Pharmacodynamic analysis of daptomycin-treated enterococcal bacteremia: It is time to change the breakpoint

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dc.contributor.authorAvery, Lindsay M
dc.contributor.authorKuti, Joseph L
dc.contributor.authorWeisser, Maja
dc.contributor.authorEgli, Adrian
dc.contributor.authorRybak, Michael J
dc.contributor.authorZasowski, Evan J
dc.contributor.authorArias, Cesar A
dc.date.accessioned2020-05-14T17:44:06Z
dc.date.available2020-05-14T17:44:06Z
dc.date.issued2019
dc.description.abstractenglishBackground Currently, there is debate over whether the daptomycin susceptibility breakpoint for enterococci (ie, minimum inhibitory concentration [MIC] ≤4 mg/L) is appropriate. In bacteremia, observational data support prescription of high doses (>8 mg/kg). However, pharmacodynamic targets associated with positive patient outcomes are undefined. Methods Data were pooled from observational studies that assessed outcomes in daptomycin-treated enterococcal bacteremia. Patients who received an additional antienterococcal antibiotic and/or a β-lactam antibiotic at any time during treatment were excluded. Daptomycin exposures were calculated using a published population pharmacokinetic model. The free drug area under the concentration-time curve to MIC ratio (fAUC/MIC) threshold predictive of survival at 30 days was identified by classification and regression tree analysis and confirmed with multivariable logistic regression. Monte Carlo simulations determined the probability of target attainment (PTA) at clinically relevant MICs. Results Of 114 patients who received daptomycin monotherapy, 67 (58.8%) were alive at 30 days. A fAUC/MIC >27.43 was associated with survival in low-acuity (n = 77) patients (68.9 vs 37.5%, P = .006), which remained significant after adjusting for infection source and immunosuppression (P = .026). The PTA for a 6-mg/kg/day (every 24 hours) dose was 1.5%–5.5% when the MIC was 4 mg/L (ie, daptomycin-susceptible) and 91.0%–97.9% when the MIC was 1 mg/L. Conclusions For enterococcal bacteremia, a daptomycin fAUC/MIC >27.43 was associated with 30-day survival among low-acuity patients. As pharmacodynamics for the approved dose are optimized only when MIC ≤1 mg/L, these data continue to stress the importance of reevaluation of the susceptibility breakpoint.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1093/cid/ciy749
dc.identifier.issn1058-4838
dc.identifier.urihttps://hdl.handle.net/20.500.12495/2776
dc.language.isoeng
dc.publisherOxford University Pressspa
dc.publisher.journalClinical Infectious Diseasesspa
dc.relation.ispartofseriesClinical Infectious Diseases, 1058-4838, Vol 68, Num 10, 2019, pag 1650–1657spa
dc.relation.urihttps://academic.oup.com/cid/article-abstract/68/10/1650/5090851?redirectedFrom=fulltext
dc.rights.creativecommons2018
dc.rights.localAcceso cerradospa
dc.subject.decsPreparaciones farmacéuticasspa
dc.subject.decsDaptomicinaspa
dc.subject.decsBacteriemiaspa
dc.subject.keywordsPharmacodynamicsspa
dc.subject.keywordsDaptomycinspa
dc.subject.keywordsEnterococcusspa
dc.subject.keywordsBacteremiaspa
dc.titlePharmacodynamic analysis of daptomycin-treated enterococcal bacteremia: It is time to change the breakpointspa
dc.title.translatedPharmacodynamic analysis of daptomycin-treated enterococcal bacteremia: It is time to change the breakpointspa
dc.typearticlespa
dc.type.hasversioninfo:eu-repo/semantics/publishedVersion
dc.type.localartículospa

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