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

Impact of Ambulatory Antibiotics Use on Nasal Carriage of Methicillin-resistant Staphylococci in Community Patients : the StaphMRG Study

In this prospective, observational, multicentric open study, the investigators will compare the acquisition rates of methicillin-resistant staphylococci (coagulase-negative staphylococci and Staphylococcus aureus) nasal carriage in community patients receiving an ambulatory antibiotic treatment by either a β-lactam (amoxicillin-clavulanate or penicillins M), a macrolide, a synergistin or a fluoroquinolone.

Study Overview

• Status: Completed
• Conditions: Methicillin Resistant Staphylococcus Aureus

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 571

Contacts and Locations

Study Locations

• France
  • Paris, France, 75018
    • Bichat-Claude Bernard teaching hospital (AP-HP) and Xavier Bichat medical school (Denis Diderot - Paris 7 university)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

community patients receiving antibiotics prescribed by their general practitioner (GP). Patients older than 18, treated by β-lactams (amoxicillin-clavulanate or penicillins M), macrolides, synergistins or fluoroquinolones for a minimal expected duration of 5 days (whatever the indication) Hospitalization within the previous 6 months, antibiotherapy within the previous 2 months, and second line antbiotherapy after inclusion will constitute exclusion criterions.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
β-lactams; amoxicillin-clavulanate or penicillins M
macrolides
fluoroquinolones
synergistins

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Short-term impact of ambulatory use of β-lactams (amoxicillin-clavulanate or penicillins M), macrolides, synergistin or fluoroquinolones on MR-CoNS nasal carriage in community patients	assessment of MR-CoNS carriage by nasal swabbing immediately before antibiotic use and within the 3 days following the scheduled end of antibiotherapy - comparison of acquisition rates between the 4 groups (β-lactams, macrolides, synergistin or fluoroquinolones)	Between 5 days and 15 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mid-term impact of ambulatory use of β-lactams (amoxicillin-clavulanate or penicillins M), macrolides, synergistin or fluoroquinolones on MR-CoNS nasal carriage in community patients	assessment of MR-CoNS carriage by nasal swabbing immediately before antibiotic use and 23 to 45 days after the scheduled end of antibiotherapy - comparison of acquisition rates between the 4 groups	23 to 45 days after the scheduled end of antibiotherapy (prescribed duration)
Short-term and mid-term impacts of ambulatory use of β-lactams (amoxicillin-clavulanate or penicillins M), macrolides, synergistin or fluoroquinolones on SA and MR-CoNS nasal co-carriage in community patients	assessment of SA and MR-CoNS co-carriage by nasal swabbing immediately before antibiotic use, and within the 3 days and 23 to 45 days after the scheduled end of antibiotherapy - comparison of rates of co-carriage between the 4 groups	within 3 days and 23 to 45 days after the scheduled end of antibiotherapy (prescribed duration)
Comparison of selection pressure of ambulatory use of β-lactams (amoxicillin-clavulanate or penicillins M), macrolides, synergistin or fluoroquinolones in terms of non-β-lactams resistances in MR-CoNS isolates colonizing community patients	assessment of non-β-lactams resistances in nasal carriage isolates of MR-CoNS colonizing community patients immediately before antibiotic use, and within the 3 days and 23 to 45 days after the scheduled end of antibiotherapy - comparison of selection pressures between the 4 groups	within 3 days and 23 to 45 days after the scheduled end of antibiotherapy (prescribed duration
Short-term and mid-term impacts of ambulatory use of β-lactams (amoxicillin-clavulanate or penicillins M), macrolides, synergistin or fluoroquinolones on the biodiversity (species, SCCmec elements) of MR-CoNS isolates colonizing community patients	assessment of the biodiversity (species, SCCmec elements) of nasal carriage isolates of MR-CoNS colonizing community patients immediately before antibiotic use, and within the 3 days and 23 to 45 days after the scheduled end of antibiotherapy - biodiversity comparison between the 4 groups	within 3 days and 23 to 45 days after the scheduled end of antibiotherapy (prescribed duration)

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Raymond Ruimy, MD, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: December 5, 2011
• First Submitted That Met QC Criteria: December 8, 2011
• First Posted (Estimate): December 12, 2011

Study Record Updates

• Last Update Posted (Estimate): January 24, 2013
• Last Update Submitted That Met QC Criteria: January 23, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: Staphylococcus aureus; Macrolides; Anti-bacterial agents; Fluoroquinolones; Coagulase-negative staphylococci; Staphylococcus epidermidis; Drug resistance, Microbial; Methicillin resistance; Β-lactams; Synergistin; General practitioners; Antibiotic selection pressure; Ambulatory antibiotherapy; Community patients
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Staphylococcal Infections
• Other Study ID Numbers: P081118; 2009-AO1344-53 (Other Identifier: french ministry)