Topical rifampin powder for orthopaedic trauma part II: Topical rifampin allows for spontaneous bone healing in sterile and contaminated wounds

Abstract

Infectious complications can reduce fracture healing rate. Broad spectrum antibiotics are commonly administered to prevent and treat musculoskeletal infections. Local antibiotics are applied to the wound site to increase therapeutic concentrations without increasing systemic toxicity, however, may hinder local tissue recovery. Rifampin has been shown to eradicate mature Staphylococcal biofilms and its use proven for treating musculoskeletal infections. In this study, a spontaneously healing defect model in a rat was used to investigate the impact rifampin powder has on endogenous bone healing in both a sterile and contaminated wound. No significant differences were identified in bone volume fraction via microcomputed tomography, radiological scoring, or histology between an empty defect and animals that received vancomycin or rifampin powder in a sterile wound. When applied to a contaminated musculoskeletal wound, the rifampin powder had significantly greater bone formation compared to the control, as measured by microcomputed tomography, plain radiology, and histology. In addition, the animals treated with rifampin powder had reduced bacteria, reduced white blood cell count and reduced number of clinical indications of infection. Interestingly, while the vancomycin group still displayed signs of infection via quantitative microbiology, plain radiology, and histology, there was significant bone formation within the defect and reduction of systemic signs of infection. We demonstrated that the use of rifampin powder allows bone to heal in both a sterile and contaminated model of musculoskeletal infection. To our knowledge, this is the first time the direct impact of local antibiotics on bone healing has been investigated. Published 2018. This article is a U.S. Government work and is in the public domain in the USA. J Orthop Res 36:3142-3150, 2018.

Rifampin‐Releasing Triple‐Layer Cross‐Linked Fresh Water Fish Collagen Sponges as Wound Dressings

“…The histological studies showed that the edges of both types of sponges were settled by cells that migrated from the surrounding tissues and that the healing process was initiated as soon as after just 5 days (Figures 13 and 14 ). This is also in agreement with previously conducted studies involving bone healing rat models in which neither rifampin nor vancomycin powder added to a bone fracture proved any signs of healing impairment [ 29 ].…”

Topical rifampicin for prevention of deep sternal wound infections in patients undergoing coronary artery bypass grafting

“…Other relevant features include: unexpensiveness and easiness of preparation and and handling. It has also been consistently shown to decrease wound infection in other surgical settings 4,7,22 . The present study is the first large scale trial to evaluate its preventive potential.…”

“…Vancomycin has minimal eradication effect on this respect. In vitro and in vivo studies have shown that Rifampicin is an effective Staphylococcal biofilm eradicator with no adverse effects on bone healing 7 . Rifampicin's mechanism of action is independent of cellular replication since its target is bacterial protein synthesis.…”

“…Indeed, despite adequate perioperative antibiotic prophylaxis there might be still an insufficient coverage of common pathogens because diabetes and atherosclerosis impair tissue perfusion. The main advantages of topical antibiotic administration include the high drug concentration and long duration of exposure combined with reduced systemic exposure and, thus, fewer adverse effects [4][5][6][7] . On these premises, the present study aimed to determine whether the introduction of topical rifampicin administration might lower the incidence of DSWI.…”

Calcium Phosphate Spacers for the Local Delivery of Sitafloxacin and Rifampin to Treat Orthopedic Infections: Efficacy and Proof of Concept in a Mouse Model of Single-Stage Revision of Device-Associated Osteomyelitis

“…Interestingly, this is consistent with previous reports. Shiels et al [77] demonstrated that the direct addition of rifampin powder to a contaminated wound led to greater callus formation when compared to untreated wounds, while vancomycin powder elicited no effect. Insignificant bone formation of CaPS containing sitafloxacin also supports studies reporting negative effects of fluoroquinolones on fracture healing [78,79].…”