Does Cement Viscosity Impact Antibiotic Elution and In Vitro Efficacy Against Common Prosthetic Joint Infection Pathogens?
Authors: Dietz Matthew J. , McGowan Brian M. , Thomas Dylan D. , Hunt Emily R. , Stewart Elizabeth , Squire Matthew W. 
Published: October 2024

Background
Polymethylmethacrylate (PMMA) antibiotic-laden bone cement (ALBC) is commonly used in total joint arthroplasty to treat and potentially prevent prosthetic joint infection (PJI). Multiple properties impact the elution characteristics of antibiotics from PMMA-based ALBC, including viscosity. What is not known is how medium-viscosity cement formulations affect antibiotic elution and how different cement products from different manufacturers compare regarding reaching the minimum inhibitory concentration (MIC) of antibiotics for common PJI-causing organisms in an in vitro setting.

Questions/purposes
(1) Does cement viscosity impact in vitro antibiotic elution characteristics when comparing medium-viscosity ALBC and high-viscosity ALBC formulations from the same manufacturer against four common PJI pathogens? (2) Does the manufacturer of the PMMA-based ALBC product and the type of aminoglycoside (gentamicin versus tobramycin) impact the in vitro antibiotic elution against four common PJI pathogens?

Methods
Three different PMMA-based ALBC products, including Palacos® R (high viscosity) plus gentamicin (PR+G), Palacos (medium viscosity) plus gentamicin (PMV+G), and Simplex™ P (low viscosity) plus tobramycin (SP+T), and controls for each cement type, including Palacos R, Palacos medium viscosity, and Simplex P, were evaluated. These cements were tested against four common PJI pathogens: methicillin-sensitive Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), methicillin-sensitive S. epidermidis (MSSE), and methicillin-resistant S. epidermidis. A 5-day elution protocol was observed using uniform cylindrical cement samples of each cement product. Each analysis was run with three separate lots of cement, with four samples created per lot and each sample run in duplicate. Standard curves with known antibiotic concentrations were created. Kirby-Bauer assays were then used to determine the zone of inhibition for each cement product against the four common PJI pathogens. The eluted antibiotic concentration was extrapolated for each product over 5 days to determine the interpolated antibiotic concentration for each of the 5 days. Area under the curve (AUC) was calculated as a surrogate for total antibiotics eluted over the 5-day period.

Results
Cement viscosity does not impact antibiotic elution characteristics when comparing a medium-viscosity ALBC and a high-viscosity ALBC from the same manufacturer. The cement products from two manufacturers containing different types of aminoglycosides differ in their in vitro activity over a 5-day period against four common PJI pathogens. There was no difference in interpolated antibiotic concentration against MSSE on Day 1 between PMV+G cement and PR+G (high-viscosity) (mean ± SD medium-viscosity cement gentamicin concentration 73.6 ± 14.0 µg/mL versus high-viscosity gentamicin concentration 80.3 ± 15.5 µg/mL, mean difference -6.8 [95% confidence interval (CI) -27 to 40]; p = 0.9); there was, however, greater interpolated effective antibiotic in PR+G when compared with tobramycin concentration of SP+T (80.3 ± 15.5 µg/mL versus 199.9 ± 81 µg/mL, mean difference -120 [95% CI -153 to -86]; p < 0.001). All antibiotic cement products had zones of inhibition that corresponded to an interpolated concentration above the MIC (> 32 mg/L) for all organisms on Day 1. Concentrations were maintained above the MIC even at Day 2 for only MRSA and MSSE for PMV+G and PR+G. Concentrations dropped below the MIC after Day 1 for all organisms for SP+T. Similar results were seen in the AUC, which was used as a surrogate for total antibiotics eluted over 5 days, where PMV+G and PR+G both had greater antibiotics eluted over 5 days than SP+T except for MSSE, which demonstrated no difference in the AUC.

Conclusion
In this study, medium-viscosity ALBC demonstrated similar elution properties compared with high-viscosity ALBC from the same manufacturer. Both the medium- and high-viscosity ALBC cement products from Palacos demonstrated superior in vitro antibiotic elution properties and activity against four common PJI pathogens compared with low-viscosity ALBC from Simplex over a 5-day period.

Clinical Relevance
This in vitro study suggests that a surgeon may choose to use Palacos medium-viscosity ALBC (PMV+G) in total joint applications without impacting the in vitro antibiotic elution properties compared with Palacos high-viscosity ALBC (PR+G), and that both the medium- and high-viscosity formulations of ALBC from Palacos may have improved activity against three of four common PJI pathogens compared with Simplex low-viscosity ALBC (SP+T). However, more related research is needed to determine the in vivo activity of these ALBC products and the overall efficacy of routine use of ALBC in general.