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Objectives: Staphylococcus aureus is the most common cause of pyogenic vertebral osteomyelitis (VO). Studies indicate that S. aureus VO results in poor outcome. We aimed to investigate risk factors for treatment failure in patients with Staphylococcus aureus bloodstream infection (SAB) and VO., Methods: We conducted a post hoc-analysis of data from a German bi-center prospective SAB cohort (2006-2014). Patients were followed-up for one year. Primary outcome was treatment failure defined as relapse and/or death within one year., Results: A total of 1069 patients with SAB were analyzed, with 92 VO patients. In addition to antibiotic treatment, surgery was performed in 60/92 patients. Treatment failed in 44/92 patients (death, n = 42; relapse, n = 2). Multivariable analysis revealed higher age (HR 1.04 [per year], 95%CI 1.01-1.07), Charlson comorbidity index (HR 1.20, 95%CI 1.06-1.36), presence of neurologic deficits (HR 2.53, 95%CI 1.15-5.53) and local abscess formation (HR 3.35, 95%CI 1.39-8.04) as independent risk factors for treatment failure. In contrast, surgery seemed to be associated with a favourable outcome (HR 0.45 (95%CI 0.20-0.997))., Conclusion: SAB patients with VO exhibit a high treatment failure rate. Red flags are older age, comorbidities, neurologic deficits and local abscess formation. Whether these patients benefit from intensified treatment (e.g. radical surgery, prolongation of antibiotics) should be investigated further., Competing Interests: Declaration of Competing Interest N.J. has received lecture fees from Gilead, Infectopharm, MSD, Bayer and Labor Stein and travel grants from Gilead, Basilea, Correvio, Pfizer and Novartis and grants from an observational study from Infectofos. A.J.K. reports personal fees from ViiV Healthcare Ltd, Merck Sharp & Dohme (MSD), BD Biosciences, bioMérieux and Limbach Gruppe SE, and a travel grant from Janssen Cilag. H.S. has received grants from German centre of Infection research (DZIF) and Accelerate and personal fees from Basilea Pharmaceuticals, Gilead, MSD, Entasis, Shinogi, ThermoFisher, bioMérieu, Becton Dickinson, Shionogi and Eumedica. All other authors: none to declare., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Staphylococcus aureus bloodstream infection (SAB) is a common, life-threatening infection with a high mortality. Survival can be improved by implementing quality of care bundles in hospitals. We previously observed marked differences in mortality between hospitals and now assessed whether mortality could serve as a valid and easy to implement quality of care outcome measure., Methods: We conducted a prospective observational study between January 2013 and April 2015 on consecutive, adult patients with SAB from 11 tertiary care centers in Germany, South Korea, Spain, Taiwan, and the United Kingdom. Factors associated with mortality at 90 days were analyzed by Cox proportional hazards regression and flexible parametric models., Results: 1851 patients with a median age of 66 years (64% male) were analyzed. Crude 90-day mortality differed significantly between hospitals (range 23-39%). Significant variation between centers was observed for methicillin-resistant S. aureus, community-acquisition, infective foci, as well as measures of comorbidities, and severity of disease. In multivariable analysis, factors independently associated with mortality at 90 days were age, nosocomial acquisition, unknown infective focus, pneumonia, Charlson comorbidity index, SOFA score, and study center. The risk of death varied over time differently for each infective focus. Crude mortality differed markedly from adjusted mortality., Discussion: We observed significant differences in adjusted mortality between hospitals, suggesting differences in quality of care. However, mortality is strongly influenced by patient mix and thus, crude mortality is not a suitable quality indicator., (Copyright © 2018 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Objectives: Ventricular assist devices (VAD) are increasingly implanted in patients with terminal heart failure. Here we describe the clinical course, management and outcome of VAD patients with S. aureus bloodstream infection (SAB)., Methods: We conducted a post hoc analysis of data from 1073 patients who had been prospectively enrolled in two consecutive SAB bicenter cohort studies. Patients with VAD in situ at the onset of SAB were identified. Follow-up of patients was at least 90 days., Results: Twelve VAD patients with SAB were identified. Compared to the overall cohort, patients with VAD presented more often with fever (92% vs. 65%) and septic shock (33% vs. 23%) and showed higher C-reactive protein levels (mean 244 vs. 132 g/ml). The median time to onset of SAB after device implantation was 161 days (range 24-790 days). 30-day mortality was comparable to the whole cohort (17% vs. 19%). Infection-related surgical interventions were performed in six patients. Hematogenous dissemination to distant foci was not found in any patient. One out of nine surviving patients required continuous suppressive antibiotic therapy., Conclusions: Mortality rates for VAD patients with SAB were comparable to SAB without VAD. No hematogenous disssemination or persistent infections were recorded, which might be associated with the prompt and aggressive antibiotic and surgical management in VAD patients. SAB per se does not preclude successful transplantation., (Copyright © 2018 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Objectives: Antibacterial chemoprophylaxis with fluoroquinolones (FQPx) has been commonly used in cancer patients with neutropenia, but its efficacy has been challenged by the emergence of fluoroquinolone resistance., Methods: The impact of FQPx on bloodstream infections (BSI) during neutropenia after high-dose chemotherapy for haematologic malignancies was evaluated through a multicenter hospital infection surveillance system for the period 2009-2014., Results: Among 8755 patients (4223 allogeneic [allo-] HSCT, 3602 autologous [auto-] HSCT, 930 high-dose chemotherapy for acute leukemia [HDC]), 5302 (61%) had received FQPx. Administration of FQPx was associated with fewer Gram-negative BSI in the overall study cohort patients (4.6% vs. 7.7%, adjusted subdistribution hazard ratio [aSHR] 0.59, 95%CI 0.50-0.70), in patients with HDC (3.7% vs. 9.2%, adjusted subdistribution hazard ratio [aSHR] 0.40, 95%CI 0.22-0.70) and auto-HSCT patients (4% vs. 9%, aSHR 0.43, 95%CI 0.33-0.56). In HDC patients, FQPx was associated with a marked reduction in all-cause mortality during neutropenia (2.3% vs. 7.8%, aSHR 0.30, 95%CI 0.15-0.58). Patients receiving FQPx had significantly more BSIs due to ESBL-positive Enterobacteriacea (0.8 vs. 0.3%, RR 2.2, 95%CI 1.17-4.26). BSIs by MRSA (n = 5) and VRE (n = 11) were rare in our cohort., Conclusions: As used in the participating centers, FQPx was associated with reduced Gram-negative BSI and improved survival among HDC patients. Among HSCT patients, the benefits were less clear. If adapted to local resistance patterns and patient characteristics, FQPx still may be useful in the management of patients with haematologic malignancies., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: Patients with rheumatoid arthritis (RA) are considered to be at increased risk of severe infections. We here describe the clinical characteristics, course and outcome of RA patients with Staphylococcus aureus bacteremia (SAB)., Methods: We conducted a post hoc analysis of data from a German bi-center prospective SAB cohort study (period 2006-2014). Patients were followed-up for one year. Primary and secondary outcomes were survival time and osteoarticular infection (OAI)., Results: A total of 1069 patients with SAB were analyzed, with 31 patients suffering from RA. RA patients showed significantly more often OAI (15/31 patients, 48% vs. 152/1038, 15%), disseminated infection (12/31, 39% vs. 164/1038, 16%) and severe sepsis/septic shock (12/31, 39% vs. 235/1038, 23%). Day-30 mortality in RA patients was 36% (vs. 19% in non-RA patients, p = 0.034), and day 90 mortality was 58% (vs. 32%, p = 0.003). Multivariate analyses confirmed RA to be an independent risk factor for death (HR 2.3, 95% CI 1.4-3.7) and OAI (OR 4.2, 95% CI 1.8-9.8)., Conclusions: Patients with RA exhibit a complicated SAB course and a high mortality, their management is challenging. Adequate antibiotic treatment, prompt invasive diagnostic and therapeutic procedures like joint lavage or surgery are of pivotal importance. Joint damage due to RA may confer a higher risk of acquiring OAI than immunosuppression., (Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Objectives: Elevated vancomycin minimum inhibitory concentrations (MIC) have been reported to adversely affect clinical outcome in methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI). We therefore examined the association between vancomycin MIC and outcome considering various potential confounders., Methods: Clinical data and bacterial isolates were prospectively collected from patients with MRSA BSI from 2006 to 2012 as part of the Invasive Staphylococcus aureus Infection Cohort (INSTINCT) study. Antimicrobial susceptibility was assessed by Etest, broth microdilution (BMD) and VITEK 2. Bacterial genotypes were determined by spa typing. Using univariate and Cox regression analyses, we investigated the impact of low (≤1.0 mg/L) and high (≥1.5 mg/L) vancomycin Etest MIC on clinical outcomes., Results: Ninety-one MRSA BSI episodes were included, of which 79 (86.8%) were caused by spa types t003, t032 and t045. High vancomycin MICs were seen only if using Etest but not confirmed using standard reference BMD. When episodes were stratified into low and high vancomycin Etest MIC groups, 30-day overall mortality was 34.5% and 27.3%, respectively (P = 0.64, OR 0.71; 95% confidence interval [CI] 0.27-1.79). Variables significantly associated with all-cause mortality in the Cox model were age (P = 0.003), acute physiology score (P = 0.0006), and Charlson comorbidity index (P = 0.018)., Conclusions: Vancomycin MICs may vary dependent on testing methodologies and local MRSA epidemiology. The patients' underlying disease and individual comorbidities rather than elevated vancomycin MICs determine adverse clinical outcomes in MRSA BSI. Routine Etest MIC testing of MRSA isolates is of limited value for treatment decisions., (Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Objectives: Staphylococcus aureus initiates cardiac device-related infection (CDI) by binding of fibronectin binding protein A (FnBPA) to the device's surface. In FnBPA, specific "binding enhancing" amino acid alterations are associated with CDI. However, no study has investigated whether these mutations also occur in geographically different regions and whether they arise during infection or are inherent properties of the infecting isolate., Methods: We analysed bacterial isolates from 34 patients with S. aureus bacteraemia and implanted cardiac devices for association with CDI, FnBPA sequence, classification into a clonal complex (CC), and binding to fibronectin (Fn)., Results: We confirmed that amino acid alterations at positions 652, 782, and 786 in FnBPA were associated with CDI (p = 0.005). Furthermore, CC15 and CC45 isolates were associated with CDI (p = 0.004). All isolates within a CC exhibited a characteristic mutation pattern, with major changes occurring in CC45 including a duplication of D1 and an altered immunogenic epitope in the D3 repeat. Isolates harbouring the "binding enhancing" mutations showed a slightly increased Fn binding capability, whereas Fn binding was decreased in CC45 isolates, according to a microtiter plate assay., Conclusions: FnBPA sequence variations are lineage specific and display inherent properties of the infecting isolate. Sequence analysis of FnBPA, as well as the bacterial genotype, may be used to predict the risk for device-related infection., (Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Objectives: Staphylococcus aureus bacteraemia is a common, often fatal infection. Our aim was to describe how its clinical presentation varies between populations and to identify common determinants of outcome., Methods: We conducted a pooled analysis on 3395 consecutive adult patients with S. aureus bacteraemia. Patients were enrolled between 2006 and 2011 in five prospective studies in 20 tertiary care centres in Germany, Spain, United Kingdom, and United States., Results: The median age of participants was 64 years (interquartile range 50-75 years) and 63.8% were male. 25.4% of infections were associated with diabetes mellitus, 40.7% were nosocomial, 20.6% were caused by methicillin-resistant S. aureus (MRSA), although these proportions varied significantly across studies. Intravenous catheters were the commonest identified infective focus (27.7%); 8.3% had endocarditis. Crude 14 and 90-day mortality was 14.6% and 29.2%, respectively. Age, MRSA bacteraemia, nosocomial acquisition, endocarditis, and pneumonia were independently associated with death, but a strong association was with an unidentified infective focus (adjusted hazard ratio for 90-day mortality 2.92; 95% confidence interval 2.33 to 3.67, p < 0.0001)., Conclusion: The baseline demographic and clinical features of S. aureus bacteraemia vary significantly between populations. Mortality could be reduced by assiduous MRSA control and early identification of the infective focus., (Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Objectives: Many physicians rely on differential time to positivity (DTP) when diagnosing catheter-related bloodstream infection (CRBSI). We evaluated whether DTP from routine blood cultures can predict catheter-related Staphylococcus aureus bloodstream infection., Methods and Patients: From 2006 to 2011 adult patients with monomicrobial S. aureus bloodstream infection and matched pairs of central and peripheral blood cultures were prospectively followed. CRBSI was defined by the absence of other infective foci and recovery of S. aureus from the catheter tip or catheter exit-site, or local signs of infection at the catheter exit site. A DTP of more than two hours (cut-off) was used to define test positivity., Results: CRBSI was present in 30 (34%, prevalence) of 87 patients. In 24 (28%) patients a DTP of more than two hours was measured: eleven patients had CRBSI, ten deep-seated infections, and in three patients an infective focus was not identified. DTP showed a positive predictive value of 0.46 [95% confidence interval (CI) 0.28 to 0.65], and a negative predictive value of 0.70 [95% CI 0.58 to 0.80]., Conclusion: The low test performance suggests that DTP is not useful in diagnosing CRBSI in routinely obtained blood cultures. Therefore, physicians should not solely rely on DTP and rather promote catheter removal and culture., (Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

We present a rare case of hemophagocytic lymphohistiocytosis (HLH) in a 70 year-old male patient with previously well-controlled HIV infection. We could confirm HLH in different organs post mortem. Since the diagnosis of HLH was delayed, the patient died despite initiation of chemotherapy. As cause for HLH, an EBV reactivation could be confirmed. In HIV infection, HLH may be the first HIV manifestation, often triggered by an opportunistic infection or immune reconstitution syndrome, but it is uncommon in the state of a well-controlled or aviremic HIV infection., (Copyright © 2011 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Objectives: To evaluate the relationship between mortality of bloodstream infection due to Staphylococcus aureus and infectious diseases specialist consultation and other factors potentially associated with outcomes., Methods: A 6-year cohort study was conducted at a 1600-bed university hospital. Consecutive adult patients with S. aureus bacteremia were assessed using a standardised data collection and review form. A new infectious diseases service increased its consultations for S. aureus bacteremia from 33% of cases in 2002 to >80% in 2007. Infectious disease consultation and other factors potentially associated with in-hospital mortality were analysed by multivariate logistic regression., Results: A total of 521 patients were studied. All-cause in-hospital mortality was 22%, 90-day mortality was 32%. Factors significantly associated with in-hospital mortality in multivariate analysis were ICU admission (OR 5.8, CI 3.5-9.7), MRSA (OR 2.6, CI 1.4-4.9), age >/=60 years (OR 2.4, CI 1.4-4.2), a diagnosis of endocarditis (OR 2.8, CI 1.4-5.7), a non-fatal underlying disease/comorbidity according to the McCabe classification (OR 0.2, CI 0.1-0.4), and infectious disease specialist consultation (OR 0.6, CI 0.4-1.0)., Conclusions: These data suggest that outcome of S. aureus bacteremia may be improved by an expert consultation service.