P3438Intestinal microbiota transplantation for patients colonised with multidrug-resistant organisms have an improvement in clinical outcomes associated with a significant increase in alpha-diversity metrics of the gastrointestinal microbiota

08. Healthcare-associated infections, infection prevention & control

08g. Infection control interventions and trials (incl. microbiota transplantation)

R. Ghani ¹, B. Mullish ¹, A. Ghazy ², R. Corbett ², N. Duncan ², G. Satta ³, M. Gilchrist ², H. Williams ¹, J. Pavlu ², A. Innes ¹, J. Macdonald ¹, J. Miguens Blanco ¹, N. Danchkert ⁴, F. Davies ¹, J. Marchesi ¹.

¹Imperial College London - London (United Kingdom), ²Imperial College NHS Healthcare Trust - London (United Kingdom), ³University College London - London (United Kingdom), ⁴Kings College London - London (United Kingdom)

Background

The intestinal microbiome has an important function in the defence against infection. Intestinal colonisation with multidrug-resistant organisms (MDROs) is a risk factor for patients at risk of developing invasive disease, carrying higher morbidity than drug-sensitive infections. Intestinal Microbiota Transplantation (IMT) is a modality to restore the gut microbiome. We utilised IMT in MDRO colonised patients and observed clinical outcomes and effect on microbiota diversity.

Methods

IMT was performed on patients with risk factors for invasive disease with known intestinal MDRO colonisation with either Carbapenemase-resistant Enterobacterales, Vancomycin-resistant Enterococci or Extended Spectrum Beta Lactamase Enterobacterales. Clinical outcomes were assessed 6 months pre- and post-IMT. Metataxonomic profiles were created from 16s rRNA gene sequencing and diversity metrics on stool samples from donors and from patients pre- and post-IMT at several time points were assessed. Statistical analysis was performed using GraphPad Prism 9.3.

Results

IMT was administered to twenty MDRO colonised patients from Imperial College NHS Healthcare Trust. Post-IMT there was a significant reduction in all and MDRO bloodstream infections (P=0.047, P=0.03, n=20), reduction in length of inpatient stay (P=0.0002 n=16), use of carbapenems (P=0.0005, n=14).

Donors (n=5) had significantly higher richness of bacteria: Chao1 (P=0.002), and alpha diversity: Shannon (P=0.0006), Inverse Simpson (P=0.002), and Faith’s PD (P=0.0034) than pre-IMT (n=16) patients colonised with MDROs. Post IMT (n=9) there was a significant increase in the Chao1 (P=0.0091), Shannon (P=0.04), and Faith’s PD (P=0.03) alpha diversity indices. There was no significant difference in beta diversity between cohorts. In paired samples (n= 9) pre- and post-IMT there was a significant increase in Chao1 (P=0.00067) and Faith-PD (P=0.03).

Conclusions

In our cohort, IMT conferred clinical benefit to patients, reducing the incidence of invasive disease from the associated MDRO. Associated with this was an increase in alpha diversity metrics more similar to donor stool. These results indicate that the microbiome may play a role in development of infection, and manipulation of its composition may be a key in preventing infection in at risk groups

Conclusions

Case(s) description

Discussion

References

Figure 1. Ladder plots demonstrating clinical outcomes

Figure 2. Box plots comparing alpha diversity indices in donor, pre- and post IMT stool

Figure 3. Ladder plots comparing the alpha diversity in paired pre and post I

Keyword 1

Antimicrobial resistance (AMR)

Keyword 2

Biofilms and microbiomes

Acknowledgement of grants/financial support, 300 characters, including spaces :

The Department of Metabolism, Digestion and Reproduction, and the Centre for Haematology at Imperial College London receive funding from the National Institute of Health Research (NIHR) Biomedical Research Centre (BRC) based at Imperial College London and Imperial College Healthcare NHS Trust. BM and AI are the recipients of NIHR Academic Clinical Lectureships, and BM was previously the recipient of a Medical Research Council (MRC) Clinical Research Training Fellowship (grant reference: MR/R000875/1). JA is a NIHR Senior Investigator, FD receives funding from the Medical Research Council (MRC) Clinical Academic Research Partnership Scheme, and JAM was the recipient of a Wellcome Trust Institutional Strategic Support Fund Springboard Fellowship.

Conflicts of interest

Do any of the authors have conflicts of interest related to the studies presented in this abstract?

Yes
Honoraria or consultation fees