Comparative effectiveness of antibiotic prophylaxis for preventing serious adverse events after primary total hip arthroplasty: a systematic review and network meta-analysis of randomized trials
DOI:
https://doi.org/10.2340/17453674.2025.44482Keywords:
Antibiotic Prophylaxis, Prevention, Prosthetic Joint Infection, Serious Adverse Events, Cemented Total Hip ArthroplastyAbstract
Background and purpose: The optimal duration of antibiotic prophylaxis for reducing serious adverse events (SAEs) after total hip arthroplasty (THA) is unclear. We aimed to assess the comparative effectiveness of different strategies of antibiotic prophylaxis in preventing SAEs after THA.
Methods: We searched Medline, Embase, CENTRAL, and the Clinical Trial Registration Database for randomized controlled trials evaluating antibiotic prophylaxis in patients undergoing primary THA. Two authors independently screened, extracted data, and assessed the risk of bias. We defined SAEs as prosthetic joint infections, other serious infections, major cardiovascular events, venous thromboembolisms, or mortality. The primary summary measures were odds ratios (ORs) with 95% confidence intervals (CI). The evidence was assessed using the confidence in network meta-analysis (CINeMA) framework.
Results: Of 6,131 identified citations, 10 trials of 2-group comparisons were included, involving 9,106 patients. Duration of antibiotics was grouped as follows: placebo (3), a single dose (3), multiple doses ≤ 24 hours (6), multiple doses (> 1 day) (6), and bone cement with antibiotics (2). Compared with placebo, point estimates suggest lower odds of SAEs after THA for most antibiotic strategies, except multiple doses > 1 day. Multiple doses showed no clear evidence of superiority to single dose: OR (multiple doses ≤ 24 hours) = 0.87 (CI 0.20–3.73; very low) or over more days (> 1 day) OR = 0.40 (CI 0.07–2.42; very low) nor were multiple doses > 1 day superior to multiple doses ≤ 24 hours, OR = 0.46 (0.11–1.90; very low).
Conclusion: Relative to placebo, point estimates suggested that most antibiotic prophylaxis regimens may reduce SAEs after THA, with no clear evidence of added benefit from multiple doses. These findings should be interpreted with caution due to the lack of precision and the corresponding very low certainty of evidence for some comparisons.
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References
Shichman I, Roof M, Askew N, Nherera L, Rozell J C, Seyler T M, et al. Projections and epidemiology of primary hip and knee arthroplasty in Medicare patients to 2040–2060. JB JS Open Access 2023; 8(1). doi: 10.2106/jbjs.Oa.22.00112. DOI: https://doi.org/10.2106/JBJS.OA.22.00112
Matharu G S, Culliford D J, Blom A W, Judge A. Projections for primary hip and knee replacement surgery up to the year 2060: an analysis based on data from the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man. Ann R Coll Surg Engl 2022; 104(6): 443-8. doi: 10.1308/rcsann.2021.0206. DOI: https://doi.org/10.1308/rcsann.2021.0206
Zimmerli W, Trampuz A, Ochsner P E. Prosthetic-joint infections. N Engl J Med 2004; 351(16): 1645-54. doi: 10.1056/NEJMra040181. DOI: https://doi.org/10.1056/NEJMra040181
Zmistowski B, Karam J A, Durinka J B, Casper D S, Parvizi J. Periprosthetic joint infection increases the risk of one-year mortality. J Bone Joint Surg Am 2013; 95(24): 2177-84. doi: 10.2106/jbjs.L.00789. DOI: https://doi.org/10.2106/JBJS.L.00789
Astagneau P, Rioux C, Golliot F, Brücker G, INCISO Network Study Group. Morbidity and mortality associated with surgical site infections: results from the 1997–1999 INCISO surveillance. J Hosp Infect 2001; 48(4): 267-74. doi: 10.1053/jhin.2001.1003. DOI: https://doi.org/10.1053/jhin.2001.1003
Gundtoft P H, Pedersen A B, Varnum C, Overgaard S. Increased mortality after prosthetic joint infection in primary THA. Clin Orthop Relat Res 2017; 475(11): 2623-31. doi: 10.1007/s11999-017-5289-6. DOI: https://doi.org/10.1007/s11999-017-5289-6
Bozic K J, Ries M D. The impact of infection after total hip arthroplasty on hospital and surgeon resource utilization. J Bone Joint Surg Am 2005; 87(8): 1746-51. doi: 10.2106/JBJS.D.02937. DOI: https://doi.org/10.2106/00004623-200508000-00012
Alijanipour P, Heller S, Parvizi J. Prevention of periprosthetic joint infection: what are the effective strategies? J Knee Surg 2014; 27(4): 251-8. doi: 10.1055/s-0034-1376332. DOI: https://doi.org/10.1055/s-0034-1376332
Doyon F, Evrard J, Mazas F, Hill C. Long-term results of prophylactic cefazolin versus placebo in total hip replacement. Lancet 1987; 1(8537): 860. doi: 10.1016/s0140-6736(87)91635-7. DOI: https://doi.org/10.1016/S0140-6736(87)91635-7
van Kasteren M E, Manniën J, Ott A, Kullberg B J, de Boer A S, Gyssens I C. 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): 921-7. doi: 10.1086/512192. DOI: https://doi.org/10.1086/512192
AlBuhairan B, Hind D, Hutchinson A. Antibiotic prophylaxis for wound infections in total joint arthroplasty: a systematic review. J Bone Joint Surg Br 2008; 90(7): 915-19. doi: 10.1302/0301-620x.90b7.20498. DOI: https://doi.org/10.1302/0301-620X.90B7.20498
Berrios-Torres S I, Umscheid C A, Bratzler D W, Leas B, Stone E C, Kelz R R, et al. Centers for Disease Control and Prevention Guideline for the Prevention of Surgical Site Infection, 2017. JAMA Surg 2017; 152(8): 784-91. doi: 10.1001/jamasurg.2017.0904. DOI: https://doi.org/10.1001/jamasurg.2017.0904
World Health Organization. Global guidelines for the prevention of surgical site infection 2nd ed. Geneva: World Health Organization; 2018.
Bratzler D W, Dellinger E P, Olsen K M, Perl T M, Auwaerter P G, Bolon M K, et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm 2013; 70(3): 195-283. doi: 10.2146/ajhp120568. DOI: https://doi.org/10.2146/ajhp120568
Parvizi J, Gehrke T, Mont M A, Callaghan J J. Introduction: Proceedings of International Consensus on Orthopedic Infections. J Arthroplasty 2019; 34(2): S1-S2. doi: 10.1016/j.arth.2018.09.038. DOI: https://doi.org/10.1016/j.arth.2018.09.038
Hansen E, Belden K, Silibovsky R, Vogt M, Arnold W, Bicanic G, et al. Perioperative antibiotics. J Orthop Res 2014; 32(Suppl 1): S31-59. doi: 10.1002/jor.22549. DOI: https://doi.org/10.1002/jor.22549
Surgical site infections: prevention and treatment (NICE guideline [NG125]). National Institute for Health and Care Excellence (NICE) 2019 [Internet]. Cited 19 March 2024. Available from: http://www.nice.org.uk/guidance/ng125/chapter/recommendations.
World Health Organization. Global Action Plan on Antimicrobial Resistance. Geneva: World Health Organization; 2015.
Branch-Elliman W, O’Brien W, Strymish J, Itani K, Wyatt C, Gupta K. Association of duration and type of surgical prophylaxis with antimicrobial-associated adverse events. JAMA Surg 2019; 154(7): 590-8. doi: 10.1001/jamasurg.2019.0569.
Tokarski A T, Karam J A, Zmistowski B, Deirmengian C A, Deirmengian G K. Clostridium difficile is common in patients with postoperative diarrhea after hip and knee arthroplasty. J Arthroplasty 2014; 29(6): 1110-13. doi: 10.1016/j.arth.2014.01.002. DOI: https://doi.org/10.1016/j.arth.2014.01.002
Jacoby G A, Munoz-Price L S. The new betalactamases. N Engl J Med 2005; 352(4): 380-91. doi: 10.1056/NEJMra041359. DOI: https://doi.org/10.1056/NEJMra041359
Laxminarayan R, Duse A, Wattal C, Zaidi A K, Wertheim H F, Sumpradit N, et al. Antibiotic resistance: the need for global solutions. Lancet Infect Dis 2013; 13(12): 1057-98. doi: 10.1016/s1473-3099(13)70318-9. DOI: https://doi.org/10.1016/S1473-3099(13)70318-9
Glassou E N, Hansen T B, Pedersen A B. Risk of pneumonia and urinary tract infection within the first week after total hip arthroplasty and the impact on survival. Clin Epidemiol 2017; 9: 31-9. doi: 10.2147/clep.S122829. DOI: https://doi.org/10.2147/CLEP.S122829
Belmont P J Jr, Goodman G P, Hamilton W, Waterman B R, Bader J O, Schoenfeld A J. Morbidity and mortality in the thirty-day period following total hip arthroplasty: risk factors and incidence. J Arthroplasty 2014; 29(10): 2025-30. doi: 10.1016/j.arth.2014.05.015. DOI: https://doi.org/10.1016/j.arth.2014.05.015
Meier C R, Jick S S, Derby L E, Vasilakis C, Jick H. Acute respiratory-tract infections and risk of first-time acute myocardial infarction. Lancet 1998; 351(9114): 1467-71. doi: 10.1016/s0140-6736(97)11084-4. DOI: https://doi.org/10.1016/S0140-6736(97)11084-4
Corrales-Medina V F, Alvarez K N, Weissfeld L A, Angus D C, Chirinos J A, Chang C C, et al. Association between hospitalization for pneumonia and subsequent risk of cardiovascular disease. JAMA 2015; 313(3): 264-74. doi: 10.1001/jama.2014.18229. DOI: https://doi.org/10.1001/jama.2014.18229
Levi M, van der Poll T, Schultz M. Infection and inflammation as risk factors for thrombosis and atherosclerosis. Semin Thromb Hemost 2012; 38(5): 506-14. doi: 10.1055/s-0032-1305782. DOI: https://doi.org/10.1055/s-0032-1305782
Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ 2015; 350: g7647. doi: 10.1136/bmj.g7647. DOI: https://doi.org/10.1136/bmj.g7647
Hutton B, Salanti G, Caldwell D M, Chaimani A, Schmid C H, Cameron C, et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med 2015; 162(11): 777-84. doi: 10.7326/m14-2385. DOI: https://doi.org/10.7326/M14-2385
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). ICH Harmonised Guideline. Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) 2016 updated 9 November 2016. Step 4 [version: 7]. Available from: https://database.ich.org/sites/default/files/E6_R2_Addendum.pdf.
National Healthcare Safety Network (NHSN). NHSN Surgical Site Infection Event (SSI) January 2022.pdf2022 07-16-2024. Available from: https://www.cdc.gov/nhsn/pdfs/pscmanual/9pscssicurrent.pdf
Bruce J, Russell E M, Mollison J, Krukowski Z H. The measurement and monitoring of surgical adverse events. Health Technol Assess 2001; 5(22): 1-194. doi: 10.3310/hta5220. DOI: https://doi.org/10.3310/hta5220
Schnell O, Rydén L, Standl E, Ceriello A. Current perspectives on cardiovascular out-come trials in diabetes. Cardiovasc Diabetol 2016; 15(1): 139. doi: 10.1186/s12933-016-0456-8. DOI: https://doi.org/10.1186/s12933-016-0456-8
Patel T, Tesfaldet B, Chowdhury I, Kettermann A, Smith J P, Pucino F, et al. Endpoints in diabetes cardiovascular outcome trials. Lancet 2018; 391(10138): 2412. doi: 10.1016/s0140-6736(18)31184-x. DOI: https://doi.org/10.1016/S0140-6736(18)31184-X
Hicks K A, Mahaffey K W, Mehran R, Nissen S E, Wiviott S D, Dunn B, et al. 2017 cardiovascular and stroke endpoint definitions for clinical trials. Circulation 2018; 137(9): 961-72. doi: 10.1161/CIRCULATIONAHA.117.033502. DOI: https://doi.org/10.1161/CIRCULATIONAHA.117.033502
Higgins J P T, Page M J, Elbers R G, Sterne J A C. Assessing risk of bias in a randomized trial. In: Higgins J P T, Thomas J, Chandler J, Cumpston M, Li T, Page M J, et al., editors. Cochrane Handbook for Systematic Reviews of Interventions; 2022. Chapter 8. Available from: https://www.cochrane.org/authors/handbooks-and-manuals/handbook#how-to-access (last updated August 2024).
Bradburn M J, Deeks J J, Berlin J A, Russell Localio A. Much ado about nothing: a comparison of the performance of meta-analytical methods with rare events. Stat Med 2007; 26(1): 53-77. doi: 10.1002/sim.2528. DOI: https://doi.org/10.1002/sim.2528
Higgins J P, Thompson S G, Deeks J J, Altman D G. Measuring inconsistency in meta-analyses. BMJ 2003; 327(7414): 557-60. doi: 10.1136/bmj.327.7414.557. DOI: https://doi.org/10.1136/bmj.327.7414.557
Salanti G, Higgins J P, Ades A E, Ioannidis J P. Evaluation of networks of randomized trials. Stat Methods Med Res 2008; 17(3): 279-301. doi: 10.1177/0962280207080643. DOI: https://doi.org/10.1177/0962280207080643
Platt R W, Leroux B G, Breslow N. Generalized linear mixed models for meta-analysis. Stat Med 1999; 18(6): 643-54. doi: 10.1002/(sici)1097-0258(19990330)18:6<643::aid-sim76>3.0.co;2-m. DOI: https://doi.org/10.1002/(SICI)1097-0258(19990330)18:6<643::AID-SIM76>3.0.CO;2-M
Casella G. An introduction to empirical Bayes data analysis. American Statistician 1985; 39(2): 83-7. doi: 10.2307/2682801. DOI: https://doi.org/10.1080/00031305.1985.10479400
Mbuagbaw L, Rochwerg B, Jaeschke R, Heels-Andsell D, Alhazzani W, Thabane L, et al. Approaches to interpreting and choosing the best treatments in network meta-analyses. Syst Rev 2017; 6(1): 79. doi: 10.1186/s13643-017-0473-z. DOI: https://doi.org/10.1186/s13643-017-0473-z
Chiocchia V, White I R, Salanti G. The complexity underlying treatment rankings: how to use them and what to look at. BMJ Evid Based Med 2023; 28(3): 180-2. doi: 10.1136/bmjebm-2021-111904. DOI: https://doi.org/10.1136/bmjebm-2021-111904
Nikolakopoulou A, Higgins J P T, Papakonstantinou T, Chaimani A, Del Giovane C, Egger M, et al. CINeMA: an approach for assessing confidence in the results of a network meta-analysis. PLoS Med 2020; 17(4): e1003082. doi: 10.1371/journal.pmed.1003082. DOI: https://doi.org/10.1371/journal.pmed.1003082
Papakonstantinou T, Nikolakopoulou A, Higgins J, Egger M, Salanti G. CINeMA: software for semiautomated assessment of the confidence in the results of network meta-analysis. Campbell Syst Rev 2020; 16. doi: 10.1002/cl2.1080. DOI: https://doi.org/10.1002/cl2.1080
Hill C, Flamant R, Mazas F, Evrard J. Prophylactic cefazolin versus placebo in total hip replacement: report of a multicentre double-blind randomised trial. Lancet 1981; 1(8224): 795-6. doi: 10.1016/s0140-6736(81)92678-7. DOI: https://doi.org/10.1016/S0140-6736(81)92678-7
Gunst J P, Deletang S, Rogez J M, Blanloeil Y, Baron D, Dixneuf B. [Prophylactic antibiotic therapy with cefamandole in total hip surgery replacement using Charnley’s tent: a randomized study]. Pathol Biol (Paris) 1984; 32(5 Pt 2): 567-9. PMID: 6379570
Ericson C, Lidgren L, Lindberg L. Cloxacillin in the prophylaxis of postoperative infections of the hip. J Bone Joint Surg Am 1973; 55(4): 808-13, 43. PMID: 4283753 DOI: https://doi.org/10.2106/00004623-197355040-00015
Josefsson G, Lindberg L, Wiklander B. Systemic antibiotics and gentamicin-containing bone cement in the prophylaxis of postoperative infections in total hip arthroplasty. Clin Orthop Relat Res 1981(159): 194-200. DOI: https://doi.org/10.1097/00003086-198109000-00027
Mauerhan D R, Nelson C L, Smith D L, Fitzgerald R H Jr, Slama T G, Petty R W, et al. Prophylaxis against infection in total joint arthroplasty: one day of cefuroxime compared with three days of cefazolin. J Bone Joint Surg Am 1994; 76(1): 39-45. doi: 10.2106/00004623-199401000-00006. DOI: https://doi.org/10.2106/00004623-199401000-00006
Centulio F, Conticello A. Antimicrobial chemoprophylaxis with ceftriaxone in surgical implantation of a non-cemented hip prosthesis: comparison of 2 dosage schemes [in Italian]. La Chirurgia degli organi di movimento 1988; 73(4): 357-61.
McQueen M M, Hughes S P, May P, Verity L. Cefuroxime in total joint arthroplasty: intravenous or in bone cement. J Arthroplasty 1990; 5(2): 169-72. doi: 10.1016/s0883-5403(06)80236-6. DOI: https://doi.org/10.1016/S0883-5403(06)80236-6
Suter F, Avai A, Fusco U, Gerundini M, Caprioli S, Maggiolo F. Teicoplanin versus cefamandole in the prevention of infection in total hip replacement. Eur J Clin Microbiol Infect Dis 1994; 13(10): 793-6. doi: 10.1007/bf02111338. DOI: https://doi.org/10.1007/BF02111338
Wymenga A, van Horn J, Theeuwes A, Muytjens H, Slooff T. 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(1): 19-24. doi: 10.3109/17453679209154842. DOI: https://doi.org/10.3109/17453679209154842
Pollard J P, Hughes S P, Scott J E, Evans M J, Benson M K. Antibiotic prophylaxis in total hip replacement. Br Med J 1979; 1(6165): 707-9. doi: 10.1136/bmj.1.6165.707. DOI: https://doi.org/10.1136/bmj.1.6165.707
Thornley P, Evaniew N, Riediger M, Winemaker M, Bhandari M, Ghert M. Postoperative antibiotic prophylaxis in total hip and knee arthroplasty: a systematic review and meta-analysis of randomized controlled trials. CMAJ Open 2015; 3(3): E338-43. doi: 10.9778/cmajo.20150012. DOI: https://doi.org/10.9778/cmajo.20150012
Siddiqi A, Forte S A, Docter S, Bryant D, Sheth N P, Chen A F. Perioperative antibiotic prophylaxis in total joint arthroplasty: a systematic review and meta-analysis. J Bone Joint Surg Am 2019; 101(9): 828-42. doi: 10.2106/JBJS.18.00990. DOI: https://doi.org/10.2106/JBJS.18.00990
Voigt J, Mosier M, Darouiche R. Systematic review and meta-analysis of randomized controlled trials of antibiotics and antiseptics for preventing infection in people receiving primary total hip and knee prostheses. Antimicrob Agents Chemother 2015; 59(11): 6696-707. doi: 10.1128/AAC.01331-15. DOI: https://doi.org/10.1128/AAC.01331-15
Blaser M J. Antibiotic use and its consequences for the normal microbiome. Science 2016; 352(6285): 544-5. doi: 10.1126/science.aad9358. DOI: https://doi.org/10.1126/science.aad9358
Branch-Elliman W, O’Brien W, Strymish J, Itani K, Wyatt C, Gupta K. Association of duration and type of surgical prophylaxis with antimicrobial-associated adverse events. JAMA Surgery 2019; 154(7): 590. EP - 8. doi: https://dx.doi.org/10.1001/jamasurg.2019.0569. DOI: https://doi.org/10.1001/jamasurg.2019.0569
Stevens V, Dumyati G, Fine L S, Fisher S G, van Wijngaarden E. Cumulative antibiotic exposures over time and the risk of Clostridium difficile infection. Clin Infect Dis 2011; 53(1): 42-8. doi: 10.1093/cid/cir301. DOI: https://doi.org/10.1093/cid/cir301
Baur D, Gladstone B P, Burkert F, Carrara E, Foschi F, Döbele S, et al. Effect of antibiotic stewardship on the incidence of infection and colonisation with antibiotic-resistant bacteria and Clostridium difficile infection: a systematic review and meta-analysis. Lancet Infec Dis 2017; 17(9): 990-1001. doi: 10.1016/S1473-3099(17)30325-0. DOI: https://doi.org/10.1016/S1473-3099(17)30325-0
Tamma P D, Avdic E, Li D X, Dzintars K, Cosgrove S E. Association of adverse events with antibiotic use in hospitalized patients. JAMA Intern Med 2017; 177(9): 1308-15. doi: 10.1001/jamainternmed.2017.1938. DOI: https://doi.org/10.1001/jamainternmed.2017.1938
Leta T H, Chang R N, Fenstad A M, Lie SA, Lygre SHL, Lindberg-Larsen M, et al. Number of doses of systemic antibiotic prophylaxis may be reduced in cemented primary knee arthroplasty irrespective of use of antibiotic in the cement: a multiregistry-based meta-analysis. JB JS Open Access 2024; 9(4). doi: 10.2106/jbjs.Oa.24.00140. DOI: https://doi.org/10.2106/JBJS.OA.24.00140
Caldwell D M, Ades A E, Higgins J P. Simultaneous comparison of multiple treatments: combining direct and indirect evidence. BMJ 2005; 331(7521): 897-900. doi: 10.1136/bmj.331.7521.897. DOI: https://doi.org/10.1136/bmj.331.7521.897
Mahomed N N, Barrett J A, Katz J N, Phillips C B, Losina E, Lew R A, et al. Rates and outcomes of primary and revision total hip replacement in the United States Medicare population. J Bone Joint Surg Am 2003; 85(1): 27-32. doi: 10.2106/00004623-200301000-00005. DOI: https://doi.org/10.2106/00004623-200301000-00005
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