Tag Archive | biofilm

Disrupting “Quorum Sensing” Could Help Fight Biofilms

Biofilm for OBuzzThis post comes from Fred Nelson, MD, an orthopaedic surgeon in the Department of Orthopedics at Henry Ford Hospital and a clinical associate professor at Wayne State Medical School. Some of Dr. Nelson’s tips go out weekly to more than 3,000 members of the Orthopaedic Research Society (ORS), and all are distributed to more than 30 orthopaedic residency programs. Those not sent to the ORS are periodically reposted in OrthoBuzz with the permission of Dr. Nelson. 

A biofilm is a complex combination of extracellular carbohydrates, proteins, lipids, and one or more species of bacteria that may adhere to an orthopaedic implant and surrounding tissue (see related OrthoBuzz post). Staphylococci bacteria are believed to account for more than 50% of all biofilm infections of medical devices.

Researchers recently summarized what we know about the biofilm formation process.1 In the attachment phase, free-floating bacteria attach to a prosthetic surface via proteins. Extracellular DNA from autolysis add to the mix. Then begins the irreversible attachment phase, during which the initial bacteria are incarcerated while more free-floating bacteria are added. During this phase, autoinducers are expressed, which serve as inter- and intrabacterial signals.

In the presence of an adequate quorum of bacteria, the maturation phase begins, during which the bacterial population cohesively shifts from replication to expression of virulence factors such as secretion systems, toxins, or biofilm formation. A mature biofilm is immune-resistant, although bacterial replication decreases. In the dispersal phase bacteria become planktonic again, potentially available to repeat the process.

Once a biofilm has formed, antibiotic administration becomes problematic because of the toxicity of the high doses needed to treat biofilm colonies. An underlying challenge with pharmacologic intervention is the variety of quorum-sensing communication pathways between bacterial species. The authors suggest that a future biofilm-fighting strategy may be to force bacteria into biofilm-forming behavior before they reach the necessary critical density to become virulent, although this notion remains unexplored. Researchers are investigating other possible strategies to disrupt the quorum-sensing communication among bacteria that enable them to behave as a “social” group.

Reference

  1. Mooney JA, Pridgen EM, Manasherob R, Suh G, Blackwell HE, Barron AE, Bollyky PL, Goodman SB, Amanatullah DF. Periprosthetic bacterial biofilm and quorum sensing. J Orthop Res. 2018 Sep;36(9):2331-2339. doi: 10.1002/jor.24019. Epub 2018 May 24.

What’s New in Musculoskeletal Basic Science 2017

Specialty Update Image for OBuzz

Every month, JBJS publishes a Specialty Update—a review of the most pertinent and impactful studies published in the orthopaedic literature during the previous year in 13 subspecialties. Click here for a collection of all OrthoBuzz Specialty Update summaries.

This month, Matthew J. Allen, VetMB, PhD, author of the December 6, 2017 Specialty Update on Musculoskeletal Basic Science, summarized the five most compelling findings from among the more than 60 noteworthy studies summarized in the article.

Cartilage Repair

–Deriving induced pluripotent stem cells (iPSCs) from peripheral blood cells1 rather than from dermal fibroblasts obviates the need for in vitro expansion. This method may also serve to boost interest in the use of commercial cell-based therapies with defined potency that are available off-the-shelf and don’t require separate cell-harvesting procedures.

–The FDA recommends that large-animal models be used to corroborate basic-science findings from small-animal models. Recent work has demonstrated the efficacy of insulin-like growth factor (IGF)-1 in supporting mechanically competent repair tissue following chondrocyte implantation in a pig model.2

Infection

–Infection, especially from organisms that have developed antimicrobial resistance and/or that produce biofilms, continues to pose a challenging problem for orthopaedic surgeons. To provide a more rational and stratified approach to managing these complex cases, Getzlaf et al. recommend the use of a multidisciplinary approach in which patient-specific information about individual microorganisms is combined with detailed understandings of the vulnerabilities of candidate bacterial species.3

Aseptic Loosening

–There is a resurgence of interest in the role of subclinical infection in the etiopathogenesis of aseptic loosening. At the same time, molecular diagnostic methods for microbial infection are moving forward.4 Such methods may serve to highlight the relevance of subclinical microbial contamination as a cause of aseptic loosening.

Cartilage Imaging

–While the goal of cartilage imaging is to develop tools that are fast, inexpensive, sensitive, accurate, and noninvasive, there is growing interest in the use of more direct, invasive techniques such as optical coherence tomography (OCT),5 which could be used in vivo at the time of surgery to analyze cartilage damage.

References

  1. Li Y, Liu T, Van Halm-Lutterodt N, Chen J, Su Q, Hai Y. Reprogramming of blood cells into induced pluripotent stem cells as a new cell source for cartilage repair. Stem Cell Res Ther.2016 Feb 17;7:31.
  2. Meppelink AM, Zhao X, Griffin DJ, Erali R, Gill TJ, Bonassar LJ, Redmond RW,Randolph MA. Hyaline articular matrix formed by dynamic self-regenerating cartilage and hydrogels. Tissue Eng Part A.2016 Jul;22(13-14):962-70. Epub 2016 Jul 7.
  3. Getzlaf MA, Lewallen EA, Kremers HM, Jones DL, Bonin CA, Dudakovic A,Thaler R, Cohen RC, Lewallen DG, van Wijnen AJ. Multi-disciplinary antimicrobial strategies for improving orthopaedic implants to prevent prosthetic joint infections in hip and knee. J Orthop Res.2016 Feb;34(2):177-86. Epub 2015 Dec 29.
  4. Palmer MP, Melton-Kreft R, Nistico L, Hiller NL, Kim LH, Altman GT, Altman DT, Sotereanos NG, Hu FZ, De Meo PJ, Ehrlich GD. Polymerase chain reaction-electrospray-time-of-flight mass spectrometry versus culture for bacterial detection in septic arthritis and osteoarthritis. Genet Test Mol Biomarkers.2016 Dec;20(12):721-31. Epub 2016 Oct 17.
  5. Novakofski KD, Pownder SL, Koff MF, Williams RM, Potter HG, Fortier LA. High-resolution methods for diagnosing cartilage damage in vivo. 2016 Jan;7(1):39-51.

What’s New in Musculoskeletal Infection: Update on Biofilms

Every month, JBJS publishes a Specialty Update—a review of the most pertinent and impactful studies published in the orthopaedic literature during the previous year in 13 subspecialties. Click here for a collection of all OrthoBuzz Specialty Update summaries.

This month, Arvind Nana, MD, co-author of the July 20, 2016 Specialty Update on musculoskeletal infection, selected the three most compelling discoveries from among the more than 100 studies cited in the Specialty Update, which focused on biofilms.

Dr. Nana and his co-authors provide a concise primer on the biology of biofilms, the network of microorganisms that adhere to implant surfaces and form a complex structure surrounded by a self-generated extracellular polymeric matrix. This matrix not only anchors bacteria to orthopaedic implants, but also provides a nearly impenetrable defense mechanism against the host immune system. Staphylococci are the most common biofilm-forming bacteria found in orthopaedics.

Persister Cells in Biofilms

So-called persister cells have an inherent tolerance to antimicrobial agents. Misconceptions about persisters have permeated the literature. The authors provide clarification about persisters:

  • Persister cells CAN be reliably killed when the antimicrobial concentration is high enough. The minimum biofilm eradication concentration (MBEC) is lower when antimicrobial exposure is continuous and prolonged.1
  • Decreasing the number of microorganisms with antimicrobial intervention is NOT good enough. Cure requires the total elimination of all viable microbes.

Biofilm in Orthopaedic Trauma

Biofilm formation in the setting of open fractures is concerning because biofilm can develop on bone and in soft tissues in a matter of hours. The assumption is that appropriate surgical techniques for open fractures, including therapeutic antibiotic administration, can decrease bioburden and provide fracture stability, thus modulating the acute, local inflammatory response and minimizing biofilm formation.2 However, current technology does not enable noninvasive quantification of biofilm activity and presence in a stable open fracture following wound closure.

Biofilm in Total Joint Arthroplasty

Traditionally, prosthesis-related biofilm infections in the US have been treated by a 2-stage exchange arthroplasty. Although biofilm from the implant is removed by extraction of the components, the potential exists for persistence of biofilm in the surrounding soft tissues. Most patients treated for periprosthetic joint infections also receive intravenous antibiotics, but a recent in vitro study demonstrated that administering cefazolin even at increased concentrations still resulted in persistent Staphylococcus biofilm on cobalt-chromium, polymethylmethacrylate, and polyethylene,3 which supports the need for explantation.

There is still room to develop novel treatment methods for eradicating biofilm in periprosthetic joint infections. Future novel treatment methods for eradicating implant biofilm will help minimize the morbidity associated with current accepted periprosthetic joint infection treatment options.

References

  1. Castaneda P, McLaren A, Tavaziva G, Overstreet D. Biofilm antimicrobial susceptibility increases with antimicrobial exposure time. Clin Orthop Relat Res. 2016 Jan 21.
  1. Pfeifer R, Darwiche S, Kohut L, Billiar TR, Pape HC. Cumulative effects of bone and soft tissue injury on systemic inflammation: a pilot study. Clin Orthop Relat Res. 2013 Sep;471(9):2815-21.
  2. Urish KL, DeMuth PW, Kwan BW, Craft DW, Ma D, Haider H, Tuan RS, Wood TK, Davis CM 3rd..Antibiotic-tolerant Staphylococcus aureus biofilm persists on arthroplasty materials. Clin Orthop Relat Res.2016 Feb 1.