Prosthetic Joint Infections Caused by Mycobacterium tuberculosis Complex-An ESGIAI-ESGMYC Multicenter, Retrospective Study and Literature Review.

PURPOSE: While tuberculosis remains a significant global health concern, prosthetic joint infections (PJIs) caused by members of the Mycobacterium tuberculosis complex are exceptionally rare. Our objective is to perform a retrospective search of new cases of this disease and analyze all cases available in the literature of tuberculous PJIs, aiming to detect factors that may influence patient outcomes. METHODS: The ESGIAI and ESGMYC study groups were used to collect information on non-published cases of tuberculous prosthetic joint infections (PJIs). Additionally, a literature review of all published cases of tuberculous PJIs was conducted. All identified cases in the retrospective study and in the literature review were merged and included in the statistical analysis, involving both univariate and multivariate analyses. RESULTS: Fifteen previously unreported cases of tuberculous prosthetic joint infections (PJIs) from four countries were detailed. Among them, ten patients were female, with a median age of 76 years. The hip was affected in 13 cases. Seven patients experienced co-infection with another microorganism. Treatment approaches varied, with 13 patients undergoing implant removal, one treated with DAIR (debridement, antibiotics, and implant retention), and one case was treated with an unknown treatment method. All patients received antibiotic therapy and achieved a cure. The literature review that was conducted detected 155 published cases. Univariate analysis revealed a statistical significance for previous tuberculosis, joint, and no importance of surgery for cure. CONCLUSIONS: Tuberculous prosthetic joint infection (PJI) is a rare condition, typically presenting as a localized chronic infection. Antibiotic treatment is essential for the management of these patients, but neither surgical treatment nor duration of treatment seems to have importance in the outcome.

Appropriate Duration of Antimicrobial Treatment for Prosthetic Joint Infections: A Narrative Review.

Prosthetic joint infections are considered difficult to treat they needing aggressive surgery and long antimicrobial treatments. However, the exact duration of these therapies has been established empirically. In the last years, several studies have explored the possibility of reducing the length of treatment in this setting, with conflicting results. In this narrative review, we critically appraise the published evidence, considering the different surgical approaches (implant retention [DAIR] and one-step and two-step exchange procedures) separately. In patients managed with DAIR, usually treated for at least 12 weeks, a large, randomized trial failed to show that 6 weeks were non-inferior. However, another randomized clinical trial supports the use of 8 weeks, as long as the surgical conditions are favorable and antibiotics with good antibiofilm activity can be administered. In patients managed with a two-step exchange procedure, usually treated during 6 weeks, a randomized clinical trial showed the efficacy of a 4-week course of antimicrobials. Also, the use of local antibiotics may allow the use of even shorter treatments. Finally, in the case of one-step exchange procedures, there is a trend towards reducing the length of therapy, and the largest randomized clinical trial supports the use of 6 weeks of therapy.

Executive summary: Guidelines for the diagnosis and treatment of septic arthritis in adults and children, developed by the GEIO (SEIMC), SEIP and SECOT.

Infection of a native joint, commonly referred to as septic arthritis, is a medical emergency because of the risk of joint destruction and subsequent sequelae. Its diagnosis requires a high level of suspicion. These guidelines for the diagnosis and treatment of septic arthritis in children and adults are intended for use by any physician caring for patients with suspected or confirmed septic arthritis. They have been developed by a multidisciplinary panel with representatives from the Bone and Joint Infections Study Group (GEIO) belonging to the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Society of Paediatric Infections (SEIP) and the Spanish Society of Orthopaedic Surgery and Traumatology (SECOT), and two rheumatologists. The recommendations are based on evidence derived from a systematic literature review and, failing that, on the opinion of the experts who prepared these guidelines. A detailed description of the background, methods, summary of evidence, the rationale supporting each recommendation, and gaps in knowledge can be found online in the complete document.

Early switch from intravenous to oral antibiotic treatment in bone and joint infections.

OBJECTIVES: The timing of the switch from intravenous (i.v.) to oral antibiotic therapy for orthopaedic bone and joint infections (BJIs) is debated. In this narrative article, we discuss the evidence for and against an early switch in BJIs. DATA SOURCES: We performed a PubMed and internet search investigating the association between the duration of i.v. treatment for BJI and remission of infection among adult orthopaedic patients. CONTENT: Among eight randomized controlled trials and multiple retrospective studies, we failed to find any minimal duration of postsurgical i.v. therapy associated with clinical outcomes. We did not find scientific data to support the prolonged use of i.v. therapy or to inform a minimal duration of i.v. THERAPY: Growing evidence supports the safety of an early switch to oral medications once the patient is clinically stable. IMPLICATIONS: After surgery for BJI, a switch to oral antibiotics within a few days is reasonable in most cases. We recommend making the decision on the time point based on clinical criteria and in an interdisciplinary team at the bedside.

Rates and Predictors of Treatment Failure in Staphylococcus aureus Prosthetic Joint Infections According to Different Management Strategies: A Multinational Cohort Study-The ARTHR-IS Study Group.

INTRODUCTION: Guidelines have improved the management of prosthetic joint infections (PJI). However, it is necessary to reassess the incidence and risk factors for treatment failure (TF) of Staphylococcus aureus PJI (SA-PJI) including functional loss, which has so far been neglected as an outcome. METHODS: A retrospective cohort study of SA-PJI was performed in 19 European hospitals between 2014 and 2016. The outcome variable was TF, including related mortality, clinical failure and functional loss both after the initial surgical procedure and after all procedures at 18 months. Predictors of TF were identified by logistic regression. Landmark analysis was used to avoid immortal time bias with rifampicin when debridement, antibiotics and implant retention (DAIR) was performed. RESULTS: One hundred twenty cases of SA-PJI were included. TF rates after the first and all surgical procedures performed were 32.8% and 24.2%, respectively. After all procedures, functional loss was 6.0% for DAIR and 17.2% for prosthesis removal. Variables independently associated with TF for the first procedure were Charlson ≥ 2, haemoglobin < 10 g/dL, bacteraemia, polymicrobial infection and additional debridement(s). For DAIR, TF was also associated with a body mass index (BMI) > 30 kg/m2 and delay of DAIR, while rifampicin use was protective. For all procedures, the variables associated with TF were haemoglobin < 10 g/dL, hip fracture and additional joint surgery not related to persistent infection. CONCLUSIONS: TF remains common in SA-PJI. Functional loss accounted for a substantial proportion of treatment failures, particularly after prosthesis removal. Use of rifampicin after DAIR was associated with a protective effect. Among the risk factors identified, anaemia and obesity have not frequently been reported in previous studies. TRIAL REGISTRATION: This study is registered at clinicaltrials.gov, registration no. NCT03826108.

Staphylococcus aureus is one of the most virulent bacteria and frequently causes prosthetic joint infections.Knowledge of the treatment of this type of infection has advanced in recent years, and treatment guidelines have led to improved management. Typically, the successful treatment of these infections has been determined by clinical cure, that is, the symptoms of infection have disappeared, but has not taken into account loss of function (such as significant difficulties walking), which is critical for the patient's quality of life. Our aim in this study was to evaluate the success of current management strategies for S. aureus prosthetic joint infection, including recovery of functionality, and the factors that predict why some of these infections are not cured, to identify areas for improvement.In a multinational cohort of 128 patients with S. aureus prosthetic joint infection, rates of treatment failure were found to be high, with significant rates of loss of function, especially when the prosthesis needed to be removed. Loss of function was less frequent when the infection was initially treated with surgical cleaning without removal of the prosthesis, even when this procedure failed at first. We found that anaemia and obesity were associated with lower treatment success, and that the probability of treatment success increased when surgical cleaning without prosthesis removal was performed early, and when the antibiotic rifampicin was used in combination with another antibiotic.

Preoperative and perioperative risk factors, and risk score development for prosthetic joint infection due to Staphylococcus aureus: a multinational matched case-control study.

OBJECTIVES: We aim to identify the preoperative and perioperative risk factors associated with post-surgical Staphylococcus aureus prosthetic joint infections (PJI) and to develop and validate risk-scoring systems, to allow a better identification of high-risk patients for more efficient targeted interventions. METHODS: We performed a multicenter matched case-control study of patients who underwent a primary hip and knee arthroplasty from 2014 to 2016. Two multivariable models by logistic regression were performed, one for the preoperative and one for perioperative variables; predictive scores also were developed and validated in an external cohort. RESULTS: In total, 130 cases and 386 controls were included. The variables independently associated with S. aureus-PJI in the preoperative period were (adjusted OR; 95% CI): body mass index >30 kg/m2 (3.0; 1.9 to 4.8), resident in a long-term care facility (2.8; 1.05 to 7.5), fracture as reason for arthroplasty (2.7; 1.4 to 5.03), skin disorders (2.5; 0.9 to 7.04), previous surgery in the index joint (2.4; 1.3 to 4.4), male sex (1.9; 1.2 to 2.9) and American Society of Anesthesiologists index score 3 to 4 (1.8; 1.2 to 2.9). The area under the receiver operating characteristic curve was 0.73 (95% CI 0.68 to 0.78). In perioperative model, the risk factors were the previous ones plus surgical antibiotic prophylaxis administered out of the first 60 minutes before incision (5.9; 2.1 to 16.2), wound drainage for >72 hours after arthroplasty (4.5; 1.9 to 19.4) and use of metal bearing material versus ceramic (1.9; 1.1 to 3.3). The area under the receiver operating characteristic curve was 0.78 (95% CI 0.72 to 0.83). The predictive scores developed were validated in the external cohort. DISCUSSION: Predictive scores for S. aureus-PJI were developed and validated; this information would be useful for implementation of specific preventive measures.

Prognosis of unexpected positive intraoperative cultures in arthroplasty revision: A large multicenter cohort.

BACKGROUND: The positive-intraoperative-cultures-type prosthetic joint infection (PIOC-PJI) is considered when surgical cultures yield microorganisms in presumed aseptic arthroplasty revisions. Herein we assess the risk factors for failure in the largest cohort of PIOC-PJI patients reported to date. METHODS: A retrospective, observational, multicenter study was performed during 2007-2017. Surgeries leading to diagnose PIOC-PJI included only one-stage procedures with either complete or partial prosthesis revision. Failure was defined as recurrence caused by the same microorganism. RESULTS: 203 cases were included (age 72 years, 52% females). Coagulase-negative staphylococci (n = 125, 62%) was the main etiology, but some episodes were caused by virulent bacteria (n = 51, 25%). Prosthesis complete and partial revision was performed in 93 (46%) and 110 (54%) cases, respectively. After a median of 3.4 years, failure occurred in 17 episodes (8.4%, 95%CI 5.3-13.1). Partial revision was an independent predictor of failure (HR 3.63; 95%CI 1.03-12.8), adjusted for gram-negative bacilli (GNB) infection (HR 2.68; 95%CI 0.91-7.89) and chronic renal impairment (HR 2.40; 95%CI 0.90-6.44). Treatment with biofilm-active antibiotics (rifampin/fluoroquinolones) had a favorable impact on infections caused by staphylococci and GNB. CONCLUSION: Overall prognosis of PIOC-PJI is good, but close follow-up is required in cases of partial revision and in infections caused by GNB.

Prosthetic Shoulder Joint Infection by Cutibacterium acnes: Does Rifampin Improve Prognosis? A Retrospective, Multicenter, Observational Study.

This retrospective, multicenter observational study aimed to describe the outcomes of surgical and medical treatment of C. acnes-related prosthetic joint infection (PJI) and the potential benefit of rifampin-based therapies. Patients with C. acnes-related PJI who were diagnosed and treated between January 2003 and December 2016 were included. We analyzed 44 patients with C. acnes-related PJI (median age, 67.5 years (IQR, 57.3-75.8)); 75% were men. The majority (61.4%) had late chronic infection according to the Tsukayama classification. All patients received surgical treatment, and most antibiotic regimens (43.2%) included ß-lactam. Thirty-four patients (87.17%) were cured; five showed relapse. The final outcome (cure vs. relapse) showed a nonsignificant trend toward higher failure frequency among patients with previous prosthesis (OR: 6.89; 95% CI: 0.80-58.90) or prior surgery and infection (OR: 10.67; 95% IC: 1.08-105.28) in the same joint. Patients treated with clindamycin alone had a higher recurrence rate (40.0% vs. 8.8%). Rifampin treatment did not decrease recurrence in patients treated with ß-lactams. Prior prosthesis, surgery, or infection in the same joint might be related to recurrence, and rifampin-based combinations do not seem to improve prognosis. Debridement and implant retention appear a safe option for surgical treatment of early PJI.

Implant Removal in the Management of Prosthetic Joint Infection by Staphylococcus aureus: Outcome and Predictors of Failure in a Large Retrospective Multicenter Study.

OBJECTIVES: To compare the characteristics and outcomes of cases with acute prosthetic joint infection (PJI; early post-surgical or hematogenous) by Staphylococcus aureus managed with implant removal (IRm) or debridement and retention (DAIR). To analyze the outcomes of all cases managed with IRm (initially or after DAIR failure). METHODS: Retrospective, multicenter, cohort study of PJI by S. aureus (2003-2010). Overall failure included mortality within 60 days since surgery and local failure due to staphylococcal persistence/relapse. RESULTS: 499 cases, 338 initially managed with DAIR, 161 with IRm. Mortality was higher in acute PJI managed initially with IRm compared to DAIR, but not associated with the surgical procedure, after propensity score matching. Underlying conditions, hemiarthroplasty, and methicillin-resistant S. aureus were risk factors for mortality. Finally, 249 cases underwent IRm (88 after DAIR failure); overall failure was 15.6%. Local failure (9.3%) was slightly higher in cases with several comorbidities, but independent of previous DAIR, type of IRm, and rifampin treatment. CONCLUSIONS: In a large multicenter study of S. aureus PJI managed with IRm, failure was low, but mortality significant, especially in cases with acute PJI and underlying conditions, but not associated with the IRm itself. Rifampin efficacy was limited in this setting.

Clinical Use of Colistin in Biofilm-Associated Infections.

Biofilm is an adaptive bacterial strategy whereby microorganisms become encased in a complex glycoproteic matrix. The low concentration of oxygen and nutrients in this environment leads to heterogeneous phenotypic changes in the bacteria, with antimicrobial tolerance being of paramount importance. As with other antibiotics, the activity of colistin is impaired by biofilm-embedded bacteria. Therefore, the recommendation for administering high doses in combination with a second drug, indicated for planktonic infections, remains valid in this setting. Notably, colistin has activity against metabolically inactive biofilm-embedded cells located in the inner layers of the biofilm structure. This is opposite and complementary to the activity of other antimicrobials that are able to kill metabolically active cells in the outer layers of the biofilm. Several experimental models have shown a higher activity of colistin when used in combination with other agents, and have reported that this can avoid the emergence of colistin-resistant subpopulations. Most experience of colistin in biofilm-associated infections comes from patients with cystic fibrosis, where the use of nebulized colistin allows high concentrations to reach the site of the infection. However, limited clinical experience is available in other scenarios, such as osteoarticular infections or device-related central nervous system infections caused by multi-drug resistant microorganisms. In the latter scenario, the use of intraventricular or intrathecal colistin also permits high local concentrations and good clinical results. Overall, the efficacy of intravenous colistin seems to be poor, but its association with a second antimicrobial significantly increases the response rate. Given its activity against inner bioflm-embedded cells, its possible role in combination with other antibiotics, beyond last-line therapy situations, should be further explored.

Timing of implant-removal in late acute periprosthetic joint infection: A multicenter observational study.

OBJECTIVES: We evaluated the treatment outcome in late acute (LA) periprosthetic joint infections (PJI) treated with debridement and implant retention (DAIR) versus implant removal. METHODS: In a large multicenter study, LA PJIs of the hip and knee were retrospectively evaluated. Failure was defined as: PJI related death, prosthesis removal or the need for suppressive antibiotic therapy. LA PJI was defined as acute symptoms <3 weeks in patients more than 3 months after the index surgery and with a history of normal joint function. RESULTS: 445 patients were included, comprising 340 cases treated with DAIR and 105 cases treated with implant removal (19% one-stage revision (n = 20), 74.3% two-stage revision (n = 78) and 6.7% definitive implant removal (n = 7). Overall failure in patients treated with DAIR was 45.0% (153/340) compared to 24.8% (26/105) for implant removal (p < 0.001). Difference in failure rate remained after 1:1 propensity-score matching. A preoperative CRIME80-score ≥3 (OR 2.9), PJI caused by S. aureus (OR 1.8) and implant retention (OR 3.1) were independent predictors for failure in the multivariate analysis. CONCLUSION: DAIR is a viable surgical treatment for most patients with LA PJI, but implant removal should be considered in a subset of patients, especially in those with a CRIME80-score ≥3.

Changing trends in the epidemiology of pyogenic vertebral osteomyelitis: the impact of cases with no microbiologic diagnosis.

OBJECTIVES: The observed higher incidence of pyogenic vertebral osteomyelitis (PVO) may entail an increasing number of patients with no microbiologic diagnosis. The true incidence of these cases, how exhaustive the etiologic diagnostic efforts must be, and the usefulness of an empirical antibiotic therapy are not well defined. METHODS: Retrospective analysis of all cases of vertebral osteomyelitis in our center (1991-2009) and retrospective analysis of cases of PVO (2005-2009). Clinical data, diagnostic procedures, treatment, and outcome were reviewed. A comparative analysis between microbiologically confirmed PVO (MCPVO) and probable PVO (PPVO) was performed. RESULTS: Increasing incidence of PVO (+0.047 episodes/100,000 inhabitants-year). During the last decade, there was an increase of PPVO (+0.059 episodes/100,000 inhabitants-year) with stable incidence of MCPVO. During 2005-2009, there were 72 patients [47 (65%) MCPVO and 25 (35%) PPVO]. 60% men; mean age was 66 years. Bacteremia was found in 59%. Computed tomographic guided vertebral biopsy, positive in 7/36 (19%), was more successful among patients with bacteremia. Among MCPVO, there was an increasing proportion of less virulent bacteria. Cases of MCPVO presented more frequently with sepsis, fever, and high acute-phase reactants, and PPVO cases were mostly treated with oral fluoroquinolones plus rifampin. No differences were found between both groups in outcome (93% success, 22% sequelae). CONCLUSIONS: An epidemiologic change of PVO is suggested by a higher incidence of PPVO and the isolation of less virulent microorganisms among MCPVO. In this setting, the availability of an oral and effective empirical antibiotic therapy may challenge an exhaustive prosecution of the etiology.

Bacteraemia due to extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) in cancer patients: clinical features, risk factors, molecular epidemiology and outcome.

OBJECTIVES: To assess the clinical features, risk factors, molecular epidemiology and outcome of extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) bacteraemia in hospitalized cancer patients. METHODS: Episodes of ESBL-EC bacteraemia were compared with a susceptible control group in a 3 year prospective study. ESBL-EC strains were studied by PCR and isoelectric focusing, and molecular typing was performed by PFGE. RESULTS: Out of 531 episodes of bacteraemia, 135 were caused by E. coli. Seventeen of these cases involved ESBL-EC-producing strains (12.6%). In the multivariate analysis, female gender [odds ratio (OR) 3.43; 95% confidence interval (CI) 1.03-11.4] and previous antibiotic therapy (OR 3.22; 95% CI 1.00-10.3) were found to be independent risk factors for ESBL acquisition. An analysis of ESBL-EC isolates revealed a polyclonal distribution with CTX-M predominance (59%). Patients with ESBL-EC bacteraemia were more likely to have received an inadequate empirical antibiotic therapy (65% versus 6%; P = 0.000), and the time to adequate therapy was longer in this group (0 versus 1.50 days; P = 0.000). The overall mortality rate was 22%, ranging from 20% to 35% (P = 0.20). Risk factors for mortality were solid tumour (OR 19.41; 95% CI 4.66-80.83), corticosteroid therapy (OR 3.04 95% CI 1.05-8.81) and intensive care unit admission (OR 248.24, 95% CI 18.49-3332.14). In neutropenic patients, ESBL-EC bacteraemia was associated with poorer outcome and a higher overall mortality rate (37.5% versus 6.5%; P = 0.01). CONCLUSIONS: In our centre, ESBL-EC bacteraemia is frequent among cancer patients, especially in those exposed to antibiotic pressure. All ESBL-EC strains were unrelated and most of them carried a CTX-M group enzyme. Patients with ESBL-EC bacteraemia received inadequate empirical antibiotic therapy more frequently than patients carrying a susceptible strain, but significant differences in mortality could not be demonstrated.

Multiple myeloma and hyperammonemic encephalopathy: review of 27 cases.

Hyperammonemic encephalopathy is a rarely reported complication of multiple myeloma (MM). We describe an illustrative case of hyperammonemia in the setting of an immunoglobulin (Ig) D-lambda MM, and perform a systematic review of the English-written literature. Our search yielded 26 more cases. Median age was 64 years, and 54% of patients were male. All presented with progressive impairment of their level of consciousness. Median ammonium concentration was 109 micromol/L (interquartile range, 73-149 micromol/L). Most were IgA type (10 cases), and there were 2 cases of IgD type. Most cases were aggressive or chemotherapy-resistant forms of MM. Eight patients were diagnosed with MM at the same time as the episode of hyperammonemia. Only 1 patient had signs of portal hypertension as a result of concomitant hyperdynamic heart failure. Determination of amino acid in 10 patients showed high levels of glycine, low levels of tyrosine, and a low Fischer ratio. Two patients did not receive chemotherapy and died. Twenty-two out of 25 patients who received chemotherapy against MM showed a decrease in ammonium blood concentration, and of those, 15 survived the episode (68%). Overall mortality was 44%. In conclusion, hyperammonemia is a severe complication of MM, associated with a high mortality. It should be considered in any patient with MM and a low level of consciousness. Chemotherapy directed against MM seems to be the most effective measure in order to achieve normal ammonium levels and clinical improvement.

Sarcoidosis and autoimmune thyroid disease. A case series of ten patients.

BACKGROUND: Sarcoidosis coexisting with autoimmune disorders, especially with autoimmune thyroid disease (ATD), has been previously described and a common immunopathogenesis has been proposed. We report a series of ten new cases of this association from a large series of patients with sarcoidosis. METHODS: The clinical records of patients diagnosed with sarcoidosis between 1984 and 2006 in the Bellvitge University Hospital were reviewed, and those who were also diagnosed as having ATD were selected. A review of the literature was performed as well. RESULTS: Ten out of 348 (2.9%) patients with sarcoidosis were identified as having ATD. Sarcoidosis presented as Löfgren's syndrome in 8 patients. Three patients developed Graves' disease, 6 Hashimoto's thyroiditis with hypothyroidism and one had postpartum thyroiditis. In one case, ATD had developed 15 years before sarcoidosis. In the remaining nine cases, sarcoidosis preceded between 4 months to 17 years the development of ATD. In 3 of these cases, sarcoidosis was active when ATD was diagnosed. In one patient, Graves' disease developed immediately after the administration of potassium iodide to treat erythema nodosum. CONCLUSIONS: Sarcoidosis may be associated with ATD at some time of its evolution, either as hyperthyroidism or hypothyroidism. Usually, ATD does not develop during the period of activity of sarcoidosis. We suggest considering personal and family past history of thyroid disease before administering potassium iodide for erythema nodosum in patients with sarcoidosis, as it could trigger hyperthyroidism, especially in patients with iodine deficiency.