Clindamycin as an Alternative to Vancomycin in Patients Undergoing Aortic Cardiac Surgery With Extracorporeal Circulation (ECC)

Condition(s) studied

Investigational drug(s) / intervention(s)

Clindamycin: Clindamycin used in the study corresponds to commercial forms of injectable clindamycin : KBI 600 mg/4 mL injectable solution, ampoule. * 1 ampoule contains 600 mg Clindamycin phosphate (expressed as Clindamycin base). * Excipients: edetate disodium, benzyl alcohol, sodium hydroxide, water for injection. * Dosage form: injectable solution 10minutes after injecting the first bolus of cefuroxime, clindamycin is reconstituted in 50 mL of 0.9% NaCl, then 900 mg of clindamycin is administered as a slow IV over 30 minutes. At H+4 from the end of the clindamycin injection, if skin closure is not effective, clindamycin at a dose of 600 mg in 50 mL 0.9% NaCl is re-injected over 20 minutes.

Study summary

Antibiotic prophylaxis is essential for all types of cardiac surgery under Extracorporeal Circulation (ECC), in order to reduce the incidence of surgical site infection (SSI). However, many patients are allergic to beta-lactam antibiotics. All the more, vancomycin antibiotic recommended as replacement is not without adverse effects and frequently administered in an inappropriate manner in terms of pre-intervention timing, linked to its complex use on peripheral venous lines complicated by venotoxicity. Non-compliance with the correct use of antibiotic prophylaxis in surgery is responsible for nosocomial infections, which have an impact on both the patient and the healthcare establishment in terms of costs, particularly in cardiac surgery.

Drug pharmacokinetics are more complex under bypass surgery (high volume of distribution), and studies are needed to determine the correct administration and diffusion of drugs.

In this respect, clindamycin is an antibiotic already used in antibiotic prophylaxis for other surgeries (thoracic, orthopedic...) in cases of allergy to beta-lactam antibiotics, but to date there are no studies examining the pharmacokinetics of this molecule in the context of cardiac surgery under ECC.

The aim of this protocol is to demonstrate the feasibility of using clindamycin in patients undergoing ECC surgery, by verifying that the plasma concentration of clindamycin exceeds the minimum inhibition concentration (MIC) of the main bacteria involved in mediastinitis throughout the surgical procedure.

Eligibility

Primary outcome measure(s)

• Plasma clindamycin concentrations — H0 (at incision), then every hour, and at the end of surgery (defined as sternal closure)
  To demonstrate the feasibility of using clindamycin in patients undergoing ECC and to assure that plasma clindamycin concentrations remain above the minimum inhibition concentration (MIC) of the main bacteria involved in mediastinitis, estimated free plasma clindamycin concentration will be verify throughout surgery. The free plasma concentration of clindamycin is estimated by measuring the total plasma concentration of clindamycin, based on a bound fraction of 80 to 94%.The epidemiological threshold MIC for S. aureus (ECOFF = 0.25 mg/L for clindamycin) was chosen for comparison with clindamycin concentrations, given that this bacterium is the main one implicated in mediastinitis.

Trial sites (1)

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