The susceptibility of Pasteurella nzultocida isolates from animals (mainly from porcine pneumonic lung) to ofloxacin (OFLX) and 17 other commonly used antibacterial agents was determined. The results were as follows.(1) All of the 37 isolates were highly susceptible to OFLX (MIC: 0.025-0.1μg/ml), followed by trimethoprim (TMP), oxolinic acid (OXA), ampicillin (ABPC), chloramphenicol (CP), and thiamphenicol (TP)(MIC: 0.1-0.8μg/ml). The susceptibility ofthe isolates to a combination product of sulfamethoxazole (SMX)-TMP (20: 1), doxycycline (DOXY), oxytetracycline (OTC), and tiamulin (TML) was moderate (MIC: 0.8-6. 25μg/ml). The isolates showed relatively low susceptibility (MIC: 12.5-50μg/ml) to streptomycin (SM), kanamycin (KM), spectinomycin (SPCM) and tylosin (TS). SMX showed the lowest activity against the isolates (MIC: 25-200μg/ml).(2) A total of 13 (35.1%) isolates were resistant to SMX, SM, ABPC or DOXY OTC. Several different resistance patterns were found. Isolates resistant only to SMX were most frequent (8 isolates), followed by those resistant to the combination of SMX and SM, ABPC, or TC (5 isolates). Those resistant isolates were susceptible to OFLX as well as the other isolates.(3) The susceptibility of the 76 isolates to OFLX and the 4 other pyridonecarboxylic acid derivatives was determined. The highest distribution of MIC of OFLX, norfloxacin (NFLX), OXA, nalidixic acid (NA), or pipemidic acid (PPA) was observed at 0.05μg/ml, 0.1%mu;g/ml, 0.8μg/ml, or 1.56μg/ml, respectively.

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We studied the in vitro antibacterial activity of cefpiramide (CPM) in combination with cefotetan (CTT) against methicillin-susceptible (MSSA) and -resistant (MRSA) Staphylococcus aureus, using the checkerboard dilution method. The combination with CPM and CTT showed good synergistic activity against moderately and highly resistant MRSA strains and also synergistic bactericidal activity. The MRSA strains grown in the presence of both CPM and CTT were autolyzed easily, and these results may represent the synergistic activity.

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The binding of antibiotics with serum protein plays an important role in the effect, distribution and excretion of antibiotics. Although there are many studies on this phenomenon, very few are concerned with the protein binding of antibiotics in renal diseases. In this study, we attempted to clarify the protein binding rate of antibiotics in patients with various renal diseases, and the cause of impaired protein binding in hemodialysis patients.
The binding of CEZ and MCIPC with protein was measured by the centrifugal ultrafiltration method in 10 nephritic, 10 nephrotic and 9 chronic hemodialysis patients. Ten normal subjects were also studied as controls.
The percentage of bound CEZ was 84.6% in nephritic, 88.1% in nephrotic, and 64.1% in chronic hemodialysis patients. With MCIPC, it was 79.6% in nephritic, 85.6% in nephrotic, and 52.1% in chronic hemodialysis patients. Namely, the binding rate of CEZ and MCIPC with protein was much lower in chronic hemodialysis patients than in normal subjects (CEZ 92.1%, MCIPC 88.3%).
Results showed that the binding of CEZ and MCIPC with protein in chronic hemodialysis patients increased after hemodialysis. This suggests that the reduced binding rate was due to some dialysable substances which accumulated in these patients.

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We conducted an investigation in animals to substantiate our previous clinical findings on crossreactivity between penams and cephems in delayed-type hypersensitivity (DTH) by testing for crossreactivity in patients displaying hypersensitivity to penams and in patients with hypersensitivity to cephems.
We used guinea pigs and five sensitizing agents: ampicillin (ABPC), cephalexin (CEX) having the same side chain structure as ABPC, 6-aminopenicillanic acid (6 APA) which is themother nucleus structure of penams, 7-aminocephalosporanic acid (7 ACA) which is a cephem, DL-a-phenylglycine (PhGly) which is itself the side chain of both ABPC and CEX. The delayed-type intradermal skin test and leucocyte migration inhibition test (LMIT) were used to examine the cross-reaction of ten agents in DTH on sensitized guinea pigs.
The results of the skin test and LMIT on sensitized guinea pigs correlated and closely agreed with our human studies. Briefly, our observations were: In DTH to ABPC they cross-reacted not only to penicillin G (PCG), which is a penam with a similar structure in the C-6 sidechain to ABPC and 6 APA, but also to CEX, which is a cephem with the same side chain as ABPC, and 7 ACA. On the other hand, in DTH to CEX they cross-reacted only to latamoxef (LMOX) and cephalothin (CET), which are cephems, and 7 ACA. Then, in DTH to 6 APA they cross-reacted not only to penams but also to 7 ACA. But although in DTH to 7 ACA they cross-reacted only to cephems, little DTH was induced by PhGly.
Our findings indicate that in DTH to penams they may cross-react to cephems witha similar structure in the side chain to the sensitizing drug, but in DTH to cephems they may cross-react little to similar penams, since cross-reactivity between penams and cephems probably depends not only upon the similarity between both side chain structures but also the cross-reactivity between both mother nucleus structures.

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This work was carried out in order to clarify the antigenic properties of fosfomycin (FOM). The results obtained were as follows.
1) Detection of degradation products of FOM: stored solution of FOM under various pH conditions and serum including FOM were measured by gel filtration, SIMS and HPLC methods. Degradation products were not observed in any test using this experiment.
2) Formation of FOM polymer: Stored FOM solution made by GRANT's method was measured by gel filtration and HPLC technique. The gel filtration pattern of the stored solution showed diffuse elution peaks between the Kay. 0.1 and 0.5 positions. The polymer fraction of FOM was therefore not clarified.
3) Non-specific adsorption of FOM to the dialysis membrane: The dialysis effect of FOM was compared with that of PCG using the countercurrent dialyzer method.
The PCG solution was completely dialyzed in 90 minutes. The dialysis speed of FOM, however, was slower and only 50% of FOM was dialyzed in 2 or 3 days.
Our results suggest that if antigenicity of FOM is expressed, its structure is derived from carrier protein to which FOM is adsorbed.

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We examined the NBT reduction activity of neutrophil and lysozyme concentrations in serum of mice treated with cefbuperazone (CBPZ) after infection with E. coli (K-14). NBT reduction activity and lysozyme concentration increased from 4-8 h, and then both decreased to normal by 24 h after subcutaneous injection with 0.1 mg or more of CBPZ/mouse. The doses in infected mice proved to be the same as in normal mice. Also, CBPZ induced the same results at concentrations from 1.0-10 μg/ml in vitro, and sera showed bactericidal action for as long as 15 h later although antibiotic activity had already disappeared.
The plaque technique of CUNNINGHAM was used to demonstrate the enhancement effect of CBPZ on antibody formation. When mice were pretreated with CBPZ and inoculated with SRBC, the number of plaque-forming cells against SRBC in the spleen increased.
From these results alone it seems that CBPZ contributes to immune bactericidal action in vivo as well as in vitro.

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A prospective randomized study was performed to compare the safety and efficacy of cefotiam with those of cefpiramide for prophylaxis in 100 patients undergoing elective biliary tract surgery from April 1986 till November 1987. Patients were allocated at random to receive an intravenous dose of 2 g of either cefotiam or cefpiramide at the beginning of surgery. The intravenous dose of cefotiam was continued at 1 g every 8 hours and of cefpiramide every 12 hours for 4 days postoperatively. Of the 100 patients, 5 were withdrawn because the operations performed were not concerned with this study. The incidence of postoperative infection was higher in the cefotiam group (n=46) than in the cefpiramide group (n=49), but no significant difference (P<0.1) was recognized.
There was also no significant difference in the rate of side effects between the two groups. Cefpiramide twice a day is thus more useful than cefotiam three times a day in preventing postoperative infections following biliary tract surgery.

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NFLX 200 mg 3 times a day for 7 to 14 days was administered as initial treatment to patients with complicated UTI without indwelling catheter.Subsequently, patients in whom NFLX treatment was not effective were excluded from the current study.The remainder, who were evaluated as excellent or moderate, were randomly divided into 2 groups. In the first group, NFLX 200 mg was administered as an evening dose for the prevention of infection. Patients in the second group were not given any drug (controls).
The recurrence rates of the NFLX and the control groups after 4 weeks were 2.9% and 41.7%, respectively.Of the treated patients, 11 received the treatment more than 10 weeks, and in these the recurrence rate was 9%(1/11).

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Using the double-blind method, we evaluated the efficacy, safety and usefulness of cefotiam hexetil (CTM-HE) for the treatment of chronic respiratory tract infections using cefaclor (CCL) as control drug. The results obtained were as follows:
Patients were given orally, in 3 divided doses, CTM-HE in a daily dose of 1200mg (as cefotiam) or CCL in a daily dose of 1500 mg for 14 consecutive days as a rule.
1) Clinical response was judged by the committee as good and excellent in 67. 3%(76/113) of thepatients on CTM-HE treatment and 65.2%(73/112) of those on CCL treatment, and by the attending physicians in 67.0%(75/112) of those on CTM-HE and 59. 8%(67/112) of those on CCL.
2) Bacteriological response by causative organisms was judged as eradicated in 64.0%(48/75) in the CTM-HE treatment group and 55.8%(43/77) in the CCL treatment group.
3) As for the safety evaluation, adverse reactions were reported in 7.6%(9/119) of the patients on CTM-HE and 8.8%(11/125) of those on CCL. Abnormal alterations of laboratory findings occured in 21.4%(24/112) of the patients on CTM-HE and 13.3%(15/113) of those on CCL. Major adverse reactions to both treatments included gastrointestinal disorders such as diarrhea. Most of the abnormal laboratory findings were increase in eosinophils and in serum transaminases, which did not particularly differ from those observed with conventionally available cephem antibiotics.
4) As to utility, the drug was judged as fairly useful and better by the committee in 66.4%(75/113) of the patients on CTM-HE and 62.6%(72/115) of those on CCL, and by the attending physicians in 65.2%(73/112) of those on CTM-HE and 59.1%(68/115) of those on CCL.
The above results indicate that the daily dose of 1200 mg of CTM-HE is comparable to 1500 mg of CCL in efficacy and safety, and we conclude that CTM-HE is useful for the treatment of chronic respiratory tract infections.

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The efficacy, safety and usefulness of lomefloxacin (NY-198) and norfloxacin (NFLX) were compared in the treatment of skin and soft tissue infections, and evaluated in a double-blind clinical trial. Patients over the age of 15 years were randomly allocated to one of the two drugs. Each drug was orally administered at a daily dose of 600 mg divided into three doses (morning, noon and late evening).
Two hundred ninety-one patients were enrolled: 147 in the NY-198 group and 144 in the NFLX group. Analysed cases were 132 in the NY-198 group and 127 in the NFLX group for efficacy, 144 in NY-198 group and 135 in NFLX group for safety, and 134 in the NY-198 group and 128 in the NFLX group for usefulness.
In the final overall clinical evaluation, improvement rates were 79. 5% in the NY 198 group and 72.4% in the NFLX group. The difference was not statistically significant. The overall safety assessment showed no statistically significant difference between the two drug groups. Nor was any statistically significant difference in usefulness obtained between the two drug groups, the usefulness rate being 76.1% in the NY-198 group and 71.1% in the NFLX group. Examination of the bacteriological effect showed that eradication rates were 82.3% in the NY 198 group and 64.6% in the NFLX group. The diference was statistically significant (p=0.013). In cases where Staphylococcus aureus was a monomicrobial isolate, the organism was eradicated during the treatment in 80.6% of NY-198 cases and in 60.8% of NFLX cases, the difference tending to be favorable to NY-198 (p=0.062).
As to side effects or abnormal changes in laboratory findings, no significant difference was seen between the two drug groups.
In conclusion, NY-198 was considered to have slight superiority over NFLX in the treatment of skin and soft tissue infections.

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