[sorry, can't get table to cut and paste]
Session: Pharmacodynamics and Efficacy of Antibiotics in
Gram-positive Infections
Location:
Exhibit Hall
Session Date:
Tuesday, 9/28/99
Session Time:
1:30 pm - 3:00 pm
The Novel Cephalosporin RWJ-54428 (MC-02,479) is Active against
Vancomycin-Intermediate S. aureus (VISA) in the Neutropenic Mouse Thigh
Model
D. Griffith, S. Chen, C. Liu, E. Corcoran, V. Tembe, K. Huie, J. Blais, S.
Chamberland, M.N. Dudley
Microcide Pharmaceuticals, Inc.: Mountain View, CA
The emergence of infections due to VISA has created an urgent need for new agents.
RWJ-54428 has previously been shown to have activity in vitro against many
drug-resistant gram-positive bacteria, including VISA. The pharmacodynamics of
subcutaneous doses of RWJ-54428 and vancomycin (V) for 2 VISA strains (HIP-5836;
HIP-5827; MICs in mg/ml for V and RWJ-54428 = 8, 8 and 0.5, 1, respectively) was
studied in the neutropenic mouse thigh model. The V dosage regimen was adjusted to
produce 24h free drug serum AUC:MIC and % of 24h free drug exceeding MIC
(%T>MIC) comparable to that for V 500 mg q 6h in humans. For RWJ-54428,
regimens that produced a 10-fold range in 24h dose and 5-fold range in %T>MIC were
tested. Results for HIP-5836 / HIP-5827 at 24 h:
In this model, RWJ-54428 dosage regimens that produced a free serum AUC:MIC ³ 41
or %T>MIC ³ 35% resulted in greater killing of these VISA strains than that observed
with V exposures mimicking dosage regimens in humans.
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