/18) to cephems with similar structures to the causative drugs in the C-7 side chain, and 0%(0/20) to cephems without. The cross-reaction rate in the LMIT of cephem-sensitive patients was 48%(31/64) to cephems, 65%(17/26) to cephems with similar structures in the C-7 side chain, 75%(12/16) to cephems with similar structures in the C-3 side chain and 9%(2/22) to cephems without. On the other hand, 3%(1/34) to penams, (1/26) to penams with similar structures in the C-6 side chain and 0%(0/8) to penams without.
Our findings indicate that in DTH there may be incomplete cross-antigenicity between penams and cephems and that the structures of both the side chain and the parent ring itself may play an important part as antigenic determinant; but this kind of cross-reaction is probably induced only at a low rate.

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Causative organisms were identified by diagnostic bronchoscopy in 21 cases of respiratory infections in which the potential pathogens seemed to be anaerobic bacteria. A brush was introduced into the inflammatory foci of the lung, withdrawn, and was immediately stabbed into and spread on portable agar medium. Eighteen strains of the potential pathogens, including 9 strains of anaerobic bacteria consisting of 2 strains each of Peptococcus niger, Fusobacterium nucleatum and Bacteroides melaninogenicus, and 1 strain each of Peptostreptococcus anaerobius, Eubacterium sp. and Veillonella sp. were isolated after 48 h of aerobic and anaerobic cultures. Eight of 9 anaerobic strains except for Veillonella sp. were considered to be causative organisms. In 12 cases of pneumonia and lung abscess, 8 strains of anaerobic bacteria were recovered. On the other hand, only 1 strain of anaerobic bacterium was recovered from 9 cases with bronchogenic carcinoma. Aspiration and the presence of underlying immunocompromised disorders were confirmed, or suggested in many cases of anaerobic infections. Aerobic bacteria were isolated concurrently in 3 of 9 cases from which anaerobic bacteria were isolate. Fetid sputum, cavity formation and fluid level in the pleuropul monary space are frequently observed in cases of anaerobic infections. In our cases, such stenosis or obstruction of the airway as that found in cases of bronchogenic carcinoma was not necessarily related to anaerobic infections, and Bacteroides fragilis, highly resistant to many β-lactams, was isolated only occasionally. Thus we are of the opinion that common β-lactams, including penicillins and first-or second-generation cephems, are the first choice for anaerobic respiratory infections.

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We studied the excretion of latamoxef (LMOX) into choledochal bile to determine the appropriate dose and route of administration.
Choledochal bile was collected every 30 or 60 minutes from 5 patients with T-tube drainage. Each patient was examined 3 times in one week (cross-over method) after (1) bolus injection of 1g intravenously (1g i. v.), (2) bolus injection of 2 g (2g i. v.) and (3) drip infusion of 2g for 60 minutes (2g d.i.v.). The concentration of LMOX was measured by agar well method.
The peak concentration and the area under the curve of LMOX in bile were as follows:(1) 1g i. v.: 87.2μg/ml, 313μg· h/ml, (2) 2g i. v.: 140 μg/ml, 542μg· h/ml and (3) 2g d.i.v.: 111μg/ml, 472μg· h/ml.
The time-concentration curve of LMOX in bile was gently sloping. The peak time (during which the concentration of the drug is higher than half the peak level) of LMOX in bile was 3.46 h (1g i. v.), 4.07 h (2g i. v.) and 4.27 h (2g d.i.v.). The concentration of LMOX in bile 10 h after administration was 9.22 μg/ml (1g i. v.), 13.7 μg/ml (2g i. v.) and 12.5 μg/ml (2g d.i.v.). The concentration of LMOX in bile remained higher than 12.5 μg/ml for 6.4 h (1g i. v.), 8.0h (2g i. v.) and 7.5 h 2g d.i.v.
That is, the higher the dose, the higher the concentration of the drug in bile. The peak concentration of LMOX in bile of 2g i. v. was significantly higher than that of 2g d.i.v.(P<0.05). But the area under the curve and the peak time of both groups were similar.
In one case of renal dysfunction, the peak time of LMOX in bile was prolonged, thereby enlarging the area under the curve.
From the above results, we consider LMOX effective in biliary tract infections at a dose of 1g, twice a day. We suggest that a single-shot injection is superior to a 60-min drip infusion for excretion of LMOX into bile.

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We used aztreonam, a monobactam antibiotic on 40 patients undergoing transurethral prostatectomy. The postoperative course was uneventful in all cases, and no major complication occurred. The incidence of Enterococcus spp. and other Gram-positive cocci, however, was found to be increasing among organisms isolated both pre- and post-operatively from the urine.

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To objectively evaluate the clinical efficacy, safety and usefulness of TE-031 (TE) in chronic respiratory tract infections, we carried out a double-blind comparative study using cefaclor (CCL) as the control drug.
As a rule, treatment was by oral administration of 400 mg (in two divided doses) of TE daily and 1, 500 mg (in three divided doses) of CCL daily for 14 consecutive days. The following results were obtained.
1. The overall clinical efficacy as judged by the committee was 77.3%(58/75 cases) for TE and 67.2%(43/64 cases) for CCL.
2. The overall clinical efficacy as judged by the doctors in charge was 82.2%(60/73) for TE and 68.8%(44/64) for CCL.
3. In the bacteriological studies, the eradication rates were 54.8%(17/31) for TE and 63.2%(24/38) for CCL.
4. The incidence of side effects was 7.9%(7/89) for TE and 2.3%(2/88) for CCL. Almost all the instances of side effects were digestive tract symptoms, and none was serious in degree.
5. The incidence of abnormal changes in laboratory test values was 15.3%(13/85) for TE and 14.1%(12/85) for CCL. Eosinophilia was detected in 7 patients in the TE group and 4 in the CCL group, while the serum transaminase values were elevated in 4 patients in each group. All changes were mild in degree and soon returned to normal.
6. The usefulness of each drug regimen was evaluated by considering the clinical efficacy, the presence or absence of side effects and of abnormal changes in laboratory test values. The overall usefulness rates (including satisfactory and very satisfactory) were 72.7%(56/77) for TE and 67.2%(43/64) for CCL.
On the basis of our results, we confirmed that the usefulness of TE, administered orally in two daily doses of 200 mg, in chronic respiratory tract infections is comparable to that of CCL administered orally in three daily doses of 500 mg.

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To evaluate objectively the efficacy, safety and usefulness of lomefloxacin (NY-198), a new synthetic quinolone antimicrobial agent, in the treatment of complicated urinary tract infections (UTI), we performed a comparative double-blind trial using norfloxacin (NFLX) as the control drug. Patients were orally administered 600 mg/day of NY-198 (t. i. d.) or 800 mg/day of NFLX (q. i. d.) for five days. The clinical efficacy was evaluated based on the criteria proposed by the Japanese UTI Committee and the following results were obtained.
1. A total of 312 patients (NY-198: 156, NFLX: 156) were treated, among whom clinical efficacy was evaluated in 249 patients (NY-198: 122, NFLX: 127); 63 cases were excluded or dropped out. There was no statistically significant difference in the background charactaristics between the two groups.
2. In the NY-198 group, clinical efficacy assessed by the attending committee was excellent in 36 and moderate in 46 cases, and the efficacy rate (excellent plus good) was 67.2%. In the NFLX group, it was excellent in 47 and moderate in 28 cases and the efficacy rate was 59.1%. There was no signifi cant difference between the two groups.
3. Pyuria was cleared or improved in 52.5% of the patients treated with NY-198 and in 57.5% of the patients with NFLX, with no significant difference between the two groups. As for bacteriological response, the overall eradication rate was 80.6% in the NY-198 group and 73.5% in the NFLX group. For Gram-positive bacteria, the eradication rate was 91.5% in the NY-198 group and 75.3% in the NFLX group, showing a significantly higher rate in the NY-198 group (p<0.01).
4. Clinical efficacy evaluated by doctors was excellent in 36 and moderate in 44 cases, and the efficacy rate was 65.6% in the NT-198 group. In the NFLX group it was excellent in 48 cases, moderate in 25 cases and the efficacy rate was 57.5%. These results were quite similar to those of the committee, and there was no significant difference between the two groups. In the usefulness evaluated by doctors, again no significant difference was observed between the two groups.
5. Side-effects were observed in 7 cases (4.6%) out of 152 in the NY-198 group and 4 cases (2.6%) out of 153 in the NFLX group. Abnormal laboratory findings were noted in 9 cases (7.6%) out of 118 in the NY-198 group and 3 cases (2.4%) out of 127 in the NFLX group. There were no signifi cant differences between the two groups.
From these results, we considered that the therapeutic effect of 600 mg/day of NY-198 (t. i. d.) was the same or greater than that of 800 mg/day of NFLX (q. i. d.) in the treatment of complicated UTI.

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