Pharmacokinetics Study of Intraperitoneal Administration of Daptomycin in Peritoneal Infection
Pharmacokinetics Study of Intraperitoneal Administration of Daptomycin in Peritoneal Infection
Peritoneal infection is still a frequent complication in peritoneal dialysis patients . In
 France, It contributes to the technique failure, responsible for about 20% of cases of
 transfer in hemodialysis. The risk of direct mortality is estimated at 1 to 6% according to
 studies. Peritoneal infection is involved in the dysfunction of the peritoneal membrane.

 Based on the recommendations of the International Society for Peritoneal Dialysis, the
 intraperitoneal route is preferentially recommended. For many antibiotics, pharmacokinetics
 (intravenous and intraperitoneal) was studied and protocols for IP administration were
 validated.

 Daptomycin, is a cyclic lipopeptide natural, active only on Gram-positive bacteria. It is
 presented as an alternative to vancomycin in infections resistant pathogens. The stability of
 daptomycin in peritoneal dialysis fluids (PDF) has been tested, and antimicrobial activity as
 well.

 Seven patients were treated with daptomycin intraperitoneally successfully. But no study has
 reported pharmacokinetics of daptomycin via the IP route. We propose a pharmacokinetic study
 of daptomycin administered intraperitoneally in 12 patients on CAPD and with Gram-positive
 peritoneal infection.
Methodology:

 Prospective, open-label, non-randomized pharmacokinetic study. Daptomycin will be given IP in
 the CAPD fluid (200mg in 2L Nutrineal) once daily, in a 6 hours-dwell time. The process of
 dialysis is done four times per day : three during the day (6,6,and 4 h) and one time at
 night (8h). Duration of treatment depends on bacteria identified (14 or 21 days).

 Analyses will be performed on data from all patients meeting the criteria for inclusion and
 exclusion.

 For each patient, plasma, dialysate and urine kinetics will be studied.

 For each parameter, mean and standard deviation are calculated.

 Number of centers & patients:

 One center, twelve patients.

 Sample size justification:

 This is an observational pharmacokinetic study of consecutive PD patients presenting to Caen
 University Hospital with peritoneal infection and who meet inclusion criterias over one year.

 Population: CAPD patients with a Gram positive peritoneal infection
Inclusion Criteria:

 Patients > 18 years

 -  Hospitalized CAPD patients with Gram positive peritoneal infection : ISPD criterias

 -  Presence of two clinical signs and symptoms : abdominal pain, nausea, vomiting,
 diarrhea, fever and cloudy dialysate

 -  Peritoneal dialysate WBC>100/µL with at least 50% polymorphonuclear neutrophil cells

 -  Demonstration of bacteria on Gram stain or culture

 -  on peritoneal dialysis for at least 3 months

 -  written consent, obtained from either the patient, one of his/her relatives, the
 trusted person who was designated beforehand or, if not possible, emergency
 enrollment.

 -  patient has a life expectancy greater than 6 months

 Exclusion Criteria:

 -  Known allergy to daptomycin

 -  Peritoneal infection with Gram negative only

 -  Patient with CPK>5UNL

 -  patients already treated with antibiotics, antifungals within 4 weeks prior to the
 event

 -  Patient with hepatic impairment

 -  Patient with arguments for an extra-peritoneal site of infection

 -  Patient with severe intercurrent illness (eg, hematologic malignancies, patients on
 chemotherapy)

 -  Infection by daptomycin-resistant germ

 -  HMGCoA reductase, fibrates or ciclosporin treatment

 -  Pregnant or breast-feeding women