Re-evaluation of the role of broad-spectrum cephalosporins against staphylococci by applying contemporary in-vitro results and pharmacokinetic-pharmacodynamic principles
Data
2007-02-01
Autores
Sader, Helio Silva 
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Artigo
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Resumo
The potency of cefepime, ceftriaxone, and ceftazidime was assessed by CLSI broth microdilution methods against 41,644 S. aureus (63.2% oxacillin-susceptible) and 14,266 coagulase-negative staphylococci (CoNS; 22.2% oxacillin-susceptible) through the SENTRY Antimicrobial Surveillance Program database (1998-2004). Using normal volunteer pharmacokinetic data and a linear intermittent intravenous infusion model, and an animal-derived pharmacokinetic/pharmacodynamic (PK-PD) target of >= 40% time above MIC, expected probabilities of target attainment (PTA) for cephems were evaluated using Monte Carlo simulation. Current CLSI breakpoints would rank the tested agents cefepime 2: ceftriaxone > ceftazidime and by PK-PD PTA cefepime > ceftazidime > ceftriaxone. Cefepime has a potency advantage over ceftazidime (four- to eight-fold) and superiority at the usual dosing over ceftriaxone (22.7-66.1%) for oxacillin-susceptible staphylococci. Ceftazidime pharmacokinetic overcomes by-weight activity disadvantages, while a low proportion (< 5%) of active free-drug penalizes ceftriaxone in the PTA calculations. PTA remained at >= 0.9 to a breakpoint of 8 mg/L for cefepime (1 g q8 or 12 hours) and ceftazidime and to a breakpoint of 2 mg/L for ceftriaxone. Regardless of applied breakpoint (CLSI or PK-PD), cefepime has the widest and most potent anti-staphylococcal activity among commonly used third- or fourth-generation cephems. When used at doses >= 3 g/day, cefepime assures maximal coverage of oxacillin-susceptible staphylococci whether using existing (CLSI) or modified (PK-PD) breakpoints. Ceftriaxone should be used with caution.
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Citação
Journal Of Chemotherapy. Florence: Esift Srl, v. 19, n. 1, p. 38-43, 2007.