In vitro elution characteristics of gentamicin-impregnated Polymethylmethacrylate: premixed with a second powder vs. liquid Lyophilization

Abstract

Background: Antibiotic-loaded bone cement, or antibiotic-impregnated polymethylmethacrylate (PMMA), were developed to prevent and treat bone and joint infections. Gentamicin is an antibiotic that is commonly used in combination with PMMA; however, gentamicin powder is hard to obtain in many countries. This study aimed to evaluate the elution characteristics of gentamicin-impregnated PMMA made with lyophilized liquid gentamicin, compared with PMMA; which is made from commercial gentamicin powder.

Methods: The experimental sample was divided into 2 groups: the gentamicin power group (PG-PMMA) and the lyophilized liquid gentamicin group (LG-PMMA). Ten cement spacers were prepared in each group. These were produced by mixing gentamicin powder, or lyophilized liquid gentamicin, with a powder polymer before adding the liquid monomer (2 g of gentamicin and 40 g of PMMA). The volume and surface area of the antibiotic-impregnated cement spacers were 50 cm³ and 110 cm², respectively. Each spacer was immersed in phosphate-buffered saline, which was changed daily under sterile conditions. The solutions were collected to measure the level of gentamicin using the enzyme multiplied immunoassay technique (EMIT), at days 1, 2, 3, 4, 5, 6, 7, 14, 21, 28, 35 and 42.

Results: The collections from both groups had high concentrations of gentamicin on day 1 (113.63 ± 23.42 mg/dL in LG-PMMA and 61.7 ±8.37 mg/dL in PG-PMMA), but experienced a continuous decrease over time. The PMMA spacers from both groups could release gentamicin for up to 6 weeks (3.28 ± 1.17 mg/dL in LG-PMMA and 1.21 ± 0.28 mg/dL in PG-PMMA). However, there were significantly higher levels of gentamicin concentrations in the LG-PMMA group compared to the PG-PMMA group at all time points (P< 0.05).

Conclusion: Gentamicin-impregnated PMMA made with lyophilized liquid gentamicin had approximately a two times higher rate of antibiotic elution in preliminary in vitro studies, as compared with PMMA made with premixed gentamicin powder.

Keywords: Antibiotic spacer; Elution characteristics; Liquid gentamicin; Lyophilization.

Fig. 1

Forty grams of methylmethacrylate polymer (Palacos® R bone cement; Heraeus Kulzer GmbH, Wehrheim, Germany) mixed with 2 g of gentamicin powder (1a); 50 ml-syringe filled with the polymer-gentamicin mixture in the dough stage to create the uniformed, cylinder shapes of the cement spacers (1b); PG-PMMA spacer group (1c) and LG-PMMA spacer group (1d)

Fig. 2

Concentration of eluted gentamicin in LG-PMMA and PG-PMMA groups during the 6-week study period

Fig. 3

Scanning electron microscope images of the surface of PMMA spacers (3a) LG-PMMA spacer; (3b) PG-PMMA spacer. The picture of the LG-PMMA spacer showed greater density of small uniformed, rounded shape pores; while the PG-PMMA spacer had a smoother surface area

Fig. 4

Disk diffusion method for antibiotic susceptibility testing; (4a) Staphylococcus aureus ATCC 25923, (4b) Escherichia coli ATCC 25922