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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.

Number of COVID-19 Infections: Vastly Underestimated?

Many scientists worldwide are engaged in predicting the course of the COVID-19 pandemic, but the exact nature of this disease and the “novel” virus that causes it remains largely mysterious.

The numbers of confirmed cases in media reports are dependent on the extent of testing, which has varied markedly from region to region in North America. The scientific community has cautioned policymakers not to rely entirely on “observable” data (i.e., testing-confirmed COVID-19 cases) because such measures are likely to under-report the extent of the problem. That’s one reason why orthopaedic surgeon Mohit Bhandari, MD and his colleagues applied machine-learning tools to estimate the number of “unobserved” COVID-19 infections in North America.

The authors’ stated goal was to contribute to the ongoing debate on detection bias (one form of which can occur when outcomes—infections in this case—cannot be reliably counted) and to present statistical tools that could help improve the robustness of COVID-19 data. Their findings suggest that “we might be grossly underestimating COVID-19 infections in North America.”

The authors’ estimates relied on 2 sophisticated analyses: “dimensionality reduction” helped uncover hidden patterns, and a “hierarchical Bayesian estimator approach” inferred past infections from current fatalities. The dimensionality-reduction analysis presumed a 13-day lag time from infection to death, and it indicated that, as of April 22, 2020, the US probably had at least 1.3 million undetected infections, and the number of undetected infections in Canada could have ranged from 60,000 to 80,000. The Bayesian estimator approach yielded similar estimates: The US had up to 1.6 million undetected infections, and Canada had at least 60,000 to 86,000 undetected infections.

In contrast, data from the Johns Hopkins University Center for Systems Science and Engineering on April 22, 2020, reported only 840,476 and 41,650 confirmed cases for the US and Canada, respectively. Based on these numbers, as of April 22, 2020, the US may have had 1.5 to 2.02 times the number of reported infections, and Canada may have had 1.44 to 2.06 times the number of reported infections.

The authors emphasize that the “real” number of asymptomatic carriers cannot be determined without widespread use of validated antibody tests, which are scarce. Bhandari et al. conclude that policymakers should “be aware of the extent to which unobservable data—infections that have still not been captured by the system—can damage efforts to ‘flatten’ the pandemic’s curve.”

Avoid the Slipstream When Walking, Running, and Cycling

Many people have taken to walking, running, and cycling for the benefit of mind and body during the COVID-19 pandemic, and many engage in those activities with others. New, unpublished research coming out of the Netherlands and Belgium suggests that 2 or more people walking, running, or cycling right behind one another should leave much more than 6 ft of space between themselves.

Using animations developed from computational fluid dynamics models, the researchers showed that a cloud of emitted respiratory droplets is entrained in the slipstream–the wake behind any moving person that pushes air slightly behind them–even when he or she exhales normally. People cycling in groups often use the slipstream of the person in front of them to reduce air resistance, but smaller slipstreams also form behind anyone who is walking or running.

Admitting that much more needs to be learned about the coronavirus-infection risk posed by such slipstream-carried droplets, the authors show that when someone walks through the droplet cloud left by the person in front of them, droplets can stick to the following person’s body.

So how far back should you be from the person in front of you when you are out doing these things? The authors recommend the following distances:

  • 13 to 16 ft (4 to 5 meters) while walking
  • 33 ft (10 meters) when running or cycling slowly
  • 65 ft (20 meters) when cycling fast

These preliminary findings suggest that exercising side by side may be safer than exercising one behind another, but doing so is often not practical or safe, especially when cycling on public roads.

Although these data are unpublished, in their white paper the authors said, “We decided it would be unethical to keep the results confidential and keep the public waiting months for the peer review process to be completed.”

OrthoBuzz would like to thank Dr. Freddie Fu, Chair of Orthopaedic Surgery at the University of Pittsburg Medical Center, for bringing this research to our attention.

Amid COVID-19, What Does “Elective” Mean?

As Sarac et al. note in the latest JBJS fast-tracked article, the phrase “elective procedure” is ambiguous, even though it is supposed to identify procedures that are being postponed to help hospitals cope with the COVID-19 pandemic. Guidelines from the Centers for Disease Control and Prevention (CDC) say that operations for “most cancers” and “highly symptomatic patients” should continue, but that leaves much of the ambiguity unresolved. What constitutes an elective procedure in orthopaedics at this unusual time remains unclear.

To help clarify the situation, the authors summarize guidance issued by states and describe the guidelines currently in use for orthopaedic surgery at their institution, The Ohio State University College of Medicine.

Here are the state-related data collected by Sarac et al., as of March 24, 2020:

  • 30 states have published guidance regarding discontinuation of elective procedures; 16 of those states provide a definition of “elective” or offer guidance for determining which procedures should continue to be performed.
  • 5 states provide guidelines specifically mentioning orthopaedic surgery; of those, 4 states explicitly permit trauma-related procedures, and 4 states recommend against performing arthroplasty.
  • 10 states provide guidelines permitting the continuation of oncological procedures.

In the Buckeye State, the Ohio Hospital Association asked each hospital and surgery center to cancel procedures that do not meet any of the following criteria:

  • Threat to a patient’s life if procedure is not performed
  • Threat of permanent dysfunction of an extremity or organ system
  • Risk of cancer metastasis or progression of staging
  • Risk of rapid worsening to severe symptoms

Mindful of those criteria, individual surgical and procedural division directors at the authors’ university developed a list of specific procedures that should continue to be performed. Respective department chairs approved the lists, which were then sent to the hospital chief clinical officer for signoff.

The authors tabulate the orthopaedic procedures that continue to be performed at their institution as of March 25, 2020, but they are quick to add that even this list is not without ambiguity. For example, surgery should continue on “select closed fractures that if left untreated for >30 days may lead to loss of function or permanent disability,” but that requires surgeons to judge, in these uncertain and fluid times, which fractures necessitate fixation in the short term.

Sarac et al. emphasize that such lists, however specific they are today, are likely to change as demands on hospitals shift. They suggest that as the pandemic evolves, a further classification of procedures into 2 time-based categories might be helpful: (1) those that need to be performed within 2 weeks and (2) those that need to be performed within 4 weeks. Sarac et al. also remind orthopaedic surgeons to provide patients waiting for surgery that has been postponed with information regarding safe and effective methods of managing their pain.