CLINDOS: Treatment of Methicillin-sensitive Staphylococcus Aureus (MSSA)
Study Details
Study Description
Brief Summary
Background:
One of the leading causes of peri-operative osteoarticular infections (OAI) is Staphylococcus aureus. Treatment usually requires surgical debridement in association with appropriate antibiotic therapy. After surgery, an intravenous (IV) antibiotic therapy is routinely indicated for 10 to 15 days, followed by a minimal one-month oral treatment. In this protocol, the latter includes clindamycin in combination with rifampin or levofloxacin. Clindamycin is considered a good option in staphylococcal infections, because of its action against biofilm formation and bacterial adherence, its high level of joint and bone penetration and its good tolerance. Rifampin, a potent cytochrome P-450 inducer, enhances the elimination of a large number of drugs. Therefore, an influence of rifampin on clindamycin pharmacokinetics must be considered.
Objectives:
The primary objective is to compare the influence of rifampin and levofloxacin respectively on the pharmacokinetics of clindamycin in a randomized series of peri-operative staphylococcal OAI. The investigators then seek to determine the optimal drug association with regard to infection control and drug tolerance.
Study design:
Monocentric, randomized, open label, comparative study
Study period:
From November 2010 to October 2011.
Materials and Methods:
Following surgical debridement and after 10 to 15 days of IV antibiotherapy, patients are randomly assigned either to the "clindamycin/rifampin" arm either to the "clindamycin/levofloxacin" arm, according to the antimicrobial susceptibility testing. Peak and trough serum concentrations of clindamycin are measured at day-1, day-15 and day-30 of oral treatment. Rifampin and levofloxacin serum concentrations are measured at the same intervals to monitor patient compliance.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
Background:
One of the leading causes of peri-operative osteoarticular infections (OAI) is Staphylococcus aureus. Treatment usually requires surgical debridement in association with appropriate antibiotic therapy. After surgery, an intravenous (IV) antibiotic therapy is routinely indicated for 10 to 15 days, followed by a minimal one-month oral treatment. In this protocol, the latter includes clindamycin in combination with rifampin or levofloxacin. Clindamycin is considered a good option in staphylococcal infections, because of its action against biofilm formation and bacterial adherence, its high level of joint and bone penetration and its good tolerance. Rifampin, a potent cytochrome P-450 inducer, enhances the elimination of a large number of drugs. Therefore, an influence of rifampin on clindamycin pharmacokinetics must be considered.
Objectives:
The primary objective is to compare the influence of rifampin and levofloxacin respectively on the pharmacokinetics of clindamycin in a randomized series of peri-operative staphylococcal OAI. The investigators then seek to determine the optimal drug association with regard to infection control and drug tolerance. Study design: monocentric, randomized, open label, comparative study
Study period:
From November 2010 to October 2011.
Materials and Methods:
Following surgical debridement and after 10 to 15 days of IV antibiotherapy, patients are randomly assigned either to the "clindamycin/rifampin" arm either to the "clindamycin/levofloxacin" arm, according to the antimicrobial susceptibility testing. Peak and trough serum concentrations of clindamycin are measured at day-1, day-15 and day-30 of oral treatment. Rifampin and levofloxacin serum concentrations are measured at the same intervals to monitor patient compliance. Infection cure is evaluated clinically, with periodic X-rays and CRP dosage in serum.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: RIFAMPIN CLINDAMYCIN + RIFAMPIN |
Drug: association of RIFAMPIN + CLINDAMYCIN
association of RIFAMPIN + CLINDAMYCIN
Other Names:
|
| Active Comparator: LEVOFLOXACIN CLINDAMYCIN + LEVOFLOXACIN |
Drug: association of LEVOFLOXACIN+ CLINDAMYCIN
association of LEVOFLOXACIN+ CLINDAMYCIN
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Measurement of peak and trough serum concentrations of clindamycin [1 month]
Measurement of peak and trough serum concentrations of clindamycin will be performed at Day 1, Day 15 and Day 30
Secondary Outcome Measures
- proportion of patients healing (as determined from absence of fever, absence of pain and favorable aspect of scar). [Day 30]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
subject over 18 years with a IOA with GERME sensitivity to three antibiotics,
-
Patient in orthopedic unit of HEGP,
-
Patient who received and understood the information and who signed consent,
Exclusion Criteria:
-
Known allergy to one of three antibiotics and / or excipients,
-
Pregnancy or during lactation,
-
Congenital galactosemia, malabsorption of glucose and galactose, or lactase deficiency,
-
History of tendinopathy with fluoroquinolones,
-
G6PD deficiency,
-
porphyria,
-
subject receiving a protease inhibitor,
-
subject receiving anticoagulants
-
Malabsorption syndrome,
-
subject unable to follow the protocol (organizational problem, intellectual disability, ...).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Assistance Publique Hopitaux de Paris | Paris | France | 75015 |
Sponsors and Collaborators
- Assistance Publique - Hôpitaux de Paris
Investigators
- Study Director: Brigitte Sabatier, PD, PhD, Department of Pharmacology
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- K000000