Ostene is a soft, synthetic, moldable hemostatic material that sticks well to cut bone surfaces and stops bleeding by mechanical occlusion. Ostene is a combination of biocompatible water-soluble polymers which are absorbed completely within 24 to 48 hours of implantation;it is non-inflammatory and also has an intrinsic anti-infective effect due to its ability to prevent bacterial adhesion to surfaces. This combination of properties makes Ostene an ideal material for delivery of antibiotics directly to the wound during any surgical procedure that involves the cutting of bone. The objective of this project is to develop a formulation of Ostene that contains vancomycin (Ostene-V). Ostene-V is intended to be used for bone hemostasis exactly like Ostene, but will also provide a high local concentration of vancomycin at the surgical site during surgery and the immediate post-operative period. The antibiotic will provide supplemental protection during the immediate post-operative period to reduce the probability of against infection of the wound or the bone (osteomyelitis) by methicillin- resistant Staphylococci (e.g., MRSA or MRSE), as an adjunct to systemic antibiotic prophylaxis. This application describes the formulation development, in vitro validations, biocompatibility testing, and in vivo animal pharmacokinetic studies. This preclinical testing plan, developed in consultation with the FDA, will be used to support a 510(k) or IDE submission, followed by a clinical study in phase II to evaluate the interoperative prophylactic use of Ostene-V to reduce the incidence and severity of surgical wound infections in patients at high risk for MRSA/MRSE infection. Ostene-V has the potential to significantly reduce the incidence of MRS wound infection, and have a major impact on post-operative infection related deaths, disability, and overall cost of treatment.
Sternal wound infections (SWIs) are a relatively common complication of cardiac surgery. In recent studies, the reported incidence of SWI after sternotomy was 6-9%, of which about two- thirds were classified as superficial, and one-third of (2-3% in total) as deep SWI or mediastinitis, which are associated with significant morbidity, often require prolonged in-patient treatment, and have a mortality rate between 10 and 20%. Over 50% of all SWI are Staphylococcal infections, the majority of which are caused by drug-resistant variants such as methicillin-resistant S. Aureus and coagulase-negative Staph species. Assuming a current average treatment cost of one SWI in the US to be $25,000, with 650,000 cardiac operations per year, a SWI incidence of 5%, of which >25% are caused by methicillin- resistant staphylococci, the total additional health care cost due to this one potentially preventable complication amounts to about $200,000,000 annually. Local delivery of vancomycin to the surgical site has the potential to significantly reduce the incidence of Staphylococcal SWI. The Ostene and vancomycin combination product to be developed under this proposal will require no additional effort to use than Ostene alone, and is expected to be effective as an adjuvant therapy to systemic antibiotic prophylaxis for prevention of SWI. Ostene is increasingly being used for hemostasis in cardiac surgery as a preferred alternative to bonewax or other hemostatic materials (e.g., thrombin, collagen, fibrin). Thus, once developed and proven effective for SWI prevention, the Ostene+ Gentamicin combination would be not expected to meet any major barrier to acceptance.