A study by Miller et al. in the February 20, 2019 issue of JBJS provides preclinical proof of concept that antibiotic-loaded coatings on orthopaedic implants could eventually reduce the incidence of implant-associated infection.
The researchers used in vivo bioluminescence imaging (BLI) and ex vivo analysis of colony-forming units (CFUs) to show the efficacy of an implant coating that released linezolid-rifampin over a 7-day period. Through a parapatellar arthrotomy, researchers reamed the femoral canal of 12 rabbits and inoculated the canals with a bioluminescent strain of MRSA. They then inserted a surgical grade titanium peg into each canal. All of the pegs were coated with a nanofiber coating; 6 of the pegs were loaded with the antibiotic coating and 6 were not.
Implants coated without antibiotics were associated with significantly increased in vivo BLI signals and significantly increased knee width, relative to implants with the antibiotic-releasing coatings. The animals were killed on day 7, and ex vivo analysis of CFUs isolated from soft tissue, bone, and implant specimens showed significantly increased CFUs in the specimens without the antibiotic-releasing coating, while CFUs were undetectable in the implants with antibiotics.
This larger-animal model to assess bacterial burden employed a clinically used orthopaedic implant and replicated a medial parapatellar arthrotomy in humans. According to the authors, the coating used is “highly versatile, and the polymers or drug concentrations could be modified for more rapid or longer release.” This rabbit model should be amenable to studying additional antibiotic-releasing strategies for possible translation to clinical research in humans.
When it comes to preventing infections associated with orthopaedic procedures, the question of which antibiotic to use is only one of several concerns. How and where to administer antibiotics is another relevant question, not only in terms of infection-fighting effectiveness but also in terms of combatting the proliferation of antibiotic-resistant microbes.
In the September 19, 2018 issue of The Journal of Bone & Joint Surgery, Sweet et al. report on findings from a study in rats that compared the infection-prevention efficacy of intravenous (IV) cefazolin (n = 20) and IV vancomycin (n = 20) with local application of 4 antimicrobials—vancomycin powder (n = 20), cefazolin powder (n = 20), tobramycin powder (n = 20), and dilute Betadine lavage (n = 20).
The researchers induced infection by surgically implanting a polytetrafluoroethylene vascular graft near each rat’s thoracic spine and inoculating it with methicillin-sensitive Staphylococcus aureus (MSSA). After 7 days, all of the rats in each of the IV cefazolin, IV vancomycin, and Betadine lavage groups had grossly positive cultures for MSSA, “with bacterial colonies too numerous to count.” Ninety percent of the rats in the local cefazolin-powder group also had positive cultures, but the infection rates with vancomycin and tobramycin powder were much lower than those with the other four approaches (p <0.000001).
In addition to the main “disclaimer” about this study (namely, that its findings cannot be extrapolated to clinical practice in humans), the authors caution that “the effect of locally applied antibiotics on the emergence of resistant organisms is unknown,” while citing evidence that systemic administration of antibiotics is “associated with the emergence of resistant organisms at an alarming rate.”
Sweet et al. say they plan to follow up this study with a similar model to investigate the efficacy of local antimicrobials against the more problematic methicillin-resistant Staphylococcus aureus (MRSA)—and they suggest further that “clinical studies should be considered to determine the relative clinical efficacy of local versus systemic antibiotics for surgical infection prophylaxis in humans.”
I may never go to the gym again!
In the January 2017 issue of JBJS Reviews, Mitchell et al. report on sport-related skin and soft tissue infections (SSTIs) as an ongoing problem across a diverse range of recreational, collegiate, and professional athletes. They note that these infections often occur during training for competitive sports or during the competition and that the majority are bacterial or fungal in origin. The review describes the mechanisms by which SSTIs occur in healthy athletes and the prevalence among players in various sports, including the effect of player position. The authors discuss the mechanisms by which SSTIs are spread and the hygiene measures that are recommended to prevent their spread. They extrapolate these lessons to the general population of so-called weekend warriors or fitness enthusiasts. This is what worries people like me, as studies have shown that these infections easily occur during regular visits to fitness centers and gymnasiums, which are sources of large quantities of bacteria that could cause SSTIs!
Studies have shown that billions of bacteria, fungi, and other microbes inhabit the skin and that the types of organisms vary between individuals and between different sites of the skin. In fact, they may vary in relation to each region of the body. Indeed, factors such as skin characteristics, sebaceous gland concentration, moisture content, temperature, and genetics as well as exogenous environmental factors can influence each so-called community of organisms. The authors hypothesize that sports in which participants have substantial skin-to-skin collisions might disrupt these ecosystems on the skin and allow microbes to be shared among players, noting that contact athletes have been shown to be potential carriers of methicillin-resistant Staphylococcus aureus (MRSA) more than twice as frequently as athletes who participate in noncontact sports. Other mechanisms by which SSTIs occur in healthy athletes include maceration of the skin due to sweating as well as strenuous training. Of particular interest is the observation that extended periods of intense exercise may temporarily depress certain aspects of the immune system, including natural killer cells, neutrophils, lymphocytes, immunoglobulin levels, and interleukin-2 levels and thus facilitate and promote infection and its potential host transfer.
The article goes on to explain how SSTIs are spread, the prevalence of SSTIs among players in various sports, the importance of personal and environmental hygiene, and specific forms of treatment of SSTIs in athletes.
When you do go to the gym or fitness center, just remember to clean off any equipment both before and after use and to change out of your workout clothes and shower as soon as possible after the workout. Be sure to cover benches with a towel, and if you practice yoga, bring your own mat.
I definitely will continue to use the gym but will pay more attention to the issues raised in this review.
Thomas A. Einhorn, MD
Editor, JBJS Reviews
Despite the relative rarity of necrotizing fasciitis (NF), orthopaedists can expect to see at least 1 case of NF in their career. This month’s “Case Connections” springboards from a recent case report about necrotizing fasciitis in which the infectious source was highly unusual, followed by three additional case reports related to NF from the JBJS Case Connector archives
- In the June 8, 2016, edition ofJBJS Case Connector, Connor et al. reported on the case of a 70-year-old man who developed necrotizing fasciitis of the thigh and calf through a colon perforation caused by sigmoid diverticulitis.
- Zani and Babigian described a case of NF in the shoulder of a 53-year-old woman following acromioplasty and open rotator cuff repair.
- The bacteriumAeromonas hydrophila caused NF in a 58-year-old non-immunocompromised man, as described in a case report by Borger van der Burg et al.
- Cheng et al. described 3 fatal cases of necrotizing fasciitis caused by methicillin-resistant Staphylococcus aureus(MRSA).
Time and teamwork are of the essence in the management of necrotizing fasciitis. To hasten diagnosis, clinicians are advised to submit blood and tissue samples for pathological analysis as soon as possible. A multidisciplinary team that includes an infectious-disease specialist should be assembled in cases of suspected NF.
Musculoskeletal (MSK) infections are highly prevalent and potentially serious, and orthopaedists are frequently faced with preventing and treating them. Wherever or however they are acquired, these pathogen-based conditions are among the most challenging to address effectively.
On Monday, May 23, 2016 at 8:00 pm EDT, The Journal of Bone & Joint Surgery will present a complimentary webinar that includes findings from two recent JBJS studies that explore how best to prevent deep infections in lower-grade open fractures, and the most effective antibiotics for treating community-acquired hand infections.
Richard Jenkinson, MD will discuss findings from a cohort study that compared deep infection rates in patients with lower-grade open fractures who were treated with either immediate wound closure or delayed wound closure. Rick Tosti, MD will examine resistance patterns of specific antibiotics to MRSA infections of the hand in an urban population.
Moderated by musculoskeletal-infection expert Jonathan Schoenecker, MD, PhD, the webinar will also feature commentaries on the studies by Lawrence Marsh, MD and Isaac Thomsen, MD.
Infections of the spine are particularly challenging to orthopaedists because they often present emergently, can be difficult to diagnose precisely, and can have catastrophic or fatal outcomes if not treated effectively.The September 23, 2015 “Case Connections” from JBJS Case Connector discusses five cases of rare but serious spinal infections.
The “Case Connections” springboards from a September 9, 2015 JBJS Case Connector case report by Rosinsky et al. that describes a sixty-five-year-old man who presented with fever and intractable lumbar pain that radiated to his right leg. In this case, a methicillin-susceptible Staphylococcus aureus (MSSA) infection had formed a large lobulated epidural abscess at L4-S1, with paraspinal muscle and intradural extension. One year after an L3-S1 laminectomy and two follow-up surgeries to treat hematomas and repair dural perforations, the patient was neurologically intact and walking independently.
The Rosinsky et al. case and the three other relevant “connections” from the JBJS Case Connector archive emphasize that prompt, definitive diagnosis and treatment of spinal infections–and enlisting the expertise of infectious-disease specialists–can lead to positive outcomes, while delay and clinical confusion can end catastrophically or fatally.
Surgical site infections (SSIs) can cancel out the benefits of surgery, and they’re the number-one cause of hospital readmissions following surgery. The most prevalent pathogenic culprit is Staphylococcus aureus.
A study of patients undergoing cardiac or hip or knee arthroplasty surgery at 20 hospitals in nine states found that the following protocol reduced the rate of complex (deep incisional or organ-space) S. aureus SSIs by about 40% overall—and by about 50% among patients undergoing hip or knee arthroplasty (an absolute difference of 17 infections per 10,000 joint replacements):
- Preoperative screening of nasal samples
- Intranasal mupirocin and chlorhexidine baths for up to five days prior to surgery for patients testing positive for methicillin-resistant S. aureus (MRSA) or methicillin-susceptible S. aureus (MSSA)
- Perioperative prophylaxis with vancomycin plus cefazolin or cefuroxime for MRSA carriers and perioperative cefazolin or cefuroxime for all others
Rates of complex SSIs decreased most substantially among patients who were fully adherent to the protocol, although only 39% of the subjects experienced implementation of all the steps. Adherence rates were especially low among those who presented in urgent and emergency settings.
In an editorial accompanying the study, Preeti Malani, MD wrote that “although the absolute difference [in infections] seems modest, each complex SSI prevented is clinically meaningful.”
The treatment of periprosthetic infection remains one of the most difficult and challenging problems in orthopaedic surgery. Conventional approaches such as the use of tissue and/or fluid cultures to identify and treat organisms are not nearly as successful as they need to be in order to address these conditions. The limitations of treatment, including the inaccessibility of microorganisms at the time of irrigation and debridement, the development of resistant strains of microorganisms, and the elaboration by microorganisms of protective biofilms, have led to unsuccessful outcomes in a large number of cases.
In this issue of JBJS Reviews, Chen and Parvizi provide an update on some of the new methods that may possibly advance this field. Molecular methods such as polymerase chain reaction to amplify bacteria can improve the likelihood of identifying the pathogen in a patient with a periprosthetic joint infection. Synovial markers such as C-reactive protein, leukocyte esterase, α-defensin, human β-defensin-2 (HBD-2) and HBD-3, and cathelicidin LL-37 are known to be elevated in patients with periprosthetic joint infection and may be used as markers for diagnosing infection at the time of operative management. Serum markers such as interleukin-4 (IL-4) and IL-6, and others such as soluble intracellular adhesion molecule-1 (sICAM-1) and procalcitonin (PCT), have been shown to be elevated in patients with periprosthetic joint infection.
Molecular detection methods probably have received the most attention and interest as an advancement that may improve our ability to diagnose periprosthetic infections. The limitations of these methods, however, include their high sensitivity and an increased rate of false-positive results. Methods to reduce the number of false-positive results are currently in development and include, among other things, the measurement of 16S ribosomal RNA in the belief that targeting RNA will result in amplification of only the genetic material of live bacteria. In addition, use of the mecA gene for identifying methicillin-resistant Staphylococcus aureus (MRSA) can reduce this rate.
Although this article does not provide definitive new approaches to the problem, the review of recent advances with the development of promising biomarkers and molecular techniques provides optimism that this field is evolving in a positive way.