Combination therapy consi8ting of cefbselis (CFSL) and amikacin (AMK) against Pseudomonas aeruginosa strains with different-susceptibility to CFSL was investigated based on their pharmaoodynamics. The mean MIC of CFSL alone for CFSL-susceptible P. aeruginosa strains was 4.11μg/mL, and ≤0.87 to 1.09μg/mL when CFSL was used in combination with AMK, tobramycin (TOB), orisepamicin (ISP). The MICs of CFSL in combination with AMK, TOB or ISPfor CFSL-resistantP. aerugiuosa strains were ≤9.69μg/mL, while the mean MIC of CFSL alone against these strains was 37.8μg/mL. Experimental therapy of murine bacteremia induced by a CFSL-resistant strain of P.aerugiuosa with acombination of CFSL and AMK in an in vivo pharmacokmetic modelsimulating human plasma levels after administration by 1-hour infUsion resulted in reduced viable bacterial counts inblood, inmarked oontrast to the low bacteriocidal activity of the respective mono-therapy regimens. Thecombination of AMK with CFSL enhanced potency against P.aeruginosa and prolonged time above the MICfor CFSL, suggesting that CFSL and AMK combination therapy should be of value in the treatment of bacteremia caused by P. aeruginosa clinically.

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Eradication therapy of Helicobacter pylori infection by standard proton pump ihhibitor-boased triple therapies (clahthromycin and amoxicillin) has been correlated with cure of pepticuloer disease.On the other hand an increase in drug-resistant H. pylori has been reported to be a clinical pmblem.Thus, the aim of this study was to clarify the effect of rifampicin by susceptibility tests and in vitro induoement of drug resistance on H.pylori.In the in vivo study, anti-H.pylori IgG antibody and the [¹³C] urea breath test were used in a total 40 tuberculosis and atypical tuberculosis patients treatgd with rifampicin. The prevalence of H.pylori in fection was low in the patientstreated with rifampidn, and the eradication rate was 23.1%.The results of this study suggested that hfampidn eradicates H.pylori in tuberculosis and atypical tuberculosis patients treated with the drug.

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We investigated the biological properties drug susceptibility of 88 strains of Staphylococcus aureus isolated from children with contagious impetigo between June and September 1999 and furthermore in vitro combined effect of cefdinir and various antibiotics which are used as external preparations.
1) Twenty-eight strains (32%) of MRSA were isolated from 88 strains of S. aureus. In coagulase types, Type III (37 strains, 42%) was most frequent, followed in descending order by Type I (10 strains, 11%) and Type II (9 strains, 10%). Enterotoxin-producing strains were 17. Of these, all the strains of MRSA produce enterotoxin C and all the strains which produced enterotoxin C produced TSST-1 with high potency.
2) The susceptibility of 88 strains of S. aureus to various oral antibiotics was shown below: The susceptibility of all the strains to minocycline (MINO) was 6.25 μg/mL or less, and the other antibiotics showed wide susceptibility distribution. MIC₈₀ values of the antibiotics for 88 strains were 3.13 μg/mL for cefdinir, 12.5 μg/mL for cefcapene, 25 μg/mL for cefpodoxime, 6.25 μ g/mL for cefditoren, 25 μg/mL for cefteram, 50 μg/mL for cefaclor, 25 μg/mL for amoxicillin, 3.13 μg/mL for oxacillin, 0.39 μg/mL for faropenem, 0.1 μg/mL for minocycline and 100 μg/mL for clarithromycin.
3) The combinations of cefdinir and erythromycin, oxytetracycline and fusidic acid were synergistic or additive against 93-100% of the 28 strains of MRSA. On the other hand, when cefdinir was combined with gentamicin, the combination was additive against MRSA but not antagonistic. The same results were obtained in the antibacterial activity of these drugs against 60 strains of MSSA. The combined effect of cefdinir with the inhibitory effect on cell wall synthesis and erythromycin, oxytetracycline, gentamicin or fusidic acid with the inhibitory effect on protein synthesis was considered to be due to the synergistic effect of these drugs in which the mechanism of action is different. Therefore, in recent years, the isolation frequency of MRSA has tended to increase in children with contagious impetigo caused by S. aureus, the main causative pathogen, but the combination therapy of oral cefdinir and topical erythromycin, oxytetracycline or fusidic acid is considered to be one of the useful means for the treatment of contagious impetigo.

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A prospective post-marketing surveillance study of Fosmicin^®-S for injection in practical use was carried out during the 5 years from July 1994 to March 1999. The purpose of the survey was to review 100, 000 case reports nationwide, mainly to accurately assess the drug's safety, with particular emphasis on the prevalence of anaphylactic shock. The following results were obtained:
1) A total of 103, 471 case reports were received from 4, 737 medical facilities nationwide, with 100, 230 case subjects for the safety assessment and 41, 477 cases for the efficacy assessment.
2) The overall rate of the cases in which adverse drug reactions occurred was0.56%, with 4 cases (0.004%) of anaphylactic shock and 1 case (0.001%) of anaphylactoid reaction being noted.
3) The rate of occurrence of adverse drug reactions was highest, 212 cases (0.21%), for liver and biliary system disorders, followed by 146 cases (0.15%) of gastro-intestinal system disorders, and then by 137 cases (0.14%) of skin and appendages disorders.
4) The incidence of adverse drug reactions after administration of Fosmicin^®-S was higher in the cases with an allergic history than in those without a history of allergy. However, even the highest rate, observed in the cases of skin and appendages disorders, was only 0.65%.
5) The incidence of adverse renal drug reactions related to concomitant use of an aminoglycoside such as arbekacin, and vancomycin was low. In 370 cases Fosmicin^®-S was administered concomitantly with antitumor agents to alleviate renal function disorders; however, no adverse drug reactions related to renal function were observed in any of these cases. These findings are promising and suggest the possibility of alleviating renal function disorders in the clinical application of Fosmicin^®-S.
6) The influence on adverse drug reactions of the solution to dissolve Fosmicin^®-S, especially physiological saline solution, was investigated. The influence of sodium on adverse drug reactions was unclear.
7) The total rate of markedly improved and improved cases in the final overall improvement rating was 81.2%, and was nearly the same as the 76.7% obtained at the time of drug reexamination.

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