Local Collagen-Gentamicin for Prevention of Sternal Wound Infections

Detta är en avhandling från Institutionen för medicin och vård

Sammanfattning: In cardiac surgery, sternal wound infection (SWI) continues to be one of the most serious postoperative complications. Coagulase-negative staphylococci (CoNS) have become the most common causative agents of SWI. Prophylaxis with intravenous beta-lactam antibiotics (cephalosporins or in Sweden most commonly isoxazolyl penicillins) is routinely practised. However, many CoNS species are resistant to beta-lactam antibiotics. Vancomycin is often the only effective antibiotic available for treatment of these infections, but its use for routine prophylaxis is strongly discouraged because of the risk of increasing the selection of resistant bacteria.The aim of this work was to develop and evaluate a new technique for antibiotic prophylaxis in cardiac surgery consisting of application of drug eluting collagen-gentamicin sponges in the sternal wound in addition to conventional intravenous antibiotics.The antibiotic concentrations in the wound and serum achieved by routine intravenous dicloxacillin prophylaxis and those after application of local collagen-gentamicin in the sternal wound were investigated. These studies showed dicloxacillin levels adequate for prevention of infections by methicillin-susceptible staphylococci, and extremely high gentamicin levels in the wound fluid, during the first 8-12 hours postoperatively with the local application.Two thousand cardiac surgery patients were then randomised to routine prophylaxis with intravenous isoxazolyl penicillin alone (control group) or to this prophylaxis combined with application of collagen-gentamicin (260 mg gentamicin) sponges within the sternotomy before wound closure. The primary end-point was any sternal wound infection within two months postoperatively.Evaluation was possible in 983 and 967 patients in the treatment and control groups, respectively. The incidence of any sternal wound infection was 4.3% in the treatment group and 9.0 % in the control group (relative risk = 0.47, (95% confidence interval 0.33 to 0.68); P<0.001). The most common microbiological agents were CoNS, followed by Staphylococcus aureus. Local gentamicin reduced the incidence of SWIs caused by all major, clinically important microbiological agents except Propionibacterium acnes.Assignment to the control group, high body mass index, diabetes mellitus, younger age, single or double internal mammary artery, left ventricular ejection fraction less than 35% and longer operation time were independent risk factors for SWI in a multivariable risk factor analysis.In patients with additional sternal fixation wires (> six wires) the collagen-gentamicin prophylaxis was associated with an approximately 70 % reduction in the incidence of SWI at all depths and the application of collagen sponges between sternal halves may require particular attention regarding the stability of fixation.A cost effectiveness analysis showed that the application of local collagen-gentamicin as prophylaxis was dominant, i.e. resulted in both lower costs and fewer wound infections.Routine use of the described prophylaxis in all adult cardiac surgery patients could be recommended.