Updates: Candida Epidemiology and Candida auris...Candida infections • Fluconazole resistance for...
Transcript of Updates: Candida Epidemiology and Candida auris...Candida infections • Fluconazole resistance for...
10/2/2018
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National Center for Emerging and Zoonotic Infectious Diseases
Tom Chiller MD MPHTM
Chief, Mycotic Diseases Branch
Updates: Candida Epidemiology and Candida auris
My usual Disclosure!
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Candidemia surveillance
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Candidemia incidence by year and EIP site, 2009–2017
0.0
5.0
10.0
15.0
20.0
25.0
30.0
2009 2010 2011 2012 2013 2014 2015 2016 2017
Inci
den
ce p
er 1
00
.00
0 p
erso
ns
Year
CA CO GA MD MN NM NY OR TN
OR
Overall incidence: ~7/100,000
NM: 5.3
OR: 4.9CA: 4.8MN: 4.7
CO: 4.3
TN
MD
GA
Fluconazole Resistance (all species) by EIP Surveillance Site 2008-2017 (n=~8000 isolates)
1.8%
9.5%
5.7%
4.7%
2.3%
14.3%
4.1%
0.0%
2.0%
4.0%
6.0%
8.0%
10.0%
12.0%
14.0%
16.0%
2008 2009 2010 2011 2012 2013 2014 2015 2016 2017
% R
esi
stan
t
Year
CA
CO
GA
MD
MN
NM
NY
OR
TN
OR,CA: 0.0 %
On average, ~7% of all isolates collected through EIP are resistant to fluconazole (intrinsic or acquired resistance)
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Echinocandin Resistance (all species) by EIP Surveillance Site2008-2017 (n=~ 8000 isolates)
1.8%1.7%1.4%
1.9%
-1.0%
1.0%
3.0%
5.0%
7.0%
9.0%
11.0%
13.0%
15.0%
2008 2009 2010 2011 2012 2013 2014 2015 2016 2017
% R
esi
stan
t
Year
CA
CO
GA
MD
MN
NM
NY
OR
TN
CA, NM, NY, OR, TN: 0.0%
On average ~ 1.5% of all isolates are resistant to echinocandins
Echinocandin-resistant C. glabrata by Surveillance Site
2008-2017 (n=2230 isolates)
5.9%6.3%
3.6%
6.5%
-1.0%
1.0%
3.0%
5.0%
7.0%
9.0%
11.0%
13.0%
15.0%
2008 2009 2010 2011 2012 2013 2014 2015 2016 2017
% R
esi
stan
t
Year
CA
CO
GA
MD
MN
NM
NY
OR
TNCA, NM, NY, OR, TN: 0.0%
On average ~ 4% of C. glabrata isolates are resistant to echinocandins
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Resistance – US surveillance
• C. albicans still causes the highest percentages of Candida infections• Fluconazole resistance for C. albicans is <1%
• Overall fluconazole resistance is ~7%• Majority of this is C. glabrata and C. krusei
• Echinocandin resistance for C. albicans, C. tropicalis, C. parapsilosis, and C. krusei has remained <1%
C. glabrata MDR in the US
• 1.1% of all C. glabrata isolates were resistant to both fluconazole and echinocandins
• 28% of all echinocandin resistant C. glabrata are fluconazole resistant
• 11% of all fluconazole resistant C. glabrata are echinocandinresistant
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Candidemia burden estimate in 2017
Projected incidence rates of candidemia, by census division(per 100,000 population)
Based on projection from 1200 cases collected through EIP surveillance in 2017: 23,000 cases of candidemia occur each year in the United States3,000 deaths (all cause mortality within 1 week of candidemia)
Tsay et al, ID Week 2018
Proportion of IDU-associated candidemia cases by site, 2017
4.8%
7.8%
3.9%
16.7%
1.4%
29.4%
8.6%
25.8%
16.3%
0%
5%
10%
15%
20%
25%
30%
CA CO GA MD MN NM NY OR TN
Pro
po
rtio
n o
f C
ase
s w
ho
Inje
ct D
rugs
(%
)
Site
Zhang et al, ID Week 2018
OVERALL: 10.2%
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0%
5%
10%
15%
20%
25%
30%
2014 2015 2016 2017
Pro
po
rtio
n o
f ca
ses
wh
o in
ject
dru
gs (
%)
Year
MD
GA
OR
Tripling of proportion of cases
Trends in Proportion of IDU by year and site, 2014-2017 at select site with previous years of data
TN
Candidemia incidence by year and EIP site, 2009–2017
0.0
5.0
10.0
15.0
20.0
25.0
30.0
2009 2010 2011 2012 2013 2014 2015 2016 2017
Inci
den
ce p
er 1
00.0
00 p
erso
ns
Year
CA CO GA MD MN NM NY OR TN
OR
NM: 5.3
OR: 4.9CA: 4.8
MN: 4.7
CO: 4.3
Note increases in incidence of candidemia in TN likely due to increases in IDU
TN
MD
GA
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Summary
▪ One in 10 candidemia cases are associated with IDU in 2017
▪ Increase since 2014, most notably in TN and MD
▪ Significant differences between IDU-associated candidemia cases and non-IDU cases
– Median age: 35 vs. 62 years
– Hepatitis C: 55% vs. 6%
– TPN: 5% vs. 27%
– In-hospital mortality: 9% v. 27%
▪ CDC is investigating IDU-associated candidemia in more detail
Antimicrobial Resistance LabortoryNetwork (ARLN)
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ARLN Labs – Candida part of CORE pathogens tested
Objectives of the Candida ARLN program
▪ Set up regional lab network for susceptibility testing
▪ Track antifungal resistance among Candida/yeast species
▪ Identify emerging resistant species like Candida auris
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468 isolates tested in 2017
257
137
57
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150
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250
300
Northeast Central Southeast West
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Species identified – Top 10
169
106
3425
16 13 13 11 7 6
0
20
40
60
80
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180
Resistance: C. glabrata (n=97)
▪ 2 isolates azole and echinocandin resistant
15.5% 3.1%Azoles Echinocandins
1.1%
Micafungin
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169 isolates confirmed as C. auris
153
115
109
101
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20
40
60
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160
180
Northeast Central Southeast
▪ 36% of all isolates
▪ 95% of all isolates identified as C. auris by the submitter
▪ 120 unique patients
Number of isolates Number of patients
C. auris update
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Candida?
A paradigm shift for Candida infectionsA Yeast that acts like a Bacteria!
▪ Resistance is the norm
▪ Thrives and persists on skin
▪ Contaminates patient rooms
▪ SPREADS IN HEALTHCARE SETTINGS
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C. auris epidemiology
Countries with Candida auris through 2015
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Countries reporting Candida auris in 2018Some hospitals with 40% candidemia
0
5
10
15
20
25
30
35
40
Nu
mb
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f cl
inic
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ases
New York New Jersey Maryland Illinois California Massachusetts
C. auris clinical cases reported by state — United States, 2013–August 2018
Solid: Confirmed case Striped: Probable case
~425 clinical cases~1180 clinical + screening cases
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States from which C. auris cases have been reported
Epidemiologic Characteristics of U.S. Cases
▪ Median age: 70; ~30% 30-day mortality
▪ Multiple underlying conditions, indwelling devices• Tracheostomy, central line, gastrostomy tube
▪ Extensive healthcare exposure • Acute care hospitals, LTACHs, vSNFs
▪ Patient have multiple other MDROs• CP-CRE is the most common co-colonizer
Per
cen
t res
ista
nt
Initial culture site of C. auris
Antifungal resistance of C. auris
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Healthcare abroad is risk factor for C. auris
▪ US C. auris cases are a result of initial introductions from abroad followed by local transmission
Isolates from U.S cases cluster to all four C. auris clades
South Americanclade
African clade
South Asianclade
East Asianclade
>300 clinical cases
> 700 additional patients colonized
Chow et al, Lancet ID in press
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CT, CA, and OK travel-related cases – South Asian clade
India Connecticut (CT)
India California (CA)
Pakistan Oklahoma (OK)
Chow et al, Lancet ID in press
Global C. auris antifungal resistance
0 10 20 30 40 50 60 70 80
Fluconazole
Amphotericin B
Echinocandins
% ResistanceN=848
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Resistance is clone-specific
• Southeast Asia• Nearly universally FluR, 40% AmpBR
• South America• Colombian isolates 25% FluR + AmpBR
• Venezuelan isolate are universally FluR
• Overall 8% EchinoR but higher in Venezuela
• Africa• Variable resistance, mostly FluR, some AmpBR
• East Asia• Universally susceptible
0
20
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60
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1 2 4 8 16 32 64 128 256
# o
f is
ola
tes
MIC ug/mL
MIC ug/mL
Resistance in C. auris is acquired, not intrinsic
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MDR C. auris
0 10 20 30 40 50 60 70 80 90
Pan susceptible
1 or more class
2 or more classes
Pan resistant
% ResistanceN=848
C. auris nationally notifiable in 2019
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C. auris Colonization: A new area for mycologists
C. auris Colonization
▪ Patients remain persistently colonized
• NYS has followed a few hundred patients
• 60% 90-day mortality
• Some colonized for over a year
• Only ~16 have “cleared” colonization
▪ Colonization means patients are:
• At risk for developing invasive infection
• 30 cases of BSI in ~600 colonized patients who are being followed 2016-2018
• Source of transmission to others
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C. auris Colonization
▪ Most sensitive (>90%) and cost-effective swab: axilla and groin
• Nares, rectal, and oral swabs have also been positive, but not as consistently as axilla/groin swabs
Detection through colonization screening
▪ Axilla and groin swabbing
▪ Enrichment broth method
• High salt/temperature
• ~25% more sensitive than direct plating
• Must hold plates for 10 days
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Question about When/Who to screen ?
▪ Contact tracing around a newly identified case
▪ Point prevalence surveys in places with some documented transmission
▪ Admission screening (pilot in NYS)
▪ Screening of patients with history of healthcare abroad, especially with a bad MDRO like CP-CRE
▪ Screening of patients in high-acuity long-term care facilities, especially those with CP-CRE and other MDROs
Rapid diagnostics
Real-time PCR
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Decolonization/source control
▪ Chlorhexidine? Another agent
▪ Antifungals? –terbinafine?
▪ Remove pressure of antibiotics and antifungals?
▪ Candida vaccine?
In vitro data on chlorhexidine looks good
Schelenz, Federation of Infection Societies Poster, 2017
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But…
▪ In vivo studies on reduction in burden of colonization have not been done
▪ Facilities where C. auris outbreaks have occurred have not seen improvements in incidence of colonization even when using aggressive CHG bathing
Environmental disinfection
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C. auris contaminates the hospital environment
Able to survive and persist on surfaces for weeks
Other places where C. auris has been cultured from:
Temperature probe
Madder et al (U.K.), bioRxviv 2017)Armstrong et al, unpublished
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Environmental disinfection: Quats don’t work well
Cadnum et al. 2017
Recommended but challenging
Not recommended
Limited data
Environmental disinfection – Hydrogen Peroxide
▪ In vitro studies promising
▪ Need real world assessments
Schelenz, Federation of Infection Societies Poster, 2017
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Environmental disinfection—UV Light
▪ Needs long exposure time at high intensity
Cadnum et al 2017
Questions about environmental disinfection
▪ What products to use ?
▪ When to use?
• Just for case patient room?
• The whole floor where the patient is admitted there?
• Pre-emptively at all long term care facilities with ventilated patients in an endemic area?
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Challenges for C auris
▪ Screening/colonization testing is not widely available and culture testing takes 10 days to call negative
▪ Rapid diagnostics are being developed but are not yet widely available
▪ Need decolonization methods
▪ Environmental disinfection options are limited (effective and safe alternatives to bleach are needed)
Where is it coming from?
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We need to live in Balance with the environment
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Esti
mat
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gric
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ura
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Met
ric
Ton
s)
Year
High Estimate
Low Estimate
Source: USGS Pesticide Data Use Project
Increasing Triazole Use in Agriculture
US Data
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For more information, contact CDC1-800-CDC-INFO (232-4636)TTY: 1-888-232-6348 www.cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
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