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‘Crapsules’: The cure for Cdiff and more?

Jon Otter PhD FRCPath

Imperial College Healthcare NHS Trust &

King’s College London

May 2015

@jonotter, www.ReflectionsIPC.com

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m Background – Clostridium difficile infection

Cdiff recurrent rate data from Medscape.

15-35%

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0

2,000

4,000

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Q1

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2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

C.

difficile infe

ction (

CD

I)I

cases

All cases

Trust apportioned

CDI cases, 2004-2013 C. difficile infection (CDI), England 2004-2013

1. Mandatory reporting, 2004

2. Targets, 2007

3. Revised guidelines, 2009

1

2

3

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Faecal microbiota transplant for recurrent CDI

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transplant

Vancomycin Vancomycin + bowel

lavage

% c

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wit

hou

t rela

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van Nood et al. N Engl J Med 2013;368:407-415.

Patients with recurrent CDI randomised to FMT (n=16), vancomycin (n=12) or vancomycin + bowel lavage (n=13)

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Introducing…the ‘crapsule’

Youngster et al. JAMA 2014;312:1772-8.

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‘Crapsule’ cure rates

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First course Second course

% o

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resolv

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Percentage of 20 patients who's recurrent CDI resolved after the first of second 2 day course on 'crapsules'

Youngster et al. JAMA 2014;312:1772-8.

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This is what a ‘crapsule’ can do for you

Youngster et al. JAMA 2014;312:1772-8.

0

1

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Day before 3 days 8 weeks

Media

n n

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of bow

el m

ovem

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Why does FMT work so spectacularly well for recurrent CDI?

Tosh & McDonald. Clin Infect Dis 2012;54:707-713.

Diversity + Composition = Happy, healthy gut microbiota

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Adapted from Peterfreund et al. PLoS ONE 2012;7:e46966.

No Abx Abx

The impact of antibiotics on the microbiome

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Tending the human microbiome

1. Microbiome-sparing antimicrobial therapy.

2. Maintain and restore indigenous microbiota.

3. Exploiting host protective mechanisms related to a happy, healthy microbiota.

Tosh & McDonald. Clin Infect Dis 2012;54:707-713.

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A cautionary tale…

5000 Hep C 1000 HIV

The number of British haemophiliacs infected with Hep C / HIV via contaminated blood products.

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Other risks – inheriting a “bad” microbiota?

Alang & Kelly. Clin infect Dis 2015 in press. Weight gain in a 32 year old women treated

using FMT for recurrent CDI.

62kg 80kg

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Recurrent CDI is just the start…

Disease group Diseases

Intestinal Recurrent CDI, Chron’s disease, ulcerative colitis, IBS, dislodging antibiotic resistant bacteria

Metabolic Metabolic syndrome, obesity, Type 2 diabetes, cardiovascular diseases, non-alcoholic liver diseases

Neuropsychiatric Parkinson’s, MS, myoclonus dystonia, autism, chronic fatigue syndrome

Autoimmune Arthritis, various other

Allergic Atopy, asthma, various cancers

Xu et al. World J Gasteroenterol 2015;21:102-111.

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THE END OF ANTIBIOTICS IS NIGH

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What’s the problem?

“CRE are nightmare bacteria.” Dr Tom Frieden, CDC Director

“If we don't take action, then we may all be back in an almost 19th Century environment where infections kill us as a result of routine operations.” Dame Sally Davies, Chief Medical Officer

“If we fail to act, we are looking at an almost unthinkable scenario where antibiotics no longer work and we are cast back into the dark ages of medicine where treatable infections and injuries will kill once again.” David Cameron, Prime Minister, UK

“The rise of antibiotic-resistant bacteria, however, represents a serious threat to public health and the economy.” Barack Obama, President USA

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CRE? Resistance

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Enterobacteriaceae Non fermenters

Organism AmpC / ESBL CPE A. baumannii

Attributable mortality Moderate

Massive (>50%)

Minimal

Shorr et al. Crit Care Med 2009;37:1463-1469. Patel et al. Iinfect Control Hosp Epidemiol 2008;29:1099-1106. Falagas et al. Emerg Infect Dis 2014;20:1170-1175.

CRE? Mortality

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Rapid spread

Clonal expansion

GI carriage

Horizontal gene

transfer

CRE? Global domination!

Understanding the enemy

Pathogen CRE1 MRSA VRE C. difficile

Resistance +++ + + +/-

Resistance genes Multiple Single Single n/a

Species Multiple Single Single Single

HA vs CA HA & CA HA HA HA

At-risk pts All Unwell Unwell Old

Decolonisation No Yes No No

Virulence +++ ++ +/- +

1. Carbapenem-resistant Enterobacteriaceae.

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m Emergence of CRE in the UK

PHE AMRHAI, 24/01/14 Courtosy of Dr Neil Woodford

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Lin et al. Clin Infect Dis 2013;57:1246-1252.

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ICU LTAC

% C

RE c

arr

iers

Point prevalence survey in 24/25 ICUs (n=910 patients) and 7/7 LTACs (n=391 patients) in the Chicago region.

CRE in the USA – Long Term Acute Care (LTAC)

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0 9 days 2 weeks 4 weeks 6 weeks

Perc

enta

ge o

f CRE p

ositiv

e

recta

l sam

ple

s

SDD

Control

Saidel-Odes et al. ICHE 2012;33:14-19.

20 CRE colonized patients in each arm given gentamicin + polymyxin (SDD arm) or placebo (Control arm)

‘Decolonisation’ using antibiotics

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Decolonisation using FMT

• 82 year old colonised with CRE.

• Carriage was delaying her admission to a nursing home.

• Single dose of FMT decolonised her at 7 and 14 days.

Laiger et al. J Hosp Infect 2015 in press. Buffie & Pamer. Nat Rev Microbiol 2013;13:790-801.

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The future…in 10 years time

• FMT will be a routine procedure for all sorts of conditions, gastrointestinal and otherwise

• Some of the traditional uses of antibiotics will have been replaced entirely by FMT

• We won’t be playing around with poo – we’ll have cracked an effective synthetic FMT

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‘A crapsule a day keeps the bad bugs away’

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GUIDE FONT SIZES GENERAL SLIDE TITLE: 28pt (Optional SLIDE SUB-TITLE: 26pt) 1ST LEVEL BULLET: 22pt SUB-BULLETS: 20pt BODY COPY/TEXT BOX: 18pt PRESENTATION SLIDE TITLE: 28pt PRESENTATION SLIDE SUB-TITLE: 22pt PRESENTATION SLIDE NAME: 18pt PAGE NUMBER, DATE, FOOTER: 8pt ALL FONT TYPEFACE TO BE IN VERDANA

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25m

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‘Crapsules’: The cure for Cdiff and more?

Jon Otter PhD FRCPath

Imperial College Healthcare NHS Trust &

King’s College London

May 2015

@jonotter, www.ReflectionsIPC.com