A new study by Yale researchers led by Francis Y. Lee, MD, PhD, the Wayne O. Southwick Professor, shows that earlier local delivery of cell- and biofilm penetrating antibiotics can reduce the spread of methicillin-resistant Staphylococcus aureus, better known as MRSA, into bone tissues.
The study, published in the February 2020 issue of Bone & Joint Research, showed that the combined use of rifampicin and other antibiotics were most effective when applied prior to treating injuries such as open fractures which frequently require debridement. The current operative care standards call for removing foreign objects from the body following a traumatic injury first, and administering antibiotics within six hours of injury. The new research shows that antibiotics should be administered within a short timeframe because bacteria can penetrate into cells as early as 15-30 minutes following infection.
“Characterizing the ability of bacteria to penetrate bone cells is critical to developing effective preventive and therapeutic strategies that maximize antimicrobial efficacy against both extracellular and intracellular musculoskeletal infection,” researchers wrote.
Lee said that the findings could help surgeons adjust their treatment protocols ahead of surgery. Lee, an orthopaedic surgeon with expertise in musculoskeletal tumors and complex reconstructive surgeries, said that the ability of bacteria to evade “antimicrobial treatments suggest that conventional methods of infection prevention and management for bone infections may be need revised to target bacteria that start to hide in host tissues and cells.” That, he added, could lead to improved outcomes.
Staphylococcus aureus, the bacteria commonly known for staph infections, is the leading cause of chronic osteomyelitis, an infection of bone and bone marrow. Once the bacteria infiltrates cells like osteoblasts, which grow bone tissue, the infection becomes more difficult to treat and is able to persist and spread for an extended period of time, researchers wrote. The osteoblasts release the infection even as they release materials needed to stimulate further bone growth.
Using tissue similar to humans but found in mice, the researchers found that the combined use of rifampicin and other antibiotics amplified the cells ability to protect against MRSA-induced toxicity, or the spread of the bacteria to other cells. Gentamicin-containing compounds were found most effective in reducing intracellular MRSA bioburden, they wrote.
The research team included Lee, third-year medical student Kristin Yu, and researchers Jungho Back, Hyuk-Kwon Kwon, Hyunwoo Paco Kang, and Lee Song.
Dr. Lee’s research programs is funded by the National Institutes of Health and National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). Dr. Lee currently serves as Chair of the NIH Skeletal Biology Structure Regeneration (SBSR) Study Section, Musculoskeletal Tumor Society Research Committee Chair, American Academy of Orthopaedic Surgeons Research Development Committee Chair, and Orthopaedic Research and Education Grant Committee.