Antibiotic containing bone cement in prevention of hip and knee prosthetic joint infections: A systematic review and meta-analysis

Sujeesh Sebastian,Yang Liu,Robin Christensen,Deepak Bushan Raina,Magnus Tägil,Lars Lidgren

doi:10.1016/j.jot.2020.04.005

Abstract

BackgroundProsthetic joint infection (PJI) is the most serious total joint arthroplasty (TJA) complication despite several aseptic and antiseptic preventive measures. There is no clear evidence or even consensus, whether antibiotic-loaded bone cement (ALBC) should be used, in addition to systemic short-term routine antibiotic prophylaxis, to reduce the risk of PJI in primary TJA. We aimed to analyze the efficacy of ALBC for prevention of PJI in patients undergoing primary TJA. MethodsWe searched systematically for randomized controlled trials (RCTs) in PubMed, Scopus, Embase, Web of Science and Cochrane library. Two reviewers independently screened potentially eligible studies according to predefined selection criteria and assessed the risk of bias using a modified version of the Cochrane risk of bias tool. PJI was prespecified as the primary outcome of interest. The meta-analyses were based on risk ratios using random-effects model per default. For the purpose of sensitivity, the corresponding fixed effects model odds ratios were calculated with the use of the Peto method as well. To evaluate a potential difference in effect sizes using different types (subgroups) of antibiotics used in bone cement, and at different follow-up periods, we performed stratified meta-analyses. ResultsThirty-seven studies were eligible for the systematic review and qualitative synthesis, and 9 trials (6507 total joint arthroplasties) were included in this meta-analysis. Overall ALBC significantly reduced the risk of PJI following primary TJAs (RRs, 0.36; 95% CIs, 0.16 to 0.80; P = 0.01) with a moderate degree of inconsistency (I2 = 47%). Based on stratified meta-analyses the use of gentamicin appeared to have a better effect (P = 0.0005) in the total hip arthroplasty. Pooled data of different antibiotics used in knee arthroplasties showed a significant association of cefuroxime (RRs, 0.08; 95% CIs, 0.01 to 0.63; P = 0.02). Further, ALBCs significantly reduced the PJI at one and two years of follow-up (P = 0.03 and P = 0.005 respectively). ConclusionsThe evidence suggests that ALBCs are effective in reducing the PJI following primary TJA; i.e. between 20 and 84% reduced risk. However, the clear limitations of the available trial evidence highlight the need for joint-specific confirmatory trials, that will need to be designed as cluster-randomized trials of clinics in countries with well-functioning arthroplasty registries.The translational potential of this article: This meta-analysis highlights the prophylactic potential of ALBCs in lowering the risk of infection following primary hip or knee arthroplasties but emphasizes the need for more recent confirmatory trials.

Highlights

Antibiotic-loaded bone cement (ALBC) was introduced by Buchholz from the ENDO-Klinik in Germany in the 1970's for cemented hip revision of prosthetic joint infection (PJI) [1]
We aimed to evaluate the body of evidence linking antibiotic-loaded bone cement (ALBC) with a reduction of Prosthetic joint infection (PJI) following primary arthroplasty based on randomized controlled trials (RCTs)
Our search strategy was based on the PICO framework [19]: As medical subject headings or keywords we used P: (“hip arthroplasty/hip replacement” odds ratios (OR) “knee arthroplasty/replacement”) AND I: (“ALBC” OR “polymethyl methacrylate (PMMA) with antibiotic” OR “bone cement” OR “gentamicin” OR “cefuroxime” OR “tobramycin” OR “vancomycin”) AND O: (“periprosthetic joint infection” OR “prosthetic joint infection” OR “prosthesis related infection”) combined with the use of the Cochrane highly sensitive search strategies for identifying randomized trials in the specific databases: (randomized controlled trial OR controlled clinical trial OR randomized OR placebo [tiab] OR clinical trials as topic [mesh:noexp] OR randomly [tiab] OR trial [ti] NOT)

Summary

Introduction

Antibiotic-loaded bone cement (ALBC) was introduced by Buchholz from the ENDO-Klinik in Germany in the 1970's for cemented hip revision of prosthetic joint infection (PJI) [1]. We aimed to evaluate the body of evidence linking ALBC with a reduction of PJI following primary arthroplasty based on randomized controlled trials (RCTs). Stratified meta-analyses were performed to compare the efficacy of various antibiotics used in bone cement, and prophylactic potential of ALBCs at different time points following primary implantation. There is no clear evidence or even consensus, whether antibiotic-loaded bone cement (ALBC) should be used, in addition to systemic short-term routine antibiotic prophylaxis, to reduce the risk of PJI in primary TJA. To evaluate a potential difference in effect sizes using different types (subgroups) of antibiotics used in bone cement, and at different follow-up periods, we performed stratified meta-analyses. The translational potential of this article: This meta-analysis highlights the prophylactic potential of ALBCs in lowering the risk of infection following primary hip or knee arthroplasties but emphasizes the need for more recent confirmatory trials

Objectives

Methods

Results

Discussion

Conclusion