Plasma and intraprostatic concentrations of ertapenem following preoperative single dose administration: a single-centre prospective experience and clinical implications-the ERTAPRO study.
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.
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.
Charles
C
Dariane
Clinical Pharmacy Department, HU Necker-Enfants malades, AP-HP, 149 rue de Sèvres, 75746 Paris, France.
Alexandre
A
Amin
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.
Olivier
O
Lortholary
Clinical Pharmacy Department, HU Necker-Enfants malades, AP-HP, 149 rue de Sèvres, 75746 Paris, France.
Alexandre
A
Lalli
Department of Urology, Hôpital européen Georges-Pompidou (HEGP), Assistance Publique-Hôpitaux de Paris (AP-HP), 20-40 rue Leblanc, 75015 Paris, France.
Constance
C
Michel
Department of Urology, Hôpital européen Georges-Pompidou (HEGP), Assistance Publique-Hôpitaux de Paris (AP-HP), 20-40 rue Leblanc, 75015 Paris, France.
Thomas
T
Le Guilchet
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.
Jean-Marc
JM
Treluyer
Laboratory of Biochemistry, HU Necker-Enfants malades, AP-HP, 149 rue de Sèvres, 75746 Paris, France.
Thao
T
Nguyen-Khoa
Biological Resources Center and Tumor Bank Platform (BB-0033-00063), Hôpital européen Georges-Pompidou, AP-HP, 20-40 rue Leblanc, 75015 Paris, France.
Claudia
C
De Toma
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.
Saïk
S
Urien
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.
Arnaud
A
Méjean
Clinical Pharmacy Department, HU Necker-Enfants malades, AP-HP, 149 rue de Sèvres, 75746 Paris, France.
Philippe
P
Bourget
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.
Marc-Olivier
MO
Timsit
D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D019072:Antibiotic Prophylaxis / Q000379:methods*; D002853:Chromatography, Liquid; D000077727:Ertapenem; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry*; D011300:Preoperative Care / Q000379:methods*; D011467:Prostate / Q000737:chemistry*; D053719:Tandem Mass Spectrometry; D055815:Young Adult; D047090:beta-Lactams / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*
D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D000077727:Ertapenem
Antibiotic prophylaxis; Chromatography; Ertapenem; Prostatic hyperplasia; Urinary tract infection