Dual- vs. Single-Antibiotic Loaded Cement for Hip Hemiarthroplasty: A Systematic Review and Meta-Analysis

Abstract

Background: Antibiotic-loaded cement (ALC) is often used to reduce the risk of surgical site infections (SSIs) in hip hemiarthroplasty; however, controversy exists regarding the use of dual antibiotic-loaded cement (DALC) and single antibiotic-loaded cement (SALC).

Objective: This systematic review and meta-analysis compare the efficacy of DALC and SALC for hip hemiarthroplasty.

Methods: For this systematic review, a search was undertaken in the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and ClinicalTrials.gov. Grey literature such as ProQuest Dissertations and Theses Global (PQDT) was also explored. The inclusion criteria comprised randomized controlled trials (RCTs) or comparative observational studies, and patients undergoing hip hemiarthroplasty with DALC or SALC. Newcastle–Ottawa Scale (NOS) and RoB 2.0 tools were used for risk of bias assessment in observational and RCTs, respectively. Review Manager (RevMan, version 5.4.1; The Cochrane Collaboration, Copenhagen, Denmark) was used for statistical analysis. The primary outcome was the incidence of deep SSIs.

Results: A total of five articles, including 28,418 participants, met the inclusion criteria. Three of the included studies were retrospective studies, one quasi-randomized study, and one RCT. The primary outcome revealed that DALC was associated with a statistically significant reduction in deep SSIs compared to SALC (RR, 0.47; 95% CI, 0.29–0.76; p = 0.002; I² = 27%). Subgroup analysis based on the study design did not show a significant difference for deep SSIs (p = 0.29). The majority of the secondary outcomes, such as superficial SSIs, mortality, participants with ≥ 1 complication, or antibiotic use, did not show any significant difference. However, DALC significantly lowered the risk of any infection (RR, 0.55; 95% CI, 0.38–0.79; p = 0.001; I² = 27%).

Conclusion: In conclusion, DALC can significantly reduce the risk of SSIs and the overall rate of any infection in hip hemiarthroplasty. A limitation of this study is that RCTs were pooled with observational studies, which decreased the power of analysis. Therefore, further research, including large RCTs, is needed to validate these findings.

Keywords

antibiotic-loaded bone cement (ALBC) / cemented arthroplasty / deep surgical site infections / surgical site infections (SSIs)

References

[1] C. Ossendorf, M. J. Scheyerer, G. A. Wanner, H.-P. Simmen, and C. M. Werner, “Treatment of Femoral Neck Fractures in Elderly Patients Over 60 Years of Age—Which Is the Ideal Modality of Primary Joint Replacement?,” Patient Safety in Surgery 4 (2010): 1-8.

[2] J. Bourget-Murray, I. Horton, J. Morris, et al., “Periprosthetic Joint Infection Following Hip Hemiarthroplasty: Factors Associated With Infection and Treatment Outcome,” Bone & Joint Open 3, no. 12 (2022): 924-932.

[3] N. Benito, I. Mur, A. Ribera, et al., “The Different Microbial Etiology of Prosthetic Joint Infections According to Route of Acquisition and Time After Prosthesis Implantation, Including the Role of Multidrug-Resistant Organisms,” Journal of Clinical Medicine 8, no. 5 (2019): 673.

[4] L. K. Vestby, T. Grønseth, R. Simm, and L. L. Nesse, “Bacterial Biofilm and Its Role in the Pathogenesis of Disease,” Antibiotics 9, no. 2 (2020): 59.

[5] A. Eka and A. F. Chen, “Patient-Related Medical Risk Factors for Periprosthetic Joint Infection of the Hip and Knee,” Annals of Translational Medicine 3, no. 16 (2015): 233, https://doi.org/10.3978/j.issn.2305-5839.2015.09.26.

[6] E. de Haan, G. R. Roukema, V. A. van Rijckevorsel, T. M. Kuijper, L. de Jong, and Collaboration cgDHFR, “Risk Factors for Prosthetic Joint Infections After Hemiarthroplasty of the Hip Following a Femoral Neck Fracture,” Injury 55, no. 2 (2024): 111195, https://doi.org/10.1016/j.injury.2023.111195.

[7] D. Crego-Vita, D. Aedo-Martín, R. Garcia-Cañas, A. Espigares-Correa, C. Sánchez-Pérez, and C. E. Berberich, “Periprosthetic Joint Infections in Femoral Neck Fracture Patients Treated With Hemiarthroplasty—Should We Use Antibiotic-Loaded Bone Cement?,” World Journal of Orthopedics 13, no. 2 (2022): 150-159.

[8] A. Bistolfi, G. Massazza, E. Verné, et al., “Antibiotic-Loaded Cement in Orthopedic Surgery: A Review,” International Scholarly Research Notices 2011, no. 1 (2011): 290851, https://doi.org/10.5402/2011/290851.

[9] A. Ismat, N. Walter, S. Baertl, et al., “Antibiotic Cement Coating in Orthopedic Surgery: A Systematic Review of Reported Clinical Techniques,” Journal of Orthopaedics and Traumatology 22 (2021): 56.

[10] J. Hendriks, J. van Horn, H. van der Mei, and H. Busscher, “Backgrounds of Antibiotic-Loaded Bone Cement and Prosthesis-Related Infection,” Biomaterials 25, no. 3 (2004): 545-556, https://doi.org/10.1016/s0142-9612(03)00554-4.

[11] V. Wall, T.-H. Nguyen, N. Nguyen, and P. A. Tran, “Controlling Antibiotic Release From Polymethylmethacrylate Bone Cement,” Biomedicine 9, no. 1 (2021): 26.

[12] E. Cacace, V. Kim, V. Varik, et al., “Systematic Analysis of Drug Combinations Against Gram-Positive Bacteria,” Nature Microbiology 8, no. 11 (2023): 2196-2212.

[13] J. Martínez-Moreno, V. Merino, A. Nácher, J. L. Rodrigo, M. Climente, and M. Merino-Sanjuán, “Antibiotic-Loaded Bone Cement as Prophylaxis in Total Joint Replacement,” Orthopaedic Surgery 9, no. 4 (2017): 331-341.

[14] P.-H. Hsieh, M. S. Lee, K.-Y. Hsu, Y.-H. Chang, H.-N. Shih, and S. W. Ueng, “Gram-Negative Prosthetic Joint Infections: Risk Factors and Outcome of Treatment,” Clinical Infectious Diseases 49, no. 7 (2009): 1036-1043.

[15] N. S. Mohamed, W. A. Wilkie, E. A. Remily, J. Nace, R. E. Delanois, and J. A. Browne, “Antibiotic Choice: The Synergistic Effect of Single vs Dual Antibiotics,” Journal of Arthroplasty 35, no. 3 (2020): S19-S23.

[16] V. Kumar, N. Yasmeen, A. Pandey, et al., “Antibiotic Adjuvants: Synergistic Tool to Combat Multi-Drug Resistant Pathogens,” Frontiers in Cellular and Infection Microbiology 13 (2023): 1293633.

[17] M. Sabater-Martos, M. A. Verdejo, L. Morata, et al., “Antimicrobials in Polymethylmethacrylate: From Prevention to Prosthetic Joint Infection Treatment: Basic Principles and Risk of Resistance,” Art 5, no. 1 (2023): 12.

[18] B. Tyas, M. Marsh, T. Oswald, R. Refaie, C. Molyneux, and M. Reed, “Antibiotic Resistance Profiles of Deep Surgical Site Infections in Hip Hemiarthroplasty; Comparing Low Dose Single Antibiotic Versus High Dose Dual Antibiotic Impregnated Cement,” Journal of Bone and Joint Infection 3, no. 3 (2018): 123-129.

[19] A. Sprowson, C. Jensen, S. Chambers, et al., “The Use of High-Dose Dual-Impregnated Antibiotic-Laden Cement With Hemiarthroplasty for the Treatment of a Fracture of the Hip: The Fractured Hip Infection Trial,” Bone & Joint Journal 98, no. 11 (2016): 1534-1541.

[20] D. Szymski, N. Walter, P. Krull, et al., “The Prophylactic Effect of Single vs. Dual Antibiotic-Loaded Bone Cement Against Periprosthetic Joint Infection Following Hip Arthroplasty for Femoral Neck Fracture: An Analysis of the German Arthroplasty Registry,” Antibiotics 12, no. 4 (2023): 732, https://doi.org/10.3390/antibiotics12040732.

[21] A. D. Hanssen and M. J. Spangehl, “Practical Applications of Antibiotic-Loaded Bone Cement for Treatment of Infected Joint Replacements,” Clinical Orthopaedics and Related Research 427 (2004): 79-85.

[22] N. R. Agni, M. L. Costa, J. Achten, et al., “High-Dose Dual-Antibiotic Loaded Cement for Hip Hemiarthroplasty in the UK (WHiTE 8): A Randomised Controlled Trial,” Lancet 402, no. 10397 (2023): 196-202.

[23] J. Slane, B. Gietman, and M. Squire, “Antibiotic Elution From Acrylic Bone Cement Loaded With High Doses of Tobramycin and Vancomycin,” Journal of Orthopaedic Research 36, no. 4 (2018): 1078-1085.

[24] S.-H. Lee, C.-L. Tai, S.-Y. Chen, C.-H. Chang, Y.-H. Chang, and P.-H. Hsieh, “Elution and Mechanical Strength of Vancomycin-Loaded Bone Cement: In Vitro Study of the Influence of Brand Combination,” PLoS One 11, no. 11 (2016): e0166545.

[25] J. Higgins, Cochrane Handbook for Systematic Reviews of Interventions (Cochrane Collaboration and John Wiley & Sons Ltd, 2008).

[26] M. J. Page, J. E. McKenzie, P. M. Bossuyt, et al., “The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews,” British Medical Journal 372 (2021): n71, https://doi.org/10.1136/bmj.n71.

[27] M. Ouzzani, H. Hammady, Z. Fedorowicz, and A. Elmagarmid, “Rayyan—A Web and Mobile App for Systematic Reviews,” Systematic Reviews 5 (2016): 1-10.

[28] J. A. Sterne, J. Savović, M. J. Page, et al., “RoB 2: A Revised Tool for Assessing Risk of Bias in Randomised Trials,” British Medical Journal 366 (2019): l4898, https://doi.org/10.1136/bmj.l4898.

[29] G. Wells, The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta-Analyses (Ottawa Hospital Research Institute, 2000).

[30] X. Wan, W. Wang, J. Liu, and T. Tong, “Estimating the Sample Mean and Standard Deviation From the Sample Size, Median, Range and/or Interquartile Range,” BMC Medical Research Methodology 14 (2014): 1-13.

[31] M. Richardson, P. Garner, and S. Donegan, “Interpretation of Subgroup Analyses in Systematic Reviews: A Tutorial,” Clinical Epidemiology and Global Health 7, no. 2 (2019): 192-198.

[32] P. Savage, M. McCormick, and O. Al-Dadah, “Arthroplasty Infection Rates in Fractured Neck of Femur: Single vs Dual Antibiotic Cement,” Annals of the Royal College of Surgeons of England 101, no. 7 (2019): 514-518.

[33] G. T. Ensing, J. R. van Horn, H. C. van der Mei, H. J. Busscher, and D. Neut, “Copal Bone Cement Is More Effective in Preventing Biofilm Formation Than Palacos R-G,” Clinical Orthopaedics and Related Research 466, no. 6 (2008): 1492-1498.

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