Postoperative orthopedic infections, particularly antibiotic-resistant infections, present a serious clinical challenge to surgeons and other treating physicians, since these infections involve surgically installed orthopedic hardware which are frequently associated with persistent microbial biofilms.1 Surgical intervention, irrigation, debridement and potential replacement of orthopedic hardware, combined with a prolonged course of systemic antibiotics (i.e. antibiotics taken intravenously or orally), is the standard of care for postoperative infections.2,3 However, outcomes associated with these infections are often poor including: chronic/recurrent infections; repeated hospitalizations; repeated surgeries; multiple courses of systemic antibiotic treatment; loss of function; disability; amputation; and death.4 Bacteria are able to adhere to foreign, implanted objects almost immediately, which can lead to rapid formation of microbial biofilms that drastically increase the resistance of wound-associated bacteria and contribute significantly to persistence and virulence of the infection.5,6
Locally administered pravibismane, comprised of a sterile suspension of pravibismane in a hydrogel formulation (named MBN-101), with its dual antimicrobial and anti-biofilm effects may provide important potential advantages over current standard of care treatment for orthopedic infections. The combined effect of locally applied pravibismane (MBN-101) along with IV administered antibiotics, is expected to improve bacteria and biofilm eradication from postoperative orthopedic site of infection, compared to IV antibiotics alone. Ineffective treatment may result in treatment failure including the need for repeat surgeries; additional rounds of systemic antibiotics; additional patient hospitalization time; and increased morbidity and mortality.
MBN-101-201 Orthopedic Infection Study
A Phase 2a clinical study to assess pravibismane (MBN-101) administered intraoperatively to osteosynthesis or osteomyelitis sites for patients diagnosed with an orthopedic infection, with or without orthopaedic hardware, is complete. The main objective of this study is to evaluate the safety and tolerability of single escalating doses of locally administered pravibismane as adjunct to standard of care antimicrobial and surgical therapy.
The randomized, single-blind, placebo-controlled dose escalation study assessed a single intraoperative application of pravibismane (MBN-101) plus standard of care treatment versus placebo plus standard of care treatment in 24 patients with orthopedic infection with or without osteomyelitis. Pravibismane was found to be safe and well tolerated and no pravibismane associated Serious Adverse Events (SAEs) were observed. There were lower Treatment Emergent Adverse Events in all pravibismane treated groups compared to placebo group. Although the study was not designed to show statistical efficacy, a numerical reduction in treatment failure in subjects treated with pravibismane was noted.
Qualified Infectious Disease Product (QIDP) designation and Fast Track status was granted for topical pravibismane (MBN-101) by the US FDA for post-surgical implant infections.
Additional information about the study can be found here:
- Hetrick EM and Schoenfisch MH. Reducing implant-related infections: active release strategies. Chem Soc Rev. 2006;35(9):780-789.
- Schmidt AH and Swiontkowski MF. Pathophysiology of infections after internal fixation of fractures. J Am Acad Orthop Surg. 2000;8(5):285-291.
- Patzakis MJ and Zalavras CG. Chronic posttraumatic osteomyelitis and infected nonunion of the tibia: current management concepts. J Am Acad Orthop Surg. 2005;13(6):417-427.
- Berkes M et al. Maintenance of hardware after early postoperative infection following fracture internal fixation. J Bone Joint Surg Am. 2010;92(4):823-828.
- Parra-Ruiz J et al. Macrolides and staphylococcal biofilms. Rev Esp Quimioter. 2012;25(1):10-16.
- Gristina AG et al. The glycocalyx, biofilm, microbes, and resistant infection. Semin Arthroplasty. 1994;5(4):160-170.