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Optimal administration of cefazolin prophylaxis for cesarean delivery

Journal of Perinatology volume 37, pages 16–20 (2017)Cite this article

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Cesarean delivery is the single most important risk factor for developing postpartum infection.1 Surgical site infection (SSI), including wound infection and endometritis, remains a significant cause of morbidity and mortality in the obstetric population undergoing cesarean delivery.2, 3 Anti-microbial prophylaxis, the most important factor in preventing SSI, significantly reduces the risk of postcesarean fever, wound infection, endometritis, urinary tract infection and serious bacterial infection.4 For the primary focus of this review, we conducted a PubMed literature search with the terms ‘pharmacokinetics’, ‘cefazolin’ and ‘pregnancy’ on 9 April and 13 September 2016. We identified 17 publications (including 1 corrigendum). A critical review by two authors found that 6 were not related to the topic and 1 was a review, leaving 10 original research articles (Table 1). Additional papers were selected as appropriate to supplement the narrative parts of the review of cefazolin in pregnancy. At the conclusion of this review, we provide up-to-date recommendations for anti-microbial prophylaxis dosing alterations in the setting of cesarean delivery.

Table 1 Relevant articles identified by PubMed literature search with the terms ‘pharmacokinetics,’ ‘cefazolin’ and ‘pregnancy’
Full size table

For anti-microbial prophylaxis to be effective, serum and tissue antibiotic concentrations must exceed the minimum inhibitory concentration (MIC) for susceptible bacteria before incision. To prevent superficial, deep and organ SSI, we should aim for antibiotic concentrations above MIC in skin, subcutaneous tissue, fascia, muscle, amniotic fluid and myometrium. These therapeutic levels should be maintained for at least the duration of surgery.5

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References

  1. Gibbs RS . Clinical risk factors for puerperal infection. Obstet Gynecol 1980; 55 (5, Suppl): 178S–184SS.

    Article  CAS  Google Scholar 

  2. Kassebaum NJ, Bertozzi-Villa A, Coggeshall MS, Shackelford KA, Steiner C, Heuton KR et al. Global, regional, and national levels and causes of maternal mortality during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2014; 384: 980–1004.

    Article  Google Scholar 

  3. Tita AT, Rouse DJ, Blackwell S, Saade GR, Spong CY, Andrews WW . Emerging concepts in antibiotic prophylaxis for cesarean delivery: a systematic review. Obstet Gynecol 2009; 113 (3): 675–682.

    Article  Google Scholar 

  4. Smaill FM, Grivell RM . Antibiotic prophylaxis versus no prophylaxis for preventing infection after cesarean section. Cochrane Database Syst Rev 2014; 10: CD007482.

    Google Scholar 

  5. Bratzler DW, Houck PM . Antimicrobial prophylaxis for surgery: an advisory statement from the National Surgical Infection Prevention Project. Clin Infect Dis 2004; 38 (12): 1706–1715.

    Article  Google Scholar 

  6. Bratzler DW, Hunt DR . The surgical infection prevention and surgical care improvement projects: national initiatives to improve outcomes for patients having surgery. Clin Infect Dis 2006; 43 (3): 322–330.

    Article  Google Scholar 

  7. Bratzler DW, Dellinger EP, Olsen KM, Perl TM, Auwaerter PG, Bolon MK et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm 2013; 70 (3): 195–283.

    Article  CAS  Google Scholar 

  8. ACOG Practice Bulletin No. 120. Use of prophylactic antibiotics in labor and delivery. Obstet Gynecol 2011; 117 (6): 1472–1483.

    Article  Google Scholar 

  9. American College of Obstetricians and Gynecologists Committee Opinion No. 465. Antimicrobial prophylaxis for cesarean delivery: timing of administration. Obstet Gynecol 2010; 116 (3): 791–792.

    Article  Google Scholar 

  10. Baaqeel H, Baaqeel R . Timing of administration of prophylactic antibiotics for caesarean section: a systematic review and meta-analysis. BJOG 2013; 120 (6): 661–669.

    Article  CAS  Google Scholar 

  11. Allegaert K, van Mieghem T, Verbesselt R, de Hoon J, Rayyan M, Devlieger R et al. Cefazolin pharmacokinetics in maternal plasma and amniotic fluid during pregnancy. Am J Obstet Gynecol 2009; 200 (2): 170 e1–170 e7.

    Article  Google Scholar 

  12. Anderson GD . Pregnancy-induced changes in pharmacokinetics: a mechanistic-based approach. Clin Pharmacokinet 2005; 44 (10): 989–1008.

    Article  CAS  Google Scholar 

  13. Smits A, Roberts JA, Vella-Brincat JW, Allegaert K . Cefazolin plasma protein binding in different human populations: more than cefazolin-albumin interaction. Int J Antimicrob Agents 2014; 43 (2): 199–200.

    Article  CAS  Google Scholar 

  14. Popovic J, Grujic Z, Sabo A . Influence of pregnancy on ceftriaxone, cefazolin and gentamicin pharmacokinetics in caesarean vs non-pregnant sectioned women. J Clin Pharm Ther 2007; 32 (6): 595–602.

    Article  CAS  Google Scholar 

  15. Philipson A, Stiernstedt G, Ehrnebo M . Comparison of the pharmacokinetics of cephradine and cefazolin in pregnant and non-pregnant women. Clin Pharmacokinet 1987; 12 (2): 136–144.

    Article  CAS  Google Scholar 

  16. Elkomy MH, Sultan P, Drover DR, Epshtein E, Galinkin JL, Carvalho B . Pharmacokinetics of prophylactic cefazolin in parturients undergoing cesarean delivery. Antimicrob Agents Chemother 2014; 58 (6): 3504–3513.

    Article  Google Scholar 

  17. Heikkila A, Erkkola R . Review of beta-lactam antibiotics in pregnancy. The need for adjustment of dosage schedules. Clin Pharmacokinet 1994; 27 (1): 49–62.

    Article  CAS  Google Scholar 

  18. Fiore Mitchell T, Pearlman MD, Chapman RL, Bhatt-Mehta V, Faix RG . Maternal and transplacental pharmacokinetics of cefazolin. Obstet Gynecol 2001; 98 (6): 1075–1079.

    Article  CAS  Google Scholar 

  19. Grujic Z, Popovic J, Bogavac M, Grujic I . Preoperative administration of cephalosporins for elective caesarean delivery. Srpski arhiv za celokupno lekarstvo 2010; 138 (9–10): 600–603.

    Article  Google Scholar 

  20. Alexander JW, Solomkin JS, Edwards MJ . Updated recommendations for control of surgical site infections. Ann Surg 2011; 253 (6): 1082–1093.

    Article  Google Scholar 

  21. van Kasteren ME, Mannien J, Ott A, Kullberg BJ, de Boer AS, Gyssens IC . Antibiotic prophylaxis and the risk of surgical site infections following total hip arthroplasty: timely administration is the most important factor. Clin Infect Dis 2007; 44 (7): 921–927.

    Article  Google Scholar 

  22. Steinberg JP, Braun BI, Hellinger WC, Kusek L, Bozikis MR, Bush AJ et al. Timing of antimicrobial prophylaxis and the risk of surgical site infections: results from the Trial to Reduce Antimicrobial Prophylaxis Errors. Ann Surg 2009; 250 (1): 10–16.

    Article  Google Scholar 

  23. Hawn MT, Richman JS, Vick CC, Deierhoi RJ, Graham LA, Henderson WG et al. Timing of surgical antibiotic prophylaxis and the risk of surgical site infection. JAMA Surg 2013; 148 (7): 649–657.

    Article  Google Scholar 

  24. Weber WP, Marti WR, Zwahlen M, Misteli H, Rosenthal R, Reck S et al. The timing of surgical antimicrobial prophylaxis. Ann Surg 2008; 247 (6): 918–926.

    Article  Google Scholar 

  25. Polk HC Jr, Trachtenberg L, Finn MP . Antibiotic activity in surgical incisions. The basis of prophylaxis in selected operations. JAMA 1980; 244 (12): 1353–1354.

    Article  Google Scholar 

  26. DiPiro JT, Vallner JJ, Bowden TA Jr, Clark BA, Sisley JF . Intraoperative serum and tissue activity of cefazolin and cefoxitin. Arch Surg 1985; 120 (7): 829–832.

    Article  CAS  Google Scholar 

  27. Kusaba T . Safety and efficacy of cefazolin sodium in the management of bacterial infection and in surgical prophylaxis. Clin Med Ther 2009; 1: 1607–1615.

    CAS  Google Scholar 

  28. Flegal KM, Carroll MD, Kit BK, Ogden CL . Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999–2010. JAMA 2012; 307 (5): 491–497.

    Article  Google Scholar 

  29. Robinson HE, O'Connell CM, Joseph KS, McLeod NL . Maternal outcomes in pregnancies complicated by obesity. Obstet Gynecol 2005; 106 (6): 1357–1364.

    Article  Google Scholar 

  30. Schneid-Kofman N, Sheiner E, Levy A, Holcberg G . Risk factors for wound infection following cesarean deliveries. Int J Gynaecol Obstet 2005; 90 (1): 10–15.

    Article  CAS  Google Scholar 

  31. Young OM, Shaik IH, Twedt R, Binstock A, Althouse AD, Venkataramanan R et al. Pharmacokinetics of cefazolin prophylaxis in obese gravidae at time of cesarean delivery. Am J Obstet Gynecol 2015; 213 (4): 541 e1–541 e7.

    Article  Google Scholar 

  32. Pevzner L, Swank M, Krepel C, Wing DA, Chan K, Edmiston CE Jr . Effects of maternal obesity on tissue concentrations of prophylactic cefazolin during cesarean delivery. Obstet Gynecol 2011; 117 (4): 877–882.

    Article  Google Scholar 

  33. Stitely M, Sweet M, Slain D, Alons L, Holls W, Hochberg C et al. Plasma and tissue cefazolin concentrations in obese patients undergoing cesarean delivery and receiving differing pre-operative doses of drug. Surg Infect 2013; 14 (5): 455–459.

    Article  Google Scholar 

  34. Swank ML, Wing DA, Nicolau DP, McNulty JA . Increased 3-gram cefazolin dosing for cesarean delivery prophylaxis in obese women. Am J Obstet Gynecol 2015; 213 (3): 415.e1–8.

    Article  CAS  Google Scholar 

  35. Maggio L, Nicolau DP, DaCosta M, Rouse DJ, Hughes BL . Cefazolin prophylaxis in obese women undergoing cesarean delivery: a randomized controlled trial. Obstet Gynecol 2015; 125 (5): 1205–1210.

    Article  CAS  Google Scholar 

  36. Ahmadzia HK, Patel EM, Joshi D, Liao C, Witter F, Heine RP et al. Obstetric surgical site infections: 2 grams compared with 3 grams of cefazolin in morbidly obese women. Obstet Gynecol 2015; 126 (4): 708–715.

    Article  CAS  Google Scholar 

  37. van Hasselt JG, Allegaert K, van Calsteren K, Beijnen JH, Schellens JH, Huitema AD . Semiphysiological versus empirical modelling of the population pharmacokinetics of free and total cefazolin during pregnancy. BioMed Res Int 2014; 2014: 897216.

    Article  Google Scholar 

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Acknowledgements

Dr. Sultan has received research capability funding from the National Institute of Health Research (award reference RCF146/PS/2014). Dr Carvalho received support from the Arline and Pete Harman Children’s Health Research Institute fund at Lucile Packard Children’s Hospital at Stanford.

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Authors and Affiliations

  1. Department of Anesthesiology, Sentara Martha Jefferson Hospital, Charlottesville, VA, USA

    A Duffield

  2. Department of Anaesthesia and Perioperative Medicine, University College London Hospital, London, UK

    P Sultan

  3. Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA

    E T Riley & B Carvalho

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Correspondence to A Duffield.

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Duffield, A., Sultan, P., Riley, E. et al. Optimal administration of cefazolin prophylaxis for cesarean delivery. J Perinatol 37, 16–20 (2017). https://doi.org/10.1038/jp.2016.210

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