Plasma and intraprostatic concentrations of ertapenem following preoperative single dose administration: a single-centre prospective experience and clinical implications-the ERTAPRO study

Int J Antimicrob Agents. 2016 Aug;48(2):168-74. doi: 10.1016/j.ijantimicag.2016.04.027. Epub 2016 Jun 2.

Abstract

The incidence of urinary tract infections caused by extended-spectrum β-lactamase (ESBL)-producing pathogens is increasing. These infections are associated with a long hospital stay in patients undergoing urological procedures. We aimed to demonstrate that significant intraprostatic diffusion of ertapenem is achieved after a single preoperative administration. A referred sample of 19 patients requiring surgery for benign prostatic hyperplasia was prospectively included. Patients received a 1 g intravenous (i.v.) dose of ertapenem 1 h (n = 10, group A) or 12 h (n = 9, group B) before blood and prostatic samples were collected. Plasma and intraprostatic concentrations of ertapenem were measured using LC-MS/MS. Intraprostatic concentrations were considered satisfactory when higher than the MIC90 value of urinary-targeted pathogens perioperatively and for 40% of the dosing interval. The Wilcoxon test and a pharmacokinetic predictive model were used. Median plasma concentrations of ertapenem were 144.3 mg/L (95% CI 126.5-157.9) in group A and 30.7 mg/L (95% CI 22.9-36.4) in group B (P < 0.001); median intraprostatic concentrations were 16.6 mg/L (95% CI 13.3-31.4 mg/L) and 4.2 mg/L (95% CI 3.1-4.9 mg/L), respectively (P < 0.001), which were above the MIC90 values of bacteria, including ESBL-producers, during surgery and for 40% of the dosing interval. The plasma-to-prostate concentration ratio was not significantly different between groups (P = 0.97). Single-dose i.v. ertapenem reached satisfactory intraprostatic concentrations, suggesting that it could be a relevant prophylactic strategy for carriers of ESBL-producing bacteria undergoing prostatic procedures, which needs to be confirmed by further prospective trials.

Keywords: Antibiotic prophylaxis; Chromatography; Ertapenem; Prostatic hyperplasia; Urinary tract infection.

MeSH terms

  • Administration, Intravenous
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / analysis
  • Anti-Bacterial Agents / pharmacokinetics*
  • Antibiotic Prophylaxis / methods*
  • Chromatography, Liquid
  • Ertapenem
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Plasma / chemistry*
  • Preoperative Care / methods*
  • Prostate / chemistry*
  • Tandem Mass Spectrometry
  • Young Adult
  • beta-Lactams / administration & dosage
  • beta-Lactams / analysis
  • beta-Lactams / pharmacokinetics*

Substances

  • Anti-Bacterial Agents
  • beta-Lactams
  • Ertapenem