This is the indepth rationale from our ID working group.
Microbiology:
As you know, the majority of surgical site infections are caused by Staphylococcus. A key determinant of successful prophylaxis is the activity of the agent against Staph. While cefazolin is often regarded as the reference drug for antimicrobial activity against Staph, various other cephalosporins, including cefuroxime, cefotaxime and ceftriaxone exhibit excellent anti-staphylococcal activity. In fact, MICs for all these agents are inferred from cefoxitin and set by the Clinical and Laboratory Standards Institute. Various microbiological studies confirm equivalent anti-staphylococcal activity of these agents (e.g. Clin Infect Dis. 2014 May; 58(9): 1287–1296.) In Island Health, the resistance to cephalosporins is much lower than to comparator agents such as clindamycin, and their rapid cell-wall activity and distribution makes them preferable to vancomycin.
Surgical Guidelines:
According the Clinical Practice Guidelines for antimicrobial prophylaxis in surgery, there are over 30 randomized controlled studies cited individually or as meta-analyses examining cardiac surgery patients. While a variety of cephalosporins were studied, there are no data supporting superiority of one antimicrobial over another, with the exception of vancomycin, which was showed inferior. A meta-analysis of 27 studies of cardiac surgeries found no difference in SSIs between cephalosporins when examining different classes of agents (J Thorac Cardiovasc Surg . 1992; 104:590–9). The guideline highlights that selection should be based on cost, availability, and local resistance patterns. (American Journal of Health-System Pharmacy, Volume 70, Issue 3, 1 February 2013, Pages 195–283). As such, ceftriaxone was chosen over other agents due to consistent availability, clinician familiarity with the drug, ease of administration as a 3-5min push, and cost.
Other Clinical Literature
There is overwhelming evidence that supports ceftriaxone use for surgical prophylaxis in general. For example, a meta-analysis of 43 randomized trials, which included cardiac surgery patients, showed that ceftriaxone actually demonstrated a slightly lower surgical wound infections (OR 0.53, CI 0.43-0.67) and post-op UTIs, particularly in contaminated procedures. (Chemotherapy. 2002 Mar;48(1):49-56.). Another large meta-analysis of over 90 studies came to the same conclusion, showing an OR of 0.68 for SSI for ceftriaxone, equating to nearly one third lower SSI risk with ceftriaxone. (World J Surg. 2009 Dec;33(12):2538-50.) 2/3 of individual studies used a single dose of 1g, which formed the basis of our therapeutic interchange. Specific to cardiac patients, the evidence is similarly strong. In open heart surgeries, for example, ceftriaxone was compared to cefazolin in 104 patients showed that tissue concentrations of ceftriaxone were higher faster and that infection rates did not differ (American Journal of Surgery [01 Oct 1984, 148(4A):8-14]). A large RCT of ceftriaxone used in CABG against other cephalosporins also demonstrated equivalent efficacy (Scandinavian Journal of Thoracic and Cardiovascular Surgery Volume 28, 1994 - Issue 3-4). An RCT of nearly 1000 patients comparing ceftriaxone to cefazolin showed infection rates of 4.5% vs 5% respectively, a NS difference. (World Journal of Surgery November 1989, Volume 13, Issue 6, pp 798–801). Ceftriaxone is broader spectrum than cefazolin, and its impact on development of resistance prevents it from routinely being used as prophylaxis over cefazolin, not lack of efficacy.
Other alternatives
As you know, the clinical order sets on which peri-operative antimicrobials are written are suggestions, and can be changed by the prescriber at their discretions. Should prescribers want to choose another cephalosporin, they are free to do so. Options include cefuroxime 1.5g or cefotaxime 2g both dosed q8h. Unfortunately neither can be pre-formulated like cefazolin and all require the same reconstitution procedures as ceftriaxone, and necessitate more doses. We recommend against using clindamycin or vancomycin due to resistance and practical issues that often lead to incomplete dosing, as well as adverse effect such as CDI and nephrotoxicity.
