Testing Lysostaphin for Post-Surgical Staph Infections

The Challenge of Delivery

Surgeons are exploring the antimicrobial enzyme Lysostaphin as a potential solution for post-surgical Staphylococcus infections associated with orthopedic implants. While Lysostaphin has shown promise in combating Staph infections within hospital settings, its application in treating surgical implants presents significant challenges, primarily concerning effective delivery to the target area.

Potential Solution: Hydrogels

Researchers suggest that hydrogels might be the key to overcoming these delivery challenges. A recent article published in the Proceedings of the National Academy of Sciences (PNAS) by a team of bioengineers from Georgia Tech outlines a novel method for preventing post-surgical infections in orthopedic implant surgeries. This approach not only aims to eliminate infections but also promotes healing.

Understanding Orthopedic Implant Infections

Prevalence and Causes

Orthopedic implant infections pose a significant clinical issue, with over 11,200 cases reported annually in the United States. Approximately 66% of these infections are linked to Staphylococcus bacteria. Infections can arise through several pathways: direct contamination of the implant, transmission from nearby infected areas, or through bacteria in the bloodstream that colonize the implant.

Limitations of Current Therapies

Current treatment options are restricted mainly to surgical removal of infected or damaged tissue or the use of systemic antibiotics, which can have various adverse effects. Systemic antibiotics carry the risk of developing antibiotic resistance and can disrupt gut microbiota, leading to opportunistic infections.

Innovative Hydrogel Design

Research Findings

In a groundbreaking study, researchers developed a polyethylene glycol (PEG)-based hydrogel that adheres to the exposed tissue and fracture surface, delivering Lysostaphin directly to infected implants in mouse models of femoral fractures. This hydrogel offers dual benefits: it releases Lysostaphin in response to local cell-based enzymes and biodegrades during tissue repair, eliminating the need for surgical removal.

Effectiveness of the Hydrogel

The study employed multiple experimental methods to assess the activity, stability, and release of Lysostaphin from the hydrogel. Results indicated that the hydrogel maintained Lysostaphin activity for over two weeks. Additionally, the injectable hydrogel demonstrated superior efficacy in eliminating bacteria from infected implants and fractures compared to prophylactic antibiotic treatments. It also facilitated fracture healing and restored a sterile inflammatory environment in the mouse models.

Implications for Future Research

The findings suggest that Lysostaphin-delivering hydrogels could be a viable solution for preventing and treating implant infections. This research raises intriguing possibilities for addressing recurrent infections in total joint arthroplasties and fracture fixation devices.

References

(1) Johnson CT, Wroe JA, Agarwal R, Martin KE, Guldberg RE, Donlan RM, Westblade LF, García AJ. Hydrogel delivery of lysostaphin eliminates orthopedic implant infection by Staphylococcus aureus and supports fracture healing. Proc Natl Acad Sci U S A. 2018; 115(22).
(2) Ankur Singh. Bactericide hydrogel prevents orthopedic implant infections. Science Translational Medicine. 2018; 10.