Clindamycin-rifampin Drug Interaction in the Treatment of Bone and Joint Infections (CLIRIFA)
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Treatment of bone and joint infections remains difficult and variable according to centres and countries. Clindamycin given intravenously and followed by an oral route is recommended for the treatment of staphylococcal, streptococcal and anaerobes bone and joint infections by the French Society for Infectious Diseases. For staphylococcal bone and implant infections, rifampin is a major drug, as it remains active in bacterial biofilm and on quiescent staphylococci. For that reasons, clindamycin-rifampin combination therapy is frequently used in these infections.Clindamycin is metabolized by the P450 3A4 cytochrome, an enzyme strongly inducible by rifampin. A retrospective study published in 2010 on 70 patients treated for bone and joint infections showed that clindamycin serum concentrations were significantly lower when clindamycin was combined with rifampin (5.3 mg/liter vs 8.9 mg/liter; p<0.02). This drug interaction could even be stronger with the oral route, because of hepatic first-past effect, ending up with very low clindamycin serum concentration, a risk of selecting resistant microorganisms and treatment failure. This latter point is an important issue, because clindamycin has an excellent oral bioavailability and is frequently used in oral regimens. In the above study, a wide variability of clindamycin serum concentration was observed in the group of patients treated with combination therapy (1-12mg/l) suggesting interindividual variability. Rifampin induction of CYP 450 3A4/A5 depends on different receptor (PXR, RXR, LXRalpha) submitted to genetic polymorphism. Hypothesis: Plasma clearance of clindamycin (CLclin) combined with rifampicin (CLclinrif) is higher when clindamycin is administered by the oral route (CLclinrif OR) compared with IV administration (CLclinrif IV).
Clindamycin-Rifampin Interactions: Effect of Rifampin's Enzyme-induction (Cytochrome P450 3A4/3A5) on Plasma Clindamycin Concentrations, With Clindamycin Given Intravenously and Orally to Treat Bone-and-joint Infections
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Layout table for eligibility information
Ages Eligible for Study:
18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:
Accepts Healthy Volunteers:
patients hospitalized for medical-surgical management of OAIs in the Department of Trauma and Bone Surgery
age ≥18 years
surgical management of OAI
Postoperative IV antibiotic therapy for 10±2 days
Chronic bone and/or joint infection (evolving for >4 weeks) with bacteriologically documented staphylococci, streptococci or susceptible anaerobes in skin flora susceptible to clindamycin and rifampin
Continuation of IV administration possible for a maximum of 25 days
Patient consent to participate in the study
Patients entitled enrolled to a French National Health Insurance
Allergy or intolerance to the family of antibiotics used, i.e. lincosamides (clindamycin, lincomycin) and rifamycins (rifampin), or to one of their constituents
Being treated with one of the following: cyclosporine and/or tacrolimus (immunosuppressants) ; midazolam (psychotropic agents)
Human immunodeficiency virus-positive patient being treated with protease inhibitors (ritonavir, amprenavir, atazanavir, indinavir, nelfinavir, lopinavir, saquinavir) or delavirdine
Cirrhosis, hepatocellular insufficiency
Creatinine clearance < 30 mL/min (according to the cockcroft and gault formula)
Severe sepsis (systolic blood pressure (SBP) <90 mm Hg; O2 saturation <90%, encephalopathy, oligo-anuria, creatininemia >176 mmol/L, platelets <100,000/mm3, INR >1.5, Glasgow coma score <13) or septic shock (persistent hypotension despite volumetric filling) at arrival in the unit
Congenital galactosemia, glucose and galactose malabsorption syndrome, lactase deficit because of the presence of lactose in the dalacin® capsules
Intolerance of fructose, glucose and galactose malabsorption syndrome, sucrase-isomaltase deficit because of the presence of saccharose in the rifadin® capsules
Major cognitive disorders, according to the DSM IV-TR (Diagnostic and Statistical Manual of Mental Disorders) definition (36)
Weight >100 kg or <50 kg
Woman of childbearing age using estrogen-progestin contraception and not wanting to switch to an effective mechanical-type contraceptive method