Novel approaches in diagnostics and treatment of i...

In our research group at the IMMH, we are investigating novel approaches to meet the urgent clinical need for diagnostic tools. To this end, we are investigating both diagnostic accuracies and clinical impact of novel combinations of host-response protein markers, thereby leveraging both bacterially- and virally-induced pathways. A recent example is a combinatorial score based on tumor necrosis factor-related apoptosis inducing ligand (TRAIL), interferon-gamma induced protein-10 (IP-10), and C-reactive protein (CRP). Other approaches include transcriptomics, rapid pathogen (multiplex) PCR, and antimicrobial susceptibility tests. We are conducting prospective clinical trials in both pediatric and adult cohorts, including patients with COVID-19. In addition, we are continuously working to refine the existing “gold standard” in infectious diseases by conducting studies to further the best available reference standard, including large multi-center point prevalence studies. If you are interested to collaborate or to work in our research group, please contact Dr. Cihan Papan via email (cihan.papan@uks.eu) or phone (+4968411623943).

Selected publications by members of the research group covering this topic:

• Papan et al. (2021) A host signature based on TRAIL, IP-10, and CRP for reducing anbiotic overuse in children by differentiating bacterial from viral infections: a prospective, multicentre cohort study. Clin Microbiol Infect. S1198-743X(21)00621-2. DOI: 10.1016/j.cmi.2021.10.019.
• Angel et al. (2021) Host Immune-Protein Signature Combining TRAIL, IP-10 and CRP for Early and Accurate Prediction of Severe COVID-19 Outcome, Open Forum Infect Dis. 8, Suppl. 1:S22-S23. doi.org/10.1093/ofid/ofab466.032
• Papan et al. (2020) Antibiotic utilization in hospitalized children under 2 years of age with influenza or respiratory syncytial virus infection – a comparative, retrospective analysis. BMC Infect Dis 20:606. DOI: 10.1186/s12879-020-05336-5.
• Papan et al. (2019) Evaluation of the multiplex PCR based assay Unyvero implant and tissue infection application for pathogen and antibiotic resistance gene detection in children and neonates. Infection 47:195-200. DOI: 10.1007/s15010-018-1192-7
• Van Houten et al. (2019) Expert panel diagnosis demonstrated high reproducibility as reference standard in infectious diseases. J Clin Epidemiol. 112:20-27. DOI: 10.1016/j.jclinepi.2019.03.010
• Tenenbaum et al. (2018) TRAIL Level and ImmunoXpert™ Score Complement Molecular Viral Detection in the Classification of Febrile Children: An Interim Analysis From the AutoPilotDx-Study. Open Forum Infectious Diseases 5, suppl_1:S568. doi.org/10.1093/ofid/ ofy210.1618
• Papan et al. (2018) Assessment of the multiplex PCR based assay Unyvero Pneumonia application for detection of bacterial pathogens and antibiotic resistance genes in children and neonates. Infection 46:189-196. DOI: 10.1007/s15010-017-1088-y

Funding sources:

• European Commission
• European Society of Clinical Microbiology and Infectious Diseases
• European Society of Paediatric Infectious Diseases
• Deutsche Gesellschaft für Pädiatrische Infektiologie
• Deutsche Gesellschaft für Krankenhaushygiene

Group members:

• Cihan Papan, MD
• Sina Tegethoff, cand. med.
• Dominik Held, cand. med.
• Franziska Fröhlich, cand. med.
• Katharina Reifenrath, cand. med.

The advent of next-generation sequencing (NGS) technology has revolutionized scientific approaches also in the field of microbiology. In order to translate the scientific discoveries of the past years into clinical practice, we are working on ways to implement and use NGS to inform healthcare practitioners at the bedside. We have performed NGS in several nosocomial infectious disease scenarios. In addition, NGS is used as a means to genetically characterize novel, emerging, and non-model microorganisms in a clinical context. Within the framework of a multidisciplinary study with the acronym IMAGINE (Identification of microbial antibiotics to protect the physiologic microbiota at body surfaces), we analyze microbiomes of a variety of body compartments, such as skin, gut, conjunctiva, gall bladder and the oral cavities. The aim is to compare the microbiomes of healthy individuals with those of diseased patients, thereby uncovering pathogens that prolong or worsen a certain common disease, and treat those specifically. On the other hand, we aim to detect beneficial commensal microbiota. Many commensal bacteria are known to produce secondary metabolites, that have a protective effect on the human host. In the course of this study, we strive to detect these microbiota and analyze the potential of novel antibiotic compounds, which they might harbor. If you are interested to learn more about this part of IMMH research, please feel free to contact Jacqueline Rehner via e-mail (jacqueline.rehner@uks.eu).

Selected publications by members of the research group covering this topic:

• Last et al. (2022) Staphylococcus massiliensis isolated from blood cultures, Germany, 2017-2020.
  Eur J Clin Microbiol Infect Dis. 26:1-7. DOI: 10.1007/s10096-022-04409-4.
• Papan et al. (2021) Combined antibiotic stewardship and infection control measures to contain an outbreak of linezolid-resistant Staphylococcus epidermidis in an intensive care unit.
  Antimicrob Resist Infect Control. 10:99. DOI: 10.1186/s13756-021-00970-3
• Alhussein et al. (2020) Human infections caused by Staphylococcus argenteus in Germany: genetic characterisation and clinical implications of novel species designation. Eur J Clin Microbiol Infect Dis.39:2461-2465. DOI: 10.1007/s10096-020-03950-4
• Eichel et al. (2020) Alteration of antibiotic regimen as an additional control measure in suspected multi-drug-resistant Enterobacter cloacae outbreak in a neonatal intensive care unit. J Hosp Infect. 104:144-149. DOI: 10.1016/j.jhin.2019.09.007
• Becker (2020) WGS for infection prevention and control in Africa. Lancet Microbe. 1:e95-e96. DOI: 10.1016/S2666-
• Schneeberger et al. (2019) Qualitative microbiome profiling along a wastewater system in Kampala, Uganda. Sci Rep. 9:17334. DOI: 10.1038/s41598-019-53569-5.
• Papan et al. (2019) Identification and containment of a cluster of two Bacillus cereus infections in a neonatal intensive care unit. Can J Infect Dis Med Microbiol. 2019:1506583. DOI: 10.1155/2019/1506583

Funding sources:

• UdS/HIPS Tandem
• HOMFOR

Group members:

• Sören Becker, MD PhD
• Jacqueline Rehner, MSc, PhD candidate
• Cihan Papan, MD
• Miriam Schuff, Master student

In cooperation with pharmaceutical sciences at UdS and the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), IMMH is also addressing the issue of AMR and the need for novel therapeutics by identifying, developing and testing new antimicrobial drug candidates or surface modifications in in vitro and in vivo assays. Susceptibilities of clinical isolates of the ESKAPE (Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterococcus spp.) group of MDR bacteria against drug candidates are tested in classical broth microdilution assays for minimal inhibitory concentrations (MICs). Drug candidates displaying a promising in vitro activity against MDR bacteria and little to no toxicity to human cell cultures are subsequently tested in different murine-based local and systemic infection models. If you are interested to hear more about this part of IMMH research, please feel free to contact Markus Bischoff or Sören Becker via e-mail (markus.bischoff@uks.eu) or phone (+49 6841 162 3963).

Selected publications by members of the research group covering this topic:

• Kaczor et al. (2021) Molecular insights into an antibiotic enhancer action of new morpholine-containing 5-arylideneimidazolones in the fight against MDR bacteria. Int J Mol Sci. 22:2062. DOI: 10.3390/ijms22042062
• Haupenthal et al. (2020) Evaluation of Bacterial RNA Polymerase Inhibitors in a Staphylococcus aureus-based Wound-Infection Model in SKH1 Mice. ACS Infect Dis. 6:2573-2581. DOI: 10.1021/acsinfecdis.0c00034
• Konstantinović et al. (2020) N-Aryl-3-mercaptosuccinimides as antivirulence agents targeting Pseudomonas aeruginosa elastase and Clostridium collagenases. J Med Chem. 63:8359-8368. DOI: 10.1021/acs.jmedchem.0c00584
• Anversa Dimer et al. (2020) PLGA nanocapsules improve the delivery of clarithromycin to kill intracellular Staphylococcus aureus and Mycobacterium abscessus. Nanomedicine 24:102125. DOI: 10.1016/j.nano.2019.102125
• Menina et al. (2019) Bioinspired liposomes for oral delivery of Colistin to combat intracellular infections by Salmonella enterica. Adv Healthc Mater. e1900564. DOI: 10.1002/adhm.201900564
• Haidar et al. (2019) PTFEP–Al2O3 hybrid nanowires reducing thrombosis and biofouling. Nanoscale Adv. 1: 4659-4664. doi.org/10.1039/C9NA00436J

Funding sources:

• Bundesministerium für Bildung und Forschung (BMBF)
• UdS/HIPS Tandem
• Deutscher Akademischer Austauschdienst (DAAD)

Group members:

• Noran Abdel-Wadood, PhD candidate
• Mostafa Abdrabou, PhD candidate
• Colya Englisch, cand. med.
• Linda Pätzold, PhD candidate
• Sören Becker, MD PhD
• Markus Bischoff, PhD