Antistaphylococcal activity of cefdinir, a new oral third-generation cephalosporin, alone and in combination with other antibiotics, at supra- and sub-MIC levels

A. Marchese, D. Saverino, E. A. Debbia, A. Pesce, G. C. Schito

Research output: Contribution to journalArticlepeer-review

Abstract

Cefdinir is one of the few oral third generation cephalosporins that shows useful activity against nosocomial Gram-positive pathogens. For this reason the antistaphylococcal potency of the new drug, alone or in combination with other drugs was further characterized. Against penicillin-resistant, oxacillin-susceptible Staphylococcus isolates, cefdinir demonstrated useful in-vitro activity. MIC90 values (in mg/L) were 0.25 for Staphylococcus aureus (30 strains), 0.06 for Staphylococcus epidermidis (24), 0.125 for Staphylococcus hominis (10), 0.5 for both Staphylococcus xylosus (15) and Staphylococcus capitis (11) and 4 for Staphylococcus saprophyticus (10), while Staphylococcus haemolyticus (12) was less susceptible with a MIC90 value of 32. Cefdinir activity was not adversely affected by several variables such as pH, inoculum size or the presence of serum or urine. The new cephem induced a PAE on all isolates studied: with S. aureus the extent of regrowth suppression ranged from 0.8 to 1 h, and with the other species from 0.5 (S, epidermidis) to 4.1 h (S. haemolyticus). Development of resistant strains was rare. At the highest level used (10 x MIC) mutants arose with a frequency of 6 x 10-8 with S. haemolyticus and 2 x 10-9 with S. epidermidis. The absence of a paradoxical effect of increasing concentrations of cefdinir on its bactericidal activity was confirmed up to a value of 500-fold the MICs. When cefdinir activity was assessed in association with ciprofloxacin, netilmicin, clarithromycin, fosfomycin, rifampicin, teicoplanin and vancomycin using the chequerboard and time-kill techniques, indifference predominated with all strains and in all combinations. Synergism was detected only in 11 out of a total of 175 tests performed by the chequerboard method. Using the time-kill technique cefdinir reacted synergically in 25 of 126 tests. Antagonism was never observed. S. aureus exposed to sub-inhibitory concentrations of cefdinir failed to grow on mannitol-salt agar and to produce haemolysins, but retained coagulase activity. Penicillinase production was also lost in about 17% of the survivors. Hydrophobicity changes were detected in all species tested with the exception of S. saprophyticus.

Original languageEnglish
Pages (from-to)53-66
Number of pages14
JournalJournal of Antimicrobial Chemotherapy
Volume35
Issue number1
Publication statusPublished - 1995

ASJC Scopus subject areas

  • Pharmacology
  • Microbiology
  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Physiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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