Development of resistant strains of <I>Staphylococcus epidermidis</I> on gentamicin-loaded bone cement in vivo

Abstract

We have compared the rates of infection and resistance in an animal model of an orthopaedic procedure which was contaminated with a low-dose inoculum of Staphylococcus epidermidis. We randomised 44 Sprague-Dawley rats to have bone cement implanted subcutaneously containing either gentamicin or saline (control). The wound was inoculated with a dilute solution of gentamicin-sensitive Staphylococcus epidermidis. At two weeks the cement was retrieved and microbiologically tested. A lower overall rate of infection was seen in the gentamicin-loaded cement group, but there was a significantly higher rate of gentamicin-resistant infection in this group (Fisher's exact test, p < 0.01). Antibiotic-impregnated cement has an optimum surface for colonisation and prolonged exposure to antibiotic allows mutational resistance to occur. Gentamicin-loaded cement may not be appropriate for revision surgery if it has been used already in previous surgery.

In Vivo Effect of Quaternized Chitosan-Loaded Polymethylmethacrylate Bone Cement on Methicillin-Resistant Staphylococcus epidermidis Infection of the Tibial Metaphysis in a Rabbit Model

“…In vitro studies suggest that up to 8% of the antibiotic in PMMA bone cement is quickly released after surgery, and the low-dose release thereafter may not be effective in fighting infection and may contribute to the problem of antibiotic resistance (8,9). Gentamicin-resistant Staphylococcus and vancomycin-resistant Staphylococcus aureus have been increasingly detected (10)(11)(12), making the management of infections more difficult. In these cases, the antibiotics in the bone cement have lost their protective effects; therefore, new antimicrobial agents have needed to be investigated constantly in recent years (13).…”

A fully functional drug-eluting joint implant

“…In addition, while drug elution into the peri-prosthetic space is desired for 3–8 weeks, the elution from antibiotic-eluting BC spacers often falls below the minimum inhibitory concentration (MIC) of common PJI bacterial contaminants within 1 week [20]. Low antibiotic concentration without complete eradication of bacteria has the potential of increasing antibiotic resistance [21]. The antibiotic concentration in BC is limited by the minimum allowed mechanical properties, but results in low interconnectivity of drug clusters (Figure 1; [22]).…”

Custom-Made Antibiotic Cement Nails in Orthopaedic Trauma: Review of Outcomes, New Approaches, and Perspectives

“…Increasing numbers of gentamicin-resistant species are reported to cause deep infections, including medullary infections [ 67 , 68 ]. One must remember that, even with antibiotics' concentrations as high as after adding up to 20% weight of the PMMA, colonization of the spacer/nail can still occur [ 69 ].…”

“…Another important complication of ACNs is resistance induction. There are two articles describing ability of bacteria to adhere to and colonize gentamicin [ 69 ] and mixed gentamicin-vancomycin-loaded cement [ 100 ] after prolonged periods of implantation and even ability to develop gentamicin resistance despite preoperative susceptibility.…”