2019 International Consensus on Antibiotic Loaded Bone Cement (ALBC) – Research Workgroup

Antibiotic-loaded bone cement (ALBC) is broadly used to treat orthopaedic infections based on the rationale that high-dose local delivery is essential to eradicate biofilm-associated bacteria.  However, ALBC formulations are empirically based on drug susceptibility from routine laboratory testing, which is known to have limited clinical relevance for biofilms. There are also dosing concerns with non-standardized, surgeon-directed, hand-mixed formulations, which have unknown release kinetics.  Based on our knowledge of in vivo biofilms,  pathogen virulence, safety issues with non-standardized ALBC formulations, and questions about the cost-effectiveness of ALBC, there is a need to evaluate the evidence for this clinical practice.  To this end, thought leaders in the field of musculoskeletal infection (MSKI) met on August 1, 2019 to review and debate published and anecdotal information, which highlighted four major concerns about current ALBC use: 1) substantial lack of Level 1 evidence to demonstrate efficacy; 2) ALBC formulations become subtherapeutic following early release, which risks induction of antibiotic resistance, and exacerbated infection from microbial colonization of the carrier; 3) the absence of standardized formulation protocols, and FDA-approved high-dose ALBC products to use following resection  in MSKI treatment; and, 4) absence of a validated assay to determine the minimum biofilm eradication concentration (MBEC) to predict ALBC efficacy against patient specific microorganisms.

Based on these and other questions, and controversies in the field, a Biofilm Symposium was held in New York City on August 1, 2019, the day before the Musculoskeletal Infection Society (MSIS) annual meeting.  Attendees included MSKI investigators, infectious disease physicians, and orthopaedic surgeons.  Primary goals of the meeting included granular discussions on: 1) current surgical debridement and post-debridement antibiotics for established MSKI and implant-related infections, 2) the effectiveness of these currently recommended treatment modalities to eradicate the four distinct biofilms known to exist in MSKI, 3) the basic science of ALBC in clinical use (antibiotic selection, antibiotic load, release kinetics, temporospatial biodistribution following local delivery), and 4) the potential of alternative local antibiotic delivery systems that are not currently available for clinical use (biodegradable controlled release carriers, anti-infective-coatings for implants, non-traditional anti-infectives, biofilm disruption and anti-quorum sensing strategies).  After the meeting, a research workgroup (RW) comprised of attendees and other experts in the field completed additional literature review to reach consensus about the science, clinical use, and future directions of local antibiotic therapy, as described in a Consensus Article submitted for publication in the Journal of Orthopaedic Research.

Schwarz EM, McLaren, AC, Sculco, TP, et al. 2019. Adjuvant Antibiotic-Loaded Bone Cement: Concerns with Current Use and Research to Make it Work

J Orthop Res Submitted for Publication

Click on each supplement to view the complete document.

Supplement 1: Formulation and Mixing Considerations for Antibiotic Loaded Bone Cement

Supplement 2: Minimal biofilm eradication concentration (MBEC) assays