A double-blind comparative study was designed to permit objective evaluation of the clinical efficacy and safety of 9, 3''-diacetyl-midecamycin (MOM; 600mg potency/day, divided into three equal doses) in the treatment of cases of acute suppurative otitis media and acute exacerbation of chronic otitis media. Midecamycin (MDM; 1, 200mg potency/day, t. i. d.) was employed as the comparative control drug, the results are described below.
1. Based on the criteria of the Evaluation Committee, the clinical efficacies of the two drugs were as follows. In the 107-patient group treated with MOM, the efficacy was excellent in 21 cases, good in 33 cases, fair in 24 cases and poor in 29 cases. The efficacy rate was thus 50.5%, In the 95-patient MDM administration group, there were 20 excellent cases, 25 good cases, 27 fair cases and 23 poor cases, resulting in an efficacy rate of 47.4%. There was no statistically significant difference between these efficacy rates, indicating that the results with these two drugs were equivalent.
2. Based on the criteria of the Evaluation Committee, the overall improvement, the bacteriological efficacy and the usefulness were evaluated for both of the administered drugs. Again, there were no significant differences between the results obtained with these two treatment regimens, and they were found to be approximately the same.
3. The MOM administration group showed a tendency for a lower incidence of side effects compared with the MDM administration group, i. e., 3.3% compared with 9.2%. The side effects seen with these two drugs were the same; that is, mild gastrointestinal symptoms, rash, etc.
Within the scope of the present study, MOM was concluded to be a drug having a high degree of safety.
On the basis of the above results, it was concluded that MOM is a safe and useful antibacterial agent which is able to provide approximately the same clinical efficacy as MDM, at only half the dosage level.

View full abstract

Thein vitroactivities of 8 newly cephem compounds, cefoxitin (CFX), cefmetazole (CMZ), latamoxef (LMOX), cefotaxime (CTX), ceftizoxime (CZX), cefmenoxime (CMX), cefotiam (CTM) and cefoperazone (CPZ), against Klebsiella spp. and Bacteroides fragilis and the therapeutic effects of them against experimental mixed infections due to K. oxytoca and B. fragilis were studied, and the following results were obtained.
1. B. fragilis GAI-588 was inoculated in the abdominal cavity of a mouse to which K. oxytoca 230-1 was preinfected. And then 100% of a death rate, although was 0% in single infection by K. oxytoca or B. fragilis, was recognized in the mixed infection.
2. Thein vitro antibacterial activity against Klebsiella spp.(54 strains) was excellent in the order of CZX>CTX>CMX>LMOX>CTM>CMZ>CFX>CPZ. Against B. fragilis (73 strains), cephamycins, CFX, CMZ and LMOX were superior to other cephalosporins tested: namely, the activity was in the order of LMOX>CFX=CMZ>CZX>CTX>CMX>CPZ>CTM.
3. The therapeutic effects of cephamycins, LMOX, CFX and CMZ, which showed resistance to hydrolysis byβ-lactamases of both K. oxytoca and B. fragilis, against experimental mixed infections due to K. oxytoca and B. fragilis were superior to oxime-cephalosporins, CTX, CZX and CMX, which showed resistance only to theβ-lactamase of K. oxytoca. CTM and CPZ, which did not show resistance to theβ-lactamases, were inferior.

View full abstract

Studies were made on the mechanism of carbadox (Cdx) resistance by using R plasmid (pNV 13) which encoded Cdx-resistance substance and was detected from Escherichia coli of porcine fecal origin.
The chemical modification of Cdx with pNV 13 was investigated. When E. coli C was used as a host, the specific adsorption (at about 375nm) disappeared from the culture fluid and another absorption appeared at a new wavelength (at about 360nm).
These changes were induced distinctly by E. coli C pNV 13 and stimulated in the presence of Lcysteine. Also in the presence of L-cysteine, the reduction of Cdx was noticed in the system of NADPH reduction with a crude enzymatic fluid obtained from E. coli C pNV 13 by treatment with osmotic shock. It was not noticed, however, in the fluid obtained from E. coli C.
On the other hand, when treated with EDTA, E. coliC pNV 13 showed no decrease in Cdx resistance, indicating that the mechanism of reduction of Cdx permeability in pNV 13 might be negative. Moreover, the E. coli AB 1157 (rec⁺) and E. coli AB 2463 (rec^-) strains were used to examined the effect of pNV 13 on the ability of the repair of damage of DNA. No effect was found, however, on stimulating it, pNV 13 was not related to recombination-proficient.
In conclusion, it was presumed that the mechanism of Cdx resistance by pNV 13 might be derived from NADPH-depended, Cdx-reducing enzyme contained in the bacterial periplasm newly.

View full abstract

The maximum binding number (n), association constant (K), and binding sites for cefoperazone (CPZ) and cefazolin (CEZ) were investigated by SCATCHARD plot and KLOTZ plot using rat serum protein.
The extent of CPZ was 50.8%-44.0% bound at the low concentration (below 100μg/ml) and CEZ was 94.2%-90.3%. The percentage of bound CPZ and CEZ in the serum decreased with an increase in drug concentration. CPZ and CEZ had two classes of the binding sites on rat serum protein, and the values ofKfor CPZ were smaller than those for CEZ.
From the results of KLOTZ plot, the main binding site for CPZ appeared to coincide with that of CEZ. The binding rate of CPZ decreased by the addition of CEZ, however, CEZ binding rate was not greatly affected by the addition of CPZ because CEZ had high affinity, compared with CPZ.
UsingnandKvalues, it was able to predict the binding rate of CPZ or CEZ in the combination of them.
The relationship between serum protein binding and pharmacokinetics were also investigated. CPZ and CEZ were singly or simultaneously administrated at a dose of 50 mg/kg with inflammatory pouch induced with croton oil. The CPZ exudate levels for simultaneous administration were significantly higher than those for single administration. This suggested that CPZ was displaced by CEZ and subsequently an increase in the concentration of the unbound drug in the serum made CPZ available for passage into inflammatory pouch.
It became clear that serum protein binding of drug was important factor affecting its pharmacokinetics.

View full abstract

[in Japanese]

View full abstract

In the four β-lactamase detecting methods (nitrocefin spot plate method, slide glass method, disk method and starch paper method), the sensitivity of nitrocefin spot plate method was the best in various β-lactamase and its viable cells. In the disk method, the sensitivity increased to 10 fold by cephaloridine substrate compared to penicillin G substrate.
It was observed that the sensitivity of Richmond type I enzyme changed depending on the sources of the enzymes. On the other hand, there was no difference between the four methods in Richmond type III, so that the detection of Richmond type III enzyme mediated by R plasmids may be useful for the clinical.

View full abstract

We investigated the availability of β-lactamase rapid detecting methods (disk method, slide glass method, starch paper method and nitrocefin spot plate method) in order to make use of the methods to clinical microbiology.
Nitrocefin spot plate method (nitrocefin 12.5 μg/ml) and disk method (substrate was penicillin G or cephaloridine) showed a higher sensitivities than other methods when penicillin G, cephaloridine, cefmetazole and cefoxitin were added to bacterial cultures in order to induce β-lactamase production.
In some species, there was a relationship between the β-lactamase production and drug-sensitivities.
Therefore, above four methods were useful to detect the β-lactamase production of clinical isolates.

View full abstract