Fosfomycin Addition to Poly(D,L-Lactide) Coating Does Not Affect Prophylaxis Efficacy in Rat Implant-Related Infection Model, But That of Gentamicin Does.

Abstract

Gentamicin is the preferred antimicrobial agent used in implant coating for the prevention of implant-related infections (IRI). However, the present heavy local and systemic administration of gentamicin can lead to increased resistance, which has made its future use uncertain, together with related preventive technologies. Fosfomycin is an alternative antimicrobial agent that lacks the cross-resistance presented by other classes of antibiotics. We evaluated the efficacy of prophylaxis of 10% fosfomycin-containing poly(D,L-lactide) (PDL) coated K-wires in a rat IRI model and compared it with uncoated (Control 1), PDL-coated (Control 2), and 10% gentamicin-containing PDL-coated groups with a single layer of coating. Stainless steel K-wires were implanted and methicillin-resistant Staphylococcus aureus (ATCC 43300) suspensions (103 CFU/10 μl) were injected into a cavity in the left tibiae. Thereafter, K-wires were removed and cultured in tryptic soy broth and then 5% sheep blood agar mediums. Sliced sections were removed from the tibiae, stained with hematoxylin-eosin, and semi-quantitatively evaluated with X-rays. The addition of fosfomycin into PDL did not affect the X-ray and histopathological evaluation scores; however, the addition of gentamicin lowered them. The addition of gentamicin showed a protective effect after the 28th day of X-ray evaluations. PDL-only coating provided no protection, while adding fosfomycin to PDL offered a 20% level protection and adding gentamicin offered 80%. Furthermore, there were 103 CFU level growths in the gentamicin-added group, while the other groups had 105. Thus, the addition of fosfomycin to PDL does not affect the efficacy of prophylaxis, but the addition of gentamicin does. We therefore do not advise the use of fosfomycin as a single antimicrobial agent in coating for IRI prophylaxis.