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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01489878
First received: December 5, 2011
Last updated: January 23, 2013
Last verified: January 2013
  Purpose

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.


Condition
Methicillin Resistant Staphylococcus Aureus

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Impact of Ambulatory Antibiotics Use on Nasal Carriage of Methicillin-resistant Staphylococci in Community Patients : the StaphMRG Study

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • 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 [ Time Frame: Between 5 days and 15 days ] [ Designated as safety issue: No ]
    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)


Secondary Outcome Measures:
  • 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 [ Time Frame: 23 to 45 days after the scheduled end of antibiotherapy (prescribed duration) ] [ Designated as safety issue: No ]
    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

  • 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 [ Time Frame: within 3 days and 23 to 45 days after the scheduled end of antibiotherapy (prescribed duration) ] [ Designated as safety issue: No ]
    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

  • 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 [ Time Frame: within 3 days and 23 to 45 days after the scheduled end of antibiotherapy (prescribed duration ] [ Designated as safety issue: No ]
    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

  • 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 [ Time Frame: within 3 days and 23 to 45 days after the scheduled end of antibiotherapy (prescribed duration) ] [ Designated as safety issue: No ]
    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


Biospecimen Retention:   Samples Without DNA

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.


Enrollment: 571
Study Start Date: March 2010
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts
β-lactams
amoxicillin-clavulanate or penicillins M
macrolides
fluoroquinolones
synergistins

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01489878

Locations
France
Bichat-Claude Bernard teaching hospital (AP-HP) and Xavier Bichat medical school (Denis Diderot - Paris 7 university)
Paris, France, 75018
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Raymond Ruimy, MD, PhD Assistance Publique - Hôpitaux de Paris
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01489878     History of Changes
Other Study ID Numbers: P081118, 2009-AO1344-53
Study First Received: December 5, 2011
Last Updated: January 23, 2013
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Coagulase-negative staphylococci
Staphylococcus epidermidis
Staphylococcus aureus
Anti-bacterial agents
Drug resistance, Microbial
Methicillin resistance
Β-lactams
Fluoroquinolones
Macrolides
Synergistin
General practitioners
Antibiotic selection pressure
Ambulatory antibiotherapy
Community patients

Additional relevant MeSH terms:
Staphylococcal Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Anti-Bacterial Agents
Methicillin
Fluoroquinolones
Antibiotics, Antitubercular
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antitubercular Agents
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 31, 2014