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Shoulder Arthroplasty: Doxy + Cefazolin No Better than Cefazolin Alone Against P. Acnes

Doxycycline for OBuzzOrthoBuzz occasionally receives posts from guest bloggers. This guest post comes from Andrew D. Duckworth, MSc, FRCSEd(Tr&Orth), PhD, in response to a recent study in JBJS.

Propionibacterium acnes (now called Cutibacterium acnes, according to an updated classification) is a ubiquitous microbe in the setting of shoulder surgery and is a well-established cause of indolent infection and prosthetic loosening1,2.  In 2016, JBJS published a study by Hsu et al. investigating single-stage revision shoulder replacement in patients with subclinical infection, and the authors reported that almost half of the patients had >2 positive cultures for P. acnes3.  However, the exact consequence of positive cultures at the time of primary surgery is unknown, and the efficacy of specific antibiotic prophylaxis against this microbe remains unclear.

In the June 6, 2018 issue of JBJS, Rao et al. randomised 56 patients scheduled to undergo a primary anatomic or reverse total shoulder replacement to receive either preoperative cefazolin alone (n=27) or a combination of cefazolin and doxycycline (n=29) 4.  All patients had standard skin preparation at the time of surgery with both alcohol and chlorhexidine.

The primary outcome measure was ≥1positive culture after 14 days of incubation from either superficial and/or deep-tissue samples taken intraoperatively. The authors deemed that a decrease of 50% in the positive culture rate would be clinically significant. However, they found no significant difference between the groups in terms of the primary outcome measure (p=0.99).  The authors carried out a secondary analysis to determine which other factors might be associated with ≥1 positive P. acnes culture and found that younger age, male sex, and a lower Charlson Comorbidity Index were predictive.  Although this study was potentially underpowered, it demonstrated that in patients undergoing primary shoulder arthroplasty, preoperative doxycycline does not significantly reduce the prevalence of positive culture rates for P. acnes.

These findings are similar to those found in previous research and should lead us to question whether preoperative antibiotics aimed specifically at preventing P. acnes infection associated with shoulder arthroplasty are truly useful. P. acnes infections are difficult to detect both clinically and via culture—which makes any intervention difficult to measure, especially in a potentially underpowered study. Consequently, larger studies in this area would help to more definitively determine whether preoperative antibiotics aimed specifically at P. acnes decrease infection rates or, instead, may be adding to the growing problem of bacterial resistance. In particular, such trials seem most useful when they focus on patients who are at higher risk of these specific infections—in this case, younger, healthy males.

Finally, as Rao et al. wisely observed, doxycycline is a bacteriostatic agent, which slows the growth and production of bacteria, rather than a bactericidal agent, which kills bacteria.  Given that antimicrobial limitation, doxycycline might not be the most appropriate prophylactic drug to be investigating for these cases.

Andrew D. Duckworth, MScFRCSEd(Tr&Orth), PhD is a consultant orthopaedic trauma surgeon at Edinburgh Orthopaedic Trauma, Royal Infirmary of Edinburgh, and he is a member of the JBJS Social Media Advisory Board.

References

  1. Gausden EB, Villa J, Warner SJ, Redko M, Pearle A, Miller A, Henry M, Lorich DG, Helfet DL, Wellman DS. Nonunion After Clavicle Osteosynthesis: High Incidence of Propionibacterium acnes.  J Orthop Trauma. 2017 Apr;31(4):229-235.
  2. Chuang MJ, Jancosko JJ, Mendoza V, Nottage WM. The Incidence of Propionibacterium acnes in Shoulder Arthroscopy.  2015 Sep;31(9):1702-7.
  3. Hsu JE, Gorbaty JD, Whitney IJ, Matsen FA III. Single-Stage Revision Is Effective for Failed Shoulder Arthroplasty with Positive Cultures for Propionibacterium. J Bone Joint Surg 2016;98:2047-2051.
  4. Rao AJ, Chalmers PN, Cvetanovich GL, O’Brien MC, Newgren JM, Cole BJ, Verma NN, Nicholson GP, Romeo AA. Preoperative Doxycycline Does Not Reduce Propionibacterium acnes in Shoulder Arthroplasty.  J Bone Joint Surg Am. 2018 Jun 6;100(11):958-964.

Alpha Defensin Lateral Flow Test for Diagnosis of Periprosthetic Joint Infection: Not a Screening but a Confirmatory Test

Determination of alpha defensin in synovial fluid has shown promising results for diagnosing periprosthetic joint infection (PJI). https://bit.ly/2rH8JuN #JBJSInfographics #JBJS

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JBJS 100: Shoulder Impingement and Distraction Osteogenesis

JBJS 100Under one name or another, The Journal of Bone & Joint Surgery has published quality orthopaedic content spanning three centuries. In 1919, our publication was called the Journal of Orthopaedic Surgery, and the first volume of that journal was Volume 1 of what we know today as JBJS.

Thus, the 24 issues we turn out in 2018 will constitute our 100th volume. To help celebrate this milestone, throughout the year we will be spotlighting 100 of the most influential JBJS articles on OrthoBuzz, making the original content openly accessible for a limited time.

Unlike the scientific rigor of Journal content, the selection of this list was not entirely scientific. About half we picked from “JBJS Classics,” which were chosen previously by current and past JBJS Editors-in-Chief and Deputy Editors. We also selected JBJS articles that have been cited more than 1,000 times in other publications, according to Google Scholar search results. Finally, we considered “activity” on the Web of Science and The Journal’s websites.

We hope you enjoy and benefit from reading these groundbreaking articles from JBJS, as we mark our 100th volume. Here are two more:

Anterior Acromioplasty for Chronic Impingement Syndrome in the Shoulder
C S Neer: JBJS, 1972 January; 54 (1): 41
For many years after its publication, this 1972 JBJS article changed the treatment approach for patients with shoulder disability. But more recently, arthroscopy and magnetic resonance imaging arthrography have identified other painful non-impingement shoulder conditions. Consequently, the liberal use of acromioplasty to treat “impingement” is being replaced by a trend toward making an anatomic diagnosis, such as a partial or complete rotator cuff tear, and performing aggressive rehabilitation prior to corrective surgery.

Use of the Ilizarov Technique for Treatment of Non-union of the Tibia Associated with Infection
G K Dendrinos, S Kontos, E Lyritsis: JBJS, 1995 June; 77 (6): 835
This case series described a technique of bone transport with bridging achieved by distraction osteogenesis. The defects averaged 6 cm, the mean duration of treatment was 10 months, and the mean time to union was 6 months. More recent research has focused on augmenting the osteogenic potential of tissues in the distraction gap with substances such as bone morphogenetic protein, platelet-rich plasma, and mesenchymal stem cells.

Topical Vancomycin in Spine Surgery: Pediatric Patients Benefit Too

Vancomycin for OBuzzWhen >10% of patients undergoing procedures to correct a spinal deformity develop one or more surgical-site infections, investigations into how to mitigate such infections seem warranted. This is especially true when a single such infection can cost nearly $1 million to treat—not to mention the physical and psychological burdens.

In the March 21, 2018 edition of JBJS, Thompson et al. report important findings from a retrospective study that sought to evaluate the efficacy of adding topical vancomycin powder to the wounds of patients undergoing growing-spine surgeries to address early-onset scoliosis. The mean patient age at the beginning of the study was 7.1 years.

Cases in which topical vancomycin powder was placed into the wounds at the time of fascial closure (n = 104 cases) had a significantly lower surgical-site infection rate (4.8%), compared with the rate in the 87 cases in which no vancomycin was used (13.8%). Furthermore, the “number needed to treat” found in this study was 11, meaning that for every 11 cases in which vancomycin powder was used, a surgical-site infection was prevented.  The authors found no complications related to the use of topical vancomycin and note that their study provides the first evidence supporting the efficacy of vancomycin powder in pediatric spine patients.

Because this study was retrospective and based out of one center, further multicenter, prospective studies are needed to verify these results and to address open questions such as appropriate vancomycin dosages. Still, considering the extremely high costs (economic, physical, social, and psychological) associated with surgical-site infections in these complex patients, it appears that a vial of vancomycin powder costing between $10 and $40 may deliver outstanding value in these scenarios.

Chad A. Krueger, MD
JBJS Deputy editor for Social Media

JBJS 100: Infection Prevention and Hip Replacement Rates

JBJS 100Under one name or another, The Journal of Bone & Joint Surgery has published quality orthopaedic content spanning three centuries. In 1919, our publication was called the Journal of Orthopaedic Surgery, and the first volume of that journal was Volume 1 of what we know today as JBJS.

Thus, the 24 issues we turn out in 2018 will constitute our 100th volume. To help celebrate this milestone, throughout the year we will be spotlighting 100 of the most influential JBJS articles on OrthoBuzz, making the original content openly accessible for a limited time.

Unlike the scientific rigor of Journal content, the selection of this list was not entirely scientific. About half we picked from “JBJS Classics,” which were chosen previously by current and past JBJS Editors-in-Chief and Deputy Editors. We also selected JBJS articles that have been cited more than 1,000 times in other publications, according to Google Scholar search results. Finally, we considered “activity” on the Web of Science and The Journal’s websites.

We hope you enjoy and benefit from reading these groundbreaking articles from JBJS, as we mark our 100th volume. Here are two more:

Prevention of Infection in Treatment of 1,025 Open Fractures of Long Bones
R B Gustilo and J T Anderson: JBJS, 1976 June; 58 (4): 453
While “best practices” for managing open long-bone fractures have changed since this landmark study was published, the Gustilo-Anderson classification still correlates well with the risk of infection in patients with comorbid medical illnesses and other complications. It remains widely accepted for research and training purposes, and it provides commonly used basic language for communicating about open fractures.

Rates and Outcomes of Primary and Revision Total Hip Replacement in the US Medicare Population
N N Mahomed, J A Barrett, J N Katz, C B Phillips, E Losina, R A Lew, E Guadagnoli, W H Harris, R Poss, J A Baron: JBJS, 2003 January; 85 (1): 27
Analyzing Medicare claims data between July 1, 1995 and June 30, 1996, the authors of this prognostic study claimed it was “the first population-based study of the rates of revision total hip replacement and its short-term outcomes.” In the last 10 years alone, more than 5,000 studies on revision THA have been published in PubMed-indexed journals, including this 2012 JBJS study, which examined THA revision risk in the same Medicare cohort over 12 years.

Latest JBJS Infographic

Next-generation sequencing is a well-established technique for sequencing of DNA and has recently gained attention in many fields of medicine.

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Rapid Alpha Defensin Test Helpful for Diagnosing PJI

Synovasure for OBuzzQuick and accurate: that’s what orthopaedic surgeons want in diagnostic tools to help them determine whether patients presenting with pain after total joint arthroplasty have an infection. A prospective Level I study by Gehrke et al. in the January 3, 2018 issue of The Journal of Bone & Joint Surgery determined that a new lateral flow version of the Synovasure Alpha Defensin Test meets those requirements.

Alpha defensin is a protein secreted by neutrophils in response to bacterial infection, prior to the development of specific immune responses. Earlier research established alpha defensin in synovial aspirates to be an excellent biomarker for periprosthetic joint infection (PJI). The original ELISA-based alpha defensin test is usually sent out for 24-hour processing, limiting its intraoperative utility. However, the lateral flow version of the test (akin to an over-the-counter pregnancy test) was approved for use in Europe—and its results are available in 10 to 15 minutes.

Gehrke et al. compared the rapid test’s results to the diagnostic criteria promulgated by the Musculoskeletal Infection Society (MSIS). According to MSIS criteria, there were 76 joints with PJI among 191 study subjects on whom 195 joint aspirations were performed. Using that as the benchmark for diagnosis, the authors analyzed results from the rapid alpha defensin tests and found the following performance:

  • 92.1% sensitivity
  • 100% specificity
  • 100% positive predictive value
  • 95.2% negative predictive value
  • 96.9% overall accuracy

Although the rapid test does not provide information about the identity of specific pathogens, the authors conclude that it “enables surgeons to start proper therapy without delay.” That ability comes at a price, however. In Germany, where this study was performed, each rapid test costs about 400 Euros, which is nearly $500 US.

In a commentary on the study, Garth Ehrlich and Michael Palmer cite another possible cost with the rapid-test scenario. Prior to using any alpha defensin test, physicians must rule out metallosis with MRI, because that non-infectious entity triggers false-positive results.

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.

Modern Irrigation/Debridement Yields Good Results for Early Post-THA Infection

Hip Debridement for OBuzzNowadays, chronic deep periprosthetic joint infections (PJIs) are typically treated with 2-stage exchange arthroplasty, but what about acute PJIs? In the December 6, 2017 edition of JBJS, Bryan et al. report on a retrospective cohort study of acute infections after hip arthroplasty. The results suggest we’ve come a long way in identifying patients with early infections and that contemporary irrigation-and-debridement protocols are more successful than older methods.

The researchers studied 6-year outcomes in 90 hips that had undergone either total or hemiarthroplasty and that were determined to have either acute early postoperative infections (n=66) or acute hematogenous infections (n=24). All the infected hips were managed with either irrigation, debridement, and modular head and liner exchange (70%) or with irrigation and debridement alone (30%). The authors stratified the patients into those without comorbidities (A), those with 1 or 2 comorbidities (B), and those with >2 comorbidities (C). Postoperatively, patients were treated with broad-spectrum intravenous antibiotics, followed by targeted therapy administered by infectious disease specialists.

Of the 90 acute infections, failure—defined as uneradicated infection, subsequent removal of any component for infection, unplanned second wound debridement for ongoing infection, or infection-related mortality—occurred in 15 hips (17%). Of those 15, 9 required component removal. The chances of treatment failure were slightly higher in cases of hematogenous infection (21%), compared with acute early postoperative infection (15%), but that difference was not statistically significant. Significant comorbidity-related failure-rate differences were found: failure occurred in 8% of the grade-A patients, 16% of grade-B patients, and 44% of grade-C patients. The most common infecting organism was methicillin-sensitive Staphylococcus aureus (MSSA).

From this overall 6-year success rate of 83%, the authors conclude that “with modern inclusion criteria for acute infection, modern surgical techniques, and modern antibiotic therapy…the rate of success was higher than in most historic reports.”

Fructosamine Bests HbA1c for Preop Glycemic Screening

Fructosamine for OBuzzPatients with diabetes have an increased risk of postoperative complications following total joint arthroplasty (TJA). Additionally, perioperative hyperglycemia has been identified as a common and independent risk factor for periprosthetic joint infection, even among patients without diabetes. Therefore, knowing a patient’s glycemic status prior to surgery is very helpful.

In the November 15, 2017 edition of The Journal of Bone & Joint Surgery, Shohat et al. demonstrate that serum fructosamine, a measure of glycemic control obtainable via a simple and inexpensive blood test, is a good predictor of adverse outcomes among TJA patients—whether or not they have diabetes.

Researchers screened 829 patients undergoing TJA for serum fructosamine and HbA1c—a common measure, levels of which <7% are typically considered good glycemic control. Patients with fructosamine levels ≥292 µmol/L had a significantly higher risk of postoperative deep infection, readmission, and reoperation, while HbA1c levels ≥7% showed no significant correlations with any of those three adverse outcomes. Among the 51 patients who had fructosamine levels ≥292 µmol/L, 39% did not have HbA1c levels ≥7%, and 35% did not have diabetes.

In addition to being more predictive of postsurgical complications than HbA1c, fructosamine is also a more practical measurement. A high HbA1c level during preop screening could mean postponing surgery for 2 to 3 months, while the patient waits to see whether HbA1c levels come down. Fructosamine levels, on the other hand, change within 14 to 21 days, so patients could be reassessed for glycemic control after only 2 or 3 weeks.

While conceding that the ≥292 µmol/L threshold for fructosamine suggested in this study should not be etched in stone, the authors conclude that “fructosamine could serve as the screening marker of choice” for presurgical glycemic assessment. However, because the study did not examine whether correcting fructosamine levels leads to reduced postoperative complications, a prospective clinical trial to answer that question is needed.