Tick-Borne Encephalitis Virus Nonstructural Protein 1 IgG Enzyme-Linked Immunosorbent Assay for Differentiating Infection versus Vaccination Antibody Responses.

Tick-borne encephalitis virus (TBEV) is an important central nervous system (CNS) infection in Europe and Asia. It is a flavivirus in the tick-borne group. Effective vaccines against TBE are available in the affected countries. However, diagnosing TBE is challenging due to cross-reactive antibodies between different viruses of the genus Flavivirus, family Flaviviridae. Differentiation between infection-induced and vaccine-induced antibodies can be difficult and in many cases impossible, due to the increasing vaccination rate against TBEV. We present a new approach to detect antibodies against the TBEV nonstructural protein 1 (NS1) as a diagnostic marker, which is exclusively indicative for virus replication in natural infection, on the basis of an enzyme-linked immunosorbent assay (ELISA). A total of 188 anonymous serum samples from the National Consultant Laboratory for TBEV were included in our study. The assay was validated according to the European Laboratory Norm DIN EN ISO 15189 for diagnostic use. The ELISA for the detection of TBEV NS1 specific IgG class antibodies has demonstrated a sensitivity of >94% and a specificity of >93% in broadly cross-reacting sera from patients with vaccinations against flaviviral diseases and single or multiple flavivirus infections, respectively. The detection of anti-NS1 antibodies is feasible and facilitates reliable differentiation between different flavivirus infections, TBEV infection, and TBE vaccination.

Tick-borne encephalitis virus vaccination breakthrough infections in Germany: a retrospective analysis from 2001 to 2018.

OBJECTIVES: There are few data available regarding the clinical course of tick-borne encephalitis virus (TBEV) vaccination breakthrough infections. The published studies suggest that vaccination breakthrough infections may have a more severe course than native TBEV infection in unvaccinated individuals-potentially due to antibody-dependent enhancement. Here we report a large analysis of vaccination breakthrough infections. METHODS: This retrospective analysis was based on a national surveillance dataset spanning the years 2001-2018. Variables reflecting disease severity, such as 'CNS symptoms', 'myelitis', 'fatal outcome' and 'hospitalization' were analysed as well as general epidemiological variables. Cases were categorized as 'unvaccinated' or 'ever vaccinated', the latter category including cases with at least one dose of a TBEV vaccine. RESULTS: A total of 6073 notified TBEV infection cases were included in our analysis. Sufficient data on vaccination status were available for 95.1% of patients (5777/6073); of these, 5298 presented with a native infection. A total of (334/5777) cases developed an infection despite having been vaccinated at least once. Comparing unvaccinated patients with those with at least one vaccination, we find an odds ratio (OR) 2.73, (95% confidence interval (CI) 0.79-9.50) regarding the variable fatal outcome that did not reach statistical significance. Analysing the clinical variables 'CNS symptoms' and 'myelitis', there is no difference between these groups (OR 0.86, 95% CI 0.68-1.08; and OR 1.30, 95% CI 0.74-2.27 respectively). Patients who were vaccinated and had an assumed protection at symptom onset (n = 100) had a higher risk for the development of myelitic symptoms (OR 2.21, 95% CI 1.01-4.86]) than unvaccinated patients. CONCLUSION: Our findings could neither verify that vaccination breakthrough infections might cause a more severe disease than native infections nor prove a clear antibody-dependent enhancement phenomenon. It remains unclear whether the increased myelitis risk in a subgroup of vaccinated patients is a true effect or confounded.

Heart transplantation as salvage therapy for progressive prosthetic valve endocarditis due to methicillin-resistant Staphylococcus epidermidis (MRSE).

BACKGROUND: Prosthetic valve endocarditis (PVE) has the highest in-hospital mortality among all cases of infective endocarditis (IE), it is estimated at about 40 %. Orthotopic heart transplantation (OHT) as a measure of last resort, may be considered in selected cases where repeated surgical procedures and conservative efforts have failed to eradicate persistent or recurrent IE. Only few clinical data are available regarding this rare indication for OHT, since active IE has traditionally been considered as a contraindication for OHT. CASE PRESENTATION: We report on a 55 year old male patient who underwent prosthetic valve replacement with a mechanical valved conduit ten years ago and developed now persistent PVE with severe complications due to methicillin-resistant Staphylococcus epidermidis (MRSE). Repeated surgical procedures and conservative efforts have failed to eradicate the pathogen. Regarding the lack of curative options, salvage OHT was discussed as a measure of last resort. 28 months after the first diagnosis of PVE, the patient was successfully transplanted and is now doing well under close follow-up (6 months post-OHT). CONCLUSIONS: PVE remains a challenging condition regarding diagnosis and treatment. The presented case underscores the urgent need for an integrated and multidisciplinary approach to patients with suspected and definitive IE - especially in PVE. OHT might be a feasible measure of last resort in selected patients with IE. Our case report adds published clinical experience to this rarely performed procedure and consolidates previous findings.

Implementing an intensified antibiotic stewardship programme targeting cephalosporin and fluoroquinolone use in a 200-bed community hospital in Germany.

BACKGROUND: Prescription of third-generation cephalosporins and fluoroquinolones has been linked to an increasing incidence of gram-negative bacteria producing extended-spectrum beta-lactamases, methicillin-resistant Staphylococcus aureus and nosocomial infection with Clostridium difficile. Antibiotic stewardship (ABS) programmes offer evidence-based tools to control antibiotic prescription rates and thereby influence the incidence of nosocomial infection and contain the development of multidrug-resistant bacteria, but there is limited experience with such programmes at community hospitals. METHODS: We implemented an ABS programme at a 200-bed community hospital and aimed at a > 30 % reduction of cephalosporin and fluoroquinolone consumption within 1 year. Pharmacy data were obtained to estimate hospital-wide drug use density expressed in WHO-ATC-defined daily doses (DDD) or hospital-adapted recommended daily doses (RDD) per 1,000 patient days. The effect of the ABS intervention on drug use density was analysed using interrupted time-series analysis for the periods between January 2011 and March 2013 as pre-intervention, and between April 2013 and March 2014 as post-intervention period. The CDI incidence was calculated based on microbiology laboratory data. RESULTS: Cephalosporin use (measured in RDD/1,000 patient days) decreased by 33 %, and fluoroquinolone use decreased by 31 %, respectively. Interrupted time-series analysis confirmed significant changes in the drug use density trends for both cephalosporins and fluoroquinolones after the intervention as well as for total antibiotic use that decreased by 11 % while no significant effect was noted for CDI incidence rates. CONCLUSION: ABS programmes can be effective in community hospitals and may help establish ecologically advantageous antibiotic strategies when needed.

[Pilot project of a pediatric antibiotic stewardship initiative at the Hauner children's hospital]. / Pilotprojekt einer pädiatrischen Antibiotic-Stewardship-Initiative am Dr. von Haunerschen Kinderspital - neue Wege der pädiatrischen Infektiologie.

The steady increase in antimicrobial resistance is of growing concern in healthcare. Antibiotic Stewardship [ABS] Strategies are important tools to control antibiotic use and -prevent antimicrobial resistance. An increasing number of institutions are developing ABS initiatives also in pediatrics. However, few data are available assessing the implementation and efficiency of these pediatric ABS programs.At the Dr. von Hauner Children's Hospital, Ludwig-Maximilian University, a tertiary care pediatric reference center, a pediatric ABS Team has been implemented. Key structural elements were the same as for adult patients, but antimicrobials agents selected for monitoring and appropriate clinical endpoints are different in pediatrics.Key features were: 1. prospective-audit with feedback and formulary restriction and 2. pre-authorization (also referred to as prior approval). The ABS team consisted of one pediatric infectious disease specialist, one clinical fellow in pediatric infectious diseases, and one clinical pharmacist with training in infectious diseases.With the implementation of a pediatric ABS strategy we could significantly influence antimicrobial consumption in our hospital. Cost-savings are estimated to be above 330 000 € per year, and concomitantly the use of broad-spectrum antibiotics and antifungal compounds was significantly reduced.Antibiotic Stewardship [ABS] Strategies may be an effective tool to control antibiotic use in the setting of a large tertiary pediatric teaching hospital. A national guideline for ABS initiatives may help to further improve rational use of antibiotics in the hospital setting.

[Hepatitis B reactivation following immunosuppressive therapy and screening adherence: a neglected problem?]. / Hepatitis-B-Reaktivierung unter Chemotherapie und Screening-Adhärenz: ein unterschätztes Problem?

BACKGROUND: Current guidelines of the "Centers for Disease Control and Prevention [CDC]" recommend routine screening for Hepatitis B before cytotoxic or immunosuppressive therapies are initiated. The national German guideline "Prophylaxis, diagnosis and therapy of hepatitis B virus infection" is in line with the CDC recommendations and underscores general HBV screening before immunosuppression is induced. However, screening adherence and acceptance of these guidelines vary in different oncological specialities. To assess the HBV screening adherence a retrospective study was performed. PATIENTS AND METHODS: Data of 140 patients were analyzed retrospectively. 37 case-records did not meet inclusion criteria. Patients diagnosed with breast-cancer (n = 43) and Hodgkin's disease (n = 14) requiring chemotherapy were included, as well as patients receiving allogenic stem cell transplantation (SCTx) therapy (n = 22) or transarterial chemoembolization (TACE) therapy of the liver (n = 24). All included case-records were reviewed regarding HBV and HCV serology. RESULTS: In the TACE group three patients were screened for HBsAg. Four patients with breast cancer and five patients in the Hodgkin disease group were screened for HBsAg. In contrast, screening adherence was 100 % in the group of patients receiving allogenic stem cell transplantation therapy (n = 22). CONCLUSION: Apart from patients with allogenic stem cell transplantation, only some patients receiving immunosuppressive therapies had been screened for HBV infection. Our data indicate that standardized checklists may improve HBV screening previous to immunosuppressive therapies. These clinical structures have led to an almost optimal screening adherence in the high-risk group of allogenic SCTx patients.

[kappa-light chain amyloidosis of the liver, a rare cause of liver enzyme elevation]. / Leichtkettenamyloidose der Leber vom kappa-Typ. Seltene Ursache einer cholestatischen Leberenzymkonstellation.

HISTORY AND ADMISSION FINDINGS: A 69-year-old man was admitted to the department of gastroenterology having for months had persistently elevated liver enzymes after discontinuing systemic antimycotic therapy. He reported loosing five kilogram of body weight in the past six months. No macroscopic or microscopic abnormalities had been found on esophago-gastroduodenoscopy. INVESTIGATIONS: Congo-red staining of the liver biopsy revealed massive sinusoidal amyloidosis of the liver. Immunoelectrophoresis of the urine and serum, as well as bone marrow biopsy, ruled out multiple myeloma or Waldenström's disease. Immunohistochemical staining identified the amyloid protein as a IgG kappa light chain (KLC). The free light chain (FLC) test confirmed KLC monoclonal gammopathy with an abnormal free kappa to lambda chain (KLLC) ratio. TREATMENT AND COURSE: Systemic KLC amyloidosis in this patient older than 65 years was given chemotherapy with melaphalan and dexamethasone (M-Dex). After three courses of M-Dex the renal clearance deteriorated and the serum N-terminal probrain natriuretic peptide (T-proBNP) had increased. COURSE: The patient was included in a phase II clinical trial which evaluates the use of bortezomib in patients with amyloidosis. Normalization of the free KLLC ratio and the NT-proBNP level will serve as important prognostic indicators. CONCLUSION: KLC amyloidosis is a rare cause of elevated liver enzymes. The nonspecific symptoms often delay the diagnosis. FLC testing is a helpful tool in identifying monoclonal gammopathies, even when immunoelectrophoretic tests are normals.