Osteoarticular Mycoses.

Osteoarticular mycoses are chronic debilitating infections that require extended courses of antifungal therapy and may warrant expert surgical intervention. As there has been no comprehensive review of these diseases, the International Consortium for Osteoarticular Mycoses prepared a definitive treatise for this important class of infections. Among the etiologies of osteoarticular mycoses are Candida spp., Aspergillus spp., Mucorales, dematiaceous fungi, non-Aspergillus hyaline molds, and endemic mycoses, including those caused by Histoplasma capsulatum, Blastomyces dermatitidis, and Coccidioides species. This review analyzes the history, epidemiology, pathogenesis, clinical manifestations, diagnostic approaches, inflammatory biomarkers, diagnostic imaging modalities, treatments, and outcomes of osteomyelitis and septic arthritis caused by these organisms. Candida osteomyelitis and Candida arthritis are associated with greater events of hematogenous dissemination than those of most other osteoarticular mycoses. Traumatic inoculation is more commonly associated with osteoarticular mycoses caused by Aspergillus and non-Aspergillus molds. Synovial fluid cultures are highly sensitive in the detection of Candida and Aspergillus arthritis. Relapsed infection, particularly in Candida arthritis, may develop in relation to an inadequate duration of therapy. Overall mortality reflects survival from disseminated infection and underlying host factors.

Factors Associated With an Intra-articular Infection After Anterior Cruciate Ligament Reconstruction: A Large Single-Institution Cohort Study.

BACKGROUND: An intra-articular infection after anterior cruciate ligament (ACL) reconstruction (ACLR) is a rare complication but one with potentially devastating consequences. The rare nature of this complication raises difficulties in detecting risk factors associated with it and with worse outcomes after one has occurred. PURPOSE: To (1) evaluate the association between an infection after ACLR and potential risk factors in a large single-center cohort of patients who had undergone ACLR and (2) assess the factors associated with ACL graft retention versus removal. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: All ACLR procedures performed at our institution between January 2010 and December 2018 were reviewed; a total of 11,451 procedures were identified. A retrospective medical record review was performed to determine the incidence of infections, patient and procedure characteristics associated with an infection, infection characteristics, incidence of ACL graft retention, and factors associated with the retention versus removal of an ACL graft. Multivariable logistic regression analysis was used to identify potential risk factors for an infection after ACLR. RESULTS: Of the 11,451 ACLR procedures, 48 infections were identified (0.42%). Multivariable logistic regression analysis revealed revision ACLR (odds ratio [OR], 3.13 [95% CI, 1.55-6.32]; P = .001) and younger age (OR, 1.06 [95% CI, 1.02-1.10]; P = .001) as risk factors for an infection. Compared with bone-patellar tendon-bone autografts, both hamstring tendon autografts (OR, 4.39 [95% CI, 2.15-8.96]; P < .001) and allografts (OR, 5.27 [95% CI, 1.81-15.35]; P = .002) were independently associated with an increased risk of infections. Overall, 15 ACL grafts were removed (31.3%). No statistically significant differences besides the number of irrigation and debridement procedures were found for retained versus removed grafts, although some trends were identified (P = .054). CONCLUSION: In a large single-center cohort of patients who had undergone ACLR and those with an infection after ACLR, patients with revision cases and younger patients were found to have a higher incidence of infection. The use of bone-patellar tendon-bone autografts was found to be associated with the lowest risk of infection after ACLR compared with both hamstring tendon autografts and allografts. Larger cohorts with a larger number of infection cases are needed to determine the factors associated with graft retention versus removal.

Sequencing of Circulating Microbial Cell-Free DNA Can Identify Pathogens in Periprosthetic Joint Infections.

BACKGROUND: Over 1 million Americans undergo joint replacement each year, and approximately 1 in 75 will incur a periprosthetic joint infection. Effective treatment necessitates pathogen identification, yet standard-of-care cultures fail to detect organisms in 10% to 20% of cases and require invasive sampling. We hypothesized that cell-free DNA (cfDNA) fragments from microorganisms in a periprosthetic joint infection can be found in the bloodstream and utilized to accurately identify pathogens via next-generation sequencing. METHODS: In this prospective observational study performed at a musculoskeletal specialty hospital in the U.S., we enrolled 53 adults with validated hip or knee periprosthetic joint infections. Participants had peripheral blood drawn immediately prior to surgical treatment. Microbial cfDNA from plasma was sequenced and aligned to a genome database with >1,000 microbial species. Intraoperative tissue and synovial fluid cultures were performed per the standard of care. The primary outcome was accuracy in organism identification with use of blood cfDNA sequencing, as measured by agreement with tissue-culture results. RESULTS: Intraoperative and preoperative joint cultures identified an organism in 46 (87%) of 53 patients. Microbial cfDNA sequencing identified the joint pathogen in 35 cases, including 4 of 7 culture-negative cases (57%). Thus, as an adjunct to cultures, cfDNA sequencing increased pathogen detection from 87% to 94%. The median time to species identification for cases with genus-only culture results was 3 days less than standard-of-care methods. Circulating cfDNA sequencing in 14 cases detected additional microorganisms not grown in cultures. At postoperative encounters, cfDNA sequencing demonstrated no detection or reduced levels of the infectious pathogen. CONCLUSIONS: Microbial cfDNA from pathogens causing local periprosthetic joint infections can be detected in peripheral blood. These circulating biomarkers can be sequenced from noninvasive venipuncture, providing a novel source for joint pathogen identification. Further development as an adjunct to tissue cultures holds promise to increase the number of cases with accurate pathogen identification and improve time-to-speciation. This test may also offer a novel method to monitor infection clearance during the treatment period. LEVEL OF EVIDENCE: Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Adjuvant antibiotic-loaded bone cement: Concerns with current use and research to make it work.

Antibiotic-loaded bone cement (ALBC) is broadly used to treat orthopaedic infections based on the rationale that high-dose local delivery is essential to eradicate biofilm-associated bacteria. However, ALBC formulations are empirically based on drug susceptibility from routine laboratory testing, which is known to have limited clinical relevance for biofilms. There are also dosing concerns with nonstandardized, surgeon-directed, hand-mixed formulations, which have unknown release kinetics. On the basis of our knowledge of in vivo biofilms, pathogen virulence, safety issues with nonstandardized ALBC formulations, and questions about the cost-effectiveness of ALBC, there is a need to evaluate the evidence for this clinical practice. To this end, thought leaders in the field of musculoskeletal infection (MSKI) met on 1 August 2019 to review and debate published and anecdotal information, which highlighted four major concerns about current ALBC use: (a) substantial lack of level 1 evidence to demonstrate efficacy; (b) ALBC formulations become subtherapeutic following early release, which risks induction of antibiotic resistance, and exacerbated infection from microbial colonization of the carrier; (c) the absence of standardized formulation protocols, and Food and Drug Administration-approved high-dose ALBC products to use following resection in MSKI treatment; and (d) absence of a validated assay to determine the minimum biofilm eradication concentration to predict ALBC efficacy against patient specific micro-organisms. Here, we describe these concerns in detail, and propose areas in need of research.

Bacterial toxins in musculoskeletal infections.

Musculoskeletal infections (MSKIs) remain a major health burden in orthopaedics. Bacterial toxins are foundational to pathogenesis in MSKI, but poorly understood by the community of providers that care for patients with MSKI, inducing an international group of microbiologists, infectious diseases specialists, orthopaedic surgeons and biofilm scientists to review the literature in this field to identify key topics and compile the current knowledge on the role of toxins in MSKI, with the goal of illuminating potential impact on biofilm formation and dispersal as well as therapeutic strategies. The group concluded that further research is needed to maximize our understanding of the effect of toxins on MSKIs, including: (i) further research to identify the roles of bacterial toxins in MSKIs, (ii) establish the understanding of the importance of environmental and host factors and in vivo expression of toxins throughout the course of an infection, (iii) establish the principles of drug-ability of antitoxins as antimicrobial agents in MSKIs, (iv) have well-defined metrics of success for antitoxins as antiinfective drugs, (v) design a cocktail of antitoxins against specific pathogens to (a) inhibit biofilm formation and (b) inhibit toxin release. The applicability of antitoxins as potential antimicrobials in the era of rising antibiotic resistance could meet the needs of day-to-day clinicians.

Assessing the Role of Daptomycin as Antibiotic Therapy for Staphylococcal Prosthetic Joint Infection.

Background: The role of daptomycin, a potent, safe, convenient anti-staphylococcal antibiotic, in treatment of prosthetic joint infection (PJI) is unclear. We evaluated our experience with the largest cohort of patients with staphylococcal PJI managed with daptomycin. Methods: A cohort of staphylococcal hip and knee PJI treated with daptomycin was identified by hospital records from 2009 to 2016. All cases met Musculoskeletal Infection Society International Consensus criteria for PJI. The primary endpoint was 2 year prosthesis retention. Univariate analyses and regression statistics were calculated. Results: 341 patients with staphylococcal PJI were analyzed. 154 two-stages (77%) and 74 DAIR procedures (52%) met criteria for treatment success at 2 years. 77 patients were treated with daptomycin, of which 34 two-stages (68%) and 15 DAIRs (56%) achieved treatment success. Pairwise and regression analysis found no association between treatment success and daptomycin use. Organism (DAIR only) and Charlson Comorbidity Index scores (DAIR and two-stage) were significantly associated with treatment outcome. Six daptomycin patients (7.8%) had adverse side effects. Discussion: Daptomycin fared no better or worse than comparable antibiotics in a retrospective cohort of staphylococcal hip and knee PJI patients, regardless of surgical strategy. Conclusion: The convenient dosing, safety, and potency of daptomycin make it an attractive antibiotic for staphylococcal PJI. However, these advantages must be weighed against higher costs and rare, but serious side effects.

Musculoskeletal Infection Society (MSIS) Update on Infection in Arthroplasty.

Periprosthetic joint infection (PJI) continues to be a devastating problem in the field of total joint arthroplasty, and recent literature can be used to make the preoperative diagnosis of PJI, guide nonsurgical and surgical treatment, and provide postoperative antimicrobial management of PJI patients. The diagnosis of PJI relies on traditional serum and synovial fluid tests, with newer biomarkers and molecular tests. Surgical treatment depends on the duration of infection, host qualities, and surgeon factors, and procedures include débridement, antibiotics, and implant retention, one-stage exchange arthroplasty, two-stage exchange arthroplasty, resection arthroplasty, fusion, or amputation. Appropriate management of PJI involves coordination with infectious disease consultants, internal medicine physicians, and orthopaedic surgeons. Antimicrobial management is guided by the organisms involved, whether it is a new or persistent infection, and antibiotic suppression should be administered on an individual case basis. The goals of this instructional course lecture are to review the most relevant recent literature and provide treating physicians and surgeons with the most up-to-date armamentarium to reduce the recurrence of PJI.

Lytic Lesion in the Proximal Humerus After a Flu Shot: A Case Report.

CASE: There has been a recent campaign to vaccinate patients in an effort to prevent widespread flu pandemic. Although the complication rate after vaccine is low, there have been reports of Guillain-Barré syndrome and shoulder injury related to vaccine administration (SIRVA). In this case presentation, we discuss a patient who developed a large lytic lesion in the proximal humerus after a deeply administered flu shot. CONCLUSIONS: SIRVA is a rare cause of shoulder pain after injections, but one that progresses and often necessitates operative management. Clinicians should be wary of persistent shoulder pain after a flu shot.

Prophylactic Postoperative Antibiotics May Not Reduce Pin Site Infections After External Fixation.

BACKGROUND: Pin infection continues to be a nuisance when using definitive external fixation. Prophylactic antibiotic treatment has been proposed in an effort to decrease pin complications. QUESTIONS/PURPOSES: We performed a prospective, randomized, single-blinded study to answer the following questions: (1) what was the effect of a 10-day course of oral prophylactic antibiotics administered immediately after external fixation surgery on the incidence of a subsequent pin infection, (2) what was the effect on the severity of a subsequent pin infection, and (3) what was the effect on the timing of a subsequent pin infection? METHODS: Patients were randomized into antibiotic treatment and control groups, and incidence, severity, and time of onset of pin infection were recorded. RESULTS: The incidence of pin infection for the entire cohort during the 90-day observation period was 46/58 (79%) without a statistically significant difference (p = 0.106). There was no statistical difference found (p = 0.512) in pin infection severity. There was no significant difference in the time of onset of infection between the two groups from the date of surgery (p = 0.553). CONCLUSIONS: Our randomized data do not suggest that oral antibiotics alter the incidence, timing, or severity of pin infection. This study does not support the use of prophylactic oral antibiotics in healthy patients.

2017 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty.

OBJECTIVE: This collaboration between the American College of Rheumatology and the American Association of Hip and Knee Surgeons developed an evidence-based guideline for the perioperative management of antirheumatic drug therapy for adults with rheumatoid arthritis (RA), spondyloarthritis (SpA) including ankylosing spondylitis and psoriatic arthritis, juvenile idiopathic arthritis (JIA), or systemic lupus erythematosus (SLE) undergoing elective total hip (THA) or total knee arthroplasty (TKA). METHODS: A panel of rheumatologists, orthopedic surgeons specializing in hip and knee arthroplasty, and methodologists was convened to construct the key clinical questions to be answered in the guideline. A multi-step systematic literature review was then conducted, from which evidence was synthesized for continuing versus withholding antirheumatic drug therapy and for optimal glucocorticoid management in the perioperative period. A Patient Panel was convened to determine patient values and preferences, and the Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of evidence and the strength of recommendations, using a group consensus process through a convened Voting Panel of rheumatologists and orthopedic surgeons. The strength of the recommendation reflects the degree of certainty that benefits outweigh harms of the intervention, or vice versa, considering the quality of available evidence and the variability in patient values and preferences. RESULTS: The guideline addresses the perioperative use of antirheumatic drug therapy including traditional disease-modifying antirheumatic drugs, biologic agents, tofacitinib, and glucocorticoids in adults with RA, SpA, JIA, or SLE who are undergoing elective THA or TKA. It provides recommendations regarding when to continue, when to withhold, and when to restart these medications, and the optimal perioperative dosing of glucocorticoids. The guideline includes 7 recommendations, all of which are conditional and based on low- or moderate-quality evidence. CONCLUSION: This guideline should help decision-making by clinicians and patients regarding perioperative antirheumatic medication management at the time of elective THA or TKA. These conditional recommendations reflect the paucity of high-quality direct randomized controlled trial data.

2017 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty.

OBJECTIVE: This collaboration between the American College of Rheumatology and the American Association of Hip and Knee Surgeons developed an evidence-based guideline for the perioperative management of antirheumatic drug therapy for adults with rheumatoid arthritis (RA), spondyloarthritis (SpA) including ankylosing spondylitis and psoriatic arthritis, juvenile idiopathic arthritis (JIA), or systemic lupus erythematosus (SLE) undergoing elective total hip (THA) or total knee arthroplasty (TKA). METHODS: A panel of rheumatologists, orthopedic surgeons specializing in hip and knee arthroplasty, and methodologists was convened to construct the key clinical questions to be answered in the guideline. A multi-step systematic literature review was then conducted, from which evidence was synthesized for continuing versus withholding antirheumatic drug therapy and for optimal glucocorticoid management in the perioperative period. A Patient Panel was convened to determine patient values and preferences, and the Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of evidence and the strength of recommendations, using a group consensus process through a convened Voting Panel of rheumatologists and orthopedic surgeons. The strength of the recommendation reflects the degree of certainty that benefits outweigh harms of the intervention, or vice versa, considering the quality of available evidence and the variability in patient values and preferences. RESULTS: The guideline addresses the perioperative use of antirheumatic drug therapy including traditional disease-modifying antirheumatic drugs, biologic agents, tofacitinib, and glucocorticoids in adults with RA, SpA, JIA, or SLE who are undergoing elective THA or TKA. It provides recommendations regarding when to continue, when to withhold, and when to restart these medications, and the optimal perioperative dosing of glucocorticoids. The guideline includes 7 recommendations, all of which are conditional and based on low- or moderate-quality evidence. CONCLUSION: This guideline should help decision-making by clinicians and patients regarding perioperative antirheumatic medication management at the time of elective THA or TKA. These conditional recommendations reflect the paucity of high-quality direct randomized controlled trial data.

2017 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty.

OBJECTIVE: This collaboration between the American College of Rheumatology and the American Association of Hip and Knee Surgeons developed an evidence-based guideline for the perioperative management of antirheumatic drug therapy for adults with rheumatoid arthritis (RA), spondyloarthritis (SpA) including ankylosing spondylitis and psoriatic arthritis, juvenile idiopathic arthritis (JIA), or systemic lupus erythematosus (SLE) undergoing elective total hip (THA) or total knee arthroplasty (TKA). METHODS: A panel of rheumatologists, orthopedic surgeons specializing in hip and knee arthroplasty, and methodologists was convened to construct the key clinical questions to be answered in the guideline. A multi-step systematic literature review was then conducted, from which evidence was synthesized for continuing versus withholding antirheumatic drug therapy and for optimal glucocorticoid management in the perioperative period. A Patient Panel was convened to determine patient values and preferences, and the Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of evidence and the strength of recommendations, using a group consensus process through a convened Voting Panel of rheumatologists and orthopedic surgeons. The strength of the recommendation reflects the degree of certainty that benefits outweigh harms of the intervention, or vice versa, considering the quality of available evidence and the variability in patient values and preferences. RESULTS: The guideline addresses the perioperative use of antirheumatic drug therapy including traditional disease-modifying antirheumatic drugs, biologic agents, tofacitinib, and glucocorticoids in adults with RA, SpA, JIA, or SLE who are undergoing elective THA or TKA. It provides recommendations regarding when to continue, when to withhold, and when to restart these medications, and the optimal perioperative dosing of glucocorticoids. The guideline includes 7 recommendations, all of which are conditional and based on low- or moderate-quality evidence. CONCLUSION: This guideline should help decision-making by clinicians and patients regarding perioperative antirheumatic medication management at the time of elective THA or TKA. These conditional recommendations reflect the paucity of high-quality direct randomized controlled trial data.

Globicatella sanguinis Osteomyelitis and Bacteremia: Review of an Emerging Human Pathogen with an Expanding Spectrum of Disease.

BACKGROUND: Globicatella sanguinis is an uncommon pathogen that may be misdiagnosed as viridans group streptococci. We review the literature of Globicatella and report 2 clinical cases in which catalase-negative Gram-positive cocci resembling viridans group streptococci with elevated minimum inhibitory concentrations (MICs) to ceftriaxone were inconsistently identified phenotypically, with further molecular characterization and ultimate identification of G sanguinis. METHODS: Two clinical strains (from 2 obese women; 1 with a prosthetic hip infection and the other with bacteremia) were analyzed with standard identification methods, followed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry, 16S recombinant ribonucleic acid (rRNA), and sodA polymerase chain reaction (PCR). The existing medical literature on Globicatella also was reviewed. RESULTS: Standard phenotypic methods failed to consistently identify the isolates. 16S PCR yielded sequences that confirmed Globicatella species. sodA sequencing provided species-level identification of G sanguinis. The review of literature reveals G sanguinis as an increasingly reported cause of infections of the urine, meninges, and blood. To our knowledge, this is the first reported case of an orthopedic infection caused by Globicatella sanguinis. A review of the 37 known cases of G sanguinis infection revealed that 83% of patients are female, and 89% are at the extremes of age (<5 or >65 years). CONCLUSIONS: Globicatella sanguinis, an uncommon pathogen with elevated minimum inhibitory concentrations to third-generation cephalosporins, is difficult to identify by phenotypic methods and typically causes infections in females at the extremes of age. It may colonize skin or mucosal surfaces. Advanced molecular techniques utilizing 16S rRNA with sodA PCR accurately identify G sanguinis.

Fungal Musculoskeletal Infections.

Fungi are rare but important causes of osteoarticular infections, and can be caused by a wide array of yeasts and molds. Symptoms are often subacute and mimic those of other more common causes of osteoarticular infection, which can lead to substantial delays in treatment. A high index of suspicion is required to establish the diagnosis. The severity of infection depends on the inherent pathogenicity of the fungi, the immune status of the host, the anatomic location of the infection, and whether the infection involves a foreign body. Treatment often involves a combination of surgical debridement and prolonged antifungal therapy.

Prosthetic joint infections secondary to rapidly growing mycobacteria: Two case reports and a review of the literature.

Rapidly growing mycobacteria (RGM) are a rare but treatable cause of prosthetic joint infections. This study reports on two patients comprising three prosthetic joint infections caused by RGM successfully treated at the institution. With removal of the infected prosthetic joint and judicious use of prolonged courses of antibiotics, patients with prosthetic joint infections secondary to RGM can both be cured and retain function of the affected joint. In addition, this study identified 40 additional cases reported during an extensive review of the literature and provide a summary of these cases. These infections can present within days of arthroplasty or can develop only decades after the index surgery. The clinical presentations often mimic those of more routine bacterial prosthetic joint infections.

Successful treatment of Candida osteoarticular infections with limited duration of antifungal therapy and orthopedic surgical intervention.

BACKGROUND: Current guidelines for treatment of Candida osteoarticular infections (COAIs) recommend a prolonged course of antifungal therapy (AFT) of 6-12 months. Based upon strategies developed at the Hospital for Special Surgery (HSS), we hypothesized that the duration of antifungal therapy may be substantially reduced for management of COAI. METHODS: This was a retrospective chart review of cases of COAI treated at the HSS for the past 14 years. COAI was documented by open biopsy and direct culture in all cases. The mean (95% confidence interval, CI) duration of documented follow-up was 39 (16-61) months. RESULTS: Among the 23 cases of COAI, the median age was 62 years (range 22-83 years) with 61% having no underlying condition. Orthopedic appliances, including joint prostheses and fracture hardware, were present in 74% of cases. All patients had COAI as the first proven site of candidiasis. Candida albicans and Candida parapsilosis were the most common species. Hip, knee, foot, and ankle were the most common sites. All patients received aggressive surgical intervention followed by AFT administered for a mean (95% CI) duration of 45 (38-83) days. Systemic AFT consisted principally of fluconazole alone (65%) or in combination with other agents (26%). Adjunctive intraoperative amphotericin B irrigation was used in 35%. Among eight cases of CAOI that required placement of a new prosthetic joint, all were successfully treated. There were no microbiologic failures. CONCLUSIONS: Candida osteoarticular infections may be successfully treated with substantially limited durations of AFT when combined with a thorough surgical approach.