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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., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Decision to start an anti-fungal therapy in intra-abdominal candidiasis (IAC) is complex. Yeast culture, considered the gold standard, suffers from a delayed response time and exposes the patient to delayed introduction of anti-fungal therapy. We sought to evaluate the performance and feasibility of measuring 1,3-β-D-glucan (1,3-BDG) in the peritoneal fluid (PF) for the diagnosis of IAC., Methods: We analyzed retrospectively all PF obtained during abdominal surgery for critically ill adult patients presenting intra-abdominal infections. For each PF sample, direct examination, bacterial and fungal culture, fungal PCR and 1,3-BDG measurements were performed. The diagnostic performance of each technique and the Peritonitis score were calculated considering the positive yeast culture as the reference. The levels of 1,3-BDG were compared between IAC and non-IAC patients., Results: During an 8-month period in 2016, 33 PF samples were recovered. Median (interquartile range) SAPS 2 and SOFA scores were 44 (9-94) and 9 (4-15), respectively. There were seven cases of IAC, 14 of bacterial peritonitis and 12 of undocumented peritonitis. All IAC cases were secondary peritonitis, with a 1,3-BDG level of 1461 (325-5000) versus 224 (68-1357) pg/mL in the non-IAC group (P=0.03). When the 1,3-BDG level was ≤310 pg/mL, its negative predictive value was 100%., Conclusions: In secondary peritonitis, a peritoneal measurement of 1,3-BDG ≤310 pg/mL could rule out IAC.