We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
OII-A-3.
- Authors
Zack, J. Z.; Forrest, A.; Bilic, S.; Kelchlin, P.; Smith, P. F.
- Abstract
Background: To predict the activity of various LZD dosage regimens for MRSA. The MIC90 of LZD against MRSA is ∼4 mg/L.Methods: For 2 clinical MRSA isolates (MIC2, MIC4), 24h kill curve experiments were fit by a PD model: capacity limited replication inhibited by LZD via a Hill function, & 1st order elimination. A mixture model described both strains as 2 populations: a predominant 'sensitive' population (EC50 = 0.4 & 0.6xMIC) & a 'resistant' subpopulation (EC50 of 3 & 5xMIC). LZD PK parameters derived from our previous population PK analysis were used to predict PD responses to 4 LZD regimens: 600mg PO q12h w/o (BID) or with (LBID) a loading dose (LD) of 900mg; 600mg PO q8h w/o (TID) or with (LTID) a LD of 1200mg. For verification, these regimens were studied against these MRSA isolates in an in vitro PK/PD infection model, over 96h.Results: All 4 regimens were effective against MIC2 (LBID≈ BID). In silico & in vitro, BID & LBID were ineffective, while TID & LTID were effective (with similar activity) against MIC4. For eg, in vitro at 48h, the log10(bacterial CFU) were decreased by 3.6 & 3.2, for MIC2, & by 1 & 2.6, for MIC4, with BID & TID regimens.Conclusions: The BID regimen might not provide adequate activity at MIC ≥ 4 mg/L (though these studies did not include any effect due to the immune system). At MIC=4, a TID regimen may offer a substantial benefit over BID. With its 'slow' rate of kill & its shallow concentration-effect curve, LZD appears to show only modest benefit for the evaluated loading doses.Clinical Pharmacology & Therapeutics (2005) 79, P4–P4; doi: 10.1016/j.clpt.2005.12.012
- Subjects
PHARMACEUTICAL research; SIDE effects of antibiotics; METHICILLIN resistance; STAPHYLOCOCCAL diseases; IMMUNE system; PHARMACOLOGY
- Publication
Clinical Pharmacology & Therapeutics, 2006, Vol 79, Issue 2, pP4
- ISSN
0009-9236
- Publication type
Article
- DOI
10.1016/j.clpt.2005.12.012