Antibiotics Use and Carriage of Methicillin-resistant Staphylococci in Community Patients

Rationale: Recent spread of community-acquired, methicillin-resistant Staphylococcus aureus (CA-MRSA) represents a major Public Health concern. MR coagulase-negative staphylococci (MR-CoNS) are a likely reservoir of the MR determinant Staphylococcal Cassette Chromosome mec (SCCmec) for S. aureus (SA). Amoxicillin-clavulanic acid, penicillins M, macrolides and synergistin are the most prescribed antistaphylococcal antibiotics in the French community, but their respective impacts on nasal colonization by MR-CoNS and SA have not been investigated in this population.

Primary objective: To compare the acquisition rate of MR-CoNS nasal carriage in community patients treated by β-lactams (amoxicillin-clavulanate or penicillins M), macrolides, synergistin or fluoroquinolones at the end of antibiotherapy.

Secondary objectives: (i) To compare the acquisition rate of MR-CoNS nasal carriage in community patients treated by β-lactams (amoxicillin-clavulanate or penicillins M), macrolides, synergistin or fluoroquinolones 23 to 45 days after the end of antibiotherapy; (ii) To describe the frequency of co-colonization by SA and MR-CoNS after antibiotic use; (iii) To compare the selection pressure of these 4 classes of antibiotics in term of antibiotic resistances associated to MR in carriage strains of staphylococci (iv) To assess the biodiversity of SCCmec in community-acquired MR-CoNS.

Sudy design and methods: investigators propose to perform a prospective, multicentric study of MR staphylococci carriage in community patients receiving antibiotics prescribed by their general practitioner (GP). Patients older than 18, treated by β-lactams (amoxicillin-clavulanate or penicillins M), macrolides, synergistin or fluoroquinolones for a minimal expected duration of 5 days (whatever the indication) and consenting to the study protocol will be eligible for inclusion. Hospitalization within the previous 6 months, antibiotherapy within the previous 2 months, and second line antibiotherapy after inclusion will constitute exclusion criterions. Demographic and medical data will be collected at inclusion. Three samples of nasal flora should be obtained for each included patient: (i) the first one before antibiotic exposure (at inclusion, by the patient's GP) (ii) the second and third ones at the GP's office at the end and 23 to 45 days after the termination of antibiotherapy, respectively. Enrolled patients will participate to the study for 5 to 7 weeks, depending on the duration of antibiotherapy. Samples will be transferred to the Bacteriology unit of the BICHAT-Claude Bernard hospital for MR-CoNS and S. aureus carriages screening, antibiotic susceptibility testing and SCCmec characterization by multiplex PCR.

Number of patients (duration of the study), statistical analysis: Carriage rate of MR-CoNS in the community is 10%-20%. Expected acquisition rates are 20% for patients treated by penicillin M and amoxicilline-clavulanic acid, and less than 5% for patients treated by synergistin. Acquisition rate is not predictable in the macrolides group. To demonstrate a significant difference in acquisition rates (power = 90%, α risk = 5%), 578 patients should definitively be included (141 in each group, including an anticipated 25%-rate of patients lost to follow-up), for a total study duration of 22 months.

Number of participating GP: 48 GP from Paris and its suburb, and affiliated with the Department of General Medicine of BICHAT medical school-Paris 7 University.

Inclusion criteria

• Age older than 18
• Prescription by a General Practitioner (investigator) of a β-lactam (amoxicillin-clavulanate or penicillins M), a macrolide, a synergistin or a fluoroquinolone for a minimal expected duration of 5 days (whatever the indication)
• Informed consent to the study protocol

NON-INCLUSION CRITERIA:

• Hospitalization within the previous 6 months
• Antibiotherapy within the previous 2 months
• Combination antibiotherapy

Exclusion criteria

• Prescription of a second-line antibiotherapy after inclusion
• Withdrawal of informed consent