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Is There a Difference in Infection Risk Between Single and Multiple Doses of Prophylactic Antibiotics? A Meta-analysis

Ryan, Sean P. MD; Kildow, Beau J. MD; Tan, Timothy L. MD; Parvizi, Javad MD, FRCS; Bolognesi, Michael P. MD; Seyler, Thorsten M. MD, PhD on behalf of the American Association of Hip and Knee Surgeons Research Committee

Clinical Orthopaedics and Related Research®: July 2019 - Volume 477 - Issue 7 - p 1577–1590
doi: 10.1097/CORR.0000000000000619
2018 MUSCULOSKELETAL INFECTION SOCIETY PROCEEDINGS
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Background The prevention of surgical site infection guidelines issued by the Centers for Disease Control and Prevention (CDC) recently recommended that only a single dose of preoperative antibiotics be administered to patients undergoing clean-contaminated procedures based on data from a variety of surgical disciplines. For orthopaedic procedures, where postoperative infections can have significant consequences, the existing evidence for this recommendation is widely debated.

Questions/purposes Is there a difference in postoperative infection risk when utilizing a single dose of preoperative antibiotics compared with multiple doses of perioperative antibiotics for orthopaedic procedures where implants are placed?

Methods MEDLINE, EMBASE, Google Scholar, and Cochrane were systematically reviewed for randomized controlled trials (RCTs) of a single dose of preoperative antibiotics compared with pre- and postoperative prophylaxis from 1980 to 2017 for all orthopaedic procedures where implants were being placed. Infection (both superficial and deep) as a primary outcome through all available followup was required for inclusion. Fourteen RCTs detailing 9691 orthopaedic procedures were included for analysis, including seven arthroplasty, one spine, and six general orthopaedic trials (two specific to hip fracture fixation). Pooled infection outcomes were analyzed with random-effects modeling in light of study heterogeneity. Bias was evaluated using the Cochrane risk of bias tool as well as a funnel plot for publication bias, and quality of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Bias was largely uncertain; however, a high risk of bias was noted in four studies. No significant overall publication bias was noted. The quality of evidence was determined to be very low based on the GRADE tool, downgraded based on risk of bias, inconsistency, and imprecision. Despite the quality of evidence, the data were pooled in light of the current recommendations from the CDC to critically evaluate the recommendation that a single dose of antibiotics be utilized.

Results There were no differences in infection risk between single- versus multiple-dose groups (single: 83 of 4263 [2%], multiple: 101 of 5428 [2%]; odds ratio, 0.92 [95% confidence interval, 0.56-1.51]; p = 0.740, I2 = 36% for statistical heterogeneity).

Conclusions There is no difference in infection risk between a single dose and multiple doses of perioperative antibiotics for orthopaedic procedures where implants are utilized, consistent with recent recommendations. However, the quality of evidence for orthopaedic procedures is low, and a randomized study with a sufficient sample size is needed to examine the issue before universal adoption of a single antibiotic dose.

Level of Evidence Level I, therapeutic study.

S. P. Ryan, B. J. Kildow, M. P. Bolognesi, T. M. Seyler, Duke University Hospital, Durham, NC, USA

T. L. Tan, J. Parvizi, Rothman Institute, Philadelphia, PA, USA

S. P. Ryan, Duke University Hospital, 2301 Erwin Road, Durham, NC 27710, USA, email: Sean.p.ryan@duke.edu

One of the authors certifies that he (JP) has or may receive payments or benefits, during the study period, an amount of USD 10,000 to USD 100,000 from Zimmer-Biomet (Warsaw, IN, USA); an amount of USD 10,000 to USD 100,000 from Stryker (Kalamazoo, MI, USA); an amount of less than USD 10,000 from TissueGene (Rockville, MD, USA); an amount of less than USD 10,000 from CeramTec (Plochingen, Germany); an amount of less than USD 10,000 from Corentec (Seoul, South Korea); an amount of less than USD 10,000 from Ethicon (Somerville, NJ, USA); an amount of less than USD 10,000 from Tenor (Gujarat, India); an amount of less than USD 10,000 from KCI (San Antonio, TX, USA); an amount of less than USD 10,000 from Heraeus (Hanau, Germany); an amount of less than USD 10,000 from DataTrace (Brooklandville, MD, USA); an amount of less than USD 10,000 from Elsevier (Amsterdam, Netherlands); an amount of less than USD 10,000 from Jaypee Publishers (New Delhi, India); an amount of less than USD 10,000 from Slack Incorporated (Thorofare, NJ, USA); and an amount of less than USD 10,000 from Wolters Kluwer (Alphen aan den Rijn, Netherlands). One of the authors certifies that he (JP) has stock options with Parvizi Surgical Innovations (Philadelphia, PA, USA); Hip Innovation Technology (Boca Raton, FL, USA); Cross Current Business Intelligence (Newtown, PA, USA); Alphaeon (Irvine, CA, USA); Joint Purification Systems (Solana Beach, CA, USA); Ceribell (Mountain View, CA, USA); MedAp (Lenzkirch, Germany); Physician Recommended Nutriceuticals (Blue Bell, PA, USA); PRN-Veterinary (Blue Bell, PA, USA); MDValuate (Centennial, CO, USA); Intellijoint (Waterloo, Ontario, Canada); and MicrogenDx (Lubbock, TX, USA). One of the authors (MB) received other from AOA Omega, personal fees in the form of royalties, as a paid speaker, and a grant in the amount of USD 100,0001 to USD 1,000,000 from Zimmer-Biomet for research support, a grant in the amount of USD 10,000 to USD 100,000 from DePuy (Raynham, MA, USA) for research support, a grant in the amount of USD 10,000 to USD 100,000 from Exactech (Gainesville, FL, USA) for research support, and a grant in the amount of USD 10,000 to USD 100,000 from PCORI (Washington, DC, USA) for research support. One or more of the authors (TMS) received research funding from the AAHKS Research Committee for further investigation of single versus multiple doses of prophylactic antibiotics in arthroplasty. One of the authors (TMS) reports other from Osteoremedies, other from Zimmer Biomet, personal fees in the amount of USD 10,000 to USD 100,000 from Total Joint Orthopaedics (Salt Lake City, UT, USA), USD 10,000 to USD 100,000 from Smith & Nephew (London, UK), less than USD 10,000 from Pfizer (New York City, NY, USA), other from Exactech (Gainesville, FL, USA), other from DePuy (Raynham, MA, USA), other from Stryker (Kalamazoo, MI, USA), other from AAHKS (Rosemont, IL, USA), other from Reflexion Health (San Diego, CA, USA), and other from KCI/Acelity (San Antonio, TX, USA), outside the submitted work.

All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request.

Clinical Orthopaedics and Related Research® neither advocates nor endorses the use of any treatment, drug, or device. Readers are encouraged to always seek additional information, including FDA approval status, of any drug or device before clinical use.

AAHKS Research Committee members: Susan M. Odum PhD, Javad Parvizi MD, FRCS, John C. Clohisy MD, David C. Markel MD, Ran Schwarzkopf MD, MSc, Sumon Nandi MD, Jesse E. Otero MD, PhD, Matthew J. Dietz MD, Timothy S. Brown MD, Carlos A. Higuera MD, Brett R. Levine MD, MS, Matthew P. Abdel MD, Muyibat A. Adelani MD, Chiara Rodgers MPH.

Received August 02, 2018

Accepted December 04, 2018

© 2019 Lippincott Williams & Wilkins LWW
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