[Fundamental and clinical studies on MIC breakpoint of SY5555 for Enterococcus faecalis in complicated urinary tract infections of moderate severity]

Kansenshogaku Zasshi. 1994 May;68(5):639-53. doi: 10.11150/kansenshogakuzasshi1970.68.639.
[Article in Japanese]

Abstract

A multicenter clinical study was carried out to investigate the clinical efficacy of SY5555 from viewpoint of its MIC breakpoint for Enterococcus faecalis. SY5555 was administered in dosages of 150 mg x 3/day and 300 mg x 3/day, for 7 days, to patients with complicated urinary tract infections of moderate severity (no indwelling catheter). Based primarily on the bacteriological efficacy (eradication) as the criterion for evaluation, the MIC breakpoint of SY5555 was investigated. SY5555 showed potent antimicrobial activity towards E. faecalis, and its MIC80 value for the clinical isolates of this bacterial species was 1.56 micrograms/ml. Analysis was carried out to determine the extent to which this in vitro activity is corroborated by the drug's clinical efficacy in eradicating E. faecalis. 1. Experimental study In a study employing an experimental model of complicated bladder infections of moderate severity, it was judged that the MIC breakpoints of SY5555 administered at 150 mg x 3/day and 300 mg x 3/day were 2 micrograms/ml and 8 micrograms/ml. 2. Clinical study SY5555 was administered at 150 mg x 3/day (7 days) to six patients and at 300 mg x 3/day (7 days) to 32 patients, and the clinical efficacy of these treatments was investigated. 2.1. Investigation of the clinical MIC breakpoint showed it to be 12.5 micrograms/ml for both the 150 mg x 3/day and 300 mg x 3/day regimens. However, since the number of cases in this study was small, analysis was performed of the data from a large number of cases by including the cases registered in a nation-wide Phase II study of SY5555. That analysis showed the clinical MIC breakpoint for the two dosages to be 3.13 micrograms/ml and 6.25 micrograms/ml. Thus, this analysis of large number of cases yielded clinical MIC breakpoint that are in agreement with the abovementioned experimental MIC breakpoints. 2.2. In the evaluation of the efficacy rate using the UTI drug efficacy evaluation criteria, cases rated as "good" or "excellent" numbered five of the six patients in the 150 mg x 3/day treatment group and 25 of the 32 (78.1%) patients in the 300 mg x 3/day treatment group, or 30/33 (78.9%) cases overall. These efficacy rates are about the same as the 82.0% reported for the nation-wide Phase II study. 2.3. Each of the strains of E. faecalis isolated from the patients was found to be eradicated by the SY5555 treatment: four strains in the 150 mg dosage group (the MIC of each was 3.13 micrograms/ml or less) and 18 strains in the 300 mg dosage group (the MIC of each was 6.25 micrograms/ml or less). Moreover, in both dosage groups, E. faecalis was not found to recur after the SY5555 treatment. 3. Conclusions In consideration of the above findings in the investigations of treatment of patients with complicated urinary tract infections of moderate severity, the following conclusions can be drawn. 3.1. In antimicrobial treatment employing SY5555 in a regimen consisting of 300 mg x 3/day for 7 days, the clinical breakpoint is in the range of 6.25-12.5 micrograms/ml. 3.2. In particular, as would be surmised from the fact that the MIC80 value of SY5555 for E. faecalis isolated is 1.56 micrograms/ml, this drug shows quite strong efficacy in the eradication of E. faecalis from cases of complicated urinary tract infection.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • English Abstract
  • Multicenter Study

MeSH terms

  • Adult
  • Carbapenems / administration & dosage*
  • Carbapenems / pharmacology
  • Enterococcus faecalis / drug effects*
  • Gram-Positive Bacterial Infections / drug therapy*
  • Humans
  • Urinary Tract Infections / drug therapy*

Substances

  • Carbapenems
  • SUN 5555