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.

Outpatient Parenteral Antimicrobial Treatment for Non-Cystic Fibrosis Bronchiectasis Exacerbations: A Prospective Multicentre Observational Cohort Study.

BACKGROUND: The recently published guidelines of the Spanish Society of Pulmonology and Thoracic Surgery encourage physicians to use outpatient antimicrobial therapy to treat exacerbations in patients with non-cystic fibrosis bronchiectasis (NCFB). The published literature on this topic, however, is scarce. METHODS: We report a prospective observational cohort study of patients with NCFB who received treatment at home for at least one exacerbation episode between September 2012 and September 2017 as part of an outpatient parenteral antimicrobial therapy (OPAT) program. Patients were included in the analysis if they fulfilled all of the following criteria: established diagnosis of bronchiectasis according to current guidelines criteria, clinical exacerbation, requiring intravenous antibiotics because of failure to respond to oral antibiotics, or isolation of a microorganism resistant to oral options. OBJECTIVES: To evaluate the effectiveness and safety of the treatment of patients with NCFB exacerbations in an OPAT program under "real-world" conditions. RESULTS: Sixty-seven patients were treated in the OPAT program due to bacterial exacerbations of NCFB. Forty-five (67.2%) patients were admitted to hospital for a median of 7 days before starting OPAT. Sixty-three (94%) patients achieved resolution of the exacerbation at the end of therapy. Four patients needed hospital readmission, and one died. The OPAT program saved 11,586 days of hospital admission, equivalent to EUR 7,866,904. CONCLUSIONS: OPAT appears to be a safe, effective, and efficient strategy for treating patients with exacerbations of NCFB.

The Different Microbial Etiology of Prosthetic Joint Infections according to Route of Acquisition and Time after Prosthesis Implantation, Including the Role of Multidrug-Resistant Organisms.

The aim of our study was to characterize the etiology of prosthetic joint infections (PJIs)-including multidrug-resistant organisms (MDRO)-by category of infection. A multicenter study of 2544 patients with PJIs was performed. We analyzed the causative microorganisms according to the Tsukayama's scheme (early postoperative, late chronic, and acute hematogenous infections (EPI, LCI, AHI) and "positive intraoperative cultures" (PIC)). Non-hematogenous PJIs were also evaluated according to time since surgery: <1 month, 2-3 months, 4-12 months, >12 months. AHIs were mostly caused by Staphylococcus aureus (39.2%) and streptococci (30.2%). EPIs were characterized by a preponderance of virulent microorganisms (S. aureus, Gram-negative bacilli (GNB), enterococci), MDROs (24%) and polymicrobial infections (27.4%). Conversely, coagulase-negative staphylococci (CoNS) and Cutibacterium species were predominant in LCIs (54.5% and 6.1%, respectively) and PICs (57.1% and 15.1%). The percentage of MDROs isolated in EPIs was more than three times the percentage isolated in LCIs (7.8%) and more than twice the proportion found in AHI (10.9%). There was a significant decreasing linear trend over the four time intervals post-surgery for virulent microorganisms, MDROs, and polymicrobial infections, and a rising trend for CoNS, streptococci and Cutibacterium spp. The observed differences have important implications for the empirical antimicrobial treatment of PJIs.

Bacteraemia due to non-ESBL-producing Escherichia coli O25b:H4 sequence type 131: insights into risk factors, clinical features and outcomes.

The epidemiology and outcomes of bloodstream infections (BSIs) caused by Escherichia coli ST131 isolates not producing extended-spectrum ß-lactamases (ESBLs) are not well defined despite being more prevalent than ESBL-producers. In this study, risk factors and the impact on outcome of BSIs caused by non-ESBL-producing ST131 E. coli versus non-ST131 E. coli were investigated. A case-control study was performed in two tertiary centres to identify risk factors for ST131. Molecular methods were used to investigate all E. coli isolates from blood cultures for those belonging to O25b:H4-ST131 clonal group. fimH alleles were characterised in ST131 isolates. Multivariate analysis was performed by logistic regression or Cox regression as appropriate. A total of 33 ST131 E. coli cases and 56 controls were studied. ST131 isolates showed higher rates of resistance to ampicillin and ciprofloxacin; fimH alleles were H30 in 14 isolates (42.4%) and H22 in 12 isolates (36.4%). Only recent surgery (OR = 7.03, 95% CI 1.71-28.84; P = 0.007) and unknown source of bacteraemia (OR = 5.37, 95% CI 0.93-30.81; P = 0.05) were associated with ST131. ST131 isolates showed no association with 30-day mortality, therapeutic failure, presentation with severe sepsis/shock or length of stay. Bacteraemia due to non-ESBL-producing O25b:H4-ST131 E. coli showed few differences in terms of risk factors as well as similar outcome to non-ST131 E. coli. These data support the notion that ST131 strains are not less clinically virulent despite showing increased antimicrobial resistance, but also that they are not more virulent than other clonal groups causing BSI.