Early Antibiotic Prophylaxis Prior to Bypass Surgery Improves Tissue Penetration

Abstract

Background We previously identified preparation of the internal mammary artery as a risk factor significantly impairing antibiotic tissue penetration into the presternal subcutaneous tissue. We, therefore, adapted our dosing schema regarding preoperative timing to overcome this risk factor.

Methods Eight patients who underwent coronary artery bypass grafting with a left internal mammary artery and vein grafts were included in this clinical trial. Cefazolin (4 g) was administered twice (3 hours and 1 hour) prior to skin incision and once during skin closure (2 g). Antibiotic concentrations were measured with subcutaneous microdialysis probes on both sternal sides. Results were directly compared with the previously published patient cohort receiving the standard schema (4 g cefazolin prior to skin incision and 2 g during closure).

Results All patients (7 male, 1 female, 69 ± 7 years, 26.3 ± 3.9 kg/m²) survived the perioperative period. Mean area under the curve on the right and left sternal side was 117.0 ± 92.5 μg/mL and 114.5 ± 83.2 μg/mL, respectively (p = 0.95). This was well above the previously measured mean peak tissue concentrations without early preoperative antibiotic administration on the side of mammary artery harvesting (52.4 ± 48.5 μg/mL vs. 13.1 ± 5.8 μg/mL; p = 0.039). The %fT > minimal inhibitory concentration (MIC) for Staphylococcus epidermidis and Staphylococcus aureus during the first 10 hours in presternal tissue was ≥ 70% but did not differ compared with standard schema.

Conclusions Early, additional preoperative administration of cefazolin was able to significantly increase peak tissue concentrations during surgery compared with the standard protocol. No difference, however, could be achieved in the percentage of time during which the concentration exceeded the MIC.

Keywords

coronary artery bypass grafts surgery - experimental - pharmacology - sternum - wound infection

• References

• 1 Borger MA, Rao V, Weisel RD. et al. Deep sternal wound infection: risk factors and outcomes. Ann Thorac Surg 1998; 65 (04) 1050-1056
• 2 Baskett RJ, MacDougall CE, Ross DB. Is mediastinitis a preventable complication? A 10-year review. Ann Thorac Surg 1999; 67 (02) 462-465
• 3 Harbarth S, Samore MH, Lichtenberg D, Carmeli Y. Prolonged antibiotic prophylaxis after cardiovascular surgery and its effect on surgical site infections and antimicrobial resistance. Circulation 2000; 101 (25) 2916-2921
• 4 Hutschala D, Skhirtladze K, Kinstner C. et al. In vivo microdialysis to measure antibiotic penetration into soft tissue during cardiac surgery. Ann Thorac Surg 2007; 84 (05) 1605-1610
• 5 Andes D, van Ogtrop ML, Peng J, Craig WA. In vivo pharmacodynamics of a new oxazolidinone (linezolid). Antimicrob Agents Chemother 2002; 46 (11) 3484-3489
• 6 Calic D, Ariano RE, Arora RC. et al. Evaluation of cefazolin antimicrobial prophylaxis during cardiac surgery with cardiopulmonary bypass. J Antimicrob Chemother 2018; 73 (03) 768-771
• 7 Andreas M, Zeitlinger M, Hutschala D. Comment on: Evaluation of cefazolin antimicrobial prophylaxis during cardiac surgery with cardiopulmonary bypass. J Antimicrob Chemother 2018; 73 (09) 2587-2588
• 8 Engelman R, Shahian D, Shemin R. et al; Workforce on Evidence-Based Medicine, Society of Thoracic Surgeons. The Society of Thoracic Surgeons practice guideline series: antibiotic prophylaxis in cardiac surgery, part II: antibiotic choice. Ann Thorac Surg 2007; 83 (04) 1569-1576
• 9 Brunner M, Pernerstorfer T, Mayer BX, Eichler HG, Müller M. Surgery and intensive care procedures affect the target site distribution of piperacillin. Crit Care Med 2000; 28 (06) 1754-1759
• 10 Eichler HG, Müller M. Drug distribution. The forgotten relative in clinical pharmacokinetics. Clin Pharmacokinet 1998; 34 (02) 95-99
• 11 Andreas M, Zeitlinger M, Hoeferl M. et al. Internal mammary artery harvesting influences antibiotic penetration into presternal tissue. Ann Thorac Surg 2013; 95 (04) 1323-1329 , discussion 1329–1330
• 12 Andreas M, Zeitlinger M, Wisser W. et al. Cefazolin and linezolid penetration into sternal cancellous bone during coronary artery bypass grafting. Eur J Cardiothorac Surg 2015; 48 (05) 758-764
• 13 Classen DC, Evans RS, Pestotnik SL, Horn SD, Menlove RL, Burke JP. The timing of prophylactic administration of antibiotics and the risk of surgical-wound infection. N Engl J Med 1992; 326 (05) 281-286
• 14 Hollenbeak CS, Murphy DM, Koenig S, Woodward RS, Dunagan WC, Fraser VJ. The clinical and economic impact of deep chest surgical site infections following coronary artery bypass graft surgery. Chest 2000; 118 (02) 397-402
• 15 Craig WA. Interrelationship between pharmacokinetics and pharmacodynamics in determining dosage regimens for broad-spectrum cephalosporins. Diagn Microbiol Infect Dis 1995; 22 (1-2): 89-96
• 16 Ceviker K, Kocaturk O, Demir D. An unusual cause of generalised seizure following cardiac surgery: with bolus cefazolin administration. Cardiovasc J Afr 2015; 26 (01) e11-e13