Influence of antibiotic treatment on microbiota-dependent Immunoglobuline A production and incidence of ventilator associated infections with Pseudomonas aeruginosa

• Applicant: Dr. Charlotte Thibeault
• Subject Area: Clinical Infectiology and Tropical Medicine
• Term: from 2018 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 400667201

The aim of this study is to contribute to the development of novel strategies for the prevention of hospital-acquired infections (HAI). There is an urgent medical need for novel approaches of prophylaxis of HAI especially since antibiotic resistances are rising. It is well known that the use of antibiotics, that is especially common on intensive care units, is a risk factor for HAI with bacteria such as Pseudomonas aeruginosa. Results of studies from our and other research groups in mice and humans show that the underlying mechanism is a disturbance of the microbiota – the physiological bacterial flora – in gut and lung caused by antibiotics, which leads to a reduction of the level of Immunoglobuline A (IgA) in the lung. IgA is an important player in the first line of defense against bacteria on mucosal barriers and its depletion makes mice more susceptible to infections with P. aeruginosa. To verify this mechanism in humans, we plan a clinical trial (case-control) in which we want to compare the level of IgA in 20 patients treated with antibiotics with 20 that were antibiotic-free. The decision to treat with antibiotics is completely independent from the clinical trial. We suppose that patients receiving antibiotics have a lower level of IgA in the lung and that this is associated with changes of their microbiota in the gut and/or lung. Furthermore, we suppose that patients treated with antibiotics suffer more often from infections with P. aeruginosa and are therefore hospitalized longer. The data that we aim to collect with this small clinical trial will be used for the conception of an interventional clinical trial (one group receiving probiotics, the second placebo), in which we want to show why patients receiving probiotics are less susceptible to HAI. It has been shown in several clinical trials that probiotics have a prophylactic effect, but until now it is unkown why. We suppose that this is at least partly due to a rescue of IgA in the lung of patients receiving probiotics. On the other hand, our study can deliver relevant data for a better risk stratification of patients regarding ventilator-associated infections, e.g. taking the IgA-level in the lung into account. The results of this study will also contribute to the development of novel therapeutic approaches such as substitution of IgA in the future.

• DFG Programme: Research Grants
• Co-Investigators: Dr. Holger Müller-Redetzky; Professor Dr. Bastian Opitz