One of the most challenging complications in orthopedic trauma surgery is the development of infection. Improved infection prophylaxis could be achieved by providing local delivery of antibiotics directly to the tissue-implant interface. Especially implant-associated bone infections caused by antibiotic-resistant pathogens pose significant clinical challenges to treating physicians. Prophylactic strategies that act against resistant organisms, such as methicillin-resistant Staphylococcus aureus (MRSA), are urgently required. The objective of this experimental study was to determine the efficacy of a biodegradable Polymer-Lipid Encapsulation MatriX (PLEX) loaded with the antibiotic doxycycline as a local prophylactic strategy against implant-associated osteomyelitis in a humeral non-fracture rabbit model. Activity of the PLEX-doxycycline-coating was tested against both a doxycycline susceptible (doxyS) methicillin-susceptible S. aureus (MSSA) as well as a doxycycline-resistant (doxyR) MRSA. In a rabbit intramedullary (IM) nail-related infection model, twelve rabbits received an inoculum of a doxyS MSSA direct into the medullary cavity of the humerus. After inoculation, animals received either a PLEX-doxycycline-coated nail, or an uncoated nail. The animals were observed for four weeks. Upon euthanasia, quantitative bacteriology was performed to determine bacterial load in tissues and biofilm formation on the implant. A second study was performed with sixteen rabbits receiving a DoxyR MRSA inoculum, again in coated and uncoated groups. In vitro elution studies revealed that 25% of the doxycycline was released from the PLEX-coated implants within the first day, followed by a 3% release per day up to day 28. Quantitative bacteriology revealed the presence of osteomyelitis in all animals receiving an uncoated nail in both the MSSA and the DoxyR MRSA studies (figure). All rabbits receiving a PLEX-doxycycline-coated nail were culture negative in the doxyS MSSA-group and the surrounding bone displayed a normal physiological appearance in both histological sections and radiographs. In the doxyR MRSA inoculated rabbits, a statistically significant reduction in the number of culture-positive samples was observed for the PLEX-doxycycline-coated group when compared to the animals that had received an uncoated nail, although the reduction in bacterial burden did not reach statistical significance. Improved prophylaxis against infection in trauma and orthopedic implant surgery is clearly required today. In this study, we investigated a PLEX-doxycycline-coated IM nail in a humeral non-fracture rabbit model. The PLEX-doxycycline coating on titanium alloy implants provided complete protection against implant-associated MSSA osteomyelitis, and resulted in a significant reduction in the number of culture positive samples when challenged with a doxycycline-resistant MRSA.
