Ceftaroline efficacy against high-MIC clinical Staphylococcus aureus isolates in an in vitro hollow-fibre infection model.
J Antimicrob Chemother
; 72(10): 2796-2803, 2017 10 01.
Article
en En
| MEDLINE
| ID: mdl-29091195
ABSTRACT
Objectives:
The current CLSI and EUCAST clinical susceptible breakpoint for 600 mg q12h dosing of ceftaroline (active metabolite of ceftaroline fosamil) for Staphylococcus aureus is ≤1 mg/L. Efficacy data for S. aureus infections with ceftaroline MIC ≥2 mg/L are limited. This study was designed to generate in-depth pharmacokinetic/pharmacodynamics (PK/PD) understanding of S. aureus isolates inhibited by ≥â2 mg/L ceftaroline using an in vitro hollow-fibre infection model (HFIM).Methods:
The PK/PD target of ceftaroline was investigated against 12 diverse characterized clinical MRSA isolates with ceftaroline MICs of 2 or 4 mg/L using q8h dosing for 24 h. These isolates carried substitutions in the penicillin-binding domain (PBD) and/or the non-PBD. Additionally, PD responses of mutants with ceftaroline MICs ranging from 2 to 32 mg/L were evaluated against the mean 600 mg q8h human-simulated dose over 72 h.Results:
The mean stasis, 1 log10-kill and 2 log10-kill PK/PD targets were 29%, 32% and 35% f T>MIC, respectively. In addition, these data suggest that the PK/PD target for MRSA is not impacted by the presence of substitutions in the non-PBD commonly found in isolates with ceftaroline MIC values of ≤â2 mg/L. HFIM studies with 600 mg q8h dosing demonstrated a sustained long-term bacterial suppression for isolates with ceftaroline MICs of 2 and 4 mg/L.Conclusions:
Overall, efficacy was demonstrated against a diverse collection of clinical isolates using HFIM indicating the utility of 600 mg ceftaroline fosamil for S. aureus isolates with MIC ≤4 mg/L using q8h dosing.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Infecciones Estafilocócicas
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Staphylococcus aureus
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Cefalosporinas
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Staphylococcus aureus Resistente a Meticilina
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Antibacterianos
Límite:
Humans
Idioma:
En
Año:
2017
Tipo del documento:
Article