High Mortality After Total Knee Arthroplasty Periprosthetic Joint Infection is Related to Preoperative Morbidity and the Disease Process but Not Treatment.

BACKGROUND: Periprosthetic joint infection (PJI) mortality rate is approximately 20%. The etiology for high mortality remains unknown. The objective of this study was to determine whether mortality was associated with preoperative morbidity (frailty), sequalae of treatment, or the PJI disease process itself. METHODS: A multicenter observational study was completed comparing 184 patients treated with septic revision total knee arthroplasty (TKA) to a control group of 38 patients treated with aseptic revision TKA. Primary outcomes included time and the cause of death. Secondary outcomes included preoperative comorbidities and Charlson Comorbidity Index (CCMI) measured preoperatively and at various postoperative timepoints. RESULTS: The septic revision TKA cohort experienced earlier mortality compared to the aseptic cohort, with a higher mortality rate at 90 days, 1, 2, and 3 years after index revision surgery (P = .01). There was no significant difference for any single cause of death (P > .05 for each). The mean preoperative CCMI was higher (P = .005) in the septic revision TKA cohort. Both septic and aseptic cohorts experienced a significant increase in CCMI from the preoperative to 3 years postoperative (P < .0001 and P = .002) and time of death (P < .0001 both) timepoints. The septic revision TKA cohort had a higher CCMI 3 years postoperatively (P = .001) and at time of death (P = .046), but not one year postoperatively (P = .119). CONCLUSION: Compared to mortality from aseptic revision surgery, septic revision TKA is associated with earlier mortality, but there is no single specific etiology. As quantified by changes in CCMI, PJI mortality was associated with both frailty and the PJI disease process, but not treatment.

Risk Factors, Screening, and Treatment Challenges in Staphylococcus aureus Native Septic Arthritis.

BACKGROUND: Staphylococcus aureus is the most common cause of native septic arthritis. Few studies have characterized this disease during the US opioid epidemic. The role of methicillin-resistant Staphylococcus aureus (MRSA) nasal screening in this disease has not been elucidated. We sought to identify risk factors and outcomes for S. aureus native septic arthritis and to evaluate MRSA screening in this disease. METHODS: A retrospective cohort study of native septic arthritis patients (2012-2016) was performed. Demographics, risk factors, and outcomes were compared between Staphylococcus aureus and other native septic arthritis infections. Sensitivity, specificity, and predictive values of MRSA screening were assessed. RESULTS: Two hundred fifteen cases of native septic arthritis were included. S. aureus was cultured in 64% (138/215). MRSA was cultured in 23% (50/215). S. aureus was associated with injection drug use (odds ratio [OR], 4.33; 95% CI, 1.74-10.81; P = .002) and switching antibiotics (OR, 3.92; 95% CI, 1.01-21.38; P = .032). For every 10-year increase in age, the odds of S. aureus decreased (OR, 0.72; 95% CI, 0.60-0.87; P = .001). For 1-unit increases in Charlson comorbidity index score, the odds of S. aureus decreased (OR, 0.82; 95% CI, 0.73-0.91; P = .0004). MRSA screening during admission demonstrated a sensitivity of 0.59, specificity of 0.96, positive predictive value of 0.85, and negative predictive value of 0.84 for MRSA native septic arthritis. CONCLUSIONS: The opioid epidemic may be contributing to a demographic shift in native septic arthritis to younger, healthier individuals. S. aureus native septic arthritis has unique risks, including injection drug use. MRSA screening may be useful to rule in MRSA native septic arthritis.

Staphylococcus epidermidis Biofilms Have a High Tolerance to Antibiotics in Periprosthetic Joint Infection.

Both Staphylococcus aureus and Staphylococcus epidermidis are commonly associated with periprosthetic joint infections (PJIs). The treatment of PJI can be challenging because biofilms are assumed to have an increased intolerance to antibiotics. This makes the treatment of PJI challenging from a clinical perspective. Although S. aureus has been previously demonstrated to have increased biofilm antibiotic tolerance, this has not been well established with Staphylococcus epidermidis. A prospective registry of PJI S. epidermidis isolates was developed. The efficacy of clinically relevant antibiotics was quantified against these isolates. S. epidermidis planktonic minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were collected using clinical laboratory standard index (CLSI) assays for eight antibiotics (doxycycline, vancomycin, daptomycin, clindamycin, rifampin, nafcillin, and trimethoprim/sulfamethoxazole). Mature biofilms were grown in vitro, after which minimum biofilm inhibitory concentration (MBIC) and minimum biofilm bactericidal concentration (MBBC) were quantified. Only rifampin and doxycycline had a measurable MBIC across all tested isolates. Based on MBBC, 64% of S. epidermidis biofilms could be eliminated by rifampin, whereas only 18% by doxycycline. S. epidermidis biofilm was observed to have a high tolerance to antibiotics as compared to planktonic culture. Isolate biofilm antibiotic tolerance varied to a larger degree than was seen in planktonic cultures.

Administration of Tranexamic Acid Improves Long-Term Outcomes in Total Knee Arthroplasty.

BACKGROUND: Blood transfusion in total knee arthroplasty (TKA) is associated with increased morbidity, including periprosthetic joint infection (PJI). Tranexamic acid (TXA) reduces blood transfusion rates, but there is limited evidence demonstrating improved outcomes in TKA resulting from TXA administration. The objectives of this study are determining whether TXA is associated with decreased rate of PJI, decreased rate of outcomes associated with PJI, and whether there are differences in rates of adverse events. METHODS: A multicenter cohort study comprising 23,421 TKA compared 4423 patients receiving TXA to 18,998 patients not receiving TXA. Primary outcome was PJI within 2 years of TKA. Secondary outcomes included revision surgery, irrigation and debridement, transfusion, and length of stay. Adverse events included readmission, deep vein thrombosis, pulmonary emboli, myocardial infarction, or stroke. Adjusted odds ratios were determined using linear mixed models controlling for age, sex, thromboembolic prophylaxis, Charlson comorbidity index, year of TKA, and surgeon. RESULTS: TXA administration reduced incidence of PJI by approximately 50% (odds ratio [OR], 0.55; P = .03). Additionally, there was decreased incidence of revision surgery at 2 years (OR, 0.66; P = .02). Patients receiving TXA had reductions in transfusion rate (OR, 0.15; P < .0001) and length of stay (P < .0001). There was no difference in the rate of pulmonary emboli (OR, 1.20; P = .39), myocardial infarction (OR, 0.78; P = .55), or stroke (OR, 1.17; P = .77). CONCLUSION: Administration of TXA in TKA resulted in reduced rate of PJI and overall revision surgery. No difference in thromboembolic events were observed. The use of TXA is safe and improves outcomes in TKA. LEVEL OF EVIDENCE: Level III, Observational Cohort Study.

Benefits and Adverse Events Associated With Extended Antibiotic Use in Total Knee Arthroplasty Periprosthetic Joint Infection.

BACKGROUND: Total knee arthroplasty (TKA) periprosthetic joint infection (PJI) can be managed with debridement, antibiotic therapy, and implant retention (DAIR). Oral antibiotics can be used after DAIR for an extended time period to improve outcomes. The objective of this study was to compare DAIR failure rates and adverse events between an initial course of intravenous antibiotic therapy and the addition of extended treatment with oral antibiotics. METHODS: A multicenter observational study of patients diagnosed with a TKA PJI who underwent DAIR was performed. The primary outcome of interest was the failure rate derived from the survival time between the DAIR procedure and future treatment failure. RESULTS: One hundred eight patients met inclusion criteria; 47% (n = 51) received an extended course of oral antibiotics. These patients had a statistically significant lower failure rate compared to those who received only intravenous antibiotics (hazard ratio, 2.47; P = .009). Multivariable analysis demonstrated that extended antibiotics independently predicted treatment success, controlling for other variables. There was no significant difference in failure rates between an extended course of oral antibiotics less or more than 12 months (P = .23). No significant difference in the rates of adverse events was observed between patients who received an initial course of antibiotics alone and those who received a combination of initial and extended antibiotic therapy (P = .59). CONCLUSIONS: Extending therapy with oral antibiotics had superior infection-free survival for TKA PJI managed with DAIR. There was no increase in adverse events, demonstrating safety. After 1 year, there appears to be no significant benefit associated with continued antibiotic therapy.

Do Culture Negative Periprosthetic Joint Infections Remain Culture Negative?

BACKGROUND: Diagnosis and treatment of culture negative total knee arthroplasty (TKA) periprosthetic joint infection (PJI) is challenging. There is debate over whether culture negative PJI confers increased risk of failure and which organisms are responsible. It is also unclear as to what factors predict conversion from culture negative to culture positivity. To address these issues, we performed an observational study to detect factors associated with transition from culture negative to culture positive TKA PJI in those patients that failed irrigation and debridement (I&D), determine the incidence of this transition, and identify those organisms that were associated with treatment failure. METHODS: A multicenter observational cohort study was performed on patients with TKA PJI as defined by Musculoskeletal Infection Society criteria without cultured organisms and treated with I&D. Primary outcome was failure defined as any subsequent surgical procedure. Secondary outcome included cultured organism within 2 years of initial I&D. RESULTS: Two hundred sixteen TKA I&D procedures were performed for PJI, and 36 met inclusion criteria. The observed treatment failure rate for culture negative PJI treated with I&D was 41.67%. Of those culture negative I&Ds that failed, 53.33% became culture positive after failure. Of those that converted to culture positive, 62.5% were Staphylococcus species. The odds ratio associated with becoming culture positive following culture negative treatment failure in the setting of antibiotic administration prior to the initial I&D procedure was 0.69 (95% confidence interval 0.14-3.47, P = .65). CONCLUSION: Many cases of culture negative TKA PJI treated with I&D eventually fail and become culture positive. Staphylococci are common organisms identified after culture negative PJI.

A Multicenter Study of Irrigation and Debridement in Total Knee Arthroplasty Periprosthetic Joint Infection: Treatment Failure Is High.

BACKGROUND: In total knee arthroplasty (TKA) periprosthetic joint infection (PJI), irrigation and debridement (I&D) with component retention is a treatment option with a wide variation in reported failure rates. The purpose of this study was to determine failure rates, outcomes, and factors that predict failure in I&D for TKA PJI. METHODS: A multicenter observational study of patients with a TKA PJI and subsequently undergoing an I&D with retention of components was conducted. The primary outcome was failure rate of I&D, where failure was defined as any subsequent surgical procedures. RESULTS: Two hundred sixteen cases of I&D with retention of components performed on 206 patients met inclusion criteria. The estimated long-term failure rate at 4 years was 57.4%. Time-to-event analyses revealed that the median survival time was 14.32 months. Five-year mortality was 19.9%. Multivariable modeling revealed that time symptomatic and organism were independent predictors of I&D failure. Culture-negative status had a higher hazard for failure than culture-positive patients. When primary organism and time symptomatic were selected to produce an optimized scenario for an I&D, the estimated failure rate was 39.6%. CONCLUSION: I&D with retention of components has a high failure rate, and there is a high incidence of more complex procedures after this option is chosen. The patient comorbidities we investigated did not predict I&D success. Our results suggest that I&D has a limited ability to control infection in TKA and should be used selectively under optimum conditions.

Pseudomonas Prosthetic Joint Infections: A Review of 102 Episodes.

Background: The outcome of patients with Pseudomonas prosthetic joint infection (PS PJI) has not been well studied. The aim of this retrospective cohort study was to assess the outcome of patients with Pseudomonas PJI and to review risk factors associated with failure of therapy. Methods: Between 1/1969 and 12/2012, 102 episodes of PS PJI in 91 patients were identified. Results: The mean age at the time of diagnosis was 67.4 years; forty three percent had knee involvement. Over 40 percent had either diabetes mellitus or a history of gastrointestinal or genitourinary surgery. Nearly half (48 out of 102 episodes) received aminoglycoside monotherapy, while 25% received an anti-pseudomonal cephalosporin. The 2-year cumulative survival free from failure was 69% (95% CI, 56%-82%). Patients treated with resection arthroplasty, two-stage exchange, and debridement with implant retention had a 2-year cumulative survival free from failure of 80% (95% CI, 66%-95%), 83% (95% CI, 60%-100%), and 26% (95% CI, 23%-29%) respectively (P=0.0001). Conclusions: PS PJI's are associated with a high failure rate. Patients treated with debridement and implant retention had a worse outcome.

Anaerobic prosthetic joint infection.

In an effort to improve mobility and alleviate pain from degenerative and connective tissue joint disease, an increasing number of individuals are undergoing prosthetic joint replacement in the United States. Joint replacement is a highly effective intervention, resulting in improved quality of life and increased independence [1]. By 2030, it is predicted that approximately 4 million total hip and knee arthroplasties will be performed yearly in the United States [2]. One of the major complications associated with this procedure is prosthetic joint infection (PJI), occurring at a rate of 1-2% [3-7]. In 2011, the Musculoskeletal Infectious Society created a unifying definition for prosthetic joint infection [8]. The following year, the Infectious Disease Society of America published practice guidelines that focused on the diagnosis and management of PJI. These guidelines focused on the management of commonly encountered organisms associated with PJI, including staphylococci, streptococci and select aerobic Gram-negative bacteria. However, with the exception of Propionibacterium acnes, management of other anaerobic organisms was not addressed in these guidelines [1]. Although making up approximately 3-6% of PJI [9,10], anaerobic microorganisms cause devastating complications, and similar to the more common organisms associated with PJI, these bacteria also result in significant morbidity, poor outcomes and increased health-care costs. Data on diagnosis and management of anaerobic PJI is mostly derived from case reports, along with a few cohort studies [3]. There is a paucity of published data outlining factors associated with risks, diagnosis and management of anaerobic PJI. We therefore reviewed available literature on anaerobic PJI by systematically searching the PubMed database, and collected data from secondary searches to determine information on pathogenesis, demographic data, clinical features, diagnosis and management. We focused our search on five commonly encountered anaerobic organisms associated with PJI. Since anaerobic PJI has also been linked to dental procedures, we also reviewed information on the use of dental procedures and prophylaxis, when available.

Cryptococcus neoformans prosthetic joint infection: case report and review of the literature.

A 77-year-old woman with diabetes mellitus, myasthenia gravis and bilateral total hip arthroplasties underwent a two-stage procedure followed by treatment with vancomycin for a coagulase-negative staphylococcal prosthetic hip infection. This was complicated by a spontaneous left hip dislocation with a hematoma that was evacuated; all intraoperative cultures grew out Cryptococcus neoformans. Treatment with intravenous liposomal amphotericin B was started. Her prosthetic device was retained, and she was treated for 12 weeks, after which she was transitioned to fluconazole for long-term therapy. The hip remained stable 1 year out from her admission, and she retained mobility with the assistance of a walker. Fungi are an uncommon but potentially devastating cause of prosthetic joint infections, and most are due to Candida species. Cryptococcus neoformans is an ubiquitous yeast with worldwide distribution that generally causes infections in patients with major T cell immune deficiencies (e.g., HIV, transplantation and receipt of corticosteroids). Cryptococcal infections of native osteoarticular structures are uncommon, but have been well described in the literature. Data regarding cryptococcal prosthetic joint infections, however, are sparse.

Three cases of dermatomyositis associated with papillary thyroid cancer.

OBJECTIVE: Dermatomyositis (DM) is considered a paraneoplastic phenomenon and cancer may precede or follow the development of clinical features by several years. Despite the prevalence of thyroid cancer, reports of an association are rare. We report 3 cases of dermatomyositis and thyroid cancer, focusing on the clinical course of the rheumatologic condition following thyroidectomy. We also performed a comprehensive review of the current literature. METHODS: We performed a chart review between 1960 and 2012 to identify patients with DM and papillary thyroid cancer (PTC) seen in Mayo Clinic, Rochester, in Minnesota, a tertiary referral center. Only 3 patients were identified using the above criteria. RESULTS: There was a significant improvement in the course of the dermatological condition after definitive treatment for thyroid cancer (i.e. thyroidectomy) in one of our patients. The risk of a first malignancy is highest at the time the diagnosis of dermatomyositis is made and remains significantly higher in the first two years following diagnosis. A comprehensive literature review identified only two patients with PTC and dermatomyositis (both in Taiwan) across 4 international population cohorts. In addition, several cases have been reported from patients in the Far East, a geographical predilection that is unexplained. CONCLUSIONS: Our case series highlights the uncommon association between thyroid cancer and dermatomyositis while illustrating prevailing knowledge about the temporal relationship between dermatomyositis and thyroid cancer. Increased vigilance for and treatment of thyroid cancer in patients with dermatomyositis may assist in the successful management of this difficult rheumatologic condition.

Atypical Omenn Syndrome due to Adenosine Deaminase Deficiency.

We present here a novel case of an atypical Omenn syndrome (OS) phenotype due to mutations in the ADA gene encoding adenosine deaminase. This case is noteworthy for a significant increase in circulating CD56(bright)CD16- cytokine-producing NK cells after treatment with steroids for skin rash.

Lower gastrointestinal tract cancer predisposition syndromes.

Although inherited predisposition to colorectal cancer (CRC) has been suspected for more than 100 years, definitive proof of Mendelian syndromes had to await maturation of molecular genetic technologies. Since the l980s, the genetics of several clinically distinct entities has been revealed. Five disorders that share a hereditary predisposition to CRC are reviewed in this article.