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.

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.

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.

Perioperative Infection Prophylaxis with Vancomycin is a Significant Risk Factor for Deep Surgical Site Infection in Spine Surgery.

STUDY DESIGN: Retrospective cohort. OBJECTIVE: The purpose of this study was to compare the efficacy of cefazolin versus vancomycin for perioperative infection prophylaxis. SUMMARY OF BACKGROUND DATA: The relative efficacy of cefazolin alternatives for perioperative infection prophylaxis is poorly understood. METHODS: This study was a single-center multi-surgeon retrospective review of all patients undergoing primary spine surgery from an institutional registry. Postoperative infection was defined by the combination of three criteria: irrigation and debridement within 3 months of the index procedure, clinical suspicion for infection, and positive intraoperative cultures. Microbiology records for all infections were reviewed to assess the infectious organism and organism susceptibilities. Univariate and multivariate analyses were performed. RESULTS: A total of 10,122 patients met inclusion criteria. The overall incidence of infection was 0.78%, with an incidence of 0.73% in patients who received cefazolin and 2.03% in patients who received vancomycin (OR 2.83, 95% CI 1.35-5.91, P-0.004). Use of IV vancomycin (OR 2.83, 95% CI 1.35-5.91, P=0.006), BMI (MD 1.56, 95% CI 0.32-2.79, P=0.014), presence of a fusion (OR 1.62, 95% CI 1.04-2.52, P=0.033), and operative time (MD 42.04, 95% CI 16.88-67.21, P=0.001) were significant risk factors in the univariate analysis. In the multivariate analysis, only non-cefazolin antibiotics (OR 2.48, 95% CI 1.18-5.22, P=0.017) and BMI (MD 1.56, 95% CI 0.32-2.79, P=0.026) remained significant independent risk factors. Neither IV antibiotic regimen nor topical vancomycin significantly impacted Gram type, organism type, or antibiotic resistance (P>0.05). The most common reason for antibiosis with vancomycin was a penicillin allergy (75.0%). CONCLUSIONS: Prophylactic antibiosis with IV vancomycin leads to a 2.5-times higher risk of infection compared to IV cefazolin in primary spine surgery. We recommend the routine use of IV cefazolin for infection prophylaxis, and caution against the elective use of alternative regimens like IV vancomycin unless clinically warranted.

Perioperative infection in the patient with rheumatic disease.

The risk of infection accompanies the benefits of surgery. Immunomodulatory chronic illnesses may increase the risk of surgical infections. Surgical patients with rheumatologic illness need close preoperative assessment regarding their infection risks (fixed and modifiable), which vary on the basis of the proposed procedure, specific rheumatologic illness, and underlying comorbidities. Modification of the medication regimens in the preoperative period may decrease risk and enhance healing. Intraoperative antisepsis and antibiotic prophylaxis remain critical in this patient population. Postoperative fevers within 3 days of surgery are usually noninfectious but require vigilance and attention. The principles of surgical infection reduction are not different in the rheumatologic and general patient populations, but best practice depends on expertise in caring for patients with these illnesses.

Candida osteomyelitis: analysis of 207 pediatric and adult cases (1970-2011).

BACKGROUND: The epidemiology, pathogenesis, clinical manifestations, management, and outcome of Candida osteomyelitis are not well understood. METHODS: Cases of Candida osteomyelitis from 1970 through 2011 were reviewed. Underlying conditions, microbiology, mechanisms of infection, clinical manifestations, antifungal therapy, and outcome were studied in 207 evaluable cases. RESULTS: Median age was 30 years (range, ≤ 1 month to 88 years) with a >2:1 male:female ratio. Most patients (90%) were not neutropenic. Localizing pain, tenderness, and/or edema were present in 90% of patients. Mechanisms of bone infection followed a pattern of hematogenous dissemination (67%), direct inoculation (25%), and contiguous infection (9%). Coinciding with hematogenous infection, most patients had ≥2 infected bones. When analyzed by age, the most common distribution of infected sites for adults was vertebra (odds ratio [OR], 0.09; 95% confidence interval [CI], .04-.25), rib, and sternum; for pediatric patients (≤18 years) the pattern was femur (OR, 20.6; 95% CI, 8.4-48.1), humerus, then vertebra/ribs. Non-albicans Candida species caused 35% of cases. Bacteria were recovered concomitantly from 12% of cases, underscoring the need for biopsy and/or culture. Candida septic arthritis occurred concomitantly in 21%. Combined surgery and antifungal therapy were used in 48% of cases. The overall complete response rate of Candida osteomyelitis of 32% reflects the difficulty in treating this infection. Relapsed infection, possibly related to inadequate duration of therapy, occurred among 32% who ultimately achieved complete response. CONCLUSIONS: Candida osteomyelitis is being reported with increasing frequency. Localizing symptoms are usually present. Vertebrae are the most common sites in adults vs femora in children. Timely diagnosis of Candida osteomyelitis with extended courses of 6-12 months of antifungal therapy, and surgical intervention, when indicated, may improve outcome.

Postoperative infections of the lumbar spine: presentation and management.

PURPOSE: Postoperative surgical site infections (SSI) are a frequent complication following posterior lumbar spinal surgery. In this manuscript we review strategies for prevention, diagnosis and treatment of SSI. METHODS: The literature was reviewed using the Pubmed database. RESULTS: We identified fifty-nine relevant manuscripts almost exclusively composed of Level III and IV studies. CONCLUSIONS: Risk factors for SSI include: 1) factors related to the nature of the spinal pathology and the surgical procedure and 2) factors related to the systemic health of the patient. Staphylococcus aureus is the most common infectious organism in reported series. Proven methods to prevent SSI include prophylactic antibiotics, meticulous adherence to aseptic technique and frequent release of retractors to prevent myonecrosis. The presentation of SSI is varied depending on the virulence of the infectious organism. Frequently, increasing pain is the only presenting complaint and can lead to a delay in diagnosis. Magnetic resonance imaging and the use of C-reactive protein laboratory studies are useful to establish the diagnosis. Treatment of SSI is centered on surgical debridement of all necrotic tissue and obtaining intra-operative cultures to guide antibiotic therapy. We recommend the involvement of an infectious disease specialist and use of minimum serial bactericidal titers to monitor the efficacy of antibiotic treatment. In the most cases, SSI can be adequately treated while leaving spinal instrumentation in place. For severe SSI, repeat debridement, delayed closure and involvement of a plastic surgeon may be necessary.

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.

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.

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.

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.

Propionibacterium acnes infection after shoulder arthroplasty: a diagnostic challenge.

HYPOTHESIS: This study reviewed a series of patients diagnosed with Propionibacterium acnes infection after shoulder arthroplasty in order to describe its clinical presentation, the means of diagnosis, and provide options for treatment. MATERIALS AND METHODS: From 2002 to 2006, 11 patients diagnosed with P acnes infection after shoulder arthroplasty were retrospectively reviewed and analyzed for (1) clinical diagnosis; (2) laboratory data, including white blood cell count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP); (3) fever; (4) number of days for laboratory growth of P acnes; (5) organism sensitivities; (6) antibiotic regimen and length of treatment; and (7) surgical management. Infection was diagnosed by 2 positive cultures. RESULTS: Five patients had an initial diagnosis of infection and underwent implant removal, placement of an antibiotic spacer, and staged reimplantation after a course of intravenous antibiotics. In the remaining 6 patients, surgical treatment varied according to the clinical diagnosis. When infection was recognized by intraoperative cultures, antibiotics were initiated. The average initial ESR and CRP values were 33 mm/h and 2 mg/dL, respectively. The average number of days from collection to a positive culture was 9. All cultures were sensitive to penicillin and clindamycin and universally resistant to metronidazole. DISCUSSION: Prosthetic joint infection secondary to P acnes is relatively rare; yet, when present, is an important cause of clinical implant failure. Successful treatment is hampered because clinical findings may be subtle, many of the traditional signs of infection are not present, and cultures may not be positive for as long as 2 weeks.

Modern treatment of infected total knee arthroplasty with a 2-stage reimplantation protocol.

The purpose of this study was to determine if 2-stage reimplantation for the treatment of infected total knee arthroplasty (TKA) is still effective for treating contemporary pathogens, many of which are multidrug resistant (MDR). The medical records of all cases of infected TKAs from April 1998 to March 2006 were retrospectively reviewed for data on infecting organism and success of treatment. Of 72 patients (75 knees), with a minimum of 2 years of follow-up, who completed the protocol, the infection was eradicated in 90.7% (68/75 knees). Thirty-one (91.2%) of 34 of MDR infections and 42 (91.3%) of 46 of non-MDR infections were successfully treated. These results support previous studies that demonstrated the effectiveness of a 2-stage reimplantation protocol with a standard 1:8 minimal bactericidal titer for treating infections after TKA, including MDR organisms.

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.

Treatment of infected total hip arthroplasty with a 2-stage reimplantation protocol: update on "our institution's" experience from 1989 to 2003.

Infection is a devastating complication of total hip arthroplasty (THA). This study aimed to determine whether 2-stage reimplantation is still effective for treating contemporary pathogens, including multidrug-resistant organisms. Records of all cases of infected THAs from 1989 to 2003 were reviewed for data on organism, presence of drug resistance, use of an antibiotic-impregnated spacer, type of reimplant, and success of treatment. Of the 87 protocol patients with 2 years of follow-up, 94.3% (82) underwent reimplantation. The original infection was eradicated in 80 of the 84 hips (78/82 patients), a success rate of 95%. All 21 multidrug-resistant infections were eradicated. There were no major differences in eradication rates when the period was split into 3 sections. These results support previous studies from our institution which demonstrated the effectiveness of a 2-stage reimplantation protocol with a standard 1:8 minimal bactericidal titer for treating infections after THA, including those due to methicillin-resistant organisms.

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.