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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
0
10
20
30
40
50
60
70
80
90
100
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.
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
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.
0
20
40
60
80
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.
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
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
0
20
40
60
80
100
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.
0
5
10
15
20
25
30
35
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?)
0
5
10
15
20
25
30
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
0
2
4
6
8
10
12
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.
0
10
20
30
40
50
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)
0
2
4
6
8
10
12
14
16
MDRO-standard No MDRO-standard MDRO-HPV
Acquis
itio
n r
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.
0
2
4
6
8
10
12
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
0
10
20
30
40
50
60
70
80
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
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