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Observational Study
. 2020 Jan 1;75(1):156-161.
doi: 10.1093/jac/dkz407.

Serum and peritoneal exudate concentrations after high doses of β-lactams in critically ill patients with severe intra-abdominal infections: an observational prospective study

Lisa Leon  1   2 , Philippe Guerci  1   2 , Elise Pape  2   3 , Nathalie Thilly  2   4 , Amandine Luc  2   4 , Adeline Germain  2   5 , Anne-Lise Butin-Druoton  1   2 , Marie-Reine Losser  1   2 , Julien Birckener  1   2 , Julien Scala-Bertola  2   3 , Emmanuel Novy  1   2
Affiliations
Observational Study

Serum and peritoneal exudate concentrations after high doses of β-lactams in critically ill patients with severe intra-abdominal infections: an observational prospective study

Lisa Leon et al. J Antimicrob Chemother. .

Abstract

Background: Critically ill patients with severe intra-abdominal infections (IAIs) requiring surgery may undergo several pharmacokinetic (PK) alterations that can lead to β-lactam underdosage.

Objectives: To measure serum and peritoneal exudate concentrations of β-lactams after high doses and optimal administration schemes.

Methods: This observational prospective study included critically ill patients with suspicion of IAI who required surgery and a β-lactam antibiotic as empirical therapy. Serum and peritoneal exudate concentrations were measured during surgery and after a 24 h steady-state period. The PK/pharmacodynamic (PD) target was to obtain serum β-lactam concentrations of 100% fT>4×MIC based on a worst-case scenario (based on the EUCAST highest epidemiological cut-off values) before bacterial documentation (a priori) and redefined following determination of the MIC for the isolated bacteria (a posteriori). Registered with ClinicalTrials.gov (NCT03310606).

Results: Forty-eight patients were included with a median (IQR) age of 64 (53-74) years and a SAPS II of 40 (32-65). The main diagnosis was secondary nosocomial peritonitis. Piperacillin/tazobactam was the most administered β-lactam antibiotic (75%). The serum/peritoneal piperacillin/tazobactam ratio was 0.88 (0.64-0.97) after a 24 h steady-state period. Prior to bacterial documentation, 16 patients (33.3%) achieved the a priori PK/PD target. The identification of microorganisms was available for 34 patients (71%). Based on the MIC for isolated bacteria, 78% of the patients achieved the serum PK/PD target.

Conclusions: In severe IAIs, high doses of β-lactams ensured 100% fT>4×MIC in the serum for 78% of critically ill patients with severe IAIs within the first 24 h. In order to define optimal β-lactam dosing, the PK/PD target should take into account the tissue penetration and local ecology.

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