rifampin and Femoral-Fractures

Pin tract infection is a frequent complication of external fixation; according to literature its frequency ranges from 2-30%. The recent introduction of silver coating of polymeric materials was found to decrease bacterial adhesion; its clinical use with Foley catheters and central venous catheters led to significant results. To verify the ability of the same silver coating to decrease the bacterial colonization on external fixation screws, a prospective randomized study was carried out on 24 male patients; a total of 106 screws were implanted in the lower limb to fix femoral or tibial diaphyseal fractures: 50 were coated with silver and 56 were commercially available stainless steel screws. Although the coated screws resulted in a lower rate of positive cultures (30.0%) than the uncoated screws (42.9%), this difference was not statistically significant (p = 0.243). The clinical behavior of the coated screws did not differ from that of the uncoated ones. Furthermore, the implant of silver-coated screws resulted in a significant increase in the silver serum level. These results led us to consider it ethically unacceptable to continue this investigation.

Topics: Adolescent; Adult; Antibiotic Prophylaxis; Bacillus; Bacteria; Bone Nails; Corynebacterium; Enterococcus faecalis; External Fixators; Femoral Fractures; Humans; Male; Middle Aged; Prosthesis Design; Rifampin; Silver; Staphylococcus; Surgical Wound Infection; Tibial Fractures

Fracture healing is impaired in the setting of infection, which begets protracted inflammation. The most problematic causative agent of musculoskeletal infection is methicillin-resistant Staphylococcus aureus (MRSA). We hypothesized that modulation of excessive inflammation combined with cell-penetrating antibiotic treatments facilitates fracture healing in a murine MRSA-infected femoral fracture model. Sterile and MRSA-contaminated open transverse femoral osteotomies were induced in 10-week-old male C57BL/6 mice and fixed via intramedullary nailing. In the initial therapeutic cohort, empty, vancomycin (V), rifampin (R), vancomycin-rifampin (VR), or vancomycin-rifampin-trametinib (VRT) hydrogels were applied to the fracture site intraoperatively. Rifampin was included because of its ability to penetrate eukaryotic cells to target intracellular bacteria. Unbiased screening demonstrated ERK activation was upregulated in the setting of MRSA infection. As such, the FDA-approved mitogen-activated protein kinase kinase (MEK)1-pERK1/2 inhibitor trametinib was evaluated as an adjunctive therapeutic agent to selectively mitigate excessive inflammation after infected fracture. Two additional cohorts were created mimicking immediate and delayed postoperative antibiotic administration. Systemic vancomycin or VR was administered for 2 weeks, followed by 2 weeks of VRT hydrogel or oral trametinib therapy. Hematologic, histological, and cytokine analyses were performed using serum and tissue isolates obtained at distinct postoperative intervals. Radiography and micro-computed tomography (μCT) were employed to assess fracture healing. Pro-inflammatory cytokine levels remained elevated in MRSA-infected mice with antibiotic treatment alone, but increasingly normalized with trametinib therapy. Impaired callus formation and malunion were consistently observed in the MRSA-infected groups and was partially salvaged with systemic antibiotic treatment alone. Mice that received VR alongside adjuvant MEK1-pERK1/2 inhibition displayed the greatest restoration of bone and osseous union. A combinatorial approach involving adjuvant cell-penetrating antibiotic treatments alongside mitigation of excessive inflammation enhanced healing of infected fractures. © 2022 American Society for Bone and Mineral Research (ASBMR).

Topics: Animals; Anti-Bacterial Agents; Cytokines; Femoral Fractures; Fracture Healing; Inflammation; Male; Methicillin-Resistant Staphylococcus aureus; Mice; Mice, Inbred C57BL; Rifampin; Staphylococcal Infections; Vancomycin; X-Ray Microtomography

Topics: Administration, Oral; Arteries; Arthralgia; Bacteremia; Brucella melitensis; Brucellosis; Child; Diagnosis, Differential; Doxycycline; Drug Therapy, Combination; Femoral Fractures; Fractures, Open; Gentamicins; Germany; Hip; Humans; Infusions, Intravenous; Knee; Male; Postoperative Complications; Refugees; Rifampin; Syria; Thigh; Ultrasonography; Veins

Topics: Cicatrix; Clarithromycin; Debridement; Diabetes Mellitus, Type 2; Disease Susceptibility; Femoral Fractures; Fracture Fixation, Internal; Fractures, Closed; Humans; Male; Middle Aged; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Osteomyelitis; Osteotomy; Ribotyping; Rifampin; Surgical Wound Infection; Vancomycin