Cefepime free minimum concentration to minimum inhibitory concentration (fCmin/MIC) ratio predicts clinical failure in patients with Gram-negative bacterial pneumonia

Samuel L. Aitken, Jerry Altshuler, David J. Guervil, Elizabeth B. Hirsch, Luis L. Ostrosky-Zeichner, Charles D. Ericsson, Vincent H. Tam

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29 Scopus citations

Abstract

Cefepime is an antibiotic commonly used in nosocomial infections. The objective of this study was to elucidate the relationship between cefepime exposure and clinical outcome in patients with Gram-negative bacterial pneumonia. A previously published population pharmacokinetic model of cefepime was validated in 12 adult patients with normal renal function by measuring plasma concentrations at steady-state. Additionally, clinical outcomes for 33 patients with Gram-negative bacterial pneumonia who received cefepime monotherapy were determined. The free minimum concentration (fCmin) to MIC ratio for each patient was determined by conditioning the validated pharmacokinetic model using patient-specific creatinine clearance (CLCr), dosing regimen and cefepime MIC of the organism isolated, and was subsequently correlated with clinical failure. Classification and regression tree (CART) analysis was used to determine the most significant drug exposure breakpoint. Mean ± S.D. CLCr and cefepime Cmin in the 12 patients were 87.5 ± 21.2 mL/min and 6.2 ± 3.8 mg/L, respectively. In comparison, the Cmin predicted by the pharmacokinetic model was 5.8 mg/L using a CLCr of 90 mL/min. MICs of organisms ranged from 0.5 mg/L to 8 mg/L. Percent time free drug above MIC of 100% was achieved in 32/33 patients, but 12 patients experienced clinical failure. CART analysis determined patients with an fCmin/MIC ≥ 2.1 had a significantly lower risk of clinical failure (OR = 0.11, 95% CI 0.02-0.67; P = 0.017). The fCmin/MIC ratio is a useful predictor of clinical failure in Gram-negative bacterial pneumonia. The clinical utility of fCmin/MIC in therapeutic drug monitoring should be further explored.

Original languageEnglish (US)
Pages (from-to)541-544
Number of pages4
JournalInternational Journal of Antimicrobial Agents
Volume45
Issue number5
DOIs
StatePublished - May 1 2015

Bibliographical note

Funding Information:
DJG has received research support from Forest Laboratories, Inc.; VHT has received unrestricted research grants from Theravance and has also received speaking/consulting honoraria from AstraZeneca , Cubist and Pfizer . All other authors declare no competing interests.

Publisher Copyright:
© 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Keywords

  • Acinetobacter
  • Clinical outcomes
  • Pharmacodynamics
  • Pharmacokinetics
  • Pseudomonas

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