Insufficient plasma concentrations of empiric anti-pseudomonal beta-lactam antibiotics in critically ill patients with suspected sepsis

Rekha Pai Mangalore, Alexander A. Padiglione, Emma Leah Martin, Hans G.F. Schneider, Lam Lan Ngo-Thai, Steven A. McGloughlin, Anton Y. Peleg, Andrew A. Udy

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Aim: To determine if empirical anti-pseudomonal beta-lactam antibiotic (BLA) dosing achieves adequate drug exposure in septic patients. Method: A single-centre, prospective pharmacokinetic study was conducted in Intensive Care Unit (ICU) patients with sepsis, receiving empirical therapy with piperacillin/tazobactam or meropenem. The pharmacokinetic/pharmacodynamic (PK/PD) targets were free BLA concentrations above the MIC at the mid-point (Concentration A, 50%f T > MIC) and end of the dosing interval (Concentration B, 100% fT > MIC). Sub-therapeutic concentrations were defined as concentration A < MIC, and sub-optimal as concentration B < MIC. The MIC breakpoint for Pseudomonas aeruginosa, as defined by The European Committee on Antimicrobial Susceptibility Testing (EUCAST) (available from <http://www.eucast.org/clinical_breakpoints>) was used. Results: Of the 37 eligible patients, 20 were receiving piperacillin/tazobactam (TZP), and 17 meropenem (MEM). PK data were available for 36 patients (concentration A) and 34 patients (concentration B). The median measured plasma concentrations (mg/L) were: piperacillin for doses 4 g 8-hourly and 4 g 6-hourly – concentration A 53.9 [14.38–123.71] and 36.44 [13.38–107.45], concentration B 8.01 [2.57–71.08] and 27.31 [3.32–59.76], MEM for doses 1 g 8-hourly and 2 g 8-hourly – concentration A 12.49 [7.35–23.63] and 30.5, concentration B 7.47 [2.97–11.33] and 9.31. 27.8% (10 of 36) of patients had sub-therapeutic concentrations (concentration A) and 50% (17 of 34) had sub-optimal concentrations (concentration B). Conclusion: Our study confirms that sub-therapeutic unbound plasma anti-pseudomonal BLA concentrations are common in critically ill septic patients and underscores the urgent need for future trials exploring the efficacy of BLA therapeutic drug monitoring in these patients.

Original languageEnglish
Number of pages6
JournalJournal of Pharmacy Practice and Research
DOIs
Publication statusAccepted/In press - 22 Jun 2020

Keywords

  • beta-lactam antibiotics
  • critically ill
  • ICU
  • pharmacodynamics
  • pharmacokinetics
  • sepsis
  • TDM

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