Is combinatory antibiotic therapy the answer to treating spinal implant infections?
New work suggests that it may not be as effective as previously thought.
- Study presents an new model for measuring the effectiveness of antibiotics for spinal implant patients
- Authors say that the combinatorial antibiotic treatment yielded positive results at the beginning but was unable to clear the infection completely.
- The study suggests that previous models for measuring the effectiveness of antibiotics could be misleading.
Biofilms forming on spinal implants is a devastating but not uncommon event post-surgery, however, there is currently no consensus on the way these biofilms should be treated. Previous work suggested that combining antibiotics such as vancomycin and rifampicin leads to complete removal of biofilms. In this study from UCLA, a team lead by Nicholas Bernthal present a new model that they believe is a more accurate representation of spinal implant surgery in order to test treatment strategies. Their results show that while combination therapy may reduce biofilm more quickly, it is not possible to completely eradicate it under the conditions that they tested. While this doesn't alleviate the treatment controversy, it does suggest that we need to be more careful when choosing treatments.
Combinatory antibiotic therapy increases rate of bacterial kill but not final outcome in a novel mouse model of Staphylococcus aureus spinal implant infection.
Management of spine implant infections (SII) are challenging. Explantation of infected spinal hardware can destabilize the spine, but retention can lead to cord compromise and biofilm formation, complicating management. While vancomycin monotherapy is commonly used, in vitro studies have shown reduced efficacy against biofilm compared to combination therapy with rifampin. Using an established in vivo mouse model of SII, we aim to evaluate whether combination therapy has increased efficacy compared to both vancomycin alone and infected controls.
An L-shaped, Kirschner-wire was transfixed into the L4 spinous process of 12-week-old C57BL/6 mice, and inoculated with bioluminescent Staphylococcus aureus. Mice were randomized into a vancomycin group, a combination group with vancomycin plus rifampin, or a control group receiving saline. Treatment began on post-operative day (POD) 7 and continued through POD 14. In vivo imaging was performed to monitor bioluminescence for 35 days. Colony-forming units (CFUs) were cultured on POD 35.
Bioluminescence peaked around POD 7 for all groups. The combination group had a 10-fold decrease in signal by POD 10. The vancomycin and control groups reached similar levels on POD 17 and 21, respectively. On POD 25 the combination group dropped below baseline, but rebounded to the same level as the other groups, demonstrating a biofilm-associated infection by POD 35. Quantification of CFUs on POD 35 confirmed an ongoing infection in all three groups.
Although both therapies were initially effective, they were not able to eliminate implant biofilm bacteria, resulting in a rebound infection after antibiotic cessation. This model shows, for the first time, why histologic-based, static assessments of antimicrobials can be misleading, and the importance of longitudinal tracking of infection. Future studies can use this model to test combinations of antibiotic therapies to see if they are more effective in eliminating biofilm prior to human trials.
Hu Y, Hegde V, Johansen D, Loftin AH, Dworsky E, et al. (2017) Combinatory antibiotic therapy increases rate of bacterial kill but not final outcome in a novel mouse model of Staphylococcus aureus spinal implant infection. PLOS ONE 12(2): e0173019. doi: 10.1371/journal.pone.0173019