Reconstituting the microbiome after pneumonia.

Community-acquired pneumonia (CAP) is the most important infection in terms of
numbers of patients for which antibiotics are given in the hospital.
Readmission and new infections in the year after hospital admission for
pneumonia is frequent, varying from 15% up to 40% in certain subgroups. It is
known that after a severe pneumonia and subsequent antibiotic treatment, the
gut microbiome is severely perturbed. There is a link between the extent of
this dysbiosis and the readmission rates for pneumonia and sepsis.

In recent years we deepened our understanding of the pivotal role that the
microbiome plays in the local and systemic immune system. Reconstituting the
severely perturbed microbiome after antibiotic treatment for pneumonia could
improve the immune status of patients and thereby ultimately lower readmission
and infection rates.

We hypothesize that 90-day treatment with a selected probiotics-mixture could
reconstitute the microbiome diversity after antibiotic treatment for CAP. This
pilot study could pave the way for a larger clinical trial powered to
investigate whether probiotics can diminish readmission and new infection rates
in the year after hospital admission for community-acquired pneumonia.

Primary objective:
1. To prove the concept that 90-day treatment with probiotics can restore
microbiome composition and diversity in patients treated for community-acquired
pneumonia.


Secondary objective:
1. Investigate possible differences in number of adverse events between groups.
2. To obtain insight in innate immune responses during CAP and the probiotic
intervention.
3. Determine incidence and duration of antibiotic-associated diarrhoea between
groups.
4. To link microbiome composition to innate immune responses and clinical
endpoints.

Pilot study, double blind, placebo-controlled randomized controlled trial.

After hospitalization and in-hospital antibiotic treatment for CAP, if patients
meet in/exclusion criteria (e.g. no sepsis, no ICU), one group will receive a
probiotic mixture (Ecologic AAD) twice daily for 90 days, while the other group
will receive a placebo twice daily for 90 days.
Patients will start with the intervention at the moment they are discharged
from the hospital.

The burden for patients participating in the RECAP study is as follows:
- We will take 30ml of blood, 6 rectal swabs and 3 nasopharyngeal swabs divided
over three time-points (day of inclusion, day 2-3 of admission, day 90 of the
intervention). The first two sampling time-points are in-hospital, while the
day 90 day sampling time-point is either at the patients home or, if possible,
combined with an outpatient appointment. Patients will need to consume either a
probiotics or placebo mixture twice daily for 90 days. This mixture can be
drank after being dissolved in a glass of water. Patients will be asked to keep
a defecation diary during the 90-day regimen of either probiotics or placebo.
Additionally, we ask patients to fill out a comprehensive questionnaire at day
90 (see appendix).

- Oral use of probiotics is deemed safe in the latest studies and systematic
reviews (see introduction and chapter 6). Three previous studies have been
performed with this specific probiotic mixture (Ecologic AAD), of which two
randomized controlled trials. In those studies, no difference in number of
adverse events was described between the groups. To lower remaining risks, the
intervention will only start after the patient is discharged from the hospital.
Furthermore, the exclusion criteria exclude the most seriously ill patients
from this study.

- Participation in this interventional randomized-controlled trial could
potentially benefit the patients in the probiotics-group. We hypothesize that
probiotics can reconstitute gut microbiota diversity, thereby improving the
immune status and possibly lowering readmission rates. Patients randomly
assigned to the placebo-group will receive standard of care and will not
benefit from participating in this study. The knowledge obtained about the
effects of probiotics on the microbiome after pneumonia could potentially
benefit future CAP patients.