Postoperative infections following orthopaedic procedures that involve placement of metallic implants can be devastating and may result in infected nonunion, removal of hardware and antibiotic spacer placement, prolonged use of antibiotics, or even amputation.

The Centers for Disease Control and Prevention (CDC) and the World Health Organization recently released a recommendation for administration of a single preoperative dose of antibiotic prophylaxis, with no further doses administered after the incision is closed in the operating room.

However, much of the literature supporting this recommendation was based on cardiothoracic, vascular, and other general surgical specialties. During the Musculoskeletal Infection Society (MSIS) 2018 Annual Meeting, Sean P. Ryan, MD, presented a meta-analysis of the current evidence related to this recommendation, specific to orthopaedic procedures with implants.

The researchers conducted a literature review and identified 14 randomized, controlled trials (RCTs) that compared a single preoperative dose of antibiotic prophylaxis to multiple perioperative doses. The RCTs, which involved 9,691 patients, included seven arthroplasty trials, four general orthopaedic studies with all patients receiving implants, two hip fracture trials, and one spine study (Fig. 1). The overall pooled infection rate of 1.9 percent for patients receiving a single preoperative dose of antibiotic was equivalent to the infection rate for patients receiving multiple perioperative doses (P = 0.740) (Table 1).

The results of the analysis suggest that a single dose of antibiotics administered preoperatively offered equivalent infection prophylaxis as multiple perioperative doses.

However, critical evaluation of the articles raises concerns about the quality of evidence. For example, a variety of antibiotic types and postoperative doses were utilized across the studies, including first-, second-, and third-generation cephalosporins, as well as teicoplanin—a synthetic glycopeptide—which is not available in the United States. Because all of these antimicrobials offer different coverage and a range of half-lives, it is difficult to compare the studies. In addition, the antibiotic that was administered as a single dose was only used 50 percent of the time for multiple doses, making it difficult to discern whether any difference in infection rate was due to the number of doses or the type of antibiotic. Also, there was no consensus on a definition of infection as the primary outcome measure, which was widely heterogenous. Lastly, none of the studies was adequately powered to detect a clinically significant difference in postoperative infection rates, which only occur in 1 percent to 2 percent of cases. Due to these concerns, the evidence was determined to be very low quality.

Thorsten Seyler, MD, PhD, of Duke University Hospital, and Sandra Berrios-Torres, MD, formerly of the CDC, debated the use of single-dose antibiotic prophylaxis during the AAOS 2018 Annual Meeting Specialty Day. Well-recognized at both the AAOS and MSIS meetings, the potential benefits of single-dose antibiotic prophylaxis include improved antibiotic stewardship, whereby a diminished antibiotic burden may contribute to a slower emergence of resistant micro-organisms and a decreased spread of resistant infections; a reduction in the cost of care by eliminating the need for hospitalization for additional doses; and fewer antibiotic adverse events, including Clostridium difficile infection, colitis, renal insufficiency, and allergic reactions.

Despite these benefits, the potential consequences of a single dose of antibiotics (e.g., possibly a higher rate of postoperative infections) have caused several organizations, including the American Association of Hip and Knee Surgeons (AAHKS), to speak out against the CDC’s single-dose recommendation until further high-quality studies can be performed. Dr. Seyler, who received the 2017 AAHKS Foundation for Arthroplasty Research and Education grant, is investigating the issue further in arthroplasty patients. Enrollment in the prospective, randomized, controlled trial began in November 2017, and other centers are encouraged to participate.

Authors of the study titled “Single vs Multiple Doses of Prophylactic Antibiotics in Orthopaedic Surgery: A Meta-analysis,” are Sean P. Ryan, MD; Beau J. Kildow, MD; Timothy Tan, MD; Javad Parvizi, MD, FRCS; Michael Bolognesi, MD; and Thorsten Seyler, MD, PhD.

Sean P. Ryan, MD, is an orthopaedic resident at Duke University Hospital in Durham, N.C.

Timothy Tan, MD, is a postgraduate year four orthopaedic resident at the Rothman Institute at Jefferson in Philadelphia.

Thorsten Seyler, MD, PhD, is an assistant professor in the Division of Adult Reconstruction at Duke University Hospital and the codirector of the Adult Reconstruction Fellowship in Durham, N.C.

References:

1. Wymenga A, van Horn J, Theeuwes A, et al: Cefuroxime for prevention of postoperative coxitis. One versus three doses tested in a randomized multicenter study of 2,651 arthroplasties. Acta Orthop Scand 1992;63:19-24.
2. Suter F, Avai A, Fusco U, Gerundini M, et al: Teicoplanin versus cefamandole in the prevention of infection in total hip replacement. Eur J Clin Microbiol Infect Dis 1994;13:793-6.
3. Ritter MA, Campbell E, Keating EM, et al: Comparison of intraoperative versus 24 hour antibiotic prophylaxis in total joint replacement. A controlled prospective study. Orthop Rev 1989;18:694-6.
4. Mollan RA, Haddock M, Webb CH: Teicoplanin vs cephamandole for antimicrobial prophylaxis in prosthetic joint implant surgery: (preliminary results). Eur J Surg Suppl 1992:19-21.
5. Kanellakopoulou K, Papadopoulos A, Varvaroussis D, et al: Efficacy of teicoplanin for the prevention of surgical site infections after total hip or knee arthroplasty: a prospective, open-label study. Int J Antimicrob Agents 2009;33:437-40.
6. Heydemann JS, Nelson CL: Short-term preventive antibiotics. Clin Orthop Relat Res 1986:184-7.
7. Periti P, Stringa G, Mini E: Comparative multicenter trial of teicoplanin versus cefazolin for antimicrobial prophylaxis in prosthetic joint implant surgery. Italian Study Group for Antimicrobial Prophylaxis in Orthopedic Surgery. Eur J Clin Microbiol Infect Dis 1999;18:113-9.
8. Liebergall M, Mosheiff R, Rand N, et al: A double-blinded, randomized, controlled clinical trial to compare cefazolin and cefonicid for antimicrobial prophylaxis in clean orthopedic surgery. Isr J Med Sci 1995;31:62-4.
9. Gatell JM, Garcia S, Lozano L, et al: Perioperative cefamandole prophylaxis against infections. J Bone Joint Surg Am 1987;69:1189-93.
10. Garotta F, Pamparana F: Antimicrobial prophylaxis with ceftizoxime versus cefuroxime in orthopedic surgery. Ceftizoxime orthopedic surgery Italian study group. J Chemother 1991;3(suppl 2):34-5.
11. Garcia S, Lozano ML, Gatell JM, et al: Prophylaxis against infection. Single-dose cefonicid compared with multiple-dose cefamandole. J Bone Joint Surg Am 1991;73:1044-8.
12. Karachalios T, Lyritis GP, Hatzopoulos E: Antibiotic prophylaxis in the surgical treatment of peritrochanteric fractures: a comparative trial between two cephalosporins. Chemotherapy 1990;36:448-53.
13. Buckley R, Hughes GN, Snodgrass T, et al: Perioperative cefazolin prophylaxis in hip fracture surgery. Can J Surg 1990;33:122-7.
14. Hellbusch LC, Helzer-Julin M, Doran SE, et al: Single-dose vs multiple-dose antibiotic prophylaxis in instrumented lumbar fusion—a prospective study. Surg Neurol 2008;70:622-7.
15. Centers for Disease Control and Prevention: National action plan for combating antibiotic-resistant bacteria. Available at: https://www.cdc.gov/drugresistance/pdf/national_action_plan_for_combating_antibotic-resistant_bacteria.pdf. Accessed August 28, 2018.