1. Bone void filler and selected antibiotics following the path of leads resistance
The effectiveness and success of the PAD-T is based in the interaction of the bone void filler carrier vehicle with the selected antibiotic(s) and the infected bone. The process of osteomyelitis is one of structural bone destruction, osseous vascular destruction, vascular congestion, and biofilm generation. Once the process of osteomyelitis initiates, bone is destroyed leaving a path of least resistance throughout the bone. This leaves large and small voids of compromised bone harboring free floating and adherent bacteria. All of these areas of bone infection are interconnected by macro and micro defects from the bone destruction. As illustrated in the long bone diagram the areas of micro bone destruction from the bone infection can very easily be missed on bone debridement and can serve as a nidus for reinfection after traditional bone debridement and IV antibiotic management.
Even in the acute osteomyelitis patient that is managed with bone debridement and irrigation that removes the free-swimming pathogens the sessile, adherent pathogens with the biofilm remain. The successful treatment of this biofilm is further diminished by the micro-vascular destruction and congestion within the infected bone, thus interfering with the body’s ability to deliver antibiotics to the area of bone infection. The PAD-T bone void filler carrier vehicle is utilized in the liquid phase before hardening occurs. This allows the bone void filler to move along the path of least resistance created by the bone infection. Once successfully delivered, the bone void filler is now in contact with all bone surfaces and biofilm within the area of osteomyelitis. The selected antibiotic(s) within the bone void filler are now in contact with all infected bone surfaces and biofilm independent of the locally compromised circulation.
2. Superior elusion of the antibiotic from the bone void filler vs. PMMA/non-absorbable cement
Ceramant with vancomycin elusion rates
In a personal communication (2010), now published, with Dr. X Yang from the Hospital for Special Surgery in New York NY, Dr Yang communicated excellent calcium sulfate/phosphate vancomycin elusion rates at three separate concentrations, recorded over ten days in
PMMA vancomycin elusion rates
comparison to PMMA vancomycin elusion rates for both the initial burst and subsequent tail. The calcium sulfate/phosphate BVF vancomycin elusion concentration initial release of Cerament was at 10+ mg/hr vs. about 0.25 mg/hr for the PMMA vancomycin elusion rates. The tail concentration plateau for calcium sulfate/phosphate BVF was maintained at 0.5 mg/hr for four weeks vs. 0.05 mg/hr plateau for the PMMA vancomycin elusion rates.
3. Significant Minimal Inhibitory Concentration antibiotic delivery
Clinical and Laboratory Standard Institute (CLSI) provide guidelines for the most up-to-date techniques for the determination of minimal inhibitory concentration of bacteria by broth micro- and macrodilution plus criteria for quality control testing.
The release of the antibiotic from the calcium sulfate/phosphate BVF discs was repeatedly uniform, extremely large, and had a rapid antibiotic diffusion. This was evident by the consistent, well shaped spherical zones of inhibition seen with all antibiotic discs. An explanation for this may be that in disc diffusion testing, as the distance from the disc increases, the concentration of the antibiotic deceases logarithmically, creating a gradient of drug concentrations in the agar surrounding the disc. If you start with a higher concentration than what is defined in the CLSI guidelines you can have a higher concentration of drug farther out from the disc, which leads to a larger zone sizes.
For MRSA the average zone of inhibition for vancomycin 1g was 30 mm or 100% greater than the minimal inhibitory zone required (15 mm) and for tobramycin 1.2g the average zone of inhibition was 25.6 mm or 173% greater than the minimal inhibitory zone required (15 mm) . For Pseudomonas aeruginosa the average zone of inhibition for tobramycin 1.2g was 43 mm or 185% greater than the minimal inhibitory zone required (15 mm).
4. Draw backs of the PAD-T
In order for the PAD-T to be successful, the infected bone needs to be intact to allow the bone void filler with antibiotics to penetrated the bones infected micro channels and micro abscesses. Meaning there are cortical defects or a partial bone resection that allows the bone void filler with antibiotics to leave the infected bone the bone void filler will not penetrate the micro channels and micro abscesses. This occurs when there is a partial bone resection such in metatarsal osteomyelitis treatment. In this scenario a bone void filler with antibiotics is used that is not flowable but can be easily packed into bone (Novogro Putty - Osteonovus).
The release of the antibiotic from the calcium sulfate/phosphate BVF discs was repeatedly uniform, extremely large, and had a rapid antibiotic diffusion. This was evident by the consistent, well shaped spherical zones of inhibition seen with all antibiotic discs. An explanation for this may be that in disc diffusion testing, as the distance from the disc increases, the concentration of the antibiotic deceases logarithmically, creating a gradient of drug concentrations in the agar surrounding the disc. If you start with a higher concentration than what is defined in the CLSI guidelines you can have a higher concentration of drug farther out from the disc, which leads to a larger zone sizes.
For MRSA the average zone of inhibition for vancomycin 1g was 30 mm or 100% greater than the minimal inhibitory zone required (15 mm) and for tobramycin 1.2g the average zone of inhibition was 25.6 mm or 173% greater than the minimal inhibitory zone required (15 mm) . For Pseudomonas aeruginosa the average zone of inhibition for tobramycin 1.2g was 43 mm or 185% greater than the minimal inhibitory zone required (15 mm).
4. Draw backs of the PAD-T
In order for the PAD-T to be successful, the infected bone needs to be intact to allow the bone void filler with antibiotics to penetrated the bones infected micro channels and micro abscesses. Meaning there are cortical defects or a partial bone resection that allows the bone void filler with antibiotics to leave the infected bone the bone void filler will not penetrate the micro channels and micro abscesses. This occurs when there is a partial bone resection such in metatarsal osteomyelitis treatment. In this scenario a bone void filler with antibiotics is used that is not flowable but can be easily packed into bone (Novogro Putty - Osteonovus).