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Efficacy of coumermycin, ofloxacin and vancomycin against methicillin-resistant Staphylococcus aureus in vitro and in experimental infections of mice.

Authors
  • Hirschl, A M
  • Georgopoulos, A
  • Stanek, G
  • Breyer, S
  • Rotter, M L
Type
Published Article
Journal
Zentralblatt für Bakteriologie, Mikrobiologie, und Hygiene. Series A, Medical microbiology, infectious diseases, virology, parasitology
Publication Date
Mar 01, 1988
Volume
267
Issue
4
Pages
541–548
Identifiers
PMID: 3164157
Source
Medline
License
Unknown

Abstract

In vitro, coumermycin (a bis-hydroxicoumarin gyrase inhibitor) proved significantly more active than ofloxacin and vancomycin against 100 strains of methicillin-resistant Staphylococcus aureus (MRSA). The MIC90 was 0.5 microgram/ml, whereas the corresponding figures for the other antimicrobials were 2.0 and 4.0 micrograms/ml. In vivo, an otherwise lethal septicemia, induced by intraperitoneal administration of a MRSA in mice, was "successfully treated" in 50% of the animals (ED50) with the following dosages (microgram/g b. wt.): coumermycin 0.9, ofloxacin 10.8, vancomycin 22.4. The ED50 of coumermycin was significantly (2 p less than 0.01) different from those of the other drugs. Renal infection as produced in mice by transcutaneous inoculation of the same MRSA was treated with either of the antimicrobials at different dosages (single doses of 0.0 or 1.6 or 6.3 or 25.0 micrograms/g b. wt., twice daily) during 6 days. The largest reductions of viable counts in the kidneys at each dosage as compared to the bacterial counts of untreated animals were achieved with coumermycin (3.4 or 5.5 or 7.7 log10). These reductions are significantly (2 p less than 0.01) different from those achieved with the comparable dosages of ofloxacin and vancomycin which were 0.1 or 1.8 or 2.8 and 0.4 or 1.4 or 3.0 log10 respectively. After a single subcutaneous injection of 250 micrograms mean concentrations in serum of mice for coumermycin were 6.2-5.0 micrograms/ml for 8 h, for ofloxacin 2.0-0.5 micrograms/ml for 2 h, and for vancomycin 14.7-2.5 micrograms/ml for 2 h. Coumermycin and ofloxacin could be alternatives to vancomycin in the therapy of human infections due to MRSA.

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