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3M™ Learning Connection 9/15/2014
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3M Infection Prevention Solutions
Not all resistant Gram-negative bacteria are created equal: Enterobacteriaceae vs. non-fermenters
September 16, 2014Jon Otter, PhD
Scientific Director, Healthcare, Bioquell
Research Fellow, CIDR, King’s College London
jonathan.otter@kcl.ac.uk
www.micro-blog.info @jonotter© 2012. All Rights Reserved.
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Disclosure
I am employed part-time by Bioquell and received payment from 3M for this webinar.
1. Aug 19: CRE and friends: what’s the problem and how to detect them?
2. Sept 16: Not all resistant Gram-negative bacteria are t d l E t b t i f tcreated equal: Enterobacteriaceae vs. non-fermenters
3. Oct 7: Filling the gaps in the guidelines to control resistant Gram-negative bacteria
1. Gain a microbiological overview of the various families of multidrug-resistant Gram-negative rods.
2. Compare the features of the key families: Enterobacteriaceae
Learner objectives
(including CRE) and non-fermenters (including A. baumannii), especially at-risk population and epidemic potential.
3. Discuss how differences in epidemiology affect approaches to infection prevention and control.
© 2012. All Rights Reserved.
3M™ Learning Connection 9/15/2014
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Rising threat from MDR-GNR
% of all HAI caused by GNRs.
Hidron et al. Infect Control Hosp Epidemiol 2008;29:966-1011.Peleg & Hooper. N Engl J Med 2010;362:1804-1813.
% of ICU HAI caused by GNRs.
Non-fermenters Acinetobacter baumanniiPseudomonas aeruginosaStenotrophomonas maltophilia
Enterobacteriaceae Klebsiella pneumoniaeEscherichia coliEnterobacter cloacae
Acronym minefield
MDR-GNR
MDR-GNBCRO
CPECPC
ESBL
CRECPE
CRC
CRABKPC
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MRSA is a CRO!MRSA is a CRO!
Poll: would you be comfortable explaining the differences between carbapemen-resistant Klebsiellapneumoniae and carbapenem-resistant Acinetobacter baumannii to a colleague?
A) YesB) No
3M™ Learning Connection 9/15/2014
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Resistant Enterobacteriaceae v non-fermentersEnterobacteriaceae (K.pneumoniae)
Non-fermenters(A. baumannii)
Microbiology Rods Coccobacilli
At-risk population Primarily acute pts ICU, burns
Risk factors Travel Trauma, ICU stay
Epidemic potential High Low
Clinical manifestation UTI VAP
Attributable mortality Stark increase (CPE) Minimal increase
Prevalence Emerging (rapidly) Patchy but stable
Sites of colonisation GI tract Resp, GI, skin
Colonization duration Months to >1 year Days to weeks
Transmission routes Hands ++, Env +/- Hands +, Env ++
Resistance Mainly acquired Intrinsic & acquired
Common clones KPC-producing ST258 Intl clones I-III
Acinetobacter baumannii Klebsiella pneumoniae
Risk factors & at-risk populationEnterobacteriaceae Non-fermenters
Risk factors LOSICU stayCatheters / devicesVentilationPrior antibioticsTravel
LOSICU stayCatheters / devicesVentilationPrior antibioticsTrauma (esp. burns)
At-risk population Patients in acute settings, particularly those with recent travel to areas of high prevalence. Potential for community spread.
High-risk patients in the ICU and burns units; rare cause of community-acquired infection.
ECDC CPE risk assessment, 2011.Peleg et al. Clin Microbiol Rev 2008;21:538-582.
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Clinical manifestation
40
50
60
70
CAI
Enterobacteriaceae
Non-Enterobacteriaceae
Klebsiella spp.
0
10
20
30
All HAI Pneumonia SSI UTI BSI GI
% H
C
Acinetobacter spp.
Zarb et al. ECDC PPS. Euro Surveill 2012;17.
Attributable mortalityEnterobacteriaceae 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. ICHE 2008;29:1099-1106.Falagas et al. Emerg Infect Dis 2014;20:1170-1175.
Invasive CR P. aeruginosa isolates (EARS-Net)
2009 2010
2011 2012
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Invasive CR K. pneumoniae isolates (EARS-Net)
2009 20102009 2010
2011 20122011 2012
40%
50%
60%
70%
inva
sive
isol
ates
Greece Italy UK
Invasive CR K. pneumoniae trends
ECDC EARS-Net
0%
10%
20%
30%
40%
2005 2006 2007 2008 2009 2010 2011 2012
CR
K.p
neum
onia
e i
Invasive CR non-fermenters trends
40%
50%
60%
40%
50%
60%
erae
mia
s(P
HE)
isol
ates
(EAR
S-N
et)
Greece - CRPA UK - CRPA Italy - CRPA UK - CRAB
P. aeruginosa: ECDC EARS-NetA. baumannii: PHE Health Protection Report 2013;7.
0%
10%
20%
30%
0%
10%
20%
30%
2006 2007 2008 2009 2010 2011 2012
CR
A. b
aum
anni
ibac
te
CR
P. a
erug
inos
a in
vasi
ve i
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Acinetobacter sp. bacteraemias
PHE Health Protection Report 2013;7.
Prevalence at Guy’s and St. Thomas’, London
1
1.2
1.4
1.6
30
35
40
45
pne
umon
iae
and
all
acea
e
in A
. bau
man
nii a
nd P
. os
a
A. baumannii P. aeruginosa K. pneumoniae All Enterobacteriaceae
0
0.2
0.4
0.6
0.8
0
5
10
15
20
25
2011 2012 2013
% m
erop
enm
resi
stan
ce in
K.
Ente
roba
cter
ia
% m
erop
enem
resi
stan
ce
aeru
gin
Hughes et al. Federation of Infection Sciences 2013.
6
8
10
12
CR
E
K. pneumoniae / oxytoca
All Enterobacteriaceae
CRE in the USA
0
2
4
2001 2011
%
NHSN / NNIS data; MMWR 2013;62:165-170.
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CRE and CRNF in the USACentral line-associated bloodstream infection (CLABSI) resistant to carbapenems in the national NHSN network.1
40
50
60
70
em re
sist
ant
Siivert et al. Infect Control Hosp Epidemiol 2013;34:1-14.
0
10
20
30
K. pneumoniae P. aeruginoas A. baumannii
% c
arba
pene
Prevalence of A. baumannii and K. pneumoniae1,677 bloodstream infections presenting on admission to New York hospitals.
20
25
30
35
40
45
stre
am in
fect
ions
Wolfe et al. J Infect Public Health 2014;7:224-232.
0
5
10
15
S. a
ureu
s
Ent
eroc
occu
s sp
.
P. a
erug
inos
a
S. p
neum
onia
e
A. b
aum
anni
i
K. p
neum
onia
e
% b
lood
s
Latin America - ESBL
30
40
50
60
ESBL
Klebsiella spp.
0
10
20
30
2003 2004 04-07 08-10 2011
% E Klebsiella spp.
E. coli
www.micro-blog.info
3M™ Learning Connection 9/15/2014
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Latin America – carbapenem resistance
50
60
70
80
carb
apen
ems
Klebsiella spp
0
10
20
30
40
97-01 04-07 08-10 2011
% re
sist
ant t
o c Klebsiella spp
A. baumanniiP. aeruginosa
www.micro-blog.info
Poll: which is the most common pathogen in your hospital at the moment:?
A) Antibiotic-resistant Enterobacteriaceae (e.g. K. pneumoniae including CRE)pneumoniae including CRE)B) Antibiotic-resistant non-fermenters (e.g. Acinetobacter baumannii)
Sites of colonisation – 103 CRAB patients
80% tracheal aspirate69% sternal skin
69% rectal25% urine
Apisarnthanarak et al. Clin Infect Dis 2013;56:1057-1059.
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Duration of colonisation - CRKPRectal or stool specimens from 103 CRKP patients over 24 months.1
40
50
60
70
ryin
g C
RKP
Range of colonisation duration 6-42 days for A. baumannii.2
1. Lubert et al. Am J Infect Control 2014;42:376-380.2. Dijkshoorn et al. Epidemiol Infect 1987;99:659-667.
0
10
20
30
1 month 3 months 6 months 12 months 24 months
% p
atie
nts
carr
Duration of colonisationAuthor Year Setting N pts Organism
Duration of colonization
Bird1 1998Elderly care facilities, Scotland
38ESBL K. pneumoniae
Mean 160 days (range 7-548)
Pacio2 2003Long term care facility, USA
8Resistant Gram-negative rods
Median 77 days (range 47-189)
Zahar3 2010Paediatric hospital,
62ESBL Median 132 days
1. Bird et al. J Hosp Infect 1998;40:243-247.2. Pacio et al. Infect Control Hosp Epidemiol 2003;24:246-250.3. Zahar et al. J Hosp Infect 2010;75:76-78.4. O'Fallon et al. Clin Infect Dis 2009;48:1375-1381.5. Zimmerman et al. Am J Infect Control 2013;41:190-194.
Zahar 2010France
62Enterobacteriaceae (range 65-228)
O'Fallon4 2009Long term care facility, USA
33Resistant Gram-negative rods
Median 144 days (range 41–349)
Zimmerman5 2013Patients discharged from hospital, Israel
97 CRE Mean 387 days
4
5
6
7
cfu
/ dis
c C. difficile
Surface survival
0
1
2
3
0 1 2 3 4 5
Log
(10)
c
Time / weeks
Acinetobacter
K. pneumoniae
Otter & French. J Clin Microbiol 2009;47:205-207.
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Surface survival – strain variation
4
5
6
7
8
g (1
0) c
fu /
disc
Klebsiella pneumoniae NCTC 9633
Otter & French. J Clin Microbiol 2009;47:205-207.
0
1
2
3
4
0 1 2 3 4 5
Log
Time / weeks
K. pneumoniae K2
K. pneumoniae K41
CRE – is surface contamination a risk?
4
5
6
7
8
cfu
per d
isc
K. pneumoniae (TSB)K. pneumoniae (water)C. freundii (TSB)C. freundii (water)
Havill et al. Infect Control Hosp Epidemiol 2014;35:445-447
0
1
2
3
0 5 10 15 20
log(
10) c
Time / daysError bars represent plus one standard deviation of the mean.
Conclusion
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
K. pneumoniae vs. E. coli
25
30
35
d Klebsiella spp
P<0.001Risk factors for ESBL-E contamination = ESBL-KP, urinary catheter;
Risk factors for ESBL-E contamination = ESBL-KP, urinary catheter;
1. Guet-Revillet et al. Am J Infect Control 2012;40:845-848.2. Gbaguidi-Haore. Am J Infect Cont 2013;41:664-665. 3. Freeman et al. Antimicrob Resist Infect Control 2014;3:5.
0
5
10
15
20
5
Rooms contaminated Sites contaminated
% c
onta
min
ated Klebsiella spp.
E. coli
P<0.001
carbapenem therapy was protective.3carbapenem therapy was protective.3
3M™ Learning Connection 9/15/2014
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ConclusionCRE surface contamination in hospitals
30
35
ith C
RE
An Israeli hospital investigated CRE environmental contamination in the vicinity of 34 CRE-carriers; mainly K. pneumoniae.
CRE was detected in the surrounding environment of most (88%) of the patients sampled.
Lerner et al. J Clin Microbiol 2013;51:177-1781.
0
5
10
15
20
25
Pillow Crotch Legs Infusion pump Bedside table
% s
ites
cont
amin
ated
wi
Persistent contamination
6
8
10
12
14
sites contaminated
% sites contaminated with A. baumannii% sites contaminated with MRSA
140 samples from 9 rooms after 2xbleach 5705 samples from 312 rooms
0
2
4
2 x bleach disinfection
4 x bleach disinfection
Bioquell
% s
Manian et al. Infect Control Hosp Epidemiol 2011;32:667-672.
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
Enterobacteriaceae are “less environmental”
5
6
7
8
9
atio
Nseir et al. Clin Microbiol Infect 2011;17:1201-1208.Ajao et al. Infect Control Hosp Epidemiol 2013;34:453-458.
0
1
2
3
4
5
Nseir A.baumannii Nseir P.aeruginosa Nseir ESBL Ajao ESBL
Odd
s ra
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Common clones – CC258 KPC K. pneumoniae
Munoz-Price et al. Lancet Infect Dis 2013;13:785-796.
Common clones – A. baumannii clones I, II, III
Diancourt et al. PLoS ONE 2010;5:e10034.
Includes ‘OXA‐23 clone 1’ & ‘South East clone’
Infection prevention and control challengesPathogen CRE1 CRAB2 MRSA VRE C. difficile
Resistance +++ +++ + + +/-
Resistance genes Multiple Multiple Single Single n/a
Species Multiple Single Single Single Single
HA vs CA HA & CA HA (ICU) HA HA HA
At risk pts All ICU Unwell Unwell OldAt-risk pts All ICU Unwell Unwell Old
Virulence +++ +/- ++ +/- +
Environment +/- +++ + ++ +++
1. Carbapenem-resistant Enterobacteriaceae.2. Carbapenem-resistant Acinetobacter baumannii.
3M™ Learning Connection 9/15/2014
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Hand hygiene
Cleaning / disinfection
SDD?Active
Antibiotic stewardship
MDR-GNR control
Topical CHX?
Education?
Contact precautions
screening
Poll: which do you consider the most important control measure to prevent the transmission of antibiotic-resistant Enterobacteriaceae (including CRE)?
A. Active surveillance and contact precautions. B C t t ti f fi d ( ith t B. Contact precautions for confirmed cases (without
active screening).C. Antibiotic stewardshipD. Hand hygiene.E. Cleaning / disinfection.
Poll: which do you consider the most important control measure to prevent the transmission of antibiotic-resistant non-fermenters (such as A. baumannii)?
A. Active surveillance and contact precautions. B C t t ti f fi d ( ith t B. Contact precautions for confirmed cases (without
active screening).C. Antibiotic stewardshipD. Hand hygiene.E. Cleaning / disinfection.
3M™ Learning Connection 9/15/2014
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Share Differ
Gram stain reaction Risk factors & at-risk population
Concerning AMR Potential for epidemic spread
Infection profile & mortality
PrevalencePrevalence
Colonisation site & duration
Transmission routes
Resistance profile & mechanisms
Summary
1. Resistant Gram-negative rods represent a more serious threat than the ‘usual suspects’, mainly due to the threat of pan-drug resistance.
2. Enterobacteriaceae (mainly K. pneumoniae) and non-fermenters(mainly A. baumannii) have fundamental differences in their ( y )epidemiology.
3. CRE and CRNF are both emerging problems, but they are not the same problem. CRO
4. The prevention and control strategy will look different for Enterobacteriaceae vs. non-fermenters.
1. Gain a microbiological overview of the various families of multidrug-resistant Gram-negative rods.
2. Compare the features of the key families: Enterobacteriaceae
Learner objectives
(including CRE) and non-fermenters (including A. baumannii), especially at-risk population and epidemic potential.
3. Discuss how differences in epidemiology affect approaches to infection prevention and control.
© 2012. All Rights Reserved.
3M™ Learning Connection 9/15/2014
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Oct 7 2014 Filling the gaps in the guidelines to control resistant Gram-negative bacteria
1. Provide an overview of the available guidelines to control CRE and other resistant Gram-negative bacteria.
2. Identify gaps in the guidelines, in terms of definitions of standard precautions, outbreak epidemiology and who should be on the ‘guidelines writing dream team’.
3. Discuss controversial areas in terms of effective interventions: patient isolation, staff cohorting and selective digestive decontamination.
© 2012. All Rights Reserved.
3M Infection Prevention Solutions
Questions?
3M.com/IPEd
Resources• CDC CRE Toolkit.
• AHRQ CRE Tookit.
• UK Public Health England CPE Tookit.• ESCMID MDR-GNR control guidelines.
© 2012. All Rights Reserved.
3M™ Learning Connection 9/15/2014
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AcknowledgementsImage credits:
‘Danger! Mines!’
‘Apples and oranges’
‘Acinetobacter baumannii’
‘Klebsiella pneumoniae’
Thank you!
3M.com/IPEd
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