Universal vs. targeted interventions: The case for targeted

Jon Otter, PhD FRCPath

Centre for Clinical Infection and Diagnostics Research (CIDR),

King's College London & Guy's and St. Thomas' NHS

Foundation Trust, London, UK.

jonathan.otter@kcl.ac.uk

www.micro-blog.info

@jonotter

mailto:jonathan.otter@kcl.ac.ukhttp://www.micro-blog.info/http://www.micro-blog.info/http://www.micro-blog.info/

DISCLOSURES

I am employed part-time by Bioquell.

I have received payment for producing educational material for 3M.

Research funding from Pfizer and the Guy’s & St Thomas’ Charity.

UNIVERSAL OR TARGETED?

Intervention Targeted (by individual)

Targeted (by population e.g. ICU)

Universal

aka ‘vertical’ aka ‘horizontal’

Decolonisation

Isolation Cleaning / disinfection

Screening

Hand hygiene Antimicrobial stewardship

Minimise invasive devices

Examples of targeted and universal interventions (adapted from Wenzel &

Edmond, via Septimus et al.).

http://www.ncbi.nlm.nih.gov/pubmed/20851010http://www.ncbi.nlm.nih.gov/pubmed/20851010http://www.jstor.org/stable/10.1086/676535http://www.jstor.org/stable/10.1086/676535http://www.jstor.org/stable/10.1086/676535

SHORT-TERM EFFECTIVENESS LONG-TERM EFFECTIVENESS

COST-EFFECTIVENESS

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SHORT-TERM EFFECTIVENESS Universal chlorhexidine ± mupirocin

Study Setting Design Intervention Results

Derde1 ICU Time series analysis

Universal CHG plus hand hygiene

Reduction in all MDROs and MRSA (but not VRE or ESBLs)

Climo2 ICU Cluster RCT Universal CHG Reductions in MRSA / VRE acquisition and all BSI; BSI mainly CoNS

Milstone3 Paed ICU

Cluster RCT Universal CHG BSI reduced; mainly CoNS

Huang4 ICU Cluster RCT Universal CHG + mupiorcin

Reduction in MRSA clinical isolates and all BSI; MRSA BSI not reduced

1. Derde et al. Lancet Infect Dis 2014;14:31-39. 2. Climo et al. N Engl J Med 2013;368:533-542. 3. Milstone et al. Lancet 2013;381:1099-1106. 4. Huang et al. N Engl J Med 2013;368:2255-2265.

SHORT-TERM EFFECTIVENESS ‘Selective’ digestive decontamination

Study Setting Design Intervention Results

de Jonge1 ICU RCT SDD Mortality and acquisition of MDR-GNR reduced

de Smet2 ICU Cluster RCT SDD or SOD Both SOD and SDD reduced mortality

Saidel-Odes3

Adults RCT SDD Reduced, but did not eliminate CRE colonisation

1. de Jonge et al. Lancet 2003;362:1011-1016. 2. de Smet et al. N Engl J Med 2009;360:20-31. 3. Saidel-Odes et al. ICHE 2012;33:14-19.

0

20

40

60

80

100

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

SHORT-TERM EFFECTIVENESS ‘Selective’ digestive decontamination

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)

LONG-TERM EFFECTIVENESS Universal decolonisation

ANTIBIOTICS ARE THE PROBLEM, NOT THE SOLUTION

‘…fighting antimicrobial resistance with more antimicrobials, although a necessary short-term strategy, is a long-term strategy destined to fail.’

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

LONG-TERM EFFECTIVENESS SDD – gentamicin and colistin resistance

Lubbert et al. Int J Antimicrob Agents 2013;42:565-570.

14 SDD patients compared with 76 non-SDD patients; all CRE colonized.

0

10

20

30

40

50

60

70

Before After Before After

Gentamicin Colistin

% isola

tes r

esis

tant

befo

re

and a

fter

SD

D

LONG-TERM EFFECTIVENESS SDD – feeding the ‘resistome’

Buelow et al. J Antimicrob Chemother 2014; 69: 2215-2223.

Repeated sampling of the microbiota of an ICU patients undergoing SDD.

6.7x Fold increase in abundance of

aminogylcoside resistance genes in the resistome.

LONG-TERM EFFECTIVENESS Universal decolonisation

THE ONLY THING ‘SELECTIVE’ ABOUT SDD IS SELCTION OF

ANTIBIOTIC RESISTANCE

LONG-TERM EFFECTIVENESS Reduced CHG susceptibility

Otter et al. J Antimicrob Chemother 2013;68:992-999.

0

10

20

30

2001-2003 2004-2009

% M

RSA c

arr

yin

g q

acA

EMRSA-15

EMRSA-16

All

p

ANTIBIOTICS = ‘A’ BOMBS

LONG-TERM EFFECTIVENESS Antibiotics = ‘A’ Bombs

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

No Abx Abx

http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046966http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046966http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046966http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046966http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046966http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046966http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046966

Decolonisation (SDD and CHG)

Short-term effectiveness

Long-term effectiveness

Cost-effectiveness

EFFECTIVENESS: DECOLONISATION

SHORT-TERM EFFECTIVENESS Universal contact precautions (BUGG)

-5

-4

-3

-2

-1

0

VRE or MRSA VRE MRSA

Absolu

te c

hange in a

cquis

itio

n r

ate

, stu

dy p

eri

od –

baseline

per

1,0

00 p

atient

days

Intervention

Control

Harris et al. JAMA 2013;310:1571-1580.

p=0.57

p=0.70

p=0.046

LONG-TERM EFFECTIVENESS Universal contact precautions (BUGG)

1. Harris et al. JAMA 2013;310:1571-1580. 2. Dhar et al. ICHE 2014;35:213-221.

85% Compliance with glove and gown use in the

BUGG study.1

29% Compliance with

correct glove and gown use in the real world.2

LONG-TERM EFFECTIVENESS Universal contact precautions (BUGG)

Dhar et al. ICHE 2014;35:213-221.

0

5

10

15

20

25

30

35

0-40% 41-60% >60%

% c

om

pliance w

ith c

onta

ct

pre

cautions

Patients under contact precautions

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SHORT-TERM EFFECTIVENESS Universal disinfection

Eckstein et al. BMC Infect Dis 2007;7:61.

0

10

20

30

40

50

60

70

80

Before disinfection

Housekeeper disinfection

Research team disinfection

% s

ites c

onta

min

ate

d

VRE

C. difficile

Samples from rooms of 17 patients with VRE and 9 with C. difficile infection.

LONG-TERM EFFECTIVENESS Universal disinfection

Manian et al. Infect Control Hosp Epidemiol 2011;32:667-672.

0

2

4

6

8

10

12

14

2 x bleach 4 x bleach

% s

ites c

onta

min

ate

d

A. baumannii

MRSA

140 samples from 9 rooms after 2xbleach; 5705 samples from 312 rooms after 4xbleach

26.6% of rooms remained contaminated with either MRSA or A. baumannii following 4

rounds of bleach disinfection

SHORT-TERM EFFECTIVENESS Hand hygiene

LONG-TERM EFFECTIVENESS Hand hygiene

40% Median hand hygiene

compliance from 95 studies.

Erasmus et al. Infect Control Hosp Epidemiol 2010;31:283-294.

Gloves & gowns Hand & environmental

hygiene

Short-term effectiveness ?

Long-term effectiveness

Cost-effectiveness ?

EFFECTIVENESS: ‘CONTACT PRECAUTIONS’, HAND & ENVIRONMENTAL HYGIENE

75% less

screens

45% carriers

undetected

262 21,699

Otter et al. J Hosp Infect 2014;87:171-174.

SHORT-TERM EFFECTIVENESS Universal MRSA screening The impact of reverting from universal to targeted screening.

COST-EFFECTIVENESS Universal MRSA screening NHS decision makers will pay £30,000 per Quality Adjusted Life Year (QALY)1

MRSA rate Cost-effective strategies

Acute

High (2.8%) All admissions to “high risk” units

Current (1.4%) All admissions to “high risk” units

Low (0.7%) All admissions to “high risk” units (with or without targeted screening of all admissions)

Teachin

g

High (2.6%) All admissions to “high risk” units

Current (1.3%) None

Low (0.7%) None

Specia

list High (2.1%) All admissions to “high risk” units

Current (1.0%) All admissions to “high risk” units or universal screening with pre-emptive isolation of previous positives

Low (0.5%) All admissions to “high risk” units or universal screening

1. Fuller et al. 2013. ‘MRSA NOW’ study. 2. Department of Health 2014. Modified MRSA

admission screening guidance.

http://www.ucl.ac.uk/medicine/documents/doh-now-report-2013http://www.ucl.ac.uk/medicine/documents/doh-now-report-2013http://www.ucl.ac.uk/medicine/documents/doh-now-report-2013http://www.ucl.ac.uk/medicine/documents/doh-now-report-2013http://www.ucl.ac.uk/medicine/documents/doh-now-report-2013http://www.ucl.ac.uk/medicine/documents/doh-now-report-2013https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/345144/Implementation_of_modified_admission_MRSA_screening_guidance_for_NHS.pdfhttps://www.gov.uk/government/uploads/system/uploads/attachment_data/file/345144/Implementation_of_modified_admission_MRSA_screening_guidance_for_NHS.pdf

MRSA screening

Short-term effectiveness ?

Long-term effectiveness

Cost-effectiveness

EFFECTIVENESS: MRSA SCREENING

Decolonisation (SDD and CHG)

Gloves & gowns

Hand & environmental

hygiene

MRSA screening

Short-term effectiveness ? ? Long-term effectiveness Cost-effectiveness ?

EFFECTIVENESS OF UNIVERSAL INTERVENTIONS

Universal interventions are appealing: No discrimination Clear message for staff You can’t reliably know who’s colonised

Universal vs. targeted interventions: The case for targeted

Jon Otter, PhD FRCPath

Centre for Clinical Infection and Diagnostics Research (CIDR),

King's College London & Guy's and St. Thomas' NHS

Foundation Trust, London, UK.

jonathan.otter@kcl.ac.uk

www.micro-blog.info

@jonotter

mailto:jonathan.otter@kcl.ac.ukhttp://www.micro-blog.info/http://www.micro-blog.info/http://www.micro-blog.info/