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

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

Author information

1
Department of Urology, Hôpital européen Georges-Pompidou (HEGP), Assistance Publique-Hôpitaux de Paris (AP-HP), 20-40 rue Leblanc, 75015 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Faculté de médecine, 15 rue de l'École de Médecine, 75006 Paris, France.
2
Clinical Pharmacy Department, HU Necker-Enfants malades, AP-HP, 149 rue de Sèvres, 75746 Paris, France.
3
Université Paris Descartes, Sorbonne Paris Cité, Faculté de médecine, 15 rue de l'École de Médecine, 75006 Paris, France; Department of Infectious and Tropical Diseases, HU Necker-Enfants malades, AP-HP, 149 rue de Sèvres, 75015 Paris, France.
4
Department of Urology, Hôpital européen Georges-Pompidou (HEGP), Assistance Publique-Hôpitaux de Paris (AP-HP), 20-40 rue Leblanc, 75015 Paris, France.
5
Université Paris Descartes, Sorbonne Paris Cité, Faculté de médecine, 15 rue de l'École de Médecine, 75006 Paris, France; Clinical Research Unity, Centre d'investigation clinique, Necker Cochin-Assistance Publique-Hôpitaux de Paris, HU Necker-Enfants malades, AP-HP, 149 rue de Sèvres, 75746 Paris, France.
6
Laboratory of Biochemistry, HU Necker-Enfants malades, AP-HP, 149 rue de Sèvres, 75746 Paris, France.
7
Biological Resources Center and Tumor Bank Platform (BB-0033-00063), Hôpital européen Georges-Pompidou, AP-HP, 20-40 rue Leblanc, 75015 Paris, France.
8
Université Paris Descartes, Sorbonne Paris Cité, Faculté de médecine, 15 rue de l'École de Médecine, 75006 Paris, France; Clinical Research Unity, Centre d'investigation clinique, Necker Cochin-Assistance Publique-Hôpitaux de Paris, HU Necker-Enfants malades, AP-HP, 149 rue de Sèvres, 75746 Paris, France; Clinical Research Unity, Hôpital Tarnier, AP-HP, 89 rue d'Assas, 75006 Paris, France.
9
Department of Urology, Hôpital européen Georges-Pompidou (HEGP), Assistance Publique-Hôpitaux de Paris (AP-HP), 20-40 rue Leblanc, 75015 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Faculté de médecine, 15 rue de l'École de Médecine, 75006 Paris, France. Electronic address: marc-olivier.timsit@egp.aphp.fr.

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

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