Pharmacology of Mupirocin in Nasal Application in Healthy Volunteers: Monocentric Study (MUPIPHARM)

Centre Hospitalier Universitaire de Saint Etienne

Status and phase: Active, not recruiting; Phase 1

Conditions: Staphylococcus Aureus Infection; Healthy

Treatments: Drug: Mupirocin (50 mg); Other: Collection of urine after Single dose part; Diagnostic Test: nasal swab after Single dose part; Diagnostic Test: nasal swab during Repeated dose part; Drug: Mupirocin (500 mg); Other: Collection of urine during Repeated dose part; Other: nasal swab after Repeated dose part; Biological: blood samples after Single dose part

Study type: Interventional

Funder types: Other

Identifiers

NCT06368856

20CH024

2020-006105-30 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 40 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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.)

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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40 participants in 6 patient groups

Single dose part : 50mg mupirocin

Active Comparator group

Description:

- Single dose part = single dose of 50 mg mupirocin in each nostril

Treatment:

Biological: blood samples after Single dose part

Diagnostic Test: nasal swab after Single dose part

Other: Collection of urine after Single dose part

Drug: Mupirocin (50 mg)

Single dose part : 500mg mupirocin

Experimental group

Description:

Single dose part = single dose of 500 mg mupirocin in each nostril

Treatment:

Biological: blood samples after Single dose part

Drug: Mupirocin (500 mg)

Diagnostic Test: nasal swab after Single dose part

Other: Collection of urine after Single dose part

Repeated dose part: Group 1 - 50 mg of mupirocin twice a day

Experimental group

Description:

50 mg of mupirocin in each nostril twice a day (morning and evening) for 5 days

Treatment:

Other: nasal swab after Repeated dose part

Other: Collection of urine during Repeated dose part

Diagnostic Test: nasal swab during Repeated dose part

Drug: Mupirocin (50 mg)

Repeated dose part: Group 2 50 mg of mupirocin 3 times a day

Experimental group

Description:

50 mg of mupirocin in each nostril 3 times a day (morning, noon and evening) for 5 days

Treatment:

Other: nasal swab after Repeated dose part

Other: Collection of urine during Repeated dose part

Diagnostic Test: nasal swab during Repeated dose part

Drug: Mupirocin (50 mg)

Repeated dose part: Group 3 500 mg of mupirocin twice a day

Experimental group

Description:

500 mg of mupirocin in each nostril twice a day (morning and evening) for 5 days

Treatment:

Other: nasal swab after Repeated dose part

Other: Collection of urine during Repeated dose part

Drug: Mupirocin (500 mg)

Diagnostic Test: nasal swab during Repeated dose part

Repeated dose part: Group 4 500 mg of mupirocin 3 times a day

Experimental group

Description:

500 mg of mupirocin in each nostril 3 times a day (morning non and evening) for 5 days

Treatment:

Other: nasal swab after Repeated dose part

Other: Collection of urine during Repeated dose part

Drug: Mupirocin (500 mg)

Diagnostic Test: nasal swab during Repeated dose part