1. To what extent does the environment contribute to gastroenteric infections?
Jon Otter, PhD FRCPath
Imperial College London
@jonotter
Blog:
You can download these slides from

3. Transfer of a surrogate marker in a NICU
Oelberg et al. Pediatrics 2000;105:

4. Transfer over time: inoculated pod

5. Transfer of a surrogate marker in a NICU

6. Colonisation of GI tract
What is a ‘GI pathogen’?
Colonisation of GI tract
Infection of GI tract
C. difficile
Yes
Always
Norovirus
A. baumannii No
CPE
Sometimes
MRSA
VRE

7. GI pathogens: challenges
Sheer numbers
Shedding
Limited decolonisation options

8. Minimum infectious dose
It’s a numbers game
Pathogen
Amount shed
Minimum infectious dose
Norovirus
Up to 1012 per g faeces
1-100
C. difficile
Up to 109 per g faeces
1 cfu / cm2
S. aureus
Up to 107 per g faeces
<15 cfu
Otter et al. Infect Control Hosp Epidemiol 2011;32:

9. Minimum infectious dose
Amount shed 1,000,000,000,000
Minimum infectious dose 1
Otter et al. Infect Control Hosp Epidemiol 2011;32:

10. Shedding
Environmental contamination on 10 standardised sites in the rooms of 8 case patients with GI carriage of MRSA, and 6 control patients with GI samples negative for MRSA
Boyce et al. Infect Control Hosp Epidemiol 2007;28:

11. Limited decolonisation options
20 CRE colonized patients in each arm given gentamicin + polymyxin (SDD arm) or placebo (Control arm)
Control
SDD
Saidel-Odes et al. Infect Control Hosp Epidemiol 2012;33:14-19.

12. Decolonisation using faecal microbiota transplantation (FMT)
82 year old colonised with CPE.
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:

13. Transmission routes
Otter et al. Infect Control Hosp Epidemiol 2011;32:

14. 86% 58% 93% 85% 59% 96% French et al. J Hosp Infect 2004;57:31-37.
Survive for extended periods
59%
96%
French et al. J Hosp Infect 2004;57:31-37.

15. Surface survival
1400
Otter and French. J Clin Microbiol 2009;47:
Wagenvoort et al. J Hosp Infect 2011;77:

16. Ineffective cleaning / disinfection
26% reduction
90% of 124 sites
66% of 124 sites
Percentage of MRSA swabs positive
(8 rooms; 2 four-bed bays previously occupied by MRSA patients)
Before cleaning
After cleaning
French et al. J Hosp Infect 2004;57:31-37.

17. Surface -> Hand -> Patient
Pathogens can be transferred from surfaces to HCW hands without direct patient contact1-2
52% of 23 HCW acquired VRE on their hands3
Contact with patient or surface = ~10% risk of acquiring VRE3
45% of 50 HCW acquired MRSA on their hands4
40% of 50 HCW acquired MRSA on their hands4
50% of 30 HCW acquired C. difficile on their hands5
Compliance with hand hygiene: 50%6
Compliance with hand hygiene: 80%6
Boyce et al. Infect Control Hosp Epidemiol 1997;18:
Bhalla et al. Infect Cont Hosp Epidemiol 2004;25:
Hayden et al. Infect Control Hosp Epidemiol 2008;29:
Stiefel et al. Infect Control Hosp Epidemiol 2011;32:
Guerrero et al. Am J Infect Control 2012;40:
Randle et al. J Hosp Infect 2010;76:

18. Your hospital room can make you sick!
Mitchell et al. J Hosp Infect 2015;91:

19. Mitigating the increased risk: HPV
30-month prospective cohort intervention study performed on 6 high-risk units (5 ICUs) including 8813 patients at Johns Hopkins Hospital.
64% reduction in the rate of MDRO acquisition
Standard cleaning / disinfection
HPV decontamination
Passaretti et al. Clin Infect Dis 2013;56:27-35.

20. Transmission Contamination level
Decontamination level ∝ transmission reduction
Transmission
Contamination level

21. Lawley et al. Appl Environ Microbiol 2010;76:6895-6900.

22. An environmental ‘dose-response’?
There was a significant correlation between burden and HAI risk (p=0.038).
Salgado et al. Infect Control Hosp Epidemiol 2013;34:

23. Rethinking the ‘inanimate’ environment
Scanning electron microscopy identified biofilm on 5/6 dry hospital surfaces from an Australian ICU (including MRSA on 3/5).1
Followup study identified biofilm on 41/44 (93%) of surfaces in an ICU; MRSA from 18%, ESBL from 11% and VRE from 8% of the samples.2
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
1. Vickery et al. J Hosp Infect 2012;80:52-55.
2. Hu et al. J Hosp Infect 2015;91:35-44.

24. Colonisation of GI tract
What is a GI pathogen?
Colonisation of GI tract
Infection of GI tract
C. difficile
Yes
Always
Norovirus
A. baumannii No
CPE
Sometimes
MRSA
VRE

25. Your hospital room can make you sick!
Mitchell et al. J Hosp Infect 2015;91:

26. Chased by an antibiotic-induced C.difficile-shaped shadow!
Significant risk factors for CDI.
Freedberg et al. JAMA Intern Med 2016 in press.

27. Contamination-sparing therapy?
n = 66 patients (rooms) and 264 surfaces for vancomycin / metronidazole, and 68 patients (rooms) and 272 surfaces for fidaxomycin. p<0.05 for both rooms and surfaces.
Biswas et al. J Hosp Infect 2015;90:

28. “It’s airborne”
Detection of C. difficile in the air samples from the rooms of 50 patients.
Best et al. Clin Infect Dis 2010; 50:

29. “It’s airborne”
Results of intensive air sampling surrounding 10 patients. C. difficile was detected in the air in 7/10.

30. 2.4 0.4 Wiping away infection cases / 1000 patient days
Impact of changing from QAC to bleach wipes for daily disinfection of all rooms. Cleaning thoroughness was 97-98% throughout the study using ATP benchmarking (<250 RLUs).
2.4
cases / 1000 patient days
0.4
cases / 1000 patient days
Orenstein et al. Infect Control Hosp Epidemiol 2011;34:

31. HPV: clinical impact
2 years before HPV, 2 years during HPV. Breakpoint model indicated significant reduction in rate of CDI when HPV implemented (1.0 to 0.4 per 1000 patient days, 60% reduction).
McCord et al. J Hosp Infect 2016.

32. 44% Scaling the reduction Study ARD system Design Outcome Confounders
McCord 2016
HPV
4 year before-after
CDI rate fell from 1.0 to 0.4 cases per 1,000 pt days; 60% reduction, p<0.001.
No data on IPC compliance / abx use.
Horn 2015
3 year before-after
CDI rate fell from 1.4 to 0.9 cases per 1,000 patient days; 36% reduction. P<0.001.
Concurrent increase in hand hygiene compliance.
Manian 2013
2 year before-after
CDI rate fell from 0.9 to 0.5 cases per 1,000 pt days; 39% reduction (IRR=0.63, CI= , p<0.001).
Bleach disinfection enhanced concurrently.
Boyce 2008
CDI rate fell from 1.9 to 0.9 cases per 1,000 pt days on high-risk wards; 53% reduction, p=0.047).
Outbreak? No significant reduction hospital wide; changes in abx usage.
Pegues 2016
UVC
2 yr before -after
CDI rate fell from 3.0 to 2.3 cases per 1,000 pt days; 27% reduction.
Monitored potential confounders
Napolitano 2015
3 yr before -after
CDI rate fell from 1.2 to 0.7 cases per 1,000 pt days; 42% reduction.
Vianna 2016
PX-UV
4 yr before - after
CDI rate fell from 0.7 to 0.4 cases per 1,000 pt days; 40% reduction.
Levin 2013
CDI rate fell from 0.9 to 0.4 cases per 1,000 pt days; 53% reduction.
Abx changes.
44%

33. Colonisation of GI tract
What is a GI pathogen?
Colonisation of GI tract
Infection of GI tract
C. difficile
Yes
Always
Norovirus
A. baumannii No
CPE
Sometimes
MRSA
VRE

34. Residual contamination: norovirus
77 samples collected from 2 wards after the bleach disinfection.
69 samples collected from the same wards after a second round of bleach.
Norovirus RNA recovered from 45% of alcohol / soap dispensers after bleach disinfection!
Morter et al. J Hosp Infect 2011;77:

35. Why it’s good to get out of economy class
Norovirus attack rate among staff on subsequent flights following an episode of vomiting in the economy cabin.
Thornley et al. Clin Infect Dis 2011;53:

36. Colonisation of GI tract
What is a GI pathogen?
Colonisation of GI tract
Infection of GI tract
C. difficile
Yes
Always
Norovirus
A. baumannii No
CPE
Sometimes
MRSA
VRE

37. CPE – in vitro surface survival
Error bars represent plus one standard deviation of the mean.
Havill et al. Infect Control Hosp Epidemiol 2014;35:

38. Klebsiella sp. survival – strain variation
Otter & French. J Clin Microbiol 2009;47:

39. Conclusion K. pneumoniae vs. E. coli
K. pneumoniae seems to be ‘more environmental’ than E. coli.1,2
Surface contamination on five standardized sites surrounding patients with ESBL- producing Klebsiella spp. (n=48) or ESBL-producing E. coli (n=46).1
P<0.001
Risk factors for ESBL-E contamination =
ESBL-KP, urinary catheter; carbapenem therapy was protective.3
P<0.001
Guet-Revillet et al. Am J Infect Control 2012;40:
Gbaguidi-Haore. Am J Infect Cont 2013;41:
Freeman et al. Antimicrob Resist Infect Control 2014;3:5. 39

40. Enterobacteriaceae “less environmental”
Increased risk from the prior room occupant in Gram-negative bacteria.
Ajao study: only 53% of the 32 odd patients that acquired when the prior occupant was positive acquired the same species of ESBL; only 6% of the 32 had an indistinguishable or closely related strain of the same species.
Nseir et al. Clin Microbiol Infect 2011;17:
Ajao et al. Infect Control Hosp Epidemiol 2013;34:

41. Colonisation of GI tract
What is a GI pathogen?
Colonisation of GI tract
Infection of GI tract
C. difficile
Yes
Always
Norovirus
A. baumannii No
CPE
Sometimes
MRSA
VRE

42. An environmental ‘dose-response’?
Setting & design: 14-month prospective study on 2 ICUs, Boston, USA.
Methods: All patients were screened on admission and twice weekly, and the environment was screened weekly for VRE. The 50 patients who acquired VRE were compared with the 588 who did not.
Independent predictors of VRE acquisition
VRE colonised prior room occupant
VRE colonised occupant in the prior 2 weeks
Hazard ratio
Drees et al. Clin Infect Dis 2008;46:

43. Taking the lottery out of the room
Baseline:
Sept 2003 – Apr 2005
Conventional cleaning / disinfection using a QAC
Intervention:
Sept 2006 – Apr 2008
Enhanced cleaning (black-light, ‘bucket method’, education)
Acquisition rates by status of the prior room occupant
Acquisition rates by status of the prior room occupant
MRSA+
3.9% acquired
MRSA-
2.9% acquired
MRSA+
1.5% acquired
MRSA-
1.5% acquired
-26%
P=0.03
±0%
P=0.79
Limitations: No environmental sampling
VRE+
4.5% acquired
VRE-
2.8% acquired
VRE+
3.5% acquired
VRE-
2.0% acquired
-61%
P=0.01
-43%
P=0.01
Datta et al. Arch Intern Med 2011;171:

44. Antimicrobial surfaces (e.g. copper)
614 pts in 3 hospitals randomised to ‘copper’ or ‘non-copper’ ICU rooms
-44%
p=0.020
Bedrails
Overbed tables
IV poles
Visitor chair arms
Nurse call button*
Computer mouse*
Computer palm rest*
Rim of monitor*
(* = some rooms only)
-58%
p=0.013
Salgado et al. Infect Control Hosp Epidemiol 2013;34:

45. To what extent does the environment contribute to gastroenteric infections?
Jon Otter, PhD FRCPath
Imperial College London
@jonotter
Blog:
You can download these slides from