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Accuracy of Rapid Alpha Defensin Test Confirmed

In June 2019, OrthoBuzz reported on the FDA approval of a rapid, lateral-flow alpha defensin test that helps detect periprosthetic joint infections (PJIs) from synovial fluid. In the January 20, 2021 issue of The Journal of Bone & Joint Surgery, Deirmengian et al. report findings from the Level II diagnostic-accuracy study that led to this FDA approval.

The authors compared diagnostic sensitivity and specificity of the lateral-flow alpha defensin test with the “gold-standard” PJI diagnostic criteria endorsed by the Musculoskeletal Infection Society (MSIS) in 2013. They made the comparison with 2 groups: a prospective patient cohort of 305 patients with a failed hip or knee arthroplasty (57 of whom were determined by MSIS criteria to have a PJI) and among a “control” cohort of 462 synovial fluid samples (65 of which met MSIS criteria for PJI).

After excluding 17 patients from the prospective cohort who had grossly bloody aspirates, the authors found a sensitivity of 94.3% and a specificity of 94.5% for the lateral-flow test in that group. Among the control cohort, the lateral-flow test’s sensitivity was 98.5% and its specificity was 98.2%. Furthermore, after combining data from the 2 cohorts, Deirmengian et al. found no performance difference between the lateral-flow test (which yields results in 10 to 15 minutes) and the lab-based alpha defensin ELISA test (which typically yields results in 24 hours). Finally, in a nonstatistical descriptive comparison between the 2 alpha defensin tests and 4 other individual lab tests used in the MISI criteria to diagnose PJI (such as synovial fluid white blood cell count and erythrocyte sedimentation rate), the authors concluded that “alpha defensin tests led to the highest raw number of correct diagnoses (accuracy).”

The 2018 International Consensus Meeting on Orthopaedic Infections included alpha defensin as a minor criterion. That decision, along with these findings and the FDA approval of the lateral-flow test, should lead to increased adoption of the rapid test—and to more data being published on its clinical utility.

What’s New in Adult Reconstructive Knee Surgery 2021

Every month, JBJS publishes 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 such OrthoBuzz specialty-update summaries.

This month, author Michael J. Taunton, MD summarizes the 5 most compelling findings from the 130 studies highlighted in the January 20, 2021 “What’s New in Adult Reconstructive Knee Surgery.”

Waiting for a Knee Replacement
–Patient wait times for joint arthroplasty, exacerbated in many places by the COVID-19 pandemic, continue to increase. As measured by the EQ-5D, the health among 12% of 2,168 patients awaiting total knee arthroplasty (TKA) in a recent cross-sectional analysis was rated as “worse than death.”1 Joint-specific function and various comorbidities were associated with these findings.

UKA vs TKA
–The multicenter randomized TOPKAT trial2 compared unicompartmental knee arthroplasty (UKA) with TKA for treating medial compartment osteoarthritis. At the 5-year follow-up, there was no between-group difference in Oxford knee scores, but UKA was more cost-effective and provided an additional 0.24 quality-adjusted life year.

Perioperative Patient Optimization
–An observational study analyzing >1,000 total joint arthroplasties3 found that implementing a “perioperative orthopaedic surgical home”—a surgeon-led screening and optimization initiative targeting 8 common modifiable comorbidities—resulted in a 1.6% 30-day readmission rate (versus 5.3% among patients not involved in the initiative).

Pain Management and Opioids
–A randomized controlled trial of >300 patients undergoing primary total knee or hip arthroplasty4 demonstrated that reducing the number of 5-mg oxycodone pills prescribed at discharge from 90 to 30 resulted in the following findings 30 days postoperatively:

  • Similar between-group pain scores
  • No between-group differences in patient-reported outcomes
  • Significant reductions in unused opioid pills and in pain pills taken in the 30-pill group

Periprosthetic Joint Infection
–Patients undergoing primary TKA who had a history of periprosthetic joint infection (PJI) in another joint had a significantly higher risk of PJI after the primary TKA, compared with the risk among a matched cohort with no history of PJI.5

References

  1. Scott CEH, MacDonald DJ, Howie CR. ‘Worse than death’ and waiting for a joint arthroplasty. Bone Joint J.2019 Aug;101-B(8):941-50.
  2. Beard DJ, Davies LJ, Cook JA, MacLennan G, Price A, Kent S, Hudson J, Carr A, Leal J, Campbell H, Fitzpatrick R, Arden N, Murray D, Campbell MK; TOPKAT Study Group. The clinical and cost-effectiveness of total versus partial knee replacement in patients with medial compartment osteoarthritis (TOPKAT): 5-year outcomes of a randomised controlled trial. 2019 Aug 31;394(10200):746-56. Epub 2019 Jul 17.
  3. Kim KY, Anoushiravani AA, Chen KK, Li R, Bosco JA, Slover JD, Iorio R. Perioperative orthopedic surgical home: optimizing total joint arthroplasty candidates and preventing readmission. J Arthroplasty.2019 Jul;34(7S):S91-6. Epub 2019 Jan 18.
  4. Hannon CP, Calkins TE, Li J, Culvern C, Darrith B, Nam D, Gerlinger TL, Buvanendran A, Della Valle CJ. The James A. Rand Young Investigator’s Award: large opioid prescriptions are unnecessary after total joint arthroplasty: a randomized controlled trial. J Arthroplasty.2019 Jul;34(7S):S4-10. Epub 2019 Feb 4.
  5. Chalmers BP, Weston JT, Osmon DR, Hanssen AD, Berry DJ, Abdel MP. Prior hip or knee prosthetic joint infection in another joint increases risk three-fold of prosthetic joint infection after primary total knee arthroplasty: a matched control study. Bone Joint J.2019 Jul;101-B(7_Supple_C):91-7.

When Does I&D Beat 2-Stage Exchange in Second rTKA?

It’s hard to contemplate “conservative treatment” in the case of a revised total knee arthroplasty (rTKA) with extensive instrumentation that needs a reoperation due to periprosthetic joint infection (PJI), because all the treatment options in that scenario are pretty complex. In the January 6, 2021 issue of JBJS, Barry et al. report on a retrospective review of 87 revisions of extensively instrumented rTKAs that found that irrigation and debridement (I&D) with chronic antibiotic suppression was as effective as 2-stage exchange in preventing another reoperation for infection—and more effective in terms of maintaining knee function.

The average follow-up of the cases studied was 3.2 years, and the authors carefully defined “extensive instrumentation.” Among the 56 patients who were managed with I&D and suppression and the 31 who were managed with the initiation of 2-stage exchange (average age in both groups approximately 67 years), no significant differences were found in the rates of reoperation for infection or mortality. However, 9 of the 31 patients (29%) in the 2-stage group never underwent the second-stage reimplantation. Among those 9, 3 died prior to reimplantation and 2 underwent amputation due to failure of infection control.

Moreover, at the time of the latest follow-up, a significantly higher percentage of patients in the I&D group were ambulatory (76.8% vs 54.8% in the 2-stage group) and were able to functionally bend their knee (85.7% vs 45.2% in the 2-stage group). The authors surmise that these 2 findings are related to the soft-tissue damage and bone loss that typically occur during stage-1 removal of rTKA components.

Barry et al. conclude that in similar situations “deviating from the so-called gold standard of 2-stage exchange and accepting the modest results of I&D may be in the best interest of the patient,” as long as there are no loose implants in the existing construct. But the “sobering” mortality rates in the study (39.3% in the I&D group and 38.7% in the 2-stage group) remind us that this clinical scenario is extremely challenging for patients and surgeons, no matter which option is selected.

Click here to view an “Author Insights” video about this study with co-author Jeffrey Barry, MD.

Antibiotic-Laden Cement Lowers TKA-Revision Rates in US Veterans

We recently celebrated Veteran’s Day with the annual tradition of rightfully honoring the men and women who have served in the Armed Forces. After their active duty ends, servicemembers are eligible for care in Veterans Health Administration (VHA) hospitals around the nation. The VHA is a “closed” medical system that affords ample opportunity for population-based research.

In the November 18, 2020 issue of The Journal, Bendich et al. utilized VHA data to compare revision rates after primary total knee arthroplasty (TKA) among veterans treated with antibiotic-laden bone cement (ALBC) or plain cement. Although results of similarly designed studies focused on this question have been equivocal, antibiotic-laden cement seems to be especially effective at preventing infection in higher-risk populations, which is what the US veteran population is considered to be.

The researchers identified 15,972 primary TKAs that were implanted using Palacos bone cement between 2007 and 2015. Approximately 70% (11,231) of those cases used cement mixed with gentamicin, while 30% (4,741) utilized plain bone cement. The authors found similar patient demographics among patients treated with ALBC and those treated with plain cement, but ALBC was used more frequently in patients with higher comorbidity scores.

Overall, utilization of ALBC increased from 50.6% of the cases in 2007 to 69.4% in 2015. At a follow-up of 5 years, ALBC TKAs had a lower all-cause revision rate (5.3%) than plain-cement TKAs (6.7%) and a lower rate of revision for infection (1.9% compared to 2.6%). Even after multivariable adjustments to account for patient, surgical, and hospital factors, these revision-rate differences remained.

Bendich et al. also found that 71 TKAs needed to be implanted with ALBC to avoid 1 revision TKA. With a cost differential of $240 per case for ALBC, I think spending $17,040 ($240 × 71) is more cost-effective than 1 revision TKA, although a formal cost analysis is warranted.

In the interest of full disclosure, as an active-duty US Air Force officer, I am inherently biased, but I feel that no cost is too great to improve the health of our veterans. The authors review arguments against using ALBC, such as a theoretical risk of poor cement mechanical properties and systemic toxicity, but the findings of this study suggest that cement with antibiotics enhances treatment outcomes among these US heroes.

Click here to view the “Author Insight” interview about this study with co-author Alfred Kuo, MD, PhD.

Matthew R. Schmitz, MD
JBJS Deputy Editor for Social Media

Balancing Antibiotic Perfusion and Tourniquet Usage

Antibiotics are an integral part of infection prophylaxis in orthopaedic surgery, and tourniquets are widely used during many of those same surgeries. The timing of antibiotic administration in relation to tourniquet use has long been debated. Hanberg et al. explore this “balancing act” in the November 4, 2020 issue of The Journal in a carefully performed animal study.

The researchers anesthetized 24 female pigs and surgically exposed both of their hind calcanei. They then placed microdialysis catheters through drill holes in each calcaneus and also into the subcutaneous adipose tissue in the hind feet. Tourniquets were applied to one hind leg on each animal, and each pig was then randomized into 1 of 3 groups, based on when the animal received 1.5 gm of cefuroxime intravenously:

  • Group A –15 minutes prior to tourniquet inflation
  • Group B – 45 minutes prior to tourniquet inflation
  • Group C – At the time of tourniquet release

Hanberg et al. inflated the tourniquets for 90 minutes in all 3 groups, and then they measured the concentrations of cefuroxime and ischemic markers at regular intervals between the time of tourniquet inflation and up to 480 minutes afterward.

The authors found that in both Groups A and B, cefuroxime concentrations were maintained above the minimum inhibitory concentration (MIC) for Staphylococcus aureus in cancellous bone and adipose tissue throughout the 90 minutes of tourniquet inflation. In addition, injecting cefuroxime at the time of tourniquet deflation (Group C) kept the tissue-antibiotic levels above the MIC on the tourniquet side for 3.5 hours after tourniquet release.

There were no differences in the time above MIC in bone or adipose tissue between the 3 groups, but the researchers noted a trend toward shorter time above MIC in bone in Group A vs. Group C (p=0.08). There was also a tendency toward higher time above MIC in bone on the tourniquet side compared to no-tourniquet side in Group B (p=0.08) and Group C (p=0.06). The researchers also found that, in all the animals, tissue ischemia persisted for 2.5 hours after tourniquet deflation in bone, while the adipose tissue recovered immediately.

This animal study provides useful data and prompts us to ponder ideas for further investigation regarding the interplay between tourniquets and antibiotic perfusion. For example, I think the prolonged ischemia in cancellous bone is a topic that warrants further investigation, and I am also curious whether adding antibiotics at the time of tourniquet release might help combat the potentially negative effects of that ischemia.

Matthew R. Schmitz, MD
JBJS Deputy Editor for Social Media

Detecting Pathogens in Pediatric Infections: Swab, Tissue, or Bottle?

Identifying the pathogenic microorganism in childhood osteomyelitis and septic arthritis is essential to tailoring appropriate treatment. But the traditional methods of swab and tissue culturing have subpar success rates in pediatric patients, identifying the pathogen in only 40% to 60% of cases. In the October 21, 2020 edition of The Journal, Shin et al. report their findings comparing microbial identification rates using pediatric blood culture bottles (BCBs), typical culture swabs, and tissue specimens.

Over 3 years, the authors prospectively collected intraoperative specimens from 40 pediatric patients (mean age of 7.2 years) who underwent surgery for a presumed osteoarticular infection. Half of the patients had received oral or intravenous antibiotics in the 3 weeks prior to surgery, while the other half had received intravenous cefazolin after culture specimens were obtained in the operating room. Intraoperative culture specimens were obtained in 3 different manners for all patients:

  1. Four 21-gauge needles were dipped into the infected fluid and were used to inoculate 4 pediatric BCBs – 2 aerobic and 2 nonaerobic.
  2. Two swabs were placed in direct contact with the infected tissue.
  3. Two solid tissue samples were collected and placed in 2 sterile containers.

In these 40 cases, the microbial identification rate of the BCB method was 68%, compared to 45% with the swab method and 38% with the tissue method—all statistically significant differences. In 9 patients (23%), the pathogen was only identified with the BCB method. No samples showed positive culture growth with the other 2 methods if the BCB culture was negative. Interestingly, in a subgroup analysis of 15 patients with methicillin-susceptible Staphylococcus aureus (MSSA), the authors found no difference in detection rates between the 3 methods, but in cases involving organisms other than MSSA, detection with BCBs was significantly higher than with both swab and tissue cultures.

The apparent superiority of BCBs to detect microbial organisms could be due to the characteristics of pediatric BCBs, which enhance microorganism growth in a small amount of liquid. Although there are some concerns that this enhanced BCB detection could lead to increased rates of false-positives from contaminants, I think the risk of false positives is a viable tradeoff if we can more quickly and accurately identify pathogens in pediatric infections. As Shin et al. emphasize, “Sequelae resulting from these infections are particularly unfortunate for pediatric patients.”

Matthew R. Schmitz, MD
JBJS Deputy Editor for Social Media

Sustained Fevers After Spinal Fusion: A Sentinel for Infection?

Postoperative fevers occur frequently. During the first 2 to 3 days after surgery, these fevers are often due to atelectasis or the increased inflammatory response that arises from tissue injury during surgery. However, persistent postoperative fevers should be cause for concern. In the August 19, 2020 issue of The Journal, Hwang et al. examine the relationship between sustained fevers after spine instrumentation and postoperative surgical site infection.

The authors retrospectively reviewed 598 consecutive patients who underwent lumbar or thoracic spinal instrumentation. They excluded patients who underwent surgery to treat tumors or infections and those with other identified causes of fever, such as a urinary tract infection or pneumonia. Sustained fevers were defined as those that began on or after postoperative day (POD) 4 and those that started on POD 1 to 3 if they persisted until or beyond POD 5.

Sixty-eight patients (11.4%) met the criteria for a sustained fever after spinal instrumentation. Nine of those 68 (13.2%) were diagnosed with a surgical site infection. Of the 530 patients who did not have a sustained fever, only 5 (0.9%) developed a surgical site infection (p<0.001 for the between-group difference).

Further analysis revealed 3 diagnostic clues for surgical site infections among the patients with sustained fevers:

  • Continuous fever (rather than cyclic or intermittent)
  • Levels of C-reactive protein (CRP) >4 mg/dL after POD 7
  • Increasing or stationary patterns of CRP level and neutrophil differential

In addition, the authors found that CRP levels >4 mg/dL between PODs 7 and 10 had much greater sensitivity for discriminating surgical site infection than gadolinium-enhanced magnetic resonance imaging data obtained within 1 month of the surgical procedure.

Although a vast majority (87%) of patients with sustained postoperative fevers in this study did not develop an infection, persistent fever after spine instrumentation surgery is something to be mindful of. The authors describe their findings as “tentative” and advise readers to interpret them with caution. Those caveats notwithstanding, I consider this information to be valuable because it might help prevent delays in the diagnosis of a potentially serious perioperative complication.

Matthew R. Schmitz, MD
JBJS Deputy Editor for Social Media

What’s New in Musculoskeletal Infection 2020

Every month, JBJS publishes 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, Thomas K. Fehring, MD, co-author of the July 15, 2020 What’s New in Musculoskeletal Infection,” selected the five most clinically compelling findings—all focused on periprosthetic joint infection (PJI)—from among the more than 80 noteworthy studies summarized in the article.

PJI Prevention
–A retrospective case-control study1 found that patients who received an allogeneic blood transfusion during or after knee or hip replacement had a higher risk of PJI than those who were not transfused.

PJI Diagnosis
–A retrospective review2 found that using inflammatory markers to diagnose PJI in immunosuppressed joint-replacement patients is not suitable and that newly described thresholds for synovial cell count and differential have better operative characteristics.

Treating PJI
–A retrospective review3 of a 2-stage debridement protocol with component retention in 83 joint-replacement patients showed an 86.7% success rate of infection control at an average follow-up of 41 months.

–A single-center study4 of perioperative antibiotic selection for patients undergoing total joint arthroplasty found that the risk of PJI was 32% lower among those who received cefazolin compared with those who received other antimicrobial agents. The findings emphasize the importance of preoperative allergy testing in patients with stated beta-lactam allergies.

–A review of regional and state antibiograms5 showed that 75% of methicillin-sensitive S. aureus (MSSA) isolates and 60% of both methicillin-resistant S. aureus (MRSA) and coagulase-negative Staphylococcus isolates were susceptible to clindamycin, whereas 99% of all isolates were susceptible to vancomycin.

References

  1. Taneja A, El-Bakoury A, Khong H, Railton P, Sharma R, Johnston KD, Puloski S, Smith C, Powell J. Association between allogeneic blood transfusion and wound infection after total hip or knee arthroplasty: a retrospective case-control study. J Bone Jt Infect. 2019 Apr 20;4(2):99-105.
  2. Lazarides AL, Vovos TJ, Reddy GB, Kildow BJ, Wellman SS, Jiranek WA, Seyler TM. Traditional laboratory markers hold low diagnostic utility for immunosuppressed patients with periprosthetic joint infections. J Arthroplasty.2019 Jul;34(7):1441-5. Epub 2019 Mar 12.
  3. Chung AS, Niesen MC, Graber TJ, Schwartz AJ, Beauchamp CP, Clarke HD, Spangehl MJ. Two-stage debridement with prosthesis retention for acute periprosthetic joint infections. J Arthroplasty.2019 Jun;34(6):1207-13. Epub 2019 Feb 16.
  4. Wyles CC, Hevesi M, Osmon DR, Park MA, Habermann EB, Lewallen DG, Berry DJ, Sierra RJ. 2019 John Charnley Award: Increased risk of prosthetic joint infection following primary total knee and hip arthroplasty with the use of alternative antibiotics to cefazolin: the value of allergy testing for antibiotic prophylaxis. Bone Joint J.2019 Jun;101-B(6_Supple_B):9-15.
  5. Nodzo SR, Boyle KK, Frisch NB. Nationwide organism susceptibility patterns to common preoperative prophylactic antibiotics: what are we covering? J Arthroplasty.2019 Jul;34(7S):S302-6. Epub 2019 Jan 17.

Revision Shoulder Arthroplasty: IV or Oral Antibiotics?

Surgeons performing revision shoulder arthroplasty typically order postoperative antibiotics to be administered while they wait for results from intraoperative cultures. Based on their index of suspicion from preoperative exams and intraoperative observations, they order either intravenous (high suspicion of infection) or oral (low suspicion) antibiotics during the waiting period. In the June 3, 2020 issue of JBJS, Yao et al. report on a retrospective review of 175 patients who underwent revision shoulder arthroplasty, finding that surgeons’ presumptive choice of antibiotic type matched the culture results in 75% of the cases.

Among the 175 patients in the study, IV antibiotics were initiated in 62, while 113 patients received oral antibiotics. Cultures from 49 of the 62 patients started on IV antibiotics came back positive, and cultures from 83 of the 113 patients started on oral antibiotics came back negative. Treatment of patients whose initial antibiotic regimen did not match culture results was modified accordingly.

After multivariate analysis Yao et al. found that male sex, prior ipsilateral infection, and intraoperative presence of a humeral membrane were 3 independent predictors of surgeons initiating IV antibiotics. Antibiotic-related adverse events (including GI, dermatologic, and allergic reactions) occurred in 19% of the patients. Not surprisingly, the rate of these complications was highest among those receiving IV antibiotics.

Although the surgeons’ empirical initiation of antibiotic administration route was “correct” 75% of the time, that still left 25% of the patients needing modification of therapy based on culture results. While the authors observe that their study was  not designed “to report the relative effectiveness of the 2 antibiotic protocols in minimizing the risk of recurrent infection,” their findings confirm that preoperative and intraoperative observations can help surgeons select the “right” type of antibiotic without culture results—and that is heartening.

How to Safely Restart Elective Surgery Amid a Pandemic

OrthoBuzz occasionally receives posts from guest bloggers. This guest post comes from Chad A. Krueger, MD, co-author of a recent fast-tracked review article in JBJS.

I’ll admit that when I first started hearing about COVID-19, I didn’t pay much attention. Life was busy, and I wasn’t going to worry about something that I figured would come and go without much fuss over the next few months. While that was obviously a faulty assumption, I think few of us could have predicted just how deadly, anxiety-provoking, and disruptive this virus would be. We are now 5 or so months into this pandemic and nothing is ”normal,” but some of the measures we have taken to help flatten the curve seem to be working. In the months ahead, figuring out how to safely regain some normalcy in our lives will require careful planning, nimble adjustments, and well-coordinated cross-functional execution.

Those three actions were also required to produce the fast-tracked Current Concepts Review article in JBJS about resuming elective orthopaedic surgery during the pandemic, which I had the privilege to co-author. Amazingly, that article progressed from an idea to a published manuscript, with input from 77 physicians, in the span of 2 weeks. This fast-paced project was driven by our knowledge that many facilities worldwide were getting ready to start performing elective surgeries again, and we wanted to ensure that practical, accurate, and relevant information was available as those plans were being made.

All the expert author-contributors offered unique insights as to how the pandemic was affecting healthcare delivery in their region of the globe, allowing us to keep the recommendations as balanced as possible. Although much of the research incorporated in this review came from outside the orthopaedic literature, it all touched on our ability to safely care for patients. The process of creating this article was a great example of how strong leadership, teamwork, and compromise can help us navigate through all aspects of these uncharted waters. Everyone who worked on this manuscript, including the peer-review and editorial teams at JBJS, had one goal in mind: to help orthopaedic surgeons safely return to caring for their patients.

The international consensus group that created this review is well aware that some of the recommendations will need to be updated, changed, or maybe even scrapped altogether as we learn more about the behavior of this virus. We drafted, discussed, and revised these guidelines while appreciating that some regions of the world have not been as adversely affected as others and that there are stark global differences in testing capabilities and supplies of personal protective equipment and other resources. We are painfully aware that some of our strongest recommendations might be impossible to implement in certain settings.

Developing a one-size-fits-all framework for restarting elective orthopaedic surgery was not possible; there are simply too many variables at play with this pandemic that are beyond any individual’s or health system’s control. However, this review provides as much evidence-based guidance as possible so that individual surgeons, practices, hospitals, and municipalities can make informed decisions about how elective surgery should reemerge. We are fully aware that some people may object to some of the recommendations in this article, even though 94% to 100% of the 77-member consensus group agreed on all of them. Nevertheless, we hope that this guidance—and updates to it as more evidence becomes available—will help us all continue to make highly informed decisions before, during, and after elective surgery to keep ourselves and our patients safe.

Chad A. Krueger, MD is an orthopaedic fellow in adult reconstructive surgery at the Rothman Institute and former Deputy Editor for Social Media at JBJS.