Advertisement

International Journal of Clinical Pharmacy

, Volume 35, Issue 5, pp 798–804 | Cite as

Blood concentrations of cefuroxime in cardiopulmonary bypass surgery

  • Daphne BertholeeEmail author
  • Peter G. J. ter Horst
  • Michel L. Hijmering
  • Alexander J. Spanjersberg
  • Wobbe Hospes
  • Bob Wilffert
Research Article

Abstract

Objectives Patients with coronary artery bypass graft (CABG) surgery are at risk for severe postoperative infections. Prophylactic cefuroxime may help to reduce this risk, however sufficient concentrations, i.e. above the breakpoint (32 mg/L), are mandatory. The aim of this study is to evaluate the blood concentrations of cefuroxime during and after CABG surgery with cardiopulmonary bypass (CPB) and hypothermia, to determine the concentration of cefuroxime in sternum fluid and to evaluate possible factors of influence. Methods Seventeen patients were enrolled in this study, given 1.5 g cefuroxime at anaesthesia induction and an additional 1.5 g at start CPB. Blood samples were collected at skin incision, start CPB, every 30 min on CPB, end CPB, at wound closure and 1 h after surgery. Cefuroxime concentrations were determined by high performance liquid chromatography. Results In 47 % of the patients the cefuroxime concentration was below the breakpoint at some point during the operation and in 59 % of the patients 1 h after surgery. A statistically significant inverse correlation between estimated glomerular filtration rate and plasma cefuroxime concentrations was found (P = 0.034). Cefuroxime levels in the sternum are not significantly different from blood levels from the radial artery catheter, taken at approximately the same time (P = 0.30). Conclusions The current antibiotic regimen used did not maintain cefuroxime concentrations above the breakpoint throughout the operation, suggesting insufficient antibiotic prophylaxis. Further research to other antibiotic regimes is therefore necessary.

Keywords

Antibiotic prophylaxis Cardiopulmonary bypass Cefuroxime Coronary artery bypass graft surgery Pharmacokinetics 

Notes

Funding

The research was funded by the Isala Klinieken, Zwolle, The Netherlands.

Conflicts of interest

None.

References

  1. 1.
    Bratzler DW, Houck PM. Antimicrobial prophylaxis for surgery: an advisory statement from the national surgical infection prevention project. Am J Surg. 2005;189:395–404.PubMedCrossRefGoogle Scholar
  2. 2.
    Edwards FH, Engelman RM, Houck P, Shahian DM, Bridges CR. The society of thoracic surgeons practice guideline series: antibiotic prophylaxis in cardiac surgery, part I: duration. Ann Thorac Surg. 2006;81:397–404.PubMedCrossRefGoogle Scholar
  3. 3.
    Burke JP. Infection control—a problem for patient safety. N Engl J Med. 2003;348(7):651–6.PubMedCrossRefGoogle Scholar
  4. 4.
    Ridderstolpe L, Gill H, Granfeldt H, Ahlfeldt H, Rutberg H. Superficial and deep sternal wound complications: incidence, risk factors and mortality. Eur J Cardiothorac Surg. 2001;20:1168–75.PubMedCrossRefGoogle Scholar
  5. 5.
    De Feo M, Renzulli A, Ismeno G, Gregorio R, la Corte A, Utili R, et al. Variables predicting adverse outcome in patients with deep sternal wound infection. Ann Thorac Surg. 2001;71:324–31.PubMedCrossRefGoogle Scholar
  6. 6.
    Gardlund B, Bitkover CY, Vaage J. Postoperative mediastinitis in cardiac surgery—microbiology and pathogenesis. Eur J Cardiothorac Surg. 2002;21:825–30.PubMedCrossRefGoogle Scholar
  7. 7.
    Kriaras I, Michalopoulos A, Turina M, Geroulanos S. Evolution of antimicrobial prophylaxis in cardiovascular surgery. Eur J Cardiothorac Surg. 2000;18:440–6.PubMedCrossRefGoogle Scholar
  8. 8.
    Bratzler DW, Houck PM. Antimicrobial prophylaxis for surgery: an advisory statement from the national surgical infection prevention project. Clin Infect Dis. 2004;38:1706–15.PubMedCrossRefGoogle Scholar
  9. 9.
    Bratzler DW, Dellinger EP, Olsen KM, Perl TM, Auwaerter PG, Bolon MK, et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. AJHP. 2013;70(3):195–283.PubMedGoogle Scholar
  10. 10.
    Clinical and Laboratory Standards Institute. Performance standards for antimicrobial disk susceptibility tests; approved standard. Ed 10 document M100–S20; 2010.Google Scholar
  11. 11.
    European Committee on Antimicrobial Susceptibility Testing (EUCAST). EUCAST breakpoint table version 3.1. Availble at http://www.eucast.org. Last accessed 4 June 2013.
  12. 12.
    Viberg A, Cars O, Karlsson MO, Jonsson S. Estimation of cefuroxime dosage using pharmacodynamic targets, MIC distributions, and minimization of a risk function. J Clin Pharmacol. 2008;48:1270–81.PubMedCrossRefGoogle Scholar
  13. 13.
    Flynn Pharma Ltd. Summary of product characteristics cefuroxime; 2009.Google Scholar
  14. 14.
    Smith BR, LeFrock JL. Cefuroxime: Antimicrobial activity, pharmacology, and clinical efficacy. [review]. Ther Drug Monit. 1983;5(2):149–60.PubMedCrossRefGoogle Scholar
  15. 15.
    Foord RD. Cefuroxime: human pharmacokinetics. Antimicrob Agents Chemother. 1976;9:741–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Nascimento JWL, Carmona MJC, Strabelli TMV, Auler JOC Jr, Santos SRCJ. Perioperative cefuroxime pharmacokinetics in cardiac surgery. Clinics. 2007;62(3):257–60.PubMedCrossRefGoogle Scholar
  17. 17.
    Mets B. The pharmacokinetics of anesthetic drugs and adjuvants during cardiopulmonary bypass. Acta Anaesthesiol Scand. 2000;44:261–73.PubMedCrossRefGoogle Scholar
  18. 18.
    Hsu LC. Biocompatibility in cardiopulmonary bypass. J Cardiothorac and Vasc Anesth. 1997;11:376–82.CrossRefGoogle Scholar
  19. 19.
    Milic R, Colombini A, Lombardi G, Lanteri P, Banfi G. Estimation of glomerular filtration rate by MDRD equation in athletes: role of body surface area. Eur J Appl Physiol. 2012;112(1):201–6.PubMedCrossRefGoogle Scholar
  20. 20.
    Braxton JH, Marrin CA, McGrath PD, Morton JR, Norotsky M, Charlesworth DC, et al. 10-year follow-up of patients with and without mediastinitis. Semin Thorac Cardiovasc Surg. 2004;16:70–6.PubMedCrossRefGoogle Scholar
  21. 21.
    Nascimento JWL, Carmona MJC, Strabelli TMV, Auler J, Santos SRCJ. Systemic availability of prophylactic cefuroxime in patients submitted to coronary artery bypass grafting with cardiopulmonary bypass. J Hosp Infect. 2005;59:299–303.PubMedCrossRefGoogle Scholar
  22. 22.
    Mandak J, Pojar M, Malakova J, Lonsky V, Palicka V, Zivny P. Tissue and plasma concentrations of cephuroxime during cardiac surgery in cardiopulmonary bypass—microdialysis study. Perfusion. 2007;22:129–36.CrossRefGoogle Scholar
  23. 23.
    Liu P, Muller M, Derendorf H. Rational dosing of antibiotics: the use of plasma concentrations versus tissue concentrations. Int J Antimicrob Agents. 2002;19:285–90.PubMedCrossRefGoogle Scholar
  24. 24.
    Pojar M, Mandak J, Malakova J, Jokesova I. Tissue and plasma concentrations of antibiotic during cardiac surgery with cardiopulmonary bypass- microdialysis study. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2008;152:139–45.PubMedCrossRefGoogle Scholar
  25. 25.
    Mouton J, Vinks A. Is continuous infusion of beta-lactam antibiotics worthwhile? Efficacy and pharmacokinetic considerations. J Antimicrob Chemother. 1996;38:5–15.PubMedCrossRefGoogle Scholar
  26. 26.
    Nicolau DP, Nightingale CH, Banevicius MA, Fu Q, Quintiliani R. Serum bactericidal activity of ceftazidime: continuous infusion versus intermittent injections. Antimicrob Agents Chemother. 1996;40:61–4.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Daphne Bertholee
    • 1
    • 2
    Email author
  • Peter G. J. ter Horst
    • 2
  • Michel L. Hijmering
    • 3
  • Alexander J. Spanjersberg
    • 3
  • Wobbe Hospes
    • 2
  • Bob Wilffert
    • 1
  1. 1.Department of Pharmacotherapy and Pharmaceutical CareUniversity of GroningenGroningenThe Netherlands
  2. 2.Department of Clinical PharmacyIsala ClinicsZwolleThe Netherlands
  3. 3.Department of Thoracic Anaesthesia and Intensive CareIsala Clinics ZwolleZwolleThe Netherlands

Personalised recommendations