Pharmacodynamics of carbapenems for the treatment of Pseudomonas aeruginosa ventilator-associated pneumonia: associations with clinical outcome and recurrence.
J Antimicrob Chemother
; 71(9): 2534-7, 2016 09.
Article
em En
| MEDLINE
| ID: mdl-27272723
ABSTRACT
OBJECTIVES:
This study was designed to evaluate the pharmacodynamics of doripenem, imipenem and meropenem as a predictor of clinical success, mortality, 28 day recurrence and development of resistance in patients treated for Pseudomonas aeruginosa ventilator-associated pneumonia (VAP). PATIENTS ANDMETHODS:
Previously published demographic and outcome data derived from patients treated for P. aeruginosa VAP with doripenem, imipenem or meropenem were utilized. Patient-specific data were used in conjunction with published population pharmacokinetic models to construct concentration-time profiles for each patient. Etest MICs were used to determine pharmacodynamic profiles. Classification and regression tree (CART) analysis was utilized to partition pharmacodynamics based on outcomes with P values of 0.05.RESULTS:
Eighty-six patients were included in the analysis. Initial carbapenem MICs ranged from 0.03 to 32 mg/L. VAP recurred in 28 patients; of these, 17 patients were initially infected with susceptible organisms, and 14 of them developed resistance. CART fT>MIC partitions identified for clinical success and survival were 19.2% (Pâ=â0.016) and 47.9% (Pâ<â0.001), respectively. No statistically significant partitions for fT>MIC were identified for recurrence or resistance development.CONCLUSIONS:
We identified fT>MIC cut-offs for positive clinical outcomes in patients with P. aeruginosa VAP that were similar to those observed in animal models of infection for stasis (â¼20%) and 1 log decreases in cfu (â¼40%). Although in vitro studies have suggested a link between drug exposure and development of resistance, we were unable to identify such a relationship clinically.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Pseudomonas aeruginosa
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Infecções por Pseudomonas
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Carbapenêmicos
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Pneumonia Associada à Ventilação Mecânica
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Antibacterianos
Tipo de estudo:
Observational_studies
/
Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Aged80
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article