3M™ Learning Connection 9/15/2014multimedia.3m.com/mws/media/995049O/not-all-resistant-gram-negative... · 3M™ Learning Connection 9/15/2014 2 Disclosure I am employed part-time

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

[email protected]

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.


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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


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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


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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


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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.


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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.


16

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.



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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.


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.



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AcknowledgementsImage credits:

‘Danger! Mines!’

‘Apples and oranges’

‘Acinetobacter baumannii’

‘Klebsiella pneumoniae’

Thank you!

3M.com/IPEd

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3M™ Learning Connection 9/15/2014multimedia.3m.com/mws/media/995049O/not-all-resistant-gram-negative... · 3M™ Learning Connection 9/15/2014 2 Disclosure I am employed part-time