Bacterial Biofilms Make Joint Infections Resistant to Antibiotics

MedicalResearch.com Interview with:
Sana Dastgheyb
National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Bethesda, MDDepartment of Orthopedic Surgery,
Thomas Jefferson University, Philadelphia, PA and

Dr. Noreen Hickok
Department of Orthopedic Surgery
Thomas Jefferson University, Philadelphia, PA

Medical Research: What are the main findings of the study?

Response: Physicians have long been resigned to the fact that staphylococcal joint infections are among the most challenging to treat. Our study points towards a definitive mechanism whereby bacteria become insensitive to antibiotics in the human joint environment. We added MRSA to synovial fluid and observed dense, biofilm-like aggregates, as well as a relative insensitivity to antibiotics as compared to ideal medium. Our findings suggest that serum/extracellular matrix proteins within synovial fluid contribute greatly to staphylococcal antibiotic insensitivity in synovial fluid. Furthermore, pre-treatment of synovial fluid with the enzyme plasmin, which degrades extracellular matrix proteins, significantly inhibits aggregate formation, and restores normal antibiotic sensitivity to MRSA.


Medical Research: What was most surprising about the results?

Response: We found that bacteria formed large aggregates in every sample of synovial fluid that we tested. These aggregates were so large that we could see them with the naked eye. Millions of bacteria in a single aggregate mean that not only are the innermost bacteria protected from antibiotics, but there is no way for immune cells to effectively engulf and kill the bacteria.

Medical Research: What should clinicians and patients take away from your report?

Response: The insidious nature of joint infections is made clear in this study. A joint infection may be biding its time, evading both antibiotics as well as the immune system. Even after antibiotic intervention, live bacteria may be buried in dense, matrix-coated aggregates in an ostensibly culture-negative joint.

Medical Research: What recommendations do you have for future research as a result of this study?

Response: Now that we know what is happening to bacteria in the joint and why they become so difficult-to-treat, the next step is to figure out a way to allow antibiotics to penetrate the large aggregates- or better yet, to block aggregate formation in the first place.

 

Citation:
Biofilms cause recalcitrance of staphylococcal joint infection to antibiotic treatment

Sana Dastgheyb, Javad Parvizi, Irving M. Shapiro, Noreen J. Hickok, and Michael Otto

Biofilms cause recalcitrance of staphylococcal joint infection to antibiotic treatment J Infect Dis. first published online September 11, 2014 doi:10.1093/infdis/jiu514