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
- 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.
- 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.
- 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.
- 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.
- 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.
More Data on Periprosthetic Hip Infections
Among >100,000 total hip arthroplasty (THA) patients ≥55 years of age whose data resides in a Canadian arthroplasty database, the 15-year cumulative incidence of periprosthetic joint infection (PJI) was 1.44%, according to a study by the McMaster Arthroplasty Collaborative in the March 18, 2020 issue of JBJS.
In addition to finding that the overall risk of developing PJI after THA has not changed over the last 15 years in this cohort, the authors found the following factors associated with increased risk of developing a PJI:
- Male sex (absolute increased risk of 0.48% at 10 years)
- Type 2 diabetes (absolute increased risk of 0.64% at 10 years)
- Discharge to a convalescent-care facility (absolute increased risk of 0.46% at 10 years)
The authors view the third bulleted item above as “a surrogate marker of frailty and poorer general health.”
Patient age, surgical approach, surgical setting (academic versus rural), use of cement, and patient income were not associated with an increased risk of PJI. Nearly two-thirds of PJI cases occurred within 2 years after surgery, and 98% occurred within 10 years postoperatively.
The authors conclude that these and other substantiated findings about PJI risk factors “should be reviewed with the patient during preoperative risk counseling.”
What’s New in Orthopaedic Rehabilitation 2019
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 summaries.
This month, co-author Nitin B. Jain, MD, MSPH selected the most clinically compelling findings from the 40 studies summarized in the November 20, 2019 “What’s New in Orthopaedic Rehabilitation.”
Pain Management
–A randomized controlled trial compared pain-related function, pain intensity, and adverse effects among 240 patients with chronic back, hip, or knee pain who were randomized to receive opioids or non-opioid medication.1 After 12 months, there were no between-group differences in pain-related function. Statistically, the pain intensity score was significantly lower in the non-opioid group, although the difference is probably not clinically meaningful. Adverse events were significantly more frequent in the opioid group.
–A series of nested case-control studies found that the use of the NSAID diclofenac was associated with an increase in the risk of myocardial infarction in patients with spondyloarthritis and osteoarthritis, relative to those taking the NSAID naproxen.2
–Intra-articular injections of corticosteroids or hyaluronic acid are often used for pain relief prior to an eventual total knee arthroplasty (TKA). An analysis of insurance data found that patients who had either type of injection within three months of a TKA had a higher risk of periprosthetic joint infection (PJI) after the operation than those who had injections >3 months prior to TKA.
Partial-Thickness Rotator Cuff Tears
–A randomized controlled trial of 78 patients with a partial-thickness rotator cuff compared outcomes of those who underwent immediate arthroscopic repair with outcomes among those who delayed operative repair until completing 6 months of nonoperative treatment, which included activity modification, PT, corticosteroid injections, and NSAIDs.3 At 2 and 12 months post-repair, both groups demonstrated improved function relative to initial evaluations. At the final follow-up, there were no significant between-group differences in range of motion, VAS, Constant score, or ASES score. Ten (29.4%) of the patients in the delayed group dropped out of the study due to symptom improvement.
Stem Cell Therapy
–A systematic review that assessed 46 studies investigating stem cell therapy for articular cartilage repair4 found low mean methodology scores, indicating overall poor-quality research. Only 1 of the 46 studies was classified as excellent, prompting the authors to conclude that evidence to support the use of stem cell therapy for cartilage repair is limited by a lack of high-quality studies and heterogeneity in the cell lines studied.
References
- Krebs EE, Gravely A, Nugent S, Jensen AC, DeRonne B, Goldsmith ES, Kroenke K, Bair MJ, Noorbaloochi S. Effect of opioid vs nonopioid medications on pain-related function in patients with chronic back pain or hip or knee osteoarthritis pain: the SPACE randomized clinical trial. JAMA. 2018 Mar 6;319(9):872-82.
- Dubreuil M, Louie-Gao Q, Peloquin CE, Choi HK, Zhang Y, Neogi T. Risk ofcmyocardial infarction with use of selected non-steroidal anti-inflammatory drugs incpatients with spondyloarthritis and osteoarthritis. Ann Rheum Dis. 2018 Aug;77(8): 1137-42. Epub 2018 Apr 19.
- Kim YS, Lee HJ, Kim JH, Noh DY. When should we repair partial-thickness rotator cuff tears? Outcome comparison between immediate surgical repair versus delayed repair after 6-month period of nonsurgical treatment. Am J Sports Med. 2018 Apr;46(5):1091-6. Epub 2018 Mar 5.
- Park YB, Ha CW, Rhim JH, Lee HJ. Stem cell therapy for articular cartilage repair: review of the entity of cell populations used and the result of the clinical application of each entity. Am J Sports Med. 2018 Aug;46(10):2540-52. Epub 2017 Oct 12.
What’s New in Musculoskeletal Infection 2019
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 17, 2019 “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 90 noteworthy studies summarized in the article.
Preventive Irrigation Solutions
–An in vitro study by Campbell et al.1 found that the chlorine-based Dakin solution forms potentially toxic precipitates when mixed with hydrogen peroxide and chlorhexidine. The authors recommend that surgeons not mix irrigation solutions in wounds during surgery.
PJI Diagnosis
–A clinical evaluation by Stone et al. showed that alpha-defensin levels in combination with synovial C-reactive protein had high sensitivity for PJI diagnosis, but the alpha-defensin biomarker can lead to false-positive results in the presence of metallosis and false-negative results in the presence of low-virulence organisms.
–In an investigation of next-generation molecular sequencing for diagnosis of PJI in synovial fluid and tissue, Tarabichi et al. found that in 28 revision cases considered to be infected, cultures were positive in only 61%, while next-generation sequencing was positive in 89%. However, next-generation sequencing also identified microbes in 25% of aseptic revisions that had negative cultures and in 35% of primary total joint arthroplasties. Identification of pathogens in cases considered to be aseptic is concerning and requires further research.
Treating PJI
–A multicenter study found that irrigation and debridement with component retention to treat PJI after total knee arthroplasty had a failure rate of 57% at 4 years.2
–Findings from an 80-patient study by Ford et al.3 challenge the assumption that 2-stage exchanges are highly successful. Fourteen (17.5%) of the patients in the study never underwent reimplantation, 30% had a serious complication, and of the 66 patients with a successful reimplantation, only 73% remained infection-free. Additionally 11% of the patients required a spacer exchange for persistent infection.
References
- Campbell ST, Goodnough LH, Bennett CG, Giori NJ. Antiseptics commonly used in total joint arthroplasty interact and may form toxic products. J Arthroplasty.2018 Mar;33(3):844-6. Epub 2017 Nov 11.
- Urish KL, Bullock AG, Kreger AM, Shah NB, Jeong K, Rothenberger SD; Infected Implant Consortium. A multicenter study of irrigation and debridement in total knee arthroplasty periprosthetic joint infection: treatment failure is high. J Arthroplasty.2018 Apr;33(4):1154-9. Epub 2017 Nov 21.
- Ford AN, Holzmeister AM, Rees HW, Belich PD. Characterization of outcomes of 2-stage exchange arthroplasty in the treatment of prosthetic joint infections. J Arthroplasty.2018 Jul;33(7S):S224-7. Epub 2018 Feb 17.
Failure Factors after 1-Stage Exchange TKA
Prior to performing a primary total joint arthroplasty, patient optimization is both possible and recommended. However, when a patient with a periprosthetic joint infection (PJI) comes in to your office, opportunities for patient optimization are limited. At that point, the patient’s BMI, kidney/liver values, and HgbA1c/fructosamine levels are not going to be dramatically improved prior to any procedure to eradicate the infection and/or salvage the implant. Still, for the purposes of care optimization and prognostic guidance, it is important to identify specific patient or wound characteristics that may help us flag patients who are at increased risk for failure after treatment of a PJI.
That was the goal of the case-control study by Citak et al. in the June 19, 2019 edition of The Journal. The authors compared 91 patients who experienced a failed 1-stage revision total knee arthroplasty that was performed to treat a PJI to a matched cohort who had a successful 1-stage revision to treat a PJI. (The authors defined “failure” as any subsequent surgical procedure regardless of reason.)
A bivariate logistic analysis revealed that patients who had a history of a previous 1-stage (OR 29.3; p< 0.001) or 2-stage (OR 5.8; p <0.001) exchange due to PJI, or who had Streptococcus (OR 6.0; p = 0.013) or Enterococcus (OR 17.3; p = 0.023) isolated from their wound were at increased risk of reinfection compared to the control group. Just as important, the authors found that patient body weight of 100 kg or above and history of deep vein thrombosis (DVT) were the only patient comorbidities related to an increased risk of a failed revision.
While these findings may not be surprising in light of previous data on this topic, they are important in aggregate. Patients whose wounds contain isolated enterococci or streptococci may not be ideal candidates for 1-stage PJI revision surgery. Additionally, the authors highlight that patients who have failed two or more attempts at a 1-stage revision should be considered for a 2-stage protocol.
While many of the patients in this study who failed the 1-stage revision may have also failed a 2-stage revision, ongoing research comparing the two protocols should help further clarify whether certain infections are more amenable to successful treatment with one protocol or the other. In the meantime, studies such as this add valuable data that surgeons can use to guide patient care and provide meaningful patient education for shared decision-making about how to treat these difficult infections.
Chad A. Krueger, MD
JBJS Deputy Editor for Social Media
Diagnosing Infection in “Dry” Prosthetic Joints
Despite a bevy of research and intense clinical focus, definitively diagnosing periprosthetic joint infections (PJIs) remains a major challenge in many patients. There is no single test that can confirm a PJI diagnosis with absolute accuracy, and surgeons often encounter clinical factors that make the diagnostic challenge even more complex. One such scenario is when a surgeon cannot aspirate enough fluid for culture from the affected joint of a patient who may have a PJI. In such situations, important microbiological data that would come from culturing synovial fluid are unavailable, leaving treating surgeons information-poor.
In the June 5, 2019 issue of The Journal, Li et al. provide surgeons with data about a controversial solution to this so-called “dry-tap” problem. The lead author performed aspirations on nearly 300 joints that were suspicious for periprosthetic infection. Eighty-two of those aspirations (29%) yielded ≤1.0 mL of synovial fluid. In those “dry-tap” cases, 10 mL of saline solution was injected into the joint, which was then reaspirated.
When comparing cultures from the aspirates that were the result of a saline lavage to those in which no lavage was performed, the authors found overlapping 95% confidence intervals in sensitivity, specificity, positive predictive value (PPV), and negative predictive value. However, the specificity (0.991 vs 0.857) and PPV (0.987 vs 0.889) were higher in the nonlavage cohort, even if those differences did not reach statistical significance. In addition, no significant differences were found between the groups in terms of relative frequencies of specific pathogen types.
Although the authors conclude that this lavage-and-reaspiration technique “is not necessarily inappropriate,” it is important to note that no post-hoc power analysis was performed, and therefore type II error needs to be considered because the study was probably underpowered. In addition, the International Consensus Meeting (ICM) recommends against lavaging a “dry” joint to obtain fluid for culture, largely because the injected saline will dilute results if a leukocyte esterase strip test or cell count is subsequently performed as part of the PJI-diagnosis process. Still, the authors point out that the data supporting the ICM’s recommendations against this practice are relatively weak, and the specificity and sensitivity data from this study are quite satisfactory.
So does this give us another option for determining whether a periprosthetic joint infection is present in patients from whom little or no synovial fluid can be obtained? Maybe. But this technique requires further investigation before it becomes widely implemented in practice. Without validation, it risks becoming just one more variable that could reinforce our own confirmation biases in these challenging cases. With further validation, however, it could allow pre-revision collection of valuable and accurate culture information from “dry” joints.
Chad A. Krueger, MD
JBJS Deputy Editor for Social Media
FDA Approves Rapid Alpha-Defensin Test for PJI
The US FDA has approved the Synovasure Alpha Defensin Lateral Flow Test Kit for helping detect periprosthetic joint infection (PJI) in the synovial fluid of patients being evaluated for revision joint replacement.
Alpha defensins are proteins released by neutrophils in early response to infection. OrthoBuzz previously summarized a 2018 JBJS study that found this rapid alpha defensin test to have 96.9% overall accuracy.
In the FDA news release about the approval, Tim Stenzel, MD, director of the FDA’s Office of In Vitro Diagnostics and Radiological Health, said the test provides health care professionals with additional information that “could potentially reduce patient risk by avoiding unnecessary revision operations for replacement joints.”
In a Commentary on the 2018 JBJS study, Garth Ehrlich, PhD and Michael Palmer, MD said the device is a “substantive advance,” but not “a panacea.” For one thing, metallosis would still need to be ruled out with MRI, because that noninfectious etiology triggers a false-positive result with this rapid test. Synovasure is also likely to miss detection of slow-growing, chronic bacterial pathogens such as Proprionibacterium acnes, the commentators said.
The Synovasure test kit received approval through the FDA’s de novo premarket pathway, which is reserved for “low- to moderate-risk devices of a new type,” according to the agency.
Diagnosing PJI: When The “Urine Dipstick” Outperforms Conventional Labs
Despite what seems like a new, high-quality study being published on the topic every week or so, orthopaedic surgeons still have an extremely hard time determining whether a prosthetic hip or knee is infected or not. We have an array of available tests and the relatively easy-to-follow criteria for a periprosthetic joint infection (PJI) from the Musculoskeletal Infection Society (MSIS), but a large number of these patients still fall into the gray zone of “possibly infected.” This predicament is especially thorny in patients who received antibiotics just prior to the diagnostic workup, which interferes with the accuracy of many tests for PJI.
In the April 17, 2019 issue of The Journal, Shahi et al. remind orthopaedic surgeons about a valuable tool that can be used in this scenario. Their retrospective study looked at 121 patients who had undergone revision hip or knee arthroplasty due to an MSIS criteria-confirmed periprosthetic infection. Shahi et al. sought to determine which diagnostic tests were least affected by prior antibiotic administration. The authors found that erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, synovial white blood cell (WBC) count, and polymorphonuclear neutrophil (PMN) percentage were all significantly lower in the 32% of patients who had received antibiotics within 2 weeks of those tests, compared with the 68% who did not receive antibiotics. The only test that was found not to be significantly affected by the prior admission of antibiotics was the urine-based leukocyte esterase strip test.
Considering the ease and rapidity with which a leukocyte esterase test can be performed and evaluated (at a patient’s bedside, with immediate results), its low cost, and the fact that it is included in the MSIS criteria, these findings are very important and useful. While we would prefer that patients with a possibly infected total hip or knee not receive antibiotics prior to their diagnostic workup, previous antibiotic exposure remains a relatively common scenario. The findings from this study can assist us in those difficult cases, and they add further evidence to support the value and reliability of the easy-to-perform leukocyte esterase test.
Chad A. Krueger, MD
JBJS Deputy Editor for Social Media
Extended Oral Antibiotics May Cut PJI Risk When Risk Factors Aren’t Modifiable
Periprosthetic joint infections (PJIs) create a significant burden for patients, surgeons, and healthcare systems. That is why so much research has gone into how best to optimize certain patients preoperatively—such as those with obesity, diabetes, or kidney disease—to decrease the risk of these potentially catastrophic complications. Still, it is not always possible or feasible to optimize every “high-risk” patient who would benefit from a total hip or knee replacement, and therefore many such patients undergo surgery with an increased risk of infection. In such cases, surgeons need additional strategies to decrease PJI risk.
In the December 19, 2018 issue of JBJS, Inabathula et al. investigate whether providing high-risk total joint arthroplasty (TJA) patients with extended postoperative oral antibiotics decreased the risk of PJI within the first 90 days after surgery. In their retrospective cohort study, the authors examined >2,100 total hip and knee replacements performed at a single suburban academic hospital. The patients in 68% of these cases had at least one risk factor for infection. Among those high-risk patients, about half received 7 days of an oral postoperative antibiotic, while the others received only the standard 24 hours of postoperative intravenous (IV) antibiotics.
Relative to those who received IV antibiotics only, those who received extended oral antibiotics experienced an 81% reduction in infection for total knee arthroplasties and a 74% reduction in infection for total hip arthroplasties. I was stunned by such large reductions in infection rates obtained simply by adding an oral antibiotic twice a day for 7 days. Most arthroplasty surgeons go to great lengths to decrease the risk of joint infection by percentages much less than that.
While further investigations are needed and legitimate concerns exist regarding the propagation of antimicrobial-resistant organisms from medical antibiotic misuse, these data are very exciting. I agree with Monti Khatod, MD, who, in his commentary on this study, says that “care pathways that aim to improve modifiable risk factors should not be seen as obsolete based on the findings of this paper.” Furthermore, the study itself is at risk for treatment and selection biases that could greatly influence its outcomes. Nevertheless, getting a successful result in these patients is challenging and, if validated with further data, this research may help surgeons obtain better outcomes when treating high-risk patients in need of hip or knee replacements.
Chad A. Krueger, MD
JBJS Deputy Editor for Social Media
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