Healthy, Staphylococcus Aureus Infection
Conditions
Keywords
Staphylococcus Aureus, Mupirocin, Pharmacokinetic
Brief summary
Mupirocin is an old antibiotic used topically since the 1970s. Initially used in the treatment of skin infections for its antistaphylococcal action, it is now part of the decolonization strategy for Staphylococcus aureus (SA) carriage, in association with chlorhexidine. This decolonization strategy has been recommended in France for preoperative cardiac surgery in nasal SA carriers since 2013 by the French Hospital Hygiene Society, and recommended for cardiac and orthopedic surgery in SA carriers by the World Health Organization (WHO) since 2016. This strategy includes nasal decolonization using mupirocin ointment nasally (2 to 3 applications/day), a daily shower with chlorhexidine soap and + /- mouthwashes all over 5 days, often pre-operatively. As a result, mupirocin is now widely used throughout the world, all the more so as, for reasons of ease of organization, many centers use this decolonization procedure universally (i.e. without prior screening for Staphylococcus aureus carriage), thus further increasing the use of this molecule. Mupirocin administration methods are very vague, ranging from 2 to 3 applications per day and the application of a match head, i.e. 50 mg, to 500 mg per nostril. Mupirocin is bacteriostatic at low doses, becoming bactericidal at higher concentrations; low concentrations could favor the selection of resistance, so using the most effective dosage seems essential. This lack of precision in administration is linked to an almost complete ignorance of the pharmacokinetics of mupirocin and its metabolite (monic acid) after nasal application. It therefore seems essential to conduct a pharmacokinetic study of this molecule, in order to eventually offer patients the regimen with the administration methods offering the best characteristics in terms of dosage and efficacy.
Interventions
DRUGMupirocin (50 mg)
50 mg de mupirocin
DRUGMupirocin (500 mg)
500 mg de mupirocin
BIOLOGICALblood samples after Single dose part
3 blood samples will be performed sampling time ater application of mupirocin (single dose part): 00h30, 1h00, 02h00
DIAGNOSTIC_TESTnasal swab after Single dose part
7 nasal swab for the detection of S. aureus (type Swab) will be performed after application of mupirocin (single dose part): 00h00, 1h00, 02h00, 04h00, 06h00, 08h00, 12h00
OTHERCollection of urine after Single dose part
Collection of urine during 12 hours after the application of mupirocin (Single dose part)
DIAGNOSTIC_TESTnasal swab during Repeated dose part
5 nasal swab for the detection of S. aureus (type Swab) will be performed during administration of mupirocin (Repeated dose part): 2, 3, 4, 5 et 6 days after the first application of mupirocin (Repeated dose part)
OTHERCollection of urine during Repeated dose part
5 collections of urine during Repeated dose part: 2, 3, 4, 5 et 6 days after the first application of mupirocin (Repeated dose part)
OTHERnasal swab after Repeated dose part
2 nasal swab for the detection of S. aureus (type Swab) will be performed: 1, 3 months after the first application of mupirocin (Repeated dose part)
Sponsors
Centre Hospitalier Universitaire de Saint Etienne
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
NONE
Intervention model description
Single-center, randomized, open-label pharmacokinetic study of mupirocin in 40 healthy subjects with 2 randomization : * first randomization - single dose part : 50mg or 500mg of mupirocin * wash-out: one month * second randomization - repeated doses part: 50mg mupirocin twice a day or 50 mg 3 times a day 500mg mupirocin twice a day or 500mg mupirocin 3 times a day
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Subject affiliated or entitled to a social security plan * Subject having signed the consent to participate in the study
Exclusion criteria
* Pregnancy in progress * Acute or chronic rhinorrhea * Allergy to mupirocin calcium or excipients * Any medication taken during the week preceding the beginning of the study * Notable medical history (cardiovascular, pulmonary, neurological pathology, etc.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| plasma concentrations of mupirocin | 0 hours 30 after mupirocin application (Single dose part) | mupirocin pharmacokinetics |
| intranasal concentrations of mupirocin | 1 hours after mupirocin application (Single dose part) | mupirocin pharmacokinetics |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| presence of Staphylococcus aureus | Days: 5 after mupirocin application (Repeated dose part) | Measured by nasal swab results |
| urinary concentrations of monic acid | Days: 2 after mupirocin application (Repeated dose part) | Analysis collection urine. |
Countries
France
Outcome results
None listed