[Therapy of cystitis with nitroxoline-NitroxWin : Prospective, multicenter, non-interventional study and microbiological resistance surveillance]. / Therapie der Zystitis mit Nitroxolin ­ NitroxWin : Prospektive, multizentrische, nicht-interventionelle Studie und mikrobiologische Untersuchungen zur Resistenzsituation.

BACKGROUND: According to German AWMF S3 guideline nitroxoline is recommended as one of the first-choice antibiotics for treatment of acute uncomplicated cystitis (UC) in women. Under real-world conditions the clinical efficacy of nitroxoline should be checked in a noninterventional, prospective and multicenter study (NIS) and the prevalence of nitroxoline resistance in E. coli be monitored. MATERIALS AND METHODS: Female patients with UC treated with nitroxoline (recommended dosage 250 mg tid for 5 days) were included by urologists, general practitioners (GPs), and internists in family medicine throughout Germany from April-December 2022 and followed for 21-28 days. The diagnosis and course of therapy were judged by the Acute Cystitis Symptom Score (ACSS) questionnaire and laboratory investigations (leukocyturia etc). Separately, a nationwide resistance surveillance was performed during 2019-2020 in collaboration with 23 laboratories to collect urinary E. coli isolates and test their susceptibility to nitroxoline. RESULTS: Of the 316 patients with mean (SD) age of 57.2 (±20.4 [median 62.5]) years who were included in the NIS, 193/248 (86.3%) in the per-protocol group and in 193/263 (81.44%) in the intention-to-treat group were clinically successful. Furthermore, 96% of the patients rated the tolerability of nitroxoline as "very good" or "good". All 272 E. coli isolates tested were susceptible to nitroxoline. CONCLUSIONS: Nitroxoline showed very good clinical results in the NIS, and 100% of the tested E. coli urine isolates were susceptible to nitroxoline. Nitroxoline can still be recommended as one of the first-choice antibiotics for treatment of UC in women.

Early treatment response to piperacillin/tazobactam in patients with bloodstream infections caused by non-ESBL ampicillin/sulbactam-resistant Escherichia coli: a binational cohort study.

PURPOSE: This study aimed to compare treatment outcomes for bloodstream infections (BSI) caused by a piperacillin/tazobactam (PIP/TAZ)-susceptible E. coli among three patient groups: BSI caused by ampicillin/sulbactam (AMP/SLB)-resistant isolates treated with PIP/TAZ, BSI caused by AMP/SLB-sensitive isolates treated with PIP/TAZ, and BSI caused by AMP/SLB-resistant isolates treated with another monotherapy. METHODS: This retrospective study was conducted in two academic centres in Europe. Adult patients with E. coli BSI were screened from 2014 to 2020. Inclusion criteria were non-ESBL BSI and initial monotherapy for ≥ 72 h. To reduce the expected bias between the patient groups, propensity score matching was performed. The primary outcome was early treatment response after 72 h and required absence of SOFA score increase in ICU/IMC patients, as well as resolution of fever, leukocytosis, and bacteraemia. RESULTS: Of the 1707 patients screened, 315 (18.5%) were included in the final analysis. Urinary tract infection was the most common source of BSI (54.9%). Monotherapies other than PIP/TAZ were cephalosporins (48.6%), carbapenems (34.3%), and quinolones (17.1%). Enhanced early treatment response rate was detected (p = 0.04) in patients with BSI caused by AMP/SLB-resistant isolates treated with another monotherapy (74.3%) compared to those treated with PIP/TAZ (57.1%), and was mainly driven by the use of cephalosporins and quinolones (p ≤ 0.03). Clinical success, 28-day mortality, and rate of relapsing BSI did not significantly differ between the groups. CONCLUSIONS: Our study suggests that initial use of PIP/TAZ may be associated with reduced early treatment response in E. coli BSI caused by AMP/SLB-resistant isolates compared to alternative monotherapies.

[Therapy-relevant antibiotic resistances in a One Health context]. / Therapierelevante Antibiotikaresistenzen im One-Health-Kontext.

One Health refers to a concept that links human, animal, and environmental health. In Germany, there is extensive data on antibiotic resistance (AMR) and multidrug-resistant (micro)organisms (MDRO) in human and veterinary medicine, as well as from studies in various environmental compartments (soil, water, wastewater). All these activities are conducted according to different specifications and standards, which makes it difficult to compare data. A focus on AMR and MDRO of human therapeutic importance is helpful to provide some guidance. Most data are available across sectors on methicillin-resistant Staphylococcus aureus (MRSA) and multiresistant Enterobacterales such as Escherichia coli and Klebsiella pneumoniae. Here, the trends of resistance are heterogeneous. Antibiotic use leads to MRE selection, which is well documented. Success in minimizing antibiotic use has also been demonstrated in recent years in several sectors and could be correlated with success in containing AMR and MDRO (e.g., decrease in MRSA in human medicine). Sector-specific measures to reduce the burden of MDRO and AMR are also necessary, as not all resistance problems are linked to other sectors. Carbapenem resistance is still rare, but most apparent in human pathogens. Colistin resistance occurs in different sectors but shows different mechanisms in each. Resistance to antibiotics of last resort such as linezolid is rare in Germany, but shows a specific One Health correlation. Efforts to harmonize methods, for example in the field of antimicrobial susceptibility testing and genome-based pathogen and AMR surveillance, are an important first step towards a better comparability of the different data collections.

Non-patient-related SARS-CoV-2 exposure from colleagues and household members poses the highest infection risk for hospital employees in a German university hospital: follow-up of the prospective Co-HCW seroprevalence study.

PURPOSE: The Co-HCW study is a prospective, longitudinal, single-center observational study that aims to assess the SARS-CoV-2 seroprevalence and infection status in staff members of Jena University Hospital (JUH) in Jena, Germany. METHODS: This follow-up study covers the observation period from 19th May 2020 to 22nd June 2021. At each of the three voluntary study visits, participants filled out a questionnaire regarding their SARS-CoV-2 exposure and provided serum samples to detect specific SARS-CoV-2 antibodies. Participants who were tested positive for antibodies against nucleocapsid and/or spike protein without previous vaccination and/or reported a positive SARS-CoV-2 PCR test were regarded to have been infected with SARS-CoV-2. Multivariable logistic regression modeling was applied to identify potential risk factors for infected compared to non-infected participants. RESULTS: Out of 660 participants that were included during the first study visit, 406 participants (61.5%) were eligible for the final analysis as their COVID-19 risk area (high-risk n = 76; intermediate-risk n = 198; low-risk n = 132) did not change during the study. Forty-four participants [10.8%, 95% confidence interval (95%CI) 8.0-14.3%] had evidence of a current or past SARS-CoV-2 infection detected by serology (n = 40) and/or PCR (n = 28). No association between SARS-CoV-2 infection and the COVID-19 risk group according to working place was detected. However, exposure to a SARS-CoV-2 positive household member [adjusted OR (AOR) 4.46, 95% CI 2.06-9.65] or colleague (AOR 2.30, 95%CI 1.10-4.79) was found to significantly increase the risk of a SARS-CoV-2 infection. CONCLUSION: Our results demonstrate that non-patient-related SARS-CoV-2 exposure posed the highest infection risk for hospital staff members of JUH.

Short-course versus long-course antibiotic treatment for uncomplicated vancomycin-resistant enterococcal bacteraemia: a retrospective multicentre cohort study.

OBJECTIVES: The optimal treatment duration for vancomycin-resistant enterococcal (VRE) bacteraemia is still a matter of debate. The aim of the present study was to compare short-course (≤9 days) and long-course (≥10 days) antibiotic treatments in hospitalized adult patients with uncomplicated VRE bacteraemia. METHODS: This retrospective study was conducted in four university hospitals in Germany. Adult patients with a positive blood culture for a VRE were screened from 1 January 2016 to 31 December 2018. Only patients who received a VRE-active antibiotic for at least 48 hours were included. The exclusion criteria were a survival of <10 days and a deep-seated source of infection requiring prolonged treatment. To compare the outcome of short-course therapy with that of long-course therapy, 30-day and 90-day overall mortality, relapse within 90 days, duration of hospitalization, and potential antibiotic-related adverse events were analysed by inverse probability of treatment weighting using the propensity score and by additional covariate adjustment. RESULTS: Of the 363 patients screened, 219 (60.3%) patients were included in the final analysis. Among them, 48 (21.9%) patients had underlying haematological diseases. Seventy-eight (35.6%) patients received short-course treatment (median, 7 days; interquartile range, 5-8 days) and 141 (64.4%) patients received long-course treatment (median, 15 days; interquartile range, 12-23.5 days). Thirty-day mortality was similar in both groups (19.2% vs. 22.0%; adjusted OR, 1.15; p 0.773). Duration of hospitalization (in total and after onset of bacteraemia) was significantly shorter (p < 0.05) in the short-course treatment group, whereas other secondary outcome parameters did not differ between both groups. DISCUSSION: Our study suggests that short-course treatment might not be associated with a worse outcome in patients with uncomplicated VRE bacteraemia.

Unmet needs in pneumonia research: a comprehensive approach by the CAPNETZ study group.

INTRODUCTION: Despite improvements in medical science and public health, mortality of community-acquired pneumonia (CAP) has barely changed throughout the last 15 years. The current SARS-CoV-2 pandemic has once again highlighted the central importance of acute respiratory infections to human health. The "network of excellence on Community Acquired Pneumonia" (CAPNETZ) hosts the most comprehensive CAP database worldwide including more than 12,000 patients. CAPNETZ connects physicians, microbiologists, virologists, epidemiologists, and computer scientists throughout Europe. Our aim was to summarize the current situation in CAP research and identify the most pressing unmet needs in CAP research. METHODS: To identify areas of future CAP research, CAPNETZ followed a multiple-step procedure. First, research members of CAPNETZ were individually asked to identify unmet needs. Second, the top 100 experts in the field of CAP research were asked for their insights about the unmet needs in CAP (Delphi approach). Third, internal and external experts discussed unmet needs in CAP at a scientific retreat. RESULTS: Eleven topics for future CAP research were identified: detection of causative pathogens, next generation sequencing for antimicrobial treatment guidance, imaging diagnostics, biomarkers, risk stratification, antiviral and antibiotic treatment, adjunctive therapy, vaccines and prevention, systemic and local immune response, comorbidities, and long-term cardio-vascular complications. CONCLUSION: Pneumonia is a complex disease where the interplay between pathogens, immune system and comorbidities not only impose an immediate risk of mortality but also affect the patients' risk of developing comorbidities as well as mortality for up to a decade after pneumonia has resolved. Our review of unmet needs in CAP research has shown that there are still major shortcomings in our knowledge of CAP.

Vaccine Response in the Immunocompromised Patient with Focus on Cellular Immunity.

During the last few years, we have experienced a shift in how we evaluate the effectiveness of vaccines [...].

Effect of Automated Telephone Infectious Disease Consultations to Nonacademic Hospitals on 30-Day Mortality Among Patients With Staphylococcus aureus Bacteremia: The SUPPORT Cluster Randomized Clinical Trial.

Importance: Staphylococcus aureus bacteremia (SAB) is a common and potentially severe infectious disease (ID). Retrospective studies and derived meta-analyses suggest that bedside infectious disease consultation (IDC) for SAB is associated with improved survival; however, such IDCs might not always be possible because of the lack of ID specialists, particularly at nonacademic hospitals. Objectives: To investigate whether unsolicited telephone IDCs (triggered by an automated blood stream infection reporting system) to nonacademic hospitals improved 30-day all-cause mortality in patients with SAB. Design, Setting, and Participants: This patient-blinded, multicenter, interventional, cluster randomized, controlled, crossover clinical trial was conducted in 21 rural, nonacademic hospitals in Thuringia, Germany. From July 1, 2016, to December 31, 2018, 1029 blood culture reports were assessed for eligibility. A total of 386 patients were enrolled, whereas 643 patients were not enrolled for the following reasons: death before enrollment (n = 59); palliative care (n = 41); recurrence of SAB (n = 9); discharge from the hospital before enrollment (n = 77); age younger than 18 years (n = 5); duplicate report from a single patient (n = 26); late report (n = 17); blood culture reported during the washout phase (n = 48); and no signed informed consent for other or unknown reasons (n = 361). Interventions: During the ID intervention phase, ID specialists from Jena University Hospital provided unsolicited telephone IDCs to physicians treating patients with SAB. During the control phase, patients were treated according to local standards. Crossover was performed after including 15 patients or, at the latest, 1 year after the first patient was included. Main Outcomes and Measures: Thirty-day all-cause mortality. Results: A total of 386 patients (median [IQR] age, 75 [63-82] years; 261 [67.6%] male) were included, with 177 randomized to the IDC group and 209 to the control group. The 30-day all-cause mortality rate did not differ between the IDC and control groups (relative risk reduction [RRR], 0.12; 95% CI, -2.17 to 0.76; P = .81). No evidence was found of a difference in secondary outcomes, including 90-day mortality (RRR, 0.17; 95% CI, -0.59 to 0.57; P = .62), 90-day recurrence (RRR, 0.10; 95% CI, -2.51 to 0.89; P = .89), and hospital readmission (RRR, 0.04; 95% CI, -0.63 to 0.48; P = .90). Exploratory evidence suggested that indicators of quality of care were potentially realized more often in the IDC group than in the control group (relative quality improvement, 0.16; 95% CI, 0.08-0.26; P = .01). Conclusions and Relevance: In this cluster randomized clinical trial, unsolicited telephone IDC, although potentially enhancing quality of care, did not improve 30-day all-cause mortality in patients with SAB. Trial Registration: drks.de Identifier: DRKS00010135.

Complicated and uncomplicated S. aureus bacteraemia: an international Delphi survey among infectious diseases experts on definitions and treatment.

OBJECTIVES: Classification of Staphylococcus aureus bacteraemia (SAB) as 'complicated' or 'uncomplicated' and management of both is based on low-quality evidence. The aim of the study was to determine the degree of agreement among infectious diseases physician experts in the management of patients with SAB. METHODS: A stepwise RAND-modified Delphi procedure with two questionnaire rounds was performed. Four aspects of management in 22 clinical scenarios were addressed: (a) classification of SAB episodes; (b) value of combination therapy; and (c) timing of and (d) preferred antibiotics for oral stepdown therapy. RESULTS: Out of 90 approached experts, 33 (36.7%) from 14 different countries and 5 continents consented to participate. The experts considered any of the discussed implanted foreign material (with no evidence of infection), except for coronary artery stents, as relevant to the classification of a complicated SAB episode. Concerning antibiotic combination therapy, the experts strongly agreed that combination therapy with rifampicin is only relevant in patients with prosthetic valve endocarditis and prosthetic joint infection. The experts considered an oral stepdown therapy in patients with an uncomplicated SAB within 14 days and only thereafter in patients with a complicated SAB episode, but never in patients with prosthetic valve endocarditis. No single antibiotic of choice for oral stepdown therapy could be identified, neither for infections with methicillin-resistant S. aureus nor methicillin-susceptible S. aureus. DISCUSSION: The Delphi survey can help physicians in their day-to-day decision-making process, and it reveals open questions that must be investigated by further studies.

Prospective surveillance study in a 1,400-bed university hospital: COVID-19 exposure at home was the main risk factor for SARS-CoV-2 point seroprevalence among hospital staff.

The Co-HCW study is a prospective cohort study among hospital staff, including healthcare workers (HCWs) and administration staff, at the Jena University Hospital (JUH), Germany. The objectives of this study were to assess SARS-CoV-2 IgG seroprevalence, individual exposure risk factors and compliance of HCWs to wear personal protective equipment (PPE). After the first nosocomial COVID-19 outbreak at JUH, mandatory masking was implemented on 20th March 2020. We evaluated point seroprevalence using two IgG detecting immunoassays and issued a questionnaire to assess COVID-19 exposure, clinical symptoms and compliance to wear PPE. Antibody retesting was offered to participants with a divergent result of both immunoassays 5-10 weeks after the first test. Between 19th May and 19th June 2020, we analysed 660 participants [out of 3,228; 20.4%]. Among them, 212 participants (32.1%) had received a previous COVID-19 test. Four of them (1.9%) reported a positive test result. After recruitment, 18 participants (2.7%) had SARS-CoV-2 antibodies in at least one immunoassay. Overall, 21 participants (3.2%) had any evidence of a past or current SARS-CoV-2 infection. Among them, 13 (61.9%) were not aware of direct COVID-19 exposure and 9 (42.9%) did not report any clinical symptoms. COVID-19 exposure at home (adjusted OR (aOR) with 95% CI: 47.82 (5.49, 416.62)) was associated with SARS-CoV-2 seroprevalence. We observed no evidence for an association between seroprevalence and exposure at work (aOR 0.48 (0.13, 1.70)) or with COVID-19 risk area according to the working place (aOR for intermediate-risk vs. high-risk: 1.97 (0.42, 9.22), aOR for low-risk versus high-risk: 2.10 (0.40, 11.06); p = .655). Reported compliance of HCWs to wear PPE differed (p < .001) between working in high-risk (98.3%) and in intermediate-risk areas (69.8%). In conclusion, compared to administration staff, we observed no additional risk to acquire SARS-CoV-2 infections by patient care, probably due to high compliance to wear PPE.

Performance of the eazyplex® BloodScreen GN as a simple and rapid molecular test for identification of Gram-negative bacteria from positive blood cultures.

The LAMP-based eazyplex® BloodScreen GN was evaluated for the detection of frequent Gram-negatives directly from positive blood culture (BC) bottles. A total of 449 BCs were analyzed. Sensitivities and specificities were 100% and 100% for Escherichia coli, 95.7% and 100% for Klebsiella pneumoniae, 100% and 100% for blaCTX-M, 100% and 100% for Klebsiella oxytoca, 100% and 99% for Proteus mirabilis, and 100% and 99.8% for Pseudomonas aeruginosa, respectively. The time to result ranged from 8 to 16 min, plus about 6 min for sample preparation. The eazyplex® BloodScreen GN is a reliable molecular assay for rapid BC testing.

Tick-Borne Encephalitis Specific Lymphocyte Response after Allogeneic Hematopoietic Stem Cell Transplantation Predicts Humoral Immunity after Vaccination.

The aim of this prospective study was to assess lymphocyte proliferative and cytokine response prior to and following tick-borne encephalitis (TBE) immunization among patients after allogeneic hematopoietic stem cell transplantation (HSCT). Seventeen adult patients 11-13 months after HSCT and eight unvaccinated healthy adults received up to three TBE vaccinations. Following in vitro stimulation with TBE-antigen, lymphocyte proliferation and cytokine secretion (IL-2, IL-10, IL-13, TNF-alpha, IFN-gamma, GM-CSF) were analyzed by thymidine incorporation assay and the Luminex system. Ten patients (59%) showed significant baseline TBE-specific lymphocyte proliferation (stimulation index (SI) > 3) prior to vaccination, but none of the unvaccinated controls (p = 0.002). All patients with a TBE-specific antibody response after two vaccinations (at least 2-fold increase of neutralization test titers) exhibited a strong TBE-specific lymphocyte proliferative response at baseline (SI > 10). Patients with sibling donors had a significantly stronger baseline TBE-specific lymphocyte proliferative and IL-13 cytokine response than patients with unrelated donors (p < 0.05). In conclusion, a relevant proportion of patients showed TBE-specific lymphocyte proliferative and cytokine responses prior to vaccination after HSCT, which predicted the humoral response to the vaccine. Patients with vaccinated sibling donors were more likely to elicit a cellular immune response than patients with unrelated donors of unknown vaccination status.

Early Treatment Outcomes for Bloodstream Infections Caused by Potential AmpC Beta-Lactamase-Producing Enterobacterales with Focus on Piperacillin/Tazobactam: A Retrospective Cohort Study.

The Gram-negative bacilli Serratia spp., Providencia spp., Morganella morganii, Citrobacter freundii complex, Enterobacter spp. and Klebsiella aerogenes are common Enterobacterales that may harbor inducible chromosomal AmpC beta-lactamase genes. The purpose of the present study was to evaluate treatment outcomes and identify predictors of early treatment response in patients with bloodstream infection caused by potential AmpC beta-lactamase-producing Enterobacterales (SPICE-BSI). This cohort study included adult patients with SPICE-BSI hospitalized between 01/2011 and 02/2019. The primary outcome was early treatment response 72 h after the start of active treatment, defined as survival, hemodynamic stability, improved or stable SOFA score, resolution of fever and leukocytosis and microbiologic resolution. Among 295 included patients, the most common focus was the lower respiratory tract (27.8%), and Enterobacter spp. (n = 155) was the main pathogen. The early treatment response rate was significantly lower (p = 0.006) in the piperacillin/tazobactam group (17/81 patients, 21.0%) than in the carbapenem group (40/82 patients, 48.8%). Independent negative predictors of early treatment response (p < 0.02) included initial SOFA score, liver comorbidity and empiric piperacillin/tazobactam treatment. In vitro piperacillin/tazobactam resistance was detected in three patients with relapsed Enterobacter-BSI and initial treatment with piperacillin/tazobactam. In conclusion, our findings show that piperacillin/tazobactam might be associated with early treatment failure in patients with SPICE-BSI.

[Pneumococcal vaccination]. / Pneumokokkenimpfstoffe.

Pneumococci are the most frequent bacterial agent of community-acquired pneumonia and are one of the most common vaccine-preventable causes of death worldwide. There is a polysaccharide vaccine that contains the capsular polysaccharides of 23 of the more than 90 known serotypes. PPV23 confers good protection against invasive pneumococcal infections but does not stimulate T cells and thus leaves no immunologic memory. It has limited efficacy in immunocompromised individuals. Initially for young children and later for adults, a 13 valent conjugate vaccine was licensed that covers fewer serotypes but leaves immunologic memory and mediates mucosal immunity, i.e. by eradicating healthy pneumococcal carriers, and thus has herd-protective effects. The German Standing Commission on Vaccination Practices (STIKO) currently recommends PPV23 for indication vaccination in various comorbidities and as standard vaccination for all above 60 years with repeat vaccination after 6 years at the earliest. Patients with immunosuppression, chronic renal failure or chronic liver failure should receive a sequential vaccination (first PCV13 followed by PPV23 after 6-12 months) due to the limited efficacy of PPV23 and their increased risk for infection.

Antibody response using six different serological assays in a completely PCR-tested community after a coronavirus disease 2019 outbreak-the CoNAN study.

OBJECTIVES: Due to a substantial proportion of asymptomatic and mild courses, many severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections remain unreported. Therefore, assessment of seroprevalence may detect the real burden of disease. We aimed to determine and characterize the rate of SARS-CoV-2 infections and the resulting seroprevalence in a defined population. The primary objective of the study was to assess SARS-CoV-2 antibody seroprevalence using six different IgG-detecting immunoassays. Secondary objectives of the study were: (a) to determine potential risk factors for symptomatic versus asymptomatic coronavirus disease 2019 courses, and (b) to investigate the rate of virus RNA-persistence. METHODS: CoNAN is a population-based cohort study performed in the community Neustadt am Rennsteig, Germany, which was quarantined from 22 March to 5 April after six SARS-CoV-2 cases were detected in the village's population. The SARS-CoV-2 outbreak comprised 51 cases and 3 deaths. The CoNAN study was performed from 13 May to 22 May 2020, 6 weeks after a SARS-CoV-2 outbreak. RESULTS: We enrolled a total of 626 participants (71% of the community population) for PCR and antibody testing in the study. All actual SARS-CoV-2 PCR tests were negative. Fifty-two out of 620 (8.4%) participants had antibodies against SARS-CoV-2 in at least two different assays. There were 38 participants with previously PCR-confirmed SARS-CoV-2 infection. Of those, only 19 (50%) displayed anti-SARS-CoV-2 antibodies. We also show that antibody-positive participants with symptoms compatible with a respiratory tract infection had significantly higher antibody levels then asymptomatic participants (EU-assay: median 2.9 versus 7.2 IgG-index, p 0.002; DS-assay: median 45.2 versus 143 AU/mL, p 0.002). Persisting viral replication was not detected. CONCLUSIONS: Our data question the relevance and reliability of IgG antibody testing to detect past SARS-CoV-2 infections 6 weeks after an outbreak. We conclude that assessing immunity for SARS-CoV-2 infection should not rely on antibody tests alone.

Clinical evaluation of two different (1,3)-ß-d-glucan assays for diagnosis of invasive fungal diseases: A retrospective cohort study.

BACKGROUND: Early diagnosis of invasive fungal diseases (IFDs) remains a major challenge in routine clinical practice. OBJECTIVES: The aim of this retrospective cohort study was to evaluate the diagnostic performance of the fungal biomarker (1,3)-ß-d-glucan (BDG) using the ß-Glucan test (GT) and the well-established Fungitell assay® (FA) in real-life clinical practice. PATIENTS/METHODS: We included 109 patients with clinical suspicion of IFD who were treated at Jena University Hospital, Germany, between November 2018 and March 2019. The patients were classified according to the latest update of the EORTC/MSG consensus definitions of IFD. The first serum sample of every patient was analysed for BDG using the FA and the GT, respectively. RESULTS: Fifty-six patients (51.4%) had at least one host factor for IFD. In patients with proven (n = 11) or probable IFDs (n = 20), median BDG concentrations were 145.0 pg/ml for the FA and 5.1 pg/ml for the GT, respectively. A positive test result of both BDG assays at manufacturer's cut-offs predicted 89.5%-98.3% of proven or probable IFD, but the sensitivity of both assays was limited: The FA identified 60.7% of IFDs (cut-off: 80 pg/ml). Reducing the GT cut-off value from 11.0 to 4.1 pg/ml increased the detection rate of IFDs from 35.5% to 54.8%. CONCLUSIONS: A positive test result of both BDG assays at manufacturer's cut-off was highly predictive for IFD, but except for Pneumocystis jirovecii pneumonia sensitivities were limited. Adjustment of the GT cut-off value equalised sensitivities of GT and FA.

Management of Staphylococcus aureus Bloodstream Infections.

Staphylococcus aureus bloodstream infections are associated with a high morbidity and mortality. Nevertheless, significance of a positive blood culture with this pathogen is often underestimated or findings are misinterpreted as contamination, which can result in inadequate diagnostic and therapeutic consequences. We here review and discuss current diagnostic and therapeutic key elements and open questions for the management of Staphylococcus aureus bloodstream infections.