What’s trending in the infection prevention and control literature? HIS 2012 -> HIS 2014

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

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.

Ebola, MERS, Influenza Universal vs targeted interventions Faecal microbiota transplantation Whole genome sequencing CRE Environmental science What will be trending at HIS 2016?

MERS Google trends

MERS coronavirus

MERS-CoV is a respiratory viruses, so the most important route of transmission is likely to be droplet spread through close contact with infected individuals.

However, airborne transmission cannot be ruled out (hence the CDC recommendation for airborne precautions).

Recent data indicate that small droplet nuclei may be emitted most of the time by influenza infected patients, which justifies airborne precautions.1

Prevention and control: droplet or airborne?

1. Bischoff et al. J Infect Dis 2013;207:1037-46.

Ebola Google trends

Declared global health emergency

“First case” in America

http://en.wikipedia.org/wiki/Outbreak_(film)

‘…the greatest medical crisis in the world is about to happen.’

Transmission routes (“it’s airborne”)

Role of quarantine PPE Lab safety

Ebola: transmission routes

1. Ftika & Maltezou. J Hosp Infect 2013;83:185-192. 2. Lee & Henderson. Curr Opin Infect Dis 2001;14:467-480. 3. Bausch et al. J Infect Dis 2007;196 Suppl 2:S142-147. 4. Forrester et al. MMWR Morb Mortal Wkly Rep 2014;63:925-929. 5. Nishiura & Chowell. Euro Surveill 2014;19. 6. Yamin et al. Ann Intern Med 2014 in press.

Direct contact with blood or body fluids incl. droplet sprays (through broken

skin or mucous membranes)1,2

Indirect contact with contaminated

environments1-4 >

R0 = 2 (Nishiura & Chowell)5

R0 significantly higher in non-survivors (2.36) than in survivors (0.66).6

Surface survival: viruses with pandemic potential

Virus Survival time

SARS-CoV Days to weeks1,2

MERS-CoV More than 2 days3

Influenza Hours to days1,4

Ebola Days to weeks* 5-6

1. Chan et al. Adv Virol 2011:734690. 2. Lai et al. Clin Infect Dis 2005;41:67-71. 3. van Doremalen et al. Euro Surveill 2013;18. 4. Dublineau et al. PLoS ONE 2011;6:e28043. 5. Sagripanti et al. Arch Virol 2010;155:2035-2039. 6. Piercy et al. J Appl Microbiol 2010;109:1531-1539.

* The study that reported survival times measured in weeks was performed at 4°C.6

Game changer: Ebola transmission US / Spain

6 Oct 2014: Madrid, Spain 12 & 15 Oct 2014: Dallas, Texas, USA 13 cases -> 3 secondary transmissions

‘Politicisation’

Images: Temperature mapping, Quarantine, Passport

Ebola: PPE design, supply and training

1. Fischer et al. Ann Intern Med 2014 in press. 2. Klompas et al. Ann Intern Med 2014 in press. 3. Edmond et al. JAMA 2014 in press. Image source: Controversies in HAI blog

Having the right PPE policy is only part of the solution – you also need to ensure PPE supply and that staff known how to don and doff safely.1,2

The MSF ‘Buddy’ system has been designed for field settings, and may be useful in acute settings.1,2

We probably need better designed PPE.3

CDC tightens PPE recommendations

Source: USA Today.

Prevention and control: theory and practise

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Masks Gloves Gowns Hand-washing All measures

% c

om

pliance

Infected Non-infected

Seto et al. Lancet 2003;361:1519-20.

Case-control study with 241 non-infected and 13 infected healthcare workers.

Targeted or universal interventions?

Examples of targeted and universal interventions (adapted from Wenzel &

Edmond, via Septimus et al.).

Targeted Universal

aka ‘vertical’ or ‘go long’ aka ‘horizontal’ or ‘go wide’

• Screening • Isolation • Contact precautions • Decolonization of carriers • Targeted cleaning / disinfection

• Minimise invasive device use • Hand hygiene • Antimicrobial stewardship • Universal decolonization • General cleaning / disinfection

Septimus et al. Infect Control Hosp Epidemiol 2014;35:797-801.

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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.

Universal chlorhexidine + mupirocin

Huang et al. N Engl J Med 2013;368:2255-2265.

Targeted screening, isolation

Universal decolonization

Targeted screening, isolation and

decolonization

74 US ICUs randomised.

‘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

Oostdijk4 ICU Cluster RCT SDD v SOD No significant difference in mortality, but SDD -> more antibiotic resistance

Saidel-Odes4

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. Oostdijk et al. JAMA 2014;312:1429-1437. 4. Saidel-Odes et al. ICHE 2012;33:14-19.

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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

Control

SDD

‘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)

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.

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100

CHG Non CHG

% isola

tes w

ith r

educed

CH

G s

usceptibility

Suwantarat et al. Infect Control Hosp Epidemiol 2014;35:1183-1186.

Proportion of BSI isolates with reduced susceptibility to chlorhexidine on units CHG daily bathing (n=28) or not (n=94).

33% (p=0.028)

Reduced CHG susceptibility

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

eriod –

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

20 US ICUs randomised.

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

Universal contact precautions (BUGG)

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

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35

0-40% 41-60% >60%

% c

om

pliance w

ith c

onta

ct

pre

cautions

Patients under contact precautions

1013 observations.

Single rooms for all?

Single Rooms Bays

Reduced HCAI1-6 Reduced risk of adverse events11-12

Some patients more satisfied5-9 Less social contact; isolation11-14

Fewer “mix up” errors10-11 through uninterrupted patient contact

Reduced staffing levels and patient: HCW ratios14,15

9. Lawson & Phiri. Health Serv J 2000;110:24–26. 10. Ulrich et al. White Paper #5. The Center for Health

Design. 2008. 11. Maben J. Nurs Manag 2009;16:18-19. 12. Stelfox et al. JAMA 2003;290:1899–1905. 13. Tarzi et al. J Hosp Infect 2001;49:250-254. 14. Young & Yarandipour. Health Estate 2007;61:85-86. 15. Mooney H. Nursing Times 2008;104:14-16.

1. Teltsch et al. Arch Intern Med 2011; 171: 32-38. 2. van de Glind et al. Health Policy 2007;84:153-161. 3. Borg MA. J Hosp Infect 2003;54:316–318. 4. Haill et al. J Hosp Infect 2012;82:30-35. 5. King et al. Building and Environment 2013;59:436-447. 6. Moore et al. J Hosp Infect 2010;76:103-107. 7. Jolley S. Nursing Standard 2005;20:41–48. 8. Barlas et al. Ann Emerg Med 2001;38:135–139.

Pennington H, Isles C. Should hospitals provide all patients with single rooms? BMJ 2013; 347: f5695.

Universal MRSA screening – cost effectiveness

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.

Fecal microbiota transplantation Google trends (HIS 2012 to HIS 2014)

Note, I had to spell it ‘wrong’ (fecal v faecal) to detect a trend. Blasted Americans.

Note, I had to spell it ‘wrong’ (fecal v faecal) to detect a trend. Blasted Americans.

Fecal microbiota transplantation Google trends (2004 to present)

Faecal microbiota transplant for recurrent CDI

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Faecal microbiota

transplant

Vancomycin Vancomycin + bowel

lavage

% c

ured

wit

ho

ut

rela

pse

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)

Introducing…the ‘crapsule’

Youngster et al. JAMA 2014 in press.

Whole genome sequencing Google trends (2004 to present)

Whole genome sequencing: C. difficile

Eyre et al. N Engl J Med 2013;369:1195-1205.

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40

Ward contact only

Hospital contact only

Ward contamination

or hospital contact

Ward contamination

only

Same GP Same post code

No epi link

% g

enetically r

ela

ted c

ases

All 1250 C. difficile isolates over 5 years from symptomatic cases typed by WGS. Only 35% of these had <2 SNVs compared with previous cases. The epidemiological links between these cases are illustrated below.

(How much CDI is hospital acquired?)

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35

Symptomatic Asymptomatic Unrelated

% H

A-C

DI iso

late

s

Curry et al. Clin Infect Dis 2013;57:1094-1102.

Relatedness of 56 hospital-acquired CDI cases to other C. difficile using MLVA (note, not WGS).

Whole genome sequencing: outbreaks

Snitkin et al. Sci Transl Med 2012;4:148ra116.

Transmission map based on epidemiological links

only.

Transmission map based on epidemiological links

+ WGS.

Carbapenem resistant Enterobacteriaceae Google trends (2004 to present)

CDC CRE Toolkit launched

CRE in the UK and USA

Invasive CR K. pneumoniae isolates (EARS-Net)

2009 2010

2011 2012

2009 2010

2011 2012

ECDC EARS-Net

0%

10%

20%

30%

40%

50%

60%

70%

2005 2006 2007 2008 2009 2010 2011 2012

CR K

.pneum

onia

e invasiv

e isola

tes

Greece Italy UK

Invasive CR K. pneumoniae trends

Colistin resistance in Italy

Monaco et al. 2014; Euro Surveill 2014;19:pii=20939.

Survey of 191 CRE from 21 labs across Italy.

43% Colistin resistant K. pneumoniae. Range = 10-80% for the 21 labs.

Emergence of CPE in the UK

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

CRE in the USA

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2001 2011

% C

RE

K. pneumoniae / oxytoca

All Enterobacteriaceae

CDC NHSN / NNIS data. MMWR 2013;62:165-170.

National survey of Enterobacteriaceae in 2001 (n=2,631) and 2011 (n=6,573).

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

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

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60

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 prevention & control

Hand hygiene

Cleaning / disinfection

SDD?

Topical CHX?

Education?

Contact precautions

Active screening

Antibiotic stewardship

Tacconelli et al. Clin Microbiol Infect 2014;20 Suppl 1:1-55

Cataldo et al. ECCMID 2014. 0125.

Type n studies Failure rate Odds ratio

Bundled intervention

75 28%

1.9 Single

intervention 11 45%

Hospital cleaning Google trends (2004 to present)

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MDRO-standard No MDRO-standard MDRO-HPV

Acquis

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ate

/ 1

000 p

t days

Hydrogen peroxide vapour decontamination

-64%

Passaretti et al. Clin Infect Dis 2013;56:27-35. McDonald & Arduino. Clin Infect Dis 2013;56:36-39.

Acquisition of MDROs in 6350 patients admitted to ICU rooms, stratified by the MDRO status of the prior room occupant, and disinfection method.

UV room disinfection

UV systems – what we know

1. UVC is fundamentally different to Pulsed-Xenon UV (PX-UV).1

2. UV systems are more effective than conventional cleaning and disinfection.2-3

3. UV systems are faster & easier, but less effective than HPV.4

4. UV systems are less effective out of direct line of sight; using multiple room locations helps to mitigate this.4-5

5. There’s some emerging evidence that UV room disinfection reduces transmission.6

1.

1. Otter et al. J Hosp Infect 2013;83:1-13. 2. Jinadatha et al. BMC Infect Dis 2014;14:187. 3. Anderson et al. Infect Control Hosp Epidemiol 2013;34:466-471. 4. Havill et al. Infect Control Hosp Epidemiol 2012;33:507-512. 5. Mahida et al. J Hosp Infect 2013; 332-335. 6. Levin et al. Am J Infect Control 2013;41:746-748.

Salgado et al. Infect Control Hosp Epidemiol 2013;34:479-486.

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14

Non copper Copper

% p

atients

who a

cquir

ed

HAI or MRSA / VRE colonisation

HAI only

Bedrails Overbed tables IV poles Visitor chair arms Nurse call button* Computer mouse* Computer palm rest* Rim of monitor* (* = some rooms only)

-44% p=0.020

-58% p=0.013

614 pts in 3 hospitals randomised to ‘copper’ or ‘non-copper’ ICU rooms

Time to ‘copperise’ our hospitals?

Hands vs. Environment

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90

0 10% 20% 30% 40% 50%

% r

eduction in M

DRO

tranm

issio

n

% improvement

Hand hygiene

Terminal cleaning

Barnes et al. Infect Control Hosp Epidemiol 2014; 35: 1156-1162

A model simulating the impact of improvements in hand or environmental hygiene on patient-to-patient transmission in a 20-bed ICU. Dotted line represents my not-very-scientific-extrapolations from eye-balling the data.

Biofilms on dry hospital surfaces

Scanning electron microscopy identified biofilm on 5/6 dry hospital surfaces from an Australian ICU.

MRSA was identified on three of the surfaces.

Vickery et al. J Hosp Infect 2012;80:52-55.

Could explain why vegetative bacteria can survive on dry hospital surfaces for so long

Be part of the reason why they are so difficult to remove or inactivate using disinfectants

Explain (to some degree) the difficulty in recovering environmental pathogens by surface sampling

Biofilms and biocide susceptibility

Otter et al. J Hosp Infect in press.

Planktonic cells

Surface attachment

Mature biofilm

Biofilm development and maturation

Up to 10x less susceptible

Up to 1000x less susceptible

Biofilms and surface survival

Espinal et al. J Hosp Infect 2012;80:56-60.

Survival of biofilm and non-biofilm forming A. baumannii.

Biofilm forming

Non-biofilm forming

Google trends for all search terms (excluding viruses) (2004 to present)

Google trends for all search terms (2004 to present)

What will be trending at HIS 2016?

Ebola, MERS, Influenza Universal vs targeted interventions Faecal microbiota transplantation Whole genome sequencing CRE (and friends) ++ Environmental science Cost effectiveness

And finally…what’s trending on Twitter?

Dyar et al. J Antimicrob Chemother 2014;69:2568-2572.

What’s trending in the infection prevention and control literature? HIS 2012 -> HIS 2014

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