[Perioperative preventive antibiotic treatment with fosfomycin in heart surgery: serum kinetics in extracorporeal circulation and determination of concentration in heart valve tissue]

Abstract

A prospective clinical study was carried out to assess the adequacy of perioperative antibiotic prophylaxis using fosfomycin in patients undergoing open-heart surgery for valve diseases for the prevention of early postoperative endocarditis, as well as for serious mediastinal infections that are caused mostly by multiresistant staphylococci and Gram-negative bacteria. Perioperative pharmacokinetics and tissue penetration were determined within the harvested heart valves and subcutaneous tissue. Reliable bactericidal serum levels were established at the first measurement 10 min after the end of intravenous infusion (203.7 +/- 44.7 micrograms/ml) and were maintained during surgery for at least 120 min (124.6 +/- 58.4 micrograms/ml), even in cases of prolonged extracorporeal circulation. Cardiopulmonary bypass did not alter the serum elimination of fosfomycin in comparison with patients not undergoing extracorporeal circulation. Peak tissue concentrations were achieved in both aortic and mitral valves after 30 min, ranging between 27.1 and 76.9 micrograms/g for aortic valves and 39.6-69.4 micrograms/g for mitral valves, depending on the degree of valvular degeneration. MIC values of 16 micrograms/g were maintained in both valves for at least up to 60 min. There was no evidence of renal impairment, adverse reactions or infections during the postoperative course or thereafter for a period of 3 months. It is concluded that perioperative intravenous antibiotic prophylaxis using fosfomycin (5 g t.i.d. in adults), beginning with induction of anesthesia and continued for 48 h postoperatively, provides rapid, reliable bactericidal serum levels and valvular tissue concentrations that will inhibit most Gram-positive and Gram-negative organisms that cause bacterial endocarditis and other serious infections following cardiac surgery.