Left ventricular assist device-associated driveline infections as a specific form of complicated skin and soft tissue infection/acute bacterial skin and skin structure infection - issues and therapeutic options.

PURPOSE OF REVIEW: This review comments on the current guidelines for the treatment of wound infections under definition of acute bacterial skin and skin structure infections (ABSSSI). However, wound infections around a catheter, such as driveline infections of a left ventricular assist device (LVAD) are not specifically listed under this definition in any of the existing guidelines. RECENT FINDINGS: Definitions and classification of LVAD infections may vary across countries, and the existing guidelines and recommendations may not be equally interpreted among physicians, making it unclear if these infections can be considered as ABSSSI. Consequently, the use of certain antibiotics that are approved for ABSSSI may be considered as 'off-label' for LVAD infections, leading to rejection of reimbursement applications in some countries, affecting treatment strategies, and hence, patients' outcomes. However, we believe driveline exit site infections related to LVAD can be included within the ABSSSI definition. SUMMARY: We argue that driveline infections meet the criteria for ABSSSI which would enlarge the 'on-label' antibiotic armamentarium for treating these severe infections, thereby improving the patients' quality of life.

Cytokine Hemoadsorption During Cardiac Surgery Versus Standard Surgical Care for Infective Endocarditis (REMOVE): Results From a Multicenter Randomized Controlled Trial.

BACKGROUND: Cardiac surgery often represents the only treatment option in patients with infective endocarditis (IE). However, IE surgery may lead to a sudden release of inflammatory mediators, which is associated with postoperative organ dysfunction. We investigated the effect of hemoadsorption during IE surgery on postoperative organ dysfunction. METHODS: This multicenter, randomized, nonblinded, controlled trial assigned patients undergoing cardiac surgery for IE to hemoadsorption (integration of CytoSorb to cardiopulmonary bypass) or control. The primary outcome (change in sequential organ failure assessment score [ΔSOFA]) was defined as the difference between the mean total postoperative SOFA score, calculated maximally to the 9th postoperative day, and the basal SOFA score. The analysis was by modified intention to treat. A predefined intergroup comparison was performed using a linear mixed model for ΔSOFA including surgeon and baseline SOFA score as fixed effect covariates and with the surgical center as random effect. The SOFA score assesses dysfunction in 6 organ systems, each scored from 0 to 4. Higher scores indicate worsening dysfunction. Secondary outcomes were 30-day mortality, duration of mechanical ventilation, and vasopressor and renal replacement therapy. Cytokines were measured in the first 50 patients. RESULTS: Between January 17, 2018, and January 31, 2020, a total of 288 patients were randomly assigned to hemoadsorption (n=142) or control (n=146). Four patients in the hemoadsorption and 2 in the control group were excluded because they did not undergo surgery. The primary outcome, ΔSOFA, did not differ between the hemoadsorption and the control group (1.79±3.75 and 1.93±3.53, respectively; 95% CI, -1.30 to 0.83; P=0.6766). Mortality at 30 days (21% hemoadsorption versus 22% control; P=0.782), duration of mechanical ventilation, and vasopressor and renal replacement therapy did not differ between groups. Levels of interleukin-1ß and interleukin-18 at the end of integration of hemoadsorption to cardiopulmonary bypass were significantly lower in the hemoadsorption than in the control group. CONCLUSIONS: This randomized trial failed to demonstrate a reduction in postoperative organ dysfunction through intraoperative hemoadsorption in patients undergoing cardiac surgery for IE. Although hemoadsorption reduced plasma cytokines at the end of cardiopulmonary bypass, there was no difference in any of the clinically relevant outcome measures. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03266302.

Towards therapeutic drug monitoring of antibiotic levels - analyzing the pharmacokinetics of levofloxacin using DUV-resonance Raman spectroscopy.

Therapeutic drug monitoring (TDM) plays an important role in clinical practice. Here, pharmacokinetics has a decisive influence on the effective antibiotic concentration during treatment. Moreover, different kinetics exist for different administration forms. Accordingly, adjusting the correct concentration depends, in addition to gender, age, weight, clinical picture, etc., on the dosage form of the antibiotic. This study investigates the capability of deep UV resonance Raman spectroscopy (DUV-RRS) to simulate the pharmacokinetics of fluoroquinolone levofloxacin after two different administration forms (intravenous and oral). Three different pre-processing methods were applied, and the best agreement with the simulation was achieved using the extended multiplicative scatter correction. The resulting spectra were used for partial least squares (PLS) regression and ordinary least squares (OLS) regression. The kinetic parameters were compared with the simulated data, with PLS showing the best performance for intravenous administration and a comparable result to OLS for oral administration, while the errors are smaller. The acquired results show the potential of DUV-RRS in combination with PLS regression as a promising supportive method for TDM.

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.

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.

The Controversial Effect of Antibiotics on Methicillin-Sensitive S. aureus: A Comparative In Vitro Study.

Methicillin-sensitive Staphylococcus (S.) aureus (MSSA) bacteremia remains a global challenge, despite the availability of antibiotics. Primary treatments include ß-lactam agents such as cefazolin and flucloxacillin. Ongoing discussions have focused on the potential synergistic effects of combining these agents with rifampicin or fosfomycin to combat infections associated with biofilm formation. Managing staphylococcal infections is challenging due to antibacterial resistance, biofilms, and S. aureus's ability to invade and replicate within host cells. Intracellular invasion shields the bacteria from antibacterial agents and the immune system, often leading to incomplete bacterial clearance and chronic infections. Additionally, S. aureus can assume a dormant phenotype, known as the small colony variant (SCV), further complicating eradication and promoting persistence. This study investigated the impact of antibiotic combinations on the persistence of S. aureus 6850 and its stable small colony variant (SCV strain JB1) focusing on intracellular survival and biofilm formation. The results from the wild-type strain 6850 demonstrate that ß-lactams combined with RIF effectively eliminated biofilms and intracellular bacteria but tend to select for SCVs in planktonic culture and host cells. Higher antibiotic concentrations were associated with an increase in the zeta potential of S. aureus, suggesting reduced membrane permeability to antimicrobials. When using the stable SCV mutant strain JB1, antibiotic combinations with rifampicin successfully cleared planktonic bacteria and biofilms but failed to eradicate intracellular bacteria. Given these findings, it is reasonable to report that ß-lactams combined with rifampicin represent the optimal treatment for MSSA bacteremia. However, caution is warranted when employing this treatment over an extended period, as it may elevate the risk of selecting for small colony variants (SCVs) and, consequently, promoting bacterial persistence.

[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.

Real-World Effectiveness of Piperacillin/Tazobactam with and without Linezolid for Spontaneous Bacterial Peritonitis.

BACKGROUND: Guidelines recommend empirical therapy with piperacillin/tazobactam (TZP) for spontaneous bacterial peritonitis (SBP) with low risk of multidrug-resistant organisms. Whether coverage of beta-lactam-resistant Gram-positive bacteria, such as ampicillin-resistant Enterococcus faecium, provides clinical benefit in such situations is unknown. METHODS: In this observational study, we investigated the real-world effectiveness of empirical therapy with TZP monotherapy versus TZP plus linezolid (LZD) combination therapy in patients with SBP from two centers. Treatment failure, defined as the need to escalate antibiotic therapy due to in vitro resistance, lack of neutrophil decrease in ascitic fluid, or clinical decision, and 30-day survival were retrospectively assessed. RESULTS: In the first cohort, 100 SBP episodes were empirically treated with TZP + LZD combination therapy (n = 50) or TZP monotherapy (n = 50). Treatment failure was recorded in 48% with TZP monotherapy compared with 16% with TZP + LZD combination therapy (p = 0.001), and this difference persisted after stratification for community-acquired versus hospital-acquired SBP. Although treatment failure after TZP therapy was associated with lower 30-day survival (56% vs. 82%; p = 0.04), 30-day survival with empirical TZP + LZD combination therapy was not different from empirical TZP monotherapy (Kaplan-Meier estimates 74% vs. 69%; p = 0.87). TZP concentrations in ascitic fluid were >32 mg/L in 94% samples after continuous administration. In a second cohort of 41 patients empirically treated with TZP, treatment failure was observed in 37%, which was also higher than in episodes treated with TZP + LZD in cohort 1 (p = 0.03). CONCLUSION: In this retrospective analysis, empirical TZP + LZD combination therapy for SBP was associated with fewer treatment failures without impact on short-term survival.

Population pharmacokinetics and probability of target attainment in patients with sepsis under renal replacement therapy receiving continuous infusion of meropenem: Sustained low-efficiency dialysis and continuous veno-venous haemodialysis.

AIMS: To describe the population pharmacokinetics (PK) and probability of target attainment (PTA) of continuous infusion (CI) of meropenem in septic patients receiving renal replacement therapy (RRT). METHODS: Fifteen patients without RRT, 13 patients receiving sustained low-efficiency dialysis and 12 patients receiving continuous veno-venous haemodialysis were included. Population PK analysis with Monte Carlo simulations for different dosing regimens was performed. For minimum inhibitory concentration 2 mg/L was chosen. The target was set as 50% time ≥4× minimum inhibitory concentration. RESULTS: The PK of meropenem was best described by a 1-compartment model with linear elimination. Serum creatinine, residual diuresis and time on RRT, with no difference between sustained low-efficiency dialysis and continuous veno-venous haemodialysis, were found to be significant covariates affecting clearance, explaining >20% of the clearance between subject variability. PTA analysis showed that in patients with RRT, 2 g/24 h, meropenem CI achieved a PTA of 95%. In patients without RRT, the target was achieved with 3 g/24 h CI or prolonged infusion of 1 g meropenem over 8 hours but not with bolus application of 1 g meropenem for 8 hours. Only 2 patients (both without RRT) had meropenem concentrations below the target level. However, approximately half of the patients with RRT receiving CI 3 g/24 h meropenem had toxic concentrations. CONCLUSION: We found relevant PK variability for meropenem CI in septic patients with or without RRT, leading to a substantial risk for overdosing in patients with RRT. This finding highlights the strong demand for personalized dosing in critically ill patients.

Influenza-associated in-hospital mortality during the 2017/2018 influenza season: a retrospective multicentre cohort study in central Germany.

The aim of this retrospective cohort study at eight hospitals in Germany was to specify influenza-associated in-hospital mortality during the 2017/2018 flu season, which was the strongest in Germany in the past 30 years. A total of 1560 patients were included in the study. Overall, in-hospital mortality was 6.7% (n = 103), in patients treated in the intensive care unit (n = 161) mortality was 22.4%. The proportion of deceased patients per hospital was between 0% and 7.0%. Influenza was the immediate cause of death in 82.8% (n = 82) of the decedents.

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.

Effect of antiviral therapy on the outcomes of mechanically ventilated patients with herpes simplex virus detected in the respiratory tract: a systematic review and meta-analysis.

BACKGROUND: Herpes simplex virus (HSV) is frequently detected in the respiratory tract of mechanically ventilated patients. The aim of this study was to assess current evidence to determine whether antiviral therapy is associated with better outcomes in these patients. METHODS: MEDLINE, ISI Web of Science, Cochrane Database and ClinicalTrials.gov were searched from inception to 25 May 2020. All clinical studies investigating the effects of antiviral therapy on the outcome of mechanically ventilated ICU patients in whom HSV was detected in the respiratory tract were eligible for inclusion, regardless of study design, publication status or language. Titles and abstracts were reviewed independently by two authors. If the articles seemed eligible, full-text articles were reviewed and data extracted. We performed a random-effects meta-analysis to estimate relative risks (RRs) with corresponding 95% confidence intervals (CIs). The primary endpoint was hospital all-cause mortality. RESULTS: Nine studies were included in the meta-analysis (one randomized controlled trial, eight cohort studies). Antiviral treatment was associated with lower hospital mortality (with antiviral treatment, 40.6% (189 out of 465 patients); without, 52.7% (193 out of 366 patients); RR 0.74 [0.64, 0.85]; eight studies, low quality of evidence). Furthermore, antiviral treatment was associated with lower 30-day mortality (RR 0.75 [0.59, 0.94]; three studies, very low quality of evidence). We did not observe evidence for differences in ICU mortality (RR 0.73 [0.51, 1.05]; three studies, very low quality of evidence). CONCLUSIONS: This meta-analysis of the available data shows that antiviral therapy might result in lower hospital and 30-day all-cause mortality in mechanically ventilated ICU patients who are positive for HSV in the respiratory tract. However, this result must be interpreted with great caution due to the high risk of bias and limited number of patients. Large, well-designed randomized controlled clinical trials are urgently needed. TRIAL REGISTRATION: The study was registered in advance on International Prospective Register of Systematic Reviews (CRD42020180053) .

Clinimetric properties and suitability of selected quality indicators for assessing antibiotic use in hospitalized adults: a multicentre point prevalence study in 24 hospitals in Germany.

OBJECTIVES: The capability to measure and monitor the quality of antibiotic prescribing is an important component of antibiotic stewardship (ABS) programmes. Several catalogues of consensus-based structure and process-of-care quality indicators (QIs) have been proposed, but only a few studies have tested and validated ABS QIs in practice tests. This multicentre study determined the clinimetric properties and suitability of a set of 33 process QIs for ABS that had earlier been developed and in part recommended in a German-Austrian hospital ABS practice guideline. METHODS: Two point prevalence surveys were conducted in a convenience sample of 24 acute care hospitals throughout Germany, and data of all screened adult inpatients with prescription of a systemic antibiotic at a given day (n=4310) were included in the study. For each QI, the following clinimetric properties were assessed: applicability, feasibility, performance, case mix stability and interobserver reliability. RESULTS: Eighteen QIs were considered sufficiently feasible, applicable and reliable, and had adequate room for improvement. The finally selected QIs primarily cover antibiotic therapy of common infections (bloodstream infection, pneumonia and urinary tract infection), while two of the QIs each address surgical prophylaxis and general aspects of antibiotic administration. CONCLUSIONS: Practice tests may be important to test the suitability of consensus process-of-care QIs in the field of hospital ABS. The 18 selected QIs considered suitable enough for hospital ABS in this study should be regarded as priority QIs useful for internal quality control and assurance. More research and additional practice tests may be needed to confirm their suitability for external quality assessment schemes.

Simultaneous Quantification of Nine Antimicrobials by LC-MS/MS for Therapeutic Drug Monitoring in Critically Ill Patients.

BACKGROUND: Adequate antibiotic treatment is a prerequisite for the successful treatment of systemic infections. Based on accumulating scientific evidence, a fixed dosage regimen can lead to insufficient and ineffective antibiotic therapy. Thus, the aim of this study was to develop and validate a simplified, but sensitive method for the simultaneous quantification of antimicrobials by using liquid chromatography with tandem mass spectrometry (LC-MS/MS) for the development of personalized therapy regimens using therapeutic drug monitoring. METHODS: A method was developed for the simultaneous quantification of 9 antimicrobials (aciclovir, ampicillin, cefuroxime, ciprofloxacin, meropenem, metronidazole, piperacillin, rifampicin, and tazobactam) in lithium-heparin plasma. A simple sample preparation method and a chromatographic run time of 10 minutes enabled the quick processing of the samples. The method was validated according to the guidelines for bioanalytical method validation of the European Medicines Agency and addressed sensitivity, specificity, linearity, accuracy, precision, dilution integrity, carry-over, recovery, matrix effects, and stability. RESULTS: The chromatographic run time was 10 minutes and antimicrobials eluted at retention times ranging from 1.1 to 2.2 minutes. Calibration curve for all antimicrobials was linear over a range of 1-100 mg/L, and a 2-fold or 5-fold dilution of the samples was possible. The method accuracy ranged from 85.1% to 114.9% for all measured antimicrobials, and the within- and between-run precision values were <11.9% and <16.5% for the lower limit of quantification. No interferences and carry-over were observed. The samples were stable for at least 5 hours at room temperature or in the autosampler (10°C). CONCLUSIONS: The LC-MS/MS method developed in this study is appropriate and practical for the therapeutic drug monitoring of antimicrobials in the daily clinical laboratory practice because of its short analysis time, the need for a small amount of plasma, high specificity, and accuracy.

M. pneumoniae and C. pneumoniae are no relevant pathogens in critically ill patients with hospital-acquired respiratory tract infections.

PURPOSE: To assess the incidence of Mycoplasma pneumoniae and Chlamydia pneumoniae in the pathogenesis of hospital-acquired respiratory tract infections (RTIs) in critically ill patients. METHODS: This is a retrospective cohort study of all ICU-patients ≥ 18 years with RTI who underwent conventional culture techniques and PCR testing for both M. pneumoniae and C. pneumoniae from respiratory tract specimens (bronchoalveolar lavage or tracheobronchial aspirates) between January 2013 to May 2017 at the Jena University Hospital. RESULTS: In total, 314 patients were included in the analysis. Of these, 210 (66.9%) patients were diagnosed with HAP, 65 (20.7%) with VAP and 39 (12.4%) with VAT. Overall, 73 (30.7%) patients were on mechanical ventilation on the day of microbiological examination. PCR-testing for M. pneumoniae was positive in two patients (0.6%) and for C. pneumoniae in zero patients. CONCLUSIONS: Our study shows that the incidence of M. pneumoniae and C. pneumoniae in the pathogenesis of hospital-acquired RTIs in critically ill patients is negligible. The results support the recommendations of the guidelines not to perform empiric therapy covering these pathogens.

Infectious disease services: a survey from four university hospitals in Germany.

PURPOSE: Involvement of infectious disease (ID) specialists in the care of hospitalized patients with infections through consultation services improves the quality of care and the outcome of patients. This survey aimed to describe activities and utilization of ID consultations at four German tertiary care hospitals. METHODS: A 1-month (March 2016) retrospective cross-sectional study at four university hospitals (Freiburg, Jena, Cologne and Regensburg) was performed. Only ID consultations with written documentation and bedside patient evaluation were included. Consultations were analyzed with regard to requesting departments, infections, case severity, and diagnostic and therapeutic recommendations. RESULTS: In the study period, 638 ID consultations were performed in 479 patients-corresponding to 3-4 consultations per 100 inpatient cases. Patients were characterized by a high disease complexity-the mean case mix index in patients with consultation was 10.1 compared to 1.6 for all patients. ID consultations were requested by many different specialties, with approximately half of the requests coming from surgical disciplines. ID consultations resulted in revised diagnoses in 34% of the cases, provided recommendations for additional diagnostic procedures in 66%, and for modifications of antimicrobial regimens in 70% of the cases. CONCLUSIONS: Infectious disease consultations were requested for patients with severe and complicated diseases and resulted in recommendations that highly impacted the diagnostic work-up and therapeutic management of patients. The results of this survey may help to estimate requirements for establishment of such services in Germany.

Diagnosis of malaria in a traveler 9 months after returning from West Africa by illumigene® LAMP assay: A case report.

Loop-mediated isothermal amplification (LAMP) is a rapid molecular technique that has been introduced into malaria diagnosis. The test is easy to perform and offers high sensitivity. We report a 53-year-old male patient who was hospitalized with fever attacks, chills, and headache caused 9 months after returning from Africa. During his stay in Africa, he used malaria chemoprophylaxis. Microscopy of thin and thick blood films and rapid diagnostic antigen testing remained negative for three times. The EDTA blood samples were tested using the Meridian illumigene® malaria LAMP assay that gave a positive result for Plasmodium spp. Diagnosis of malaria was subsequently specified as P. ovale infection by real-time PCR. Ovale malaria often manifests with delay and low parasitemia. The patient was treated with atovaquone-proguanil, followed by primaquine for prophylaxis of relapse. This case illustrates the usefulness of the illumigene® malaria LAMP assay for initial screening of malaria parasites.

[Staphylococcus aureus Bacteraemia - an Interdisciplinary Challenge]. / Staphylococcus-aureus-Blutstrominfektion ­ eine interdisziplinäre Herausforderung.

BACKGROUND: Staphylococcus aureus is the second-most-common pathogen among bloodstream infections. Due to a high hospital mortality rate (15 - 40%), frequent complications and recurrences the clinical management of Staphylococcus aureus bacteremia (SAB) is distinct from bacteremia from other pathogens. METHODS: A literature search was performed using PubMed. Guidelines and best practice expert recommendations were included. RESULTS: The detection of S. aureus in blood culture should always be considered clinically relevant. The drug of choice for treatment of a bloodstream infection with methicillin-sensitive S. aureus is flucloxacillin (8 - 12 g i. v./d). In a bloodstream infection with methicillin-resistant S. aureus (MRSA) vancomycin or daptomycin (the latter not in pneumonic focus) are recommended. Follow-up blood cultures, source identification, including transoesophageal echocardiography in patients with risk profile, and rapid source control are important measures. The duration of therapy is at least 14 days with uncomplicated SAB, whereby the entire therapy should be carried out intravenously. In case of complicated SAB, a total therapy duration of at least 4 - 6 weeks is recommended. Adherence to this set of measures can reduce mortality by up to 50%. CONCLUSION: SAB is associated with high morbidity and mortality. Clinical management is complex. By adhering to diagnostic and therapeutic measures, the prognosis can be improved.

Perceptions and attitudes regarding antibiotic resistance in Germany: a cross-sectoral survey amongst physicians, veterinarians, farmers and the general public.

Background: Drivers of antibiotic (AB) resistance (ABR) include outpatient treatment, hospital care and animal husbandry. During the first phase of the One Health project RAI (Responsible Antibiotic Use via Information and Communication) surveys were conducted in these sectors. Objectives: To compare perceptions and attitudes towards ABR among general practitioners (GPs), hospital physicians, veterinarians, pig farmers and the general public. Methods: Cross-sectional questions on AB use and ABR were integrated in group-specific surveys of GPs, hospital physicians, veterinarians, pig farmers and the German general population. Results: A total of 1789 participants (340 GPs, 170 hospital physicians, 215 pig farmers, 60 veterinarians and 1004 members of the public) responded. Each group tended to identify drivers of ABR as being from outside its own area of activity. Guidelines were shown to be an important information source for AB therapy for all prescriber groups, but the frequency of routine use differed (39% of GPs, 65% of hospital physicians and 53% of veterinarians). Regarding further information sources, hospital physicians preferred smartphone apps and e-learning, GPs preferred non-sponsored training and veterinarians preferred multidisciplinary networks and e-learning. Farmers were predominantly satisfied with existing solutions. Farmers had three times better basic knowledge of ABR and knew twice as many people with MDR organism problems than the general public. They also received information on ABR more often from their veterinarians than patients did from their doctors. Conclusions: This study reveals considerable differences in perceptions and attitudes to ABR among the groups investigated. The results can help to tailor future interventions. Furthermore, they promote mutual understanding and thus support the One Health approach.

Isavuconazole shortens the QTc interval.

Isavuconazole is a novel antifungal drug approved for the treatment of adults with invasive aspergillosis and mucormycosis. While azoles as a class effect are known to prolong QTc interval, clinical trials have shown that isavuconazole administration may cause shortening in a dose-related manner. Here, we assessed the effects of isavuconazole on the length of QTc interval. The objective of the study was to describe changes in the QTc interval induced by isavuconazole treatment. A total of 26 adult patients from 7 hospitals were included. Patients received isavuconazole for the treatment of invasive fungal infection and, in 1 case, for prophylaxis due to QTc prolongation under fluconazole. Twelve-channel electrocardiograms (ECGs) were performed before and during treatment. Out of 26 patients, 24 showed shortening of QTc interval. In patients with QTc shortening, QTc during isavuconazole treatment showed a mean decrease of 7.4 ± 5.8% (36.5 ± 38.8 ms, range 7-202; P = .004), compared to pre-isavuconazole ECG. One patient with available long-term follow-up showed further decrease in QTc on days 55 and 110. Apart from 1 case report, these are the first data outside controlled clinical trials showing QTc shortening. Knowledge about cardiac effects of isavuconazole will serve to better manage the use of concomitant medications.