COMBINED ANTIFUNGAL THERAPY IS SUPERIOR TO MONOTHERAPY IN PULMONARY SCEDOSPORIOSIS IN CYSTIC FIBROSIS
Carsten Schwarz1, Claudia Brandt1, Volker Melicha², Christoph Runge3, Eberhard Heuer3, Hany Sahly4, Martin Schebek5, Holger Köster6, Jean-Philippe Bouchara7, Thomas Biedermann8, Peter Meißner9, Jörg Große-Onnebrink10, Heino Skopnik11, Dominik Hartl12, Ludwig Sedlacek3, Kathrin Tintelnot14
1Christiane Herzog Zentrum Berlin/Charité – Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
2Klinikum Erlangen, Loschgestraße 15, 91054 Erlangen, Germany
3CF-Zentrum Hamburg-Altona, Friesenweg 2, 22763 Hamburg, Germany 4Labor Lademannbogen MVZ Hamburg, Lademannbogen 61, 22339 Hamburg, Germany
5Klinikum Kassel, Mönchebergstraße 41-43, 34125 Kassel, Germany 6Klinikum Oldenburg, Rahel-Straus-Straße 10, 26133 Oldenburg, Germany
7Angers University Hospital, 4 rue Larrey, 49933 Angers Cedex 9, France 8Helios Klinikum Buch, Schwanebecker Chaussee 50, 13125
9Universitätsklinikum Ulm, Eythstr. 24, 89075 Ulm, Germany
10Universitätsklinikum des Saarlandes, Kirrberger Straße, 66421 Homburg, Germany
11Klinikum Worms, Gabriel-von-Seidl-Straße 81, 67550 Worms, Germany
12Universitätsklinikum Tübingen, Hoppe-Seyler-Str. 1, 72076 Tübingen, Germany
13Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
14Robert Koch Institute, Nordufer 20, 13353 Berlin, Germany
What was your research question?
To find out the effectiveness of anti-fungal therapy in people with cystic fibrosis who experienced a fungal lung infection caused by Scedosporium and Lomentospora species. The main research question was to answer if treatment with two or three anti-fungal drugs is more beneficial that one anti-fungal drug for people with cystic fibrosis.
Why is this important?
Lung disease in people with cystic fibrosis is of major interest as it influences quality of life as well as life expectancy. Scedosporium and Lomentospora species belong to the group of filamentous fungi that can cause scedosporiosis, a severe lung infection. Fungi causing scedosporiosis infection in cystic fibrosis are rare but very resistant to anti-fungal treatment. It is also of high interest to know whether the individual is only colonized with this fungus or infected but criteria to help differentiate between these two stages had not been defined prior to the start of the study. Overall, it is very importantfor healthcare professionals to have guidance to help diagnose and treat scedosporiosis infection effectively.
What did you do?
In this multi-centre study, individuals with a fungal lung infection were included that was highly suspected to be caused by a Scedosporium or Lomentospora species. To have an accurate diagnosis of scedosporiosis lung infection the authors established a definition for fungal infection of the lung in cystic fibrosis. To determine the best therapy, the authors studied the treatments of people with cystic fibrosis who had a scedosporiosis lung infection. The anti-fungal treatments were assessedfor outcomes including findings from lung X-rays, clinical symptoms (cough, amount and colour of sputum, difficulty breathing, and exercise capacity) and lung function test results. These outcomes were measured at the beginning of suspected scedosporiosis infection and at follow up.
What did you find?
A total number of 36 episodes of pulmonary fungal infections caused by Scedosporium or Lomentospora species, which occurred in 31 people with CF, were analysed in this study. The results of this study demonstrate a superiority of combined anti-fungal treatment compared to single-drug treatment. This difference was statistical significant. Only one patient of the combined therapy group did not respond. The duration of the anti-fungal treatment is recommended to be longer than a normal antibacterial treatment period which is usually not longer than 14 days. But people with scedosporiosis lung infection should be treated 28 days or longer as in the study the mean duration of treatment was 3.9 month.
What does this mean and reasons for caution?
Scedosporiosis infection can be very difficult to diagnose as symptoms of normal exacerbation and fungal infection might be overlapping. The definition used in this study might be a helpful tool to confirm a fungal infection due to Scedosporium or Lomentospora in cystic fibrosis. If the diagnosis of scedosporiosis lung infection is verified, treatment will depends on the exact species of the fungus identified. However, single-drug therapy should be avoided in favour of combination therapy. In close cooperation with the individual the treatment has to be followed-up to ensure that the response to anti-fungal therapy is adequate.
New biomarkers are being tested in clinical studies to ease the diagnosis of scedosporiosis infection in people with cystic fibrosis.