Pharmacological Interaction of Rifampicin on Clindamycin in Staphylococcic Osteoarticular Infections

Study Overview
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Brief Summary
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Clindamycin and rifampicin are authorized in osteoarticular infection treatment (IDSA guidelines) but some interaction is observed. The objective of this study is to evaluate and quantify rifampicin interaction on clindamycin

Detailed Description
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It could suggest modification of recommended doses or incitement to antibiotic dosage. Thus, theses antibiotics, if association is allowed, could limit fluoroquinolones prescription and avoid some antibiotic resistance.

Official Title
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Pharmacological Interaction of Rifampicin on Clindamycin in Staphylococcic Osteoarticular Infections

Conditions
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Staphylococcal Infections

Intervention / Treatment
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* Biological: Clindamycin and rifampicin dosages


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients ≥18 years of age osteoarticular infection staphylococcus detected in bacteriological sampling sensibility to rifampicin, erythromycin and clindamycin active intravenous antibiotherapy against staphylococcus detected in bacteriological sampling Exclusion Criteria: septic shock or severe initial sepsis osteoarticular infection with other microorganism than staphylococcus contraindication to clindamycin or rifampicin including case of hypersensibility to one of these two antibiotics pre-existing renal insufficiency or severe renal insufficiency (creatinine clearance <30 ml/min) serious cognitive disorders patient under guardianship, trusteeship or non affiliated to social security or CMU (beneficiary or assignee) refusal to take part in the study and to sign the consent form pregnancy lactation administration of clindamycin or rifampicin within the month before inclusion treatment with enzymatic inductor or inhibitor within the month before inclusion participation to another study modifying antibiotic treatment administration

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Clindamycin and rifampicin dosages<br>blood samples for clindamycin and rifampicin dosages (for each patient) | Biological: Clindamycin and rifampicin dosages<br>* blood samples for clindamycin and rifampicin dosages (for each patient)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clindamycin AUC (area under curve) at steady state and after rifampicin introduction | this AUC of clindamycin will be compared to AUC before rifampicin introduction, at day 0 | clindamycin AUC will be evaluated after rifampicin interaction, so at day 14 of introduction | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rifampicin auto induction | rifampicin autoinduction will be studied with rifampicin AUC, according time, for each patient, at day 4 and day 14. Comparison of AUC with student's test | AUC of rifampicin at day 4 (before autoinduction ant at steady state) and day 14 (after autoinduction) | 
| clinical outcome | resolution of symptoms first described (pain, swelling, fever…) with specific scale | at day 4, day 14, day 28 (or day 60 if osteosynthesis) | 
| biological outcome | resolution of inflammatory syndrome (measure of C reactive protein) and hyperleucocytosis (WBC) | at day 4, day 14, day 28 (or day 60 if osteosynthesis) | 
| side effects and toxicity: number of participants with treatment related adverse events as assessed by CTCAE v4.0 | skin lesion, digestive symptoms, clostridium infection, liver cytolysis, hematological disorders (leucopenia, hemolytic anemia, thrombopenia)… | at day 2, day 4, day 14, day 28 (or day 60 if osteosynthesis) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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clindamycin, osteoarticular infection, rifampicin, enzymatic induction, antibiotherapy resistance