Publications by authors named "Christoph Steininger"

59 Publications

Heterosubtypic, cross-reactive immunity to human Cytomegalovirus glycoprotein B.

Clin Exp Immunol 2022 Apr 8. Epub 2022 Apr 8.

Department of Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Austria.

Cytomegalovirus (CMV) genome is highly variable and heterosubtypic immunity should be considered in vaccine development since it can enhance protection in a cross-reactive manner. Here, we developed a protein array to evaluate heterosubtypic immunity to CMV glycoprotein B (gB) in natural infection and vaccination. DNA sequences of four antigenic domains (AD1, AD2, AD4/5 and AD5) of gB were amplified from six reference and 12 clinical CMV strains, and the most divergent genotypes were determined by phylogenetic analysis. Assigned genotypes were in vitro translated and immobilized on protein array. Then, we tested immune response of variable serum groups (primarily infected patients, reactivated CMV infections and healthy individuals with latent CMV infection, as well gB-vaccinated rabbits) with protein in situ array (PISA). Serum antibodies of all patient cohorts and gB-vaccinated rabbits recognized many genetic variants of ADs on protein array, including but not limited to the subtype of infecting strain. High-grade cross-reactivity was observed. In several patients, we observed none or neglectable immune response to AD1 and AD2, while the same patients showed high antibody response to AD4/5 and AD5. Among the primary infected patients, AD5 was the predominant antigenic domain, in antibody response. The most successful CMV vaccine to date contains gB and demonstrates only 50% efficacy. In this study, we showed that heterosubtypic and cross-reactive immunity to CMV gB is extensive. Therefore, the failure of CMV gB vaccines cannot be explained by a highly, strain-specific immunity. Our observations suggest that other CMV antigens should be addressed in vaccine design.
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http://dx.doi.org/10.1093/cei/uxac031DOI Listing
April 2022

Proposal of a population wide genome-based testing for Covid-19.

Sci Rep 2022 04 4;12(1):5618. Epub 2022 Apr 4.

University of Bonn, Bonn, Germany.

Our lives (and deaths) have by now been dominated for two years by COVID-19, a pandemic that has caused hundreds of millions of disease cases, millions of deaths, trillions in economic costs, and major restrictions on our freedom. Here we suggest a novel tool for controlling the COVID-19 pandemic. The key element is a method for a population-scale PCR-based testing, applied on a systematic and repeated basis. For this we have developed a low cost, highly sensitive virus-genome-based test. Using Germany as an example, we demonstrate by using a mathematical model, how useful this strategy could have been in controlling the pandemic. We show using real-world examples how this might be implemented on a mass scale and discuss the feasibility of this approach.
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http://dx.doi.org/10.1038/s41598-022-08934-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8978767PMC
April 2022

Reliable quantification of Cytomegalovirus DNAemia in Letermovir treated patients.

Antiviral Res 2022 May 27;201:105299. Epub 2022 Mar 27.

Division of Infectious Diseases and Tropical Medicine, Department of Medicine I, Medical University of Vienna, Vienna, Austria; Karl Landsteiner Institute of Microbiome Research, St. Pölten, Austria. Electronic address:

Polymerase chain reaction (PCR) based methods are a fast and sensitive approach to detect and monitor viral load in Cytomegalovirus (CMV) patients. Letermovir (LMV) acts at a late stage during the CMV replication cycle and does not inhibit CMV DNA replication per se. Therefore, quantitative nucleic acid amplification testing might lead to the overestimation of viral load in patients treated with LMV and underestimate treatment success. To study this discrepancy, we treated infected cells with LMV or Ganciclovir (GCV) and compared viral progeny DNA levels. Prior to nucleic acid extraction and qPCR measurements we pretreated cell lysates and cell culture supernatants from infected cells with DNase I. This step assumes the degradation of DNA which is not protected from a viral capsid. LMV treatment did not reduce genomic copies (GC) in samples from whole cell lysates compared to samples treated with GCV. DNase treatment prior to DNA extraction, decreased GC in the LMV treated group to comparable levels as seen in the GCV group. In cell culture supernatants, LMV or GCV treatment led to an equivalent reduction of CMV GC. In this case, DNase treatment exerted a negligible effect on both groups. We conclude that the accumulation of concatemeric DNA within cells seems to be a confounding variable when monitoring LMV efficacy via qPCR. However, qPCR shows to be a reliable method to evaluate antiviral efficacy of LMV in cell free specimens. These results have strong clinical implications for the monitoring of CMV therapy during LMV treatment.
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http://dx.doi.org/10.1016/j.antiviral.2022.105299DOI Listing
May 2022

Oral Abundance of Actinomyces spp. in Breast Cancer Patients.

Oncology 2022 20;100(4):221-227. Epub 2022 Jan 20.

Division of Infectious Diseases and Tropical Medicine, Department of Medicine I, Medical University of Vienna, Vienna, Austria.

Objectives: Pathophysiology of medication-related osteonecrosis of the jaw (MRONJ) is still unclear, and disease development is associated with adverse reaction of bisphosphonates and denosumab, and Actinomyces spp. as well. In this study, we evaluated the abundance of Actinomyces spp. in breast cancer patients undergoing chemotherapy compared to healthy controls.

Methods: Oropharyngeal samples were collected from treatment-naive early-stage breast cancer patients, who were scheduled for standard of care therapy (eight samples throughout chemotherapy, one prior to radiotherapy and one after a year of start), as well as from healthy controls at matched timepoints. We quantified Actinomyces spp. in the samples with a highly sensitive and specific quantitative polymerase chain reaction.

Results: Twenty-one patients and 16 healthy subjects were enrolled. Forty-eight percent of patients suffered from estrogen receptor-positive/progesterone receptor-positive or -negative/human epidermal growth factor receptor 2 (HER2)-negative disease, 38% were HER2-positive, and 14% were triple-negative. Comparison of Actinomyces spp. loads in cancer patients and healthy controls did not reveal significant difference. Fluctuations on bacterial quantity were observed in both groups over time. Tumor receptor status or different chemotherapy schemes of patients were not correlated with a particular pattern on abundance of Actinomyces spp.

Conclusions: We suggest that Actinomyces spp. are not the initiative factors in MRONJ development. These bacteria are not altered in abundance during chemotherapy, but they behave opportunistic when there is a bone disruption in the oropharynx in the first place caused by antiresorptive drugs or dental trauma and proliferate in their new niche. Thus, Actinomyces spp. plays a latter role in MRONJ development, rather than a primary causative one.
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http://dx.doi.org/10.1159/000522070DOI Listing
April 2022

Evolution of SARS-CoV-2 Key Mutations in Vienna Detected by Large Scale Screening Program.

Viruses 2021 10 7;13(10). Epub 2021 Oct 7.

Division of Infectious Diseases, Department of Medicine 1, Medical University of Vienna, 1090 Vienna, Austria.

Currently countries across the globe are preparing for the fourth wave of SARS-CoV-2 infections, which is mainly driven by the rapid spread of novel SARS-CoV-2 variants. Austria and, in particular, the capital city of Vienna, witnessed a disproportionally steep rise in SARS-CoV-2 infection rates during the last wave of infections. By the end of January 2021, the government of Vienna launched an innovative, state-wide SARS-CoV-2 screening program based on PCR analysis of self-collected mouthwash samples. More than 400,000 mouthwash samples were collected in Vienna during the third wave of infection from January to March 2021. All preanalytical and analytical steps were carried out in a highly standardized manner at a single certified testing center. SARS-CoV-2 specific PCR analysis revealed in these samples a positivity rate of 0.43%. The relative proportion of N501Y positive virus samples increased continually to 68% of weekly samples. Mutation K417N was detected only in three samples. With this study, we were able to map the temporal occurrence of SARS-CoV-2 variants in a highly unbiased manner. Positivity rates and variant prevalence rates in this study were lower than in other nationwide programs. The results presented in this study indicate that actual virus prevalence tends to be overestimated by surveillance programs such as results of cluster analysis or contact tracing programs.
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http://dx.doi.org/10.3390/v13102014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538562PMC
October 2021

Protein Phosphatase 1 Regulates Human Cytomegalovirus Protein Translation by Restraining AMPK Signaling.

Front Microbiol 2021 15;12:698603. Epub 2021 Jul 15.

Division of Infectious Diseases and Tropical Medicine, Department of Medicine I, Medical University of Vienna, Vienna, Austria.

Human cytomegalovirus (HCMV) carries the human protein phosphatase 1 (PP1) and other human proteins important for protein translation in its tegument layer for a rapid supply upon infection. However, the biological relevance behind PP1 incorporation and its role during infection is unclear. Additionally, PP1 is a difficult molecular target due to its promiscuity and similarities between the catalytic domain of multiple phosphatases. In this study, we circumvented these shortcomings by using 1E7-03, a small molecule protein-protein interaction inhibitor, as a molecular tool of noncatalytic PP1 inhibition. 1E7-03 treatment of human fibroblasts severely impaired HCMV replication and viral protein translation. More specifically, PP1 inhibition led to the deregulation of metabolic signaling pathways starting at very early time points post-infection. This effect was at least partly mediated by the prevention of AMP-activated protein kinase dephosphorylation, leading to elongation factor 2 hyperphosphorylation and reduced translation rates. These findings reveal an important mechanism of PP1 for lytic HCMV infection.
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http://dx.doi.org/10.3389/fmicb.2021.698603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320725PMC
July 2021

Bone turnover markers can predict healing time in medication-related osteonecrosis of the jaw.

Support Care Cancer 2021 Dec 30;29(12):7895-7902. Epub 2021 Jun 30.

Department of Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Objectives: Medication-related osteonecrosis of the jaw (MRONJ) is a severe and difficult-to-treat adverse event of bone-modifying agents. Therefore predictive strategies determining patients at risk for a prolonged healing duration are needed to optimize treatment. Thus, the present study evaluates whether or not bone turnover markers can be used to predict the healing duration in MRONJ patients.

Materials And Methods: The present study is a retrospective data analysis of patients suffering from MRONJ and positive histology for Actinomyces spp., who were identified at the General Hospital Vienna from 2014 to 2018. During the first visit, the patients' demographics and levels of bone formation parameters were compiled. Healing times were analysed by Cox regression in dependence on these factors.

Results: A total of 52 patients were identified who fulfilled the inclusion criteria. The indication for bone-modifying agents was breast cancer (n = 21), prostate cancer (n = 14), multiple myeloma (n = 6) and other malignant diseases (n = 11). In 43 (82.7%) of our patients, we were able to document complete mucosal healing. Furthermore, patients who responded faster to therapy showed higher levels of C-telopeptide (P < 0.05), osteocalcin (P < 0.05) and bone-specific alkaline phosphatase (P < 0.05), but lower levels of 1.25-dihydroxyvitamin D (P < 0.05) than slower responding patients. No correlation was found regarding parathyroid hormone or calcitonin levels. Interestingly, patients who had a slower response were less likely to report dental procedures, but more likely to report a history of chemotherapy.

Conclusion: CTX and osteocalcin levels may be used for predicting healing duration for MRONJ.
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http://dx.doi.org/10.1007/s00520-021-06361-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8550071PMC
December 2021

A Longitudinal Seroprevalence Study Evaluating Infection Control and Prevention Strategies at a Large Tertiary Care Center with Low COVID-19 Incidence.

Int J Environ Res Public Health 2021 04 15;18(8). Epub 2021 Apr 15.

Division of Infectious Diseases and Tropical Medicine, Department of Medicine I, Medical University of Vienna, 1090 Vienna, Austria.

Personal protective equipment and adherence to disinfection protocols are essential to prevent nosocomial severe acute respiratory syndrome coronavirus (SARS-CoV-2) transmission. Here, we evaluated infection control measures in a prospective longitudinal single-center study at the Vienna General Hospital, the biggest tertiary care center in Austria, with a structurally planned low SARS-CoV-2 exposure. SARS-CoV-2-specific antibodies were assessed by Abbott ARCHITECT chemiluminescent assay (CLIA) in 599 health care workers (HCWs) at the start of the SARS-CoV-2 epidemic in early April and two months later. Neutralization assay confirmed CLIA-positive samples. A structured questionnaire was completed at both visits assessing demographic parameters, family situation, travel history, occupational coronavirus disease 2019 (COVID-19) exposure, and personal protective equipment handling. At the first visit, 6 of 599 participants (1%) tested positive for SARS-CoV-2-specific antibodies. The seroprevalence increased to 1.5% (8/553) at the second visit and did not differ depending on the working environment. Unprotected SARS-CoV-2 exposure ( = 0.003), positively tested family members ( = 0.04), and travel history ( = 0.09) were more frequently reported by positively tested HCWs. Odds for COVID-19 related symptoms were highest for congestion or runny nose ( = 0.002) and altered taste or smell ( < 0.001). In conclusion, prevention strategies proved feasible in reducing the risk of transmission of SARS-CoV-2 from patients and among HCWs in a low incidence hospital, not exceeding the one described in the general population.
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http://dx.doi.org/10.3390/ijerph18084201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071361PMC
April 2021

Surveillance of respiratory syncytial virus infections in adults, Austria, 2017 to 2019.

Sci Rep 2021 04 26;11(1):8939. Epub 2021 Apr 26.

Division of Infectious Diseases and Tropical Medicine, Department of Medicine I, Medical University of Vienna, Waehringer Guertel 18-10, 1090, Vienna, Austria.

Respiratory syncytial virus (RSV) testing is generally available in most care centres, but it is rarely performed because clinicians' seldom suspect RSV to be the underlying pathogen in adults with respiratory disease. Here, we evaluate the impact of broad combined influenza/RSV testing on the clinical practice. Overall, 103 patients were tested positively for RSV. Our study indicates that positively tested patients were mostly of advanced age and suffered from chronic diseases. Mortality was significant in our cohort and higher in patients with advanced age. Further, we report a significant increase in detected RSV cases but also in detection rate. Together, these findings suggest that implementation of a combined influenza/RSV testing led to a significant increase in detection rate, supported clinicians establishing the correct diagnosis and allowed a safe and controlled handling of RSV patients.
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http://dx.doi.org/10.1038/s41598-021-88537-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076173PMC
April 2021

Antimicrobial Resistance of in Gastric Biopsy Samples from Lima/Peru.

Microb Drug Resist 2021 Jul 20;27(7):951-955. Epub 2020 Oct 20.

Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria.

prevalence and gastric cancer rates are remarkably high in Peru. Effective antimicrobial regimens are essential for successful eradication. We aimed at assessing antimicrobial resistance rates to first- and second-line therapeutic agents in strains detected in gastric biopsy samples. Gastric biopsy samples (antrum and corpus) were collected from therapy-naive patients ( = 154). presence in the samples was confirmed by histopathology. Genotypic resistance to clarithromycin and quinolones was determined by real-time PCR. Histology results were 100% concordant with PCR results (97/154; 63% -positive in both). In 6% (6/97) of the patients, we found discordant results of infection in antrum and corpus samples from the same patient. Resistance rates to clarithromycin and quinolone were 34% (33/97) and 68% (56/82), respectively. Antimicrobial resistance to both antimicrobials was 30% (25/82). Antimicrobial resistance rates of to clarithromycin and quinolones are very high in Lima, Peru. Many first- and second-line, empiric eradication regimens may not be recommended for Peruvian patients.
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http://dx.doi.org/10.1089/mdr.2020.0241DOI Listing
July 2021

Unexpected complete recovery of a patient with severe tick-borne encephalitis treated with favipiravir.

Antiviral Res 2020 12 12;184:104952. Epub 2020 Oct 12.

Division of Infectious Diseases and Tropical Medicine, Department of Medicine I, Medical University Vienna, Vienna, Austria.

We report a case of tick-borne encephalitis (TBE) in a 22-year-old man, who was admitted to the Medical University of Vienna hospital with severe meningoencephalitis, unresponsive and dependent on a respirator. He had given a history of a recent tick bite, but because he had previously received a full course of vaccination against TBE, West Nile virus infection was suspected. Because the antiviral drug favipiravir has been reported to be active against WNV, therapy was initiated, and continued even after a diagnosis of TBE was confirmed, due to significant improvement of symptoms. Within days, the patient's symptoms resolved, and he was discharged after complete recovery at 15 days after onset. Although this single case does not permit any conclusion as to the role of favipiravir in the favorable outcome, it suggests that the drug should be further evaluated in laboratory animal models and in appropriate clinical settings.
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http://dx.doi.org/10.1016/j.antiviral.2020.104952DOI Listing
December 2020

Letermovir for the compassionate therapeutic use of cytomegalovirus infection.

Eur J Clin Microbiol Infect Dis 2021 Feb 11;40(2):435-439. Epub 2020 Sep 11.

Division of Infectious Diseases and Tropical Medicine, Department of Medicine I, Medical University Vienna, Vienna, Austria.

Purpose: Data on the efficacy, dosing and safety of letermovir for the compassionate therapeutic use of CMV infections are limited.

Methods: Clinical and virological efficacy of letermovir was assessed in a retrospective single-centre study of patients who received letermovir for the compassionate therapeutic use of CMV infections.

Results: Letermovir initiation yielded prompt treatment response in 7 out of 9 patients (77.7%).

Conclusion: Letermovir may be an effective and well tolerated option in the compassionate treatment of CMV infections, although recurrence of CMV and emergence of resistance may be issues.
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http://dx.doi.org/10.1007/s10096-020-03990-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817558PMC
February 2021

Cytomegalovirus Infection Downregulates Vitamin D Receptor in Patients Undergoing Hematopoietic Stem Cell Transplantation.

Transplantation 2021 07;105(7):1595-1602

Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria.

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative option for patients with hematologic diseases but is associated with high mortality and morbidity. Cytomegalovirus (CMV) infection is common in HSCT patients and modulates vitamin D metabolism in vitro. We aimed at validating CMV-associated vitamin D metabolism in vivo in HSCT.

Methods: Patients treated for significant CMV viremia after HSCT were evaluated for CMV load before, during, and after antiviral treatment. RNA was isolated from whole-blood samples to test for regulation of key components of the vitamin D receptor (VDR) pathway during different phases of CMV viremia.

Results: CMV viremia developed a mean time of 102 (±34) d post-HSCT. Maximum levels of CMV-DNA reached a mean of 5668 (±7257) copies/mL. VDR expression was downregulated to a mean of 64.3% (±42.5%) relative to the VDR expression pre-CMV viremia (P = 0.035) and lagged in recovery following antiviral treatment. Toll-like receptor (TLR) 2 mRNA was upregulated to 225.4% during CMV viremia relative to the expression pre-CMV viremia (P = 0.012) but not TLR6/7/8 and the TLR-adaptor protein MyD88. Levels of 25-OH vitamin D were reduced in all viremic patients (48.0 ± 4.8 versus 25.1 ± 3.7 ng/mL) and were even lower after periods of CMV viremia compared with the control group (48.3 ± 3.5 versus 17.8 ± 1.8 ng/mL; P = 0.008).

Conclusions: CMV viremia is associated with significant dysregulation of vitamin D metabolism in HSCT patients.
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http://dx.doi.org/10.1097/TP.0000000000003448DOI Listing
July 2021

Highly Sensitive Virome Characterization of and Complex from Central Europe and the Caribbean Reveals Potential for Interspecies Viral Transmission.

Pathogens 2020 Aug 21;9(9). Epub 2020 Aug 21.

Division of Infectious Diseases, Department of Medicine 1, Medical University of Vienna, 1090 Vienna, Austria.

Mosquitoes are the most important vectors for arthropod-borne viral diseases. Mixed viral infections of mosquitoes allow genetic recombination or reassortment of diverse viruses, turning mosquitoes into potential virologic mixing bowls. In this study, we field-collected mosquitoes of different species ( and ), from different geographic locations and environments (central Europe and the Caribbean) for highly sensitive next-generation sequencing-based virome characterization. We found a rich virus community associated with a great diversity of host species. Among those, we detected a large diversity of novel virus sequences that we could predominately assign to circular Rep-encoding single-stranded (CRESS) DNA viruses, including the full-length genome of a yet undescribed species. Moreover, we report for the first time the detection of a potentially zoonotic CRESS-DNA virus ( in mosquito vectors. This study expands the knowledge on virus diversity in medically important mosquito vectors, especially for CRESS-DNA viruses that have previously been shown to easily recombine and jump the species barrier.
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http://dx.doi.org/10.3390/pathogens9090686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559857PMC
August 2020

Correction to: Real‑world experience with dalbavancin therapy in gram‑positive skin and soft tissue infection, bone and joint infection.

Infection 2020 Feb;48(1):149

Division of Infectious Diseases and Tropical Medicine, Department of Medicine I, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

The original version of this article unfortunately contained a mistake. The presentation of Fig. 1 was incorrect. The corrected figure is given below.
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http://dx.doi.org/10.1007/s15010-019-01372-9DOI Listing
February 2020

Real-world experience with dalbavancin therapy in gram-positive skin and soft tissue infection, bone and joint infection.

Infection 2019 Dec 13;47(6):1013-1020. Epub 2019 Sep 13.

Division of Infectious Diseases and Tropical Medicine, Department of Medicine I, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Purpose: Dalbavancin is a novel lipoglycopeptide with potent activity against several gram-positive pathogens, an excellent safety profile and a long elimination half-life.

Methods: In this case series observed at the University Hospital of Vienna between 2015 and 2017, all adult patients with gram-positive infections who received at least one dosage of dalbavancin were screened (n = 118). A total of 72 patients were included in the final analysis. The number of included patients stratified by the source of infection was: skin and soft tissue infection (SSTI) (n = 26), osteomyelitis (n = 20), spondylodiscitis (n = 14), acute septic arthritis (n = 4) and prosthetic joint infection (n = 8).

Results: In 46 patients (64%), clinical cure was detected at the end of dalbavancin therapy without additional antibiotic therapy. Of the 26 patients who received additional antibiotic therapy other than dalbavancin, 15 patients (21%) showed no clinical improvement under dalbavancin therapy, four patients (5%) had side effects (nausea n = 1, exanthema n = 2, hyperglycemia n = 1), and in seven patients (10%) clinical improvement under dalbavancin therapy was detected but antibiotic therapy was de-escalated to an oral drug.

Conclusion: We demonstrated high clinical effectiveness of dalbavancin for acute gram-positive infections primarily acute SSTI, acute septic arthritis, acute osteomyelitis and spondylodiscitis. In patients with biofilm-associated infection (chronic infection or joint prosthesis), source control was absolutely necessary for treatment success.
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http://dx.doi.org/10.1007/s15010-019-01354-xDOI Listing
December 2019

Review: Epidemiology of Helicobacter pylori infection.

Helicobacter 2019 Sep;24 Suppl 1:e12635

Department of Medicine I, Medical University of Vienna, Vienna, Austria.

This review summarizes recent publications on the epidemiology of Helicobacter pylori. Two major systemic analyses, from Malaysia and Ethiopia, were published. The Brazilian Consensus Conference has stated that H pylori infection is an infectious disease with an indication for antimicrobial therapy. A continuous decrease in H pylori prevalence was reported from many regions worldwide, including Korea, China, Iran, and Austria. A cross-sectional H pylori prevalence study conducted in the United Arab Emirates found 41% prevalence in a group of healthy children and adults. Several studies from Asia addressed H pylori prevalence in adults undergoing regular checkup. The largest of such studies, performed in Korea, involved 24 471 subjects and reported 41.5% seroprevalence. A relatively smaller study from East China on 3252 subjects reported 27.5% prevalence. In contrast, a study from Spain reported 87.2% seroprevalence. A report on the association between smoking and H pylori seropositivity was published on behalf of the Stomach Cancer Pooling (StoP) Project-a consortium of epidemiological studies of gastric cancer. Also, other potential risk factors, including occupational risk factors, water supply, and food were analyzed. Gastroesophageal reflux and sexual partners has been associated with a higher risk for H pylori acquisition, and gut microbiota was suggested to play a role in intrafamilial transmission of H pylori. Finally, in a few studies (from Mexico and Japan), the catalytic model for predicting the potential risk of acquiring H pylori infection in the future was used. As anticipated, a further decline in H pylori-related disease was demonstrated by applying the modeling.
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http://dx.doi.org/10.1111/hel.12635DOI Listing
September 2019

Minimal Reconstitution of Membranous Web Induced by a Vesicle-Peptide Sol-Gel Transition.

Biomacromolecules 2019 04 26;20(4):1709-1718. Epub 2019 Mar 26.

Centre for Biomimetic Sensor Science , Nanyang Technological University , 50 Nanyang Drive 637553 , Singapore.

Positive strand RNA viruses replicate in specialized niches called membranous web within the cytoplasm of host cells. These virus replication organelles sequester viral proteins, RNA, and a variety of host factors within a fluid, amorphous matrix of clusters of endoplasmic reticulum (ER) derived vesicles. They are thought to form by the actions of a nonstructural viral protein NS4B, which remodels the ER and produces dense lipid-protein condensates. Here, we used in vitro reconstitution to identify the minimal components and elucidate physical mechanisms driving the web formation. We found that the N-terminal amphipathic domain of NS4B (peptide 4BAH2) and phospholipid vesicles (∼100-200 nm in diameter) were sufficient to produce a gel-like, viscoelastic condensate. This condensate coexists with the surrounding aqueous phase and affords rapid exchange of molecules. Together, it recapitulates the essential properties of the virus-induced membranous web. Our data support a novel phase separation mechanism in which phospholipid vesicles provide a supramolecular template spatially organizing multiple self-associating peptides thereby generating programmable multivalency de novo and inducing macroscopic phase separation.
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http://dx.doi.org/10.1021/acs.biomac.9b00081DOI Listing
April 2019

Oxygen Management at the Microscale: A Functional Biochip Material with Long-Lasting and Tunable Oxygen Scavenging Properties for Cell Culture Applications.

ACS Appl Mater Interfaces 2019 Mar 26;11(10):9730-9739. Epub 2019 Feb 26.

Institute of Chemical Technologies and Analytics, Institute of Applied Synthetic Chemistry , Vienna University of Technology , Getreidemarkt 9 , 1060 Vienna , Austria.

Oxygen plays a pivotal role in cellular homeostasis, and its partial pressure determines cellular function and fate. Consequently, the ability to control oxygen tension is a critical parameter for recreating physiologically relevant in vitro culture conditions for mammalian cells and microorganisms. Despite its importance, most microdevices and organ-on-a-chip systems to date overlook oxygen gradient parameters because controlling oxygen often requires bulky and expensive external instrumental setups. To overcome this limitation, we have adapted an off-stoichiometric thiol-ene-epoxy polymer to efficiently remove dissolved oxygen to below 1 hPa and also integrated this modified polymer into a functional biochip material. The relevance of using an oxygen scavenging material in microfluidics is that it makes it feasible to readily control oxygen depletion rates inside the biochip by simply changing the surface-to-volume aspect ratio of the microfluidic channel network as well as by changing the temperature and curing times during the fabrication process.
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http://dx.doi.org/10.1021/acsami.8b19641DOI Listing
March 2019

Dalbavancin as Primary and Sequential Treatment for Gram-Positive Infective Endocarditis: 2-Year Experience at the General Hospital of Vienna.

Clin Infect Dis 2018 08;67(5):795-798

Department of Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Austria.

The clinical outcomes and safety of dalbavancin as primary and sequential treatment of gram-positive bacteremia with infective endocarditis were evaluated retrospectively. The clinical success rate was high (92.6%), but in 24 of 27 patients dalbavancin was used only after clearance of bacteria from the bloodstream.
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http://dx.doi.org/10.1093/cid/ciy279DOI Listing
August 2018

The Human Gastric Microbiome Is Predicated upon Infection with .

Front Microbiol 2017 14;8:2508. Epub 2017 Dec 14.

Division of Infectious Diseases, Department of Medicine I, Medical University of Vienna, Vienna, Austria.

The human gastric lumen is one of the most hostile environments of the human body suspected to be sterile until the discovery of (H.p.). State of the art next generation sequencing technologies multiply the knowledge on H.p. functional genomics as well as on the colonization of supposed sterile human environments like the gastric habitat. Here we studied in a prospective, multicenter, clinical trial the 16S rRNA gene amplicon based bacterial microbiome in a total of 30 homogenized and frozen gastric biopsy samples from eight geographic locations. The evaluation of the samples for H.p. infection status was done by histopathology and a specific PCR assay. CagA status was determined by a CagA-specific PCR assay. Patients were grouped accordingly as H.p.-negative, H.p.-positive but CagA-negative and H.p.-positive and CagA-positive ( = 10, respectively). Here we show that H.p. infection of the gastric habitat dominates the gastric microbiota in most patients and is associated with a significant decrease of the microbial alpha diversity from H.p. negative to H.p. positive with CagA as a considerable factor. The genera , and are significantly different between the H.p.-positive and H.p.-negative sample groups. Differences in microbiota found between CagA-positive and CagA-negative patients were not statistically significant and need to be re-evaluated in larger sample cohorts. In conclusion, H.p. infection dominates the gastric microbiome in a multicentre cohort of patients with varying diagnoses.
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http://dx.doi.org/10.3389/fmicb.2017.02508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5735373PMC
December 2017

A multicenter prospective study on the diagnostic performance of a new liquid rapid urease test for the diagnosis of infection.

Gut Pathog 2017 22;9:78. Epub 2017 Dec 22.

Department of Medicine I, Infectious Diseases, Internal Medicine I, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.

Background: () causes a diversity of gastric diseases. Rapid urease tests (RUT) are well established for the point-of-care, invasive diagnosis of infection. The study aimed to evaluate the diagnostic performance of a new liquid RUT, the preOx-HUT, within a prospective cohort of treatment-naïve patients.

Methods: The multicenter prospective clinical trial was conducted at nine Austrian centers for gastrointestinal endoscopy. Patients referred for a diagnostic upper gastrointestinal endoscopy underwent gastric biopsy sampling for routine histological evaluation, and in parallel, the preOx-HUT. Histology served as reference standard to evaluate the diagnostic performance of the preOx-HUT.

Results: From January 2015 to January 2016, a total of 183 consecutive patients (54 males and 129 females, median age 50 years) were included. Endoscopy revealed pathological findings in 149/183 cases (81%), which were mostly gastritis (59%) and gastro-esophageal reflux disease (27%). infection was detected by histology in 41/183 (22%) cases. In relation to histology, the preOx-HUT had a sensitivity of 85%, a specificity of 94%, a positive predictive value of 80% and a negative predictive value of 96%. Performance of preOx-HUT was not affected significantly by concomitant PPI-use as present in 15% of cases (P = 0.73).

Conclusions: This was the first study evaluating the preOx-HUT in a prospective, multicenter clinical setting. We found a high diagnostic accuracy for the point-of-care, invasive diagnostic test of infection. Hence, this test may be a valuable diagnostic adjunct to the clinical presentation of patients with suspected infection. EK 1548/2014, Name of registry: Register der Ethikkommission der Medizinischen Universität Wien, URL of registry: https://ekmeduniwien.at/core/catalog/2012/, Date of registration: 24.09.2014, Date of enrolment of the first participant to the trial: 15.01.2015.
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http://dx.doi.org/10.1186/s13099-017-0226-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5740919PMC
December 2017

Absence of CMV viremia in high-grade glioma patients under low dosage glucocorticoid treatment.

Neuro Oncol 2017 09;19(9):1280-1282

Department of Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna, Austria; Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria.

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http://dx.doi.org/10.1093/neuonc/nox065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5570214PMC
September 2017

Viruses comprise an extensive pool of mobile genetic elements in eukaryote cell cultures and human clinical samples.

FASEB J 2017 05 8;31(5):1987-2000. Epub 2017 Feb 8.

Division of Infectious Diseases, Department of Medicine 1, Medical University of Vienna, Vienna, Austria;

Viruses shape a diversity of ecosystems by modulating their microbial, eukaryotic, or plant host metabolism. The complexity of virus-host interaction networks is progressively fathomed by novel metagenomic approaches. By using a novel metagenomic method, we explored the virome in mammalian cell cultures and clinical samples to identify an extensive pool of mobile genetic elements in all of these ecosystems. Despite aseptic treatment, cell cultures harbored extensive and diverse phage populations with a high abundance of as yet unknown and uncharacterized viruses (viral dark matter). Unknown phages also predominated in the oropharynx and urine of healthy individuals and patients infected with cytomegalovirus despite demonstration of active cytomegalovirus replication. The novelty of viral sequences correlated primarily with the individual evaluated, whereas relative abundance of encoded protein functions was associated with the ecologic niches probed. Together, these observations demonstrate the extensive presence of viral dark matter in human and artificial ecosystems.-Thannesberger, J., Hellinger, H.-J., Klymiuk, I., Kastner, M.-T., Rieder, F. J. J., Schneider, M., Fister, S., Lion, T., Kosulin, K., Laengle, J., Bergmann, M., Rattei, T., Steininger, C. Viruses comprise an extensive pool of mobile genetic elements in eukaryote cell cultures and human clinical samples.
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http://dx.doi.org/10.1096/fj.201601168RDOI Listing
May 2017

Human cytomegalovirus phosphoproteins are hypophosphorylated and intrinsically disordered.

J Gen Virol 2017 Mar 1;98(3):471-485. Epub 2017 Apr 1.

Department of Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna, Austria.

Protein phosphorylation has important regulatory functions in cell homeostasis and is tightly regulated by kinases and phosphatases. The tegument of human cytomegalovirus (CMV) contains not only several proteins reported to be extensively phosphorylated but also cellular protein phosphatases (PP1 and PP2A). To investigate this apparent inconsistency, we evaluated the phosphorylation status of the tegument proteins pUL32 and pp65 by enzymatic dephosphorylation and MS. Enzymatic dephosphorylation with bacterial λ phosphatase, but not with PP1, shifted the pUL32-specific signal on reducing SDS-PAGE from ~150 to ~148 kDa, a mass still much larger than the ~118 kDa obtained from our diffusion studies and from the calculated protein mass of ~113 kDa. Remarkably, inhibition of phosphatases through treatment with the phosphatase inhibitors calyculin A and okadaic acid resulted in a shift to ~190 or ~180 kDa, respectively, indicating that a considerable number of potential phosphorylated residues on pUL32 are not phosphorylated under normal conditions. MS revealed a general state of hypophosphorylation of CMV phosphoproteins with only 17 phosphorylated residues detected on pUL32 and 19 on pp65, respectively. Moreover, bioinformatics analysis shows that the C-terminal two-thirds of pUL32 are intrinsically disordered and that most phosphorylations map to this region. In conclusion, we show that important CMV tegument proteins are indeed phosphorylated, though to a lesser extent than previously reported, and the difference in mobility on SDS-PAGE and calculated mass of pUL32 may not be attributed to phosphorylation but more likely due to the partially intrinsically disordered nature of pUL32.
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http://dx.doi.org/10.1099/jgv.0.000675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705059PMC
March 2017

Clinical significance of the single nucleotide polymorphism TLR2 R753Q in heart transplant recipients at risk for cytomegalovirus disease.

J Clin Virol 2016 11 4;84:64-69. Epub 2016 Oct 4.

Department of Medicine I, Div. of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Austria. Electronic address:

Background: The toll-like receptor 2 (TLR2) is a significant component of innate immunity against cytomegalovirus (CMV) infection but information on the clinical significance of the single nucleotide polymorphism (SNP) (R753Q) is conflicting.

Objectives: The inconsistent observations of the immunological and clinical significance of the TLR2 R753Q polymorphism for CMV infection indicates the influence of confounders.

Study Design: The presence of the TLR2 polymorphism was determined by a genotyping assay of 175 HTX patients and 281 healthy blood donors and evaluated in relation to selected virological and clinical parameters.

Results: Relative frequency of TLR2 polymorphism was similar in HTX patients and blood donors (homozygous wild-type, 94.3% vs. 94.0%; heterozygous, 5.1% vs. 5.7%; homozygous mutated, <1%). CMV viremia was detectable in 108 (61.7%) of HTX patients. The TLR2 polymorphism was neither associated with occurrence or level of CMV infection nor with survival, graft failure or rejection, or CMV serostatus of patient before transplantation. Nevertheless, CMV viremia occurred in 83.1% of R+/D+, 77.1% of R+/D-, and 64.3% of R-/D+ patients. Time of first CMV viremia was in R-/D+ patients later than in CMV-seropositive patients (median, 182days versus 23 days; P<0.001) corresponding to the duration of antiviral prophylaxis in R-/D+ patients.

Conclusions: The TLR2 R753Q polymorphism is extremely rare in the general population and HTX patients. Screening for this risk factor of CMV disease may not be cost-effective in contrast to testing for CMV viremia.
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http://dx.doi.org/10.1016/j.jcv.2016.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705056PMC
November 2016

Microbial Cryptotopes are Prominent Targets of B-cell Immunity.

Sci Rep 2016 08 19;6:31657. Epub 2016 Aug 19.

Department of Medicine I, Div. of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna, Austria.

B-cell recognition of microbial antigens may be limited by masking of epitopes within three-dimensional structures (cryptotopes). Here we report that unmasking of cryptotopes by unfolding whole cytomegalovirus (CMV) antigen preparations with the chaotropic reagent Urea and probing with immune sera from healthy individuals (n = 109) increased ELISA signals by 36% in comparison to folded CMV antigens (P < 0.001). ELISA signals increased also significantly upon unfolding of S. aureus or E. coli antigens, whereas unfolded influenza H1N1 or respiratory syncitial virus antigens yielded reduced or unchanged reactivity in comparison to folded ones, respectively. Blocking of CMV cryptotope-specific Abs by incubation of an immunoglobuline preparation and three sera with unfolded CMV antigens enhanced clearly the neutralizing capacity of this immunoglobuline preparation against CMV infection. Thus, B-cell immunity frequently targets cryptotopes on CMV but these Abs are non-neutralizing, may reduce the neutralizing effectiveness of pathogen-specific Abs, and increase during immune maturation following primary CMV infection. The observation of functional consequences of Abs specific for cryptotopes may open whole new avenues to a better understanding of the humoral immune response to CMV and development of more effective vaccines and immunoglobuline preparations.
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http://dx.doi.org/10.1038/srep31657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4990913PMC
August 2016

The association of medication-related osteonecrosis of the jaw with Actinomyces spp. infection.

Sci Rep 2016 08 17;6:31604. Epub 2016 Aug 17.

Department of Medicine I, Medical University of Vienna, Austria.

Medication-related osteonecrosis of the jaw (MRONJ) represents a complication of bisphosphonate treatment that responds poorly to standard treatment. In a retrospective cohort study we investigated a possible role of Actinomyces spp. in the pathogenesis of MRONJ. Deep biopsies of necrotic bone were collected during surgical treatment of MRONJ and evaluated by histology and microbiology for the presence of Actinomyces spp. Microbiological, demographic and clinicpathological data were analyzed for risk of Actinomyces-associated MRONJ. Between 2005 and 2014, 111 patients suffering from histologically-confirmed MRONJ were identified. Actinomyces spp. were detected in 99 cases (89%) by histology and in six further patients by microbiological culture. A diverse microbial flora was found in all specimens without association with Actinomyces spp. Demographic and clinicopathological characteristics did not separate significantly Actinomyces-positive from Actinomyces-negative cases. Our observations confirm previous reports of a high prevalence of Actinomyces spp. in MRONJ in the single largest cohort available up to now. The high prevalence of Actinomyces spp. and the lack of clinicopathological risk factors underline the prominent role of Actinomyces spp. in MRONJ and may change the current understanding of MRONJ. Established prolonged antimicrobial treatment regimens against Actinomyces spp. infection could therefore be a mainstay of future MRONJ management.
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http://dx.doi.org/10.1038/srep31604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4987681PMC
August 2016

Human cytomegalovirus infection downregulates vitamin-D receptor in mammalian cells.

J Steroid Biochem Mol Biol 2017 01 9;165(Pt B):356-362. Epub 2016 Aug 9.

Department of Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna, Austria. Electronic address:

Vitamin D (VD) is essential for the human body and involved in a wide variety of critical physiological processes including bone, muscle, and cardiovascular health, as well as innate immunity and antimicrobial responses. Here, we elucidated the significance of the VD system in cytomegalovirus (CMV) infection, which is one of the most common opportunistic infections in immunocompromised or -suppressed patients. We found that expression of vitamin D receptor (VDR) was downregulated in CMV-infected cells within 12h [hrs] post infection [p.i.] to 12% relative to VDR expression in mock-infected fibroblasts and did not recover during the CMV replication cycle of 96h. None of the biologically active metabolites of VD, cholecalciferol, calcidiol, or calcitriol, inhibit CMV replication significantly in human fibroblasts. In a feedback loop, expression of CYP24A1 dropped to 3% by 12h p.i. and expression of CYP27B1 increased gradually during the replication cycle of CMV to 970% probably as a consequence of VDR inhibition. VDR expression was not downregulated during influenza virus or adenovirus replication. The potent synthetic vitamin D analog EB-1089 was not able to inhibit CMV replication or antagonize its effect on VDR expression. Only CMV replication, and none of the other viral pathogens evaluated, inhibited the vitamin D system in vitro. In view of the pleiotropism of VDR, CMV-mediated downregulation may have far-reaching virological, immunological, and clinical implications and thus warrant further evaluations in vitro and in vivo.
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http://dx.doi.org/10.1016/j.jsbmb.2016.08.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705058PMC
January 2017

Risk factors for Clostridium difficile infection in hemato-oncological patients: A case control study in 144 patients.

Sci Rep 2016 08 11;6:31498. Epub 2016 Aug 11.

Department of Internal Medicine I, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria.

Evidence on risk factors for Clostridium difficile infection (CDI) in hemato-oncologic patients is conflicting. We studied risk factors for CDI in a large, well-characterized cohort of hemato-oncological patients. 144 hemato-oncological patients were identified in this retrospective, single center study with a microbiologically confirmed CDI-associated diarrhea. Patients were compared with 144 age and sex matched hemato-oncologic patients with CDI negative diarrhea. Risk factors such as prior antimicrobial therapy, type of disease, chemotherapy and survival were evaluated. CDI-positive patients received more frequently any antimicrobial agent and antimicrobial combination therapy than CDI-negative patients (79% vs. 67%; OR = 2.26, p = 0.038 and OR = 2.62, p = 0.003, respectively). CDI positive patients were treated more frequently with antimicrobial agents active against C. difficile than CDI negative ones (25% vs. 13%; OR = 2.2, p = 0.039). The interval between last chemotherapy and onset of diarrhea was significantly shorter in patients without CDI (median, 17 days vs 36 days; p < 0.001). Our study demonstrates that chemotherapy is not a significant risk factor for CDI but for early onset CDI negative diarrhea. The predominant modifiable risk factor for CDI is in hemato-oncological patients antimicrobial treatment. These findings should be taken into account in the daily clinical practice to avoid CDI associated complications and excess health care costs.
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http://dx.doi.org/10.1038/srep31498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4980611PMC
August 2016
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