Re-evaluation of the role of broad-spectrum cephalosporins against staphylococci by applying contemporary in-vitro results and pharmacokinetic-pharmacodynamic principles

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dc.contributor.authorSader, Helio Silva [UNIFESP]
dc.contributor.authorBhavnani, S. M.
dc.contributor.authorAmbrose, P. G.
dc.contributor.authorJones, R. N.
dc.contributor.authorPfaller, M. A.
dc.contributor.institutionJMI Labs
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionOrdway Res Inst
dc.contributor.institutionTufts Univ
dc.contributor.institutionUniv Iowa
dc.contributor.institutionColl Publ Hlth
dc.date.accessioned2018-06-15T17:53:10Z
dc.date.available2018-06-15T17:53:10Z
dc.date.issued2007-02-01
dc.description.abstractThe 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.en
dc.description.affiliationJMI Labs, Beaver Kreek Ctr 345, N Liberty, IA 52317 USA
dc.description.affiliationUniv Fed Sao Paulo, Div Infect Dis, Sao Paulo, Brazil
dc.description.affiliationOrdway Res Inst, Inst Clin Pharmacodynam, Albany, NY USA
dc.description.affiliationTufts Univ, Sch Med, Boston, MA 02111 USA
dc.description.affiliationUniv Iowa, Coll Med, Dept Pathol, Iowa City, IA 52242 USA
dc.description.affiliationUniv Iowa, Coll Med, Dept Epidemiol, Iowa City, IA 52242 USA
dc.description.affiliationColl Publ Hlth, Iowa City, IA 52242 USA
dc.description.affiliationUnifespUniv Fed Sao Paulo, Div Infect Dis, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.format.extent38-43
dc.identifierhttp://dx.doi.org/10.1179/joc.2007.19.1.38
dc.identifier.citationJournal Of Chemotherapy. Florence: Esift Srl, v. 19, n. 1, p. 38-43, 2007.
dc.identifier.doi10.1179/joc.2007.19.1.38
dc.identifier.issn1120-009X
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/44239
dc.identifier.wosWOS:000244130500004
dc.language.isoeng
dc.publisherEsift Srl
dc.relation.ispartofJournal Of Chemotherapy
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectcefepimeen
dc.subjectceftriaxoneen
dc.subjectceftazidimeen
dc.subjectpharmacokinetic-pharmacodynamic (PK-PD)en
dc.subjectMonte Carlo simulationen
dc.subjectStaphylococcus aureusen
dc.subjectcoagulase-negative staphylococcien
dc.titleRe-evaluation of the role of broad-spectrum cephalosporins against staphylococci by applying contemporary in-vitro results and pharmacokinetic-pharmacodynamic principlesen
dc.typeinfo:eu-repo/semantics/article
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