During the 14 months from May 1985 to June 1986, enterococci were isolated from clinical materials at Chiba University Hospital.
During this period, 429 strains were collected, of which 309 were Enterococcus faecalis, 65 Enterococcus faecium, 52 Enterococcus avium, and 2 Enterococcus durans. Ampicillin (ABPC)-resistant strains (MIC:≥16μg/ml) were found in E. faecium, E. avium, and E. durans, but in E. faecalis no ABPC-resistant strains were found.
After this period, 2 ABPC-resistant strains were found in Enterococcus casselifiavus. E. faecium isolates were the most resistant of the enterococcal strains against β-lactams, and ABPC-resistant strains in all Enterococcus spp. were susceptible only to vancomycin. ABPC-resistant strains of Enterococcus spp. were mainly isolated from the patients who had polymicrobial infections, severe underlying diseases, and antibiotic premedication. Some characteristic differences were found between ABPC-susceptible (MIC:≤8μg/ml) and-resistant strains of E. faecium and E. avium.
In E. faecium, not all ABPC-susceptible strains fermented sorbitol, but 89.8% of ABPC-susceptible strains did; and in E. avium, most ABPC-resistant strains produced β-galactocidase and fermented raffinose, whereas few ABPC-susceptible strains showed those characteristics.

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In a previous study, we compared the induction rates of β-lactamase produced by cefoxitin in many Pseudomonas strains and found various induction rates among those tested. The inducibility was highest in Pseudomonas aeruginosa. In the present study, we investigated the induction in P. aeruginosa of β-lactamase by various antipseudomonal β-lactams and drug susceptibility after the induction.
Fifteen clinical isolates of P. aeruginosa were each treated with sub-inhibitory concentrations of 8 antipseudomonal β-lactams such as sulbenicillin, ticarcillin, piperacillin, cefsulodin, cefoperazone, cefpiramide, ceftazidime and aztreonam at 377deg;C for 2 hours to induce β-lactamase production. The βlactamase inducibility of these antibiotics differed among the test strains;β-lactamase activity was augmented sharply in the moderate β-lactamase producers after the induction. However, the enzyme activity of the constitutive and non-constitutive β-lactamase producers increased only slightly or not at all. On the other hand, the P. aeruginosa strains, which largely produced the β-lactamase after induction with these antibiotics, became resistant to them.

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To examine the effect of β-lactams on the induction of β-lactamase in Pseudomonas aeruginosa, we used the disc method. When an imipenem disc was placed adjacent to a β-lactam disc the inhibition zone produced by the β-lactam disc was truncated on the side closest to the imipenem disc. When enzyme synthesis was induced by these double disc tests, the activity of most β-lactams was antagonised significantly against β-lactamase-inducible strains. A mpicillin, penicillin G, cephaloridine and cefmetazole in addition to imipenem also induced β-lactamase production in P.aeruginosa. In more than 90% of clinical isolates of P.aeruginosa strains, β-lactamase synthesis was induced by β-lactam disc. Using the disc method, we estimated the optimal concentration of β-lactam for β-lactamase induction.
β-Lactam higly resistant mutants were isolated at a frequency of about 10^-5 to 10^-6 by the disc method. Most of the mutants selected by the β-lactams produced inducible β-lactamases at a high level. However, the mutants isolated by imipenem disc were resistant to imipenem only, and the enzyme activities of these resistant mutants were almost the same as those of theparent strains.

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We made a clinical study of postoperative infection due to Pseudomonas aeruginosa in adult cases of digestive tract surgery from January 1985 to August 1988. Thirty-four strains of P.aeruginosa were isolated from 29 patients with postoperative infection. In these 29 cases, risk factors such as metachronous double cancers, diabetes mellitus, and hypertension were recognized in 4, 4, and 3 cases, respectively, and 22 (75.9%) were operated for malignant diseases. The blood-loss during the operation exceeded 1, 000 ml in 11 cases (37.9%) and antibiotics administered for prophylaxis were not effective against P.aeruginosa in 15 cases. The infections in 23 cases (67.6%) were related to the site of the operation, and intraabdominal sepsis and wound infection were frequent. The interval between surgery and onset was more than 8 days in 26 cases (76.5%). Ten strains (29.4%) were isolated along with other bacteria, and the incidence of mixed infections was high in cases of intraabdominal sepsis and wound infection. The minimum inhibitory concentrations (MICs) of P. aeruginosa, isolated from clinical cases from January 1985 to November 1988, were measured and compared with those isolated from 1982 to 1984. The MIC₈₀, value decreased for piperacillin, cefsulodin, cefoperazone, ceftazidime and aztreonam, and increased for imipenem, amikacin, gentamicin, ofloxacin and ciprofloxacin.

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We compared the effect on coagulability of third-generation cephems with and without a N-methyltetrazolethiol base (NMTT). Cefotaxime (CTX) and ceftazidime (CAZ) were selected as the drugs without NMTT and administered in 48 cases. Cefmenoxime (CMX) and latamoxef (LMOX) were selected as the drugs with NMTT and administered in 46 cases. Prothrombin time (PT), activated partial thromboplastin time (APTT), thrombotest, hepaplastin test and PIVKA-II were examined before and after treatment.
No definite change in PT, APTT and thrombotest before and after treatment was observed. Although a significant decrease in hepaplastin test after treatment was observed, no significant difference in hepaplastin time was shown between the groups with and without NMTT base. The coagulability of each group changed after treatment as follows: In the CTX and CAZ groups, PT decreased by 2.1%, APTT 4.2%, thrombotest 2.1%, hepaplastin test 4.2%, and PIVKA-II 0%. In the CMX and LMOX groups, PT decreased by 8.7%, APTT 8.7%, thrombotest 10.9%, hepaplastin test 13.0% and PIVKA-II 10.9%. The CMX and LMOX groups showed a higher incidence of abnormal coagulability.
Most cases showing abnormal coagulability were accompanied by malnutrition.
These results suggest that antibiotics which have an NMTT base show a higher tendency to abnormal coagulability, especially in patients with malnutrition. Accordingly, when administered to such patients, careful observation with frequent measurement of coagulatory function is necessary.

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Klebsiella pneumoniae 163 was grown in the presence of 1/4 MIC of cefodizime (CDZM) or cefpimizole (CPIZ) for 3 hours. The killing rate of drug-treated bacteria by human polymorphonuclear leukocytes (PMNs) was significantly enhanced, compared with that of the untreated bacteria (p<0.01). Study of opsonization kinetics by a chemiluminescence assay demonstrated that drug-treated bacteria were opsonized more rapidly than control bacteria (p<0.01), and serum complement was consumed much faster when Klebsiella pneumoniae was preincubated with each drug (P<0.01). Furthermore, Klebsiella pneumoniae treated with 1/4 MIC of CDZM or CPIZ was more sensitive to hydrogen peroxide (H₂O₂), one of the oxygen-free radicals produced by phagocytes (P<0.01). These results show that Klebsiella pneumoniae treated by 1/4 MIC of CDZM or CPIZ is much more susceptible to the bactericidal activity of human PMNs than untreated controls. This potentiation of host defense by sub-MICs of antibiotics might be a favorable consequence in patients treated with these drugs for infections caused by Klebsiella pneumoniae.

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The transfer of ofloxacin (OFLX) to the bronchoalveolar system was studied using bronchoalveolar lavage (BAL), and the findings were compared with our previous results for cefmenoxime (CMX) and astromicin (ASTM). The subjects were 23 patients with various respiratory diseases: 9 cases of lung cancer, 5 of chronic inflammation, 5 of interstitial pneumonia, 3 of pulmonary tuberculosis and 1 of non-specific bronchial ulcer. BAL was performed 60 minutes after a single oral administration of 200 mg of OFLX, and the concentration of OFLX, total protein and albumin were measured in serum and BAL fluid (BALF), respectively. The OFLX concentration was measured by bioassay (in serum) and new fluorimetric high perfomance liquid chromatography (in BALF) And the following results were obtained.
1) The concentration of OFLX was 0.04-4.31μg/ml in serum, and 2.4-322 ng/ml in BALF.
2) The mean value±standard deviation of OFLX concentration was 1.83±1.36μg/ml in serum, and 79.84±77.62 ng/ml in BALF.
3) The BALF/serum ratio of OFLX was 0.058±0.036 and the OFLX concentration was thought to reflect that in serum. The OFLX concentration in serum was higher after 120 minutes than 60 minutes.
4) The transfer of OFLX to BALF was similar to that of CMX and ASTM in the previous study, and smooth transfer to the bronchoalveolar system was recognized.
5) The OFLX/albumin ratio was higher in BALF than in serum.

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