Limited strength evidence supports the use of any of the following perioperative antibiotics in reducing risk of PJI, though no studies reviewed were powered to detect a significant difference among those listed:

• 1st generation cephalosporin (e.g. cefazolin)
• 2nd generation cephalosporin (e.g. cefuroxime)
• Glycopeptide (e.g. vancomycin)

Rationale
A total of 13 studies met the inclusion criteria to evaluate evidence for the use of one preoperative antibiotic over another in the prevention of hip and knee PJI. Of those, 3 were classified as high-quality studies (Bryan, 1998; Soriano 2008; and Suter, 1994), 5 were classified as moderate quality  Chareancholvanich, 2012; DeBenedictis, 1984; Periti, 1999; Soave, 1986; and Wall, 1998), and 5 were classified as low quality (Josefsson, 1993; Tyllianakis, 2010; Robertsson, 2017; Soriano, 2008; and Wu, 2016). 

Three of the studies compared 1st and 2nd generation cephalosporins (Bryan, 1988; DeBenedictis, 1984; and Soave, 1986), and showed no difference in post-operative PJI. Tyllianakis et al found no difference in infection comparing cefuroxime with fusidic acid after THA or TKA. A comparison of 2nd generation cephalosporins cefamandole and cefuroxime with glycopeptides teicoplanin and vancomycin, by Suter et al (1994) and Tyllianakis et al (2010), respectively, also failed to show benefit of one antibiotic class over the other. One RCT evaluated timing of antibiotic relative to tourniquet inflation versus deflation in TKA, finding no significant differences between the two treatment arms (Mensa et al, #3020). Because most of these studies were lacking in statistical power, the strength of this recommendation was reduced to limited, and a definitive statement on the superiority of one antibiotic over another cannot be made.

There is no current reliable evidence to support one antibiotic versus the other:
• Glycopeptide vs. 1st generation cephalosporin
• 2nd generation cephalosporin vs. fusidic acid
• Fusidic acid vs. glycopeptide
• Lincosamides (e.g. clindamycin) vs. penicillinase resistant penicillin
• Fosfomycin vs 2nd generation cephalosporin

POSSIBLE HARMS OF IMPLEMENTATION
The use of perioperative antibiotics for hip and knee arthroplasty surgery has become the standard of care, and the implementation of this guideline will likely not add risk to the arthroplasty patient population. Preoperative antibiotics should be administered routinely, and the antibiotic selected should reflect the antibiogram of the individual institution, the individual risk factors of the patient, and multidisciplinary support of institutional infection control panels. The inclusion criteria for this guideline excludes in vitro studies. As such, the practitioner should understand the effectiveness of the selected antimicrobial on common pathogens for PJI and specifically consider this with respect to vancomycin as a stand alone perioperative prophylactic agent.

FUTURE RESEARCH
Future research opportunities on the choice of perioperative antibiotics should focus on the optimal timing and the number of post-operative doses required to reduce the incidence of PJI. The Centers for Disease Control and Prevention (CDC) has issued a recommendation that a single dose of preoperative antibiotic prophylaxis is sufficient prior to lower extremity arthroplasty surgery, but there is concern that the data used to arrive at this conclusion may not be specifically applicable to the hip or knee arthroplasty patient, and as such, this recommendation has been received with a certain degree of reluctance among practicing arthroplasty surgeons (Barríos-Torres, 2017). A multi-center RCT specifically designed to answer this question is currently underway.
 
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