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U NIVERSITYof HOUSTON COLLEGE OF PHARMACY
Active surveillance for C. diff and Candida auris in Texas
If your name starts with a “C”, we are looking for you!!
Kevin W. Garey, PharmD, MS, FASHP Professor and Chair
Dept of Pharmacy Practice and Translational Research
Objectives
• Defend the need for increased surveillance of MDRO organisms.
• Explain the importance of the emergence and antifungal resistance in Candida auris
• Create the shell of a registry to identify MDRO organisms
Components of an active surveillance system: C difficile
Clinical or environmental
sample
C. diff growth and confirmation
Biobank / long-term storage Regrowth QA
Ribotyping
DNA extraction
MLVA/WGS
Long-term storage
Cytotoxicity testing
Stool DNA extraction
16S RNA analysis
Long-term storage
Blood
DNA
Serum
Clinical data BUG
Microbiome
Immune response
···~r-~
, ilton Houston Pl zr:i/Medic 1 r:.
Center I
more ..... B~r Cli
McClendon St , r ~ Best . t:,
Wes rn edical la! _,$ Center ~
W Holcombe Blvd
c;_;f ~
H S riners Hospital
for Oh1I -ren
�
ou on Mamo at the Te !I;
Medical Center i:.t
St L kes Ept:soopal H
Heal h System
Holcomtre Blvd
exes M eo,caJ H Center
- rll-"
H Be 1aub General Hosp al
I f
HoJcombe sr'ld
TMC C. diff surveillance network
Methodist Hospital (Pat Cernoch) 200 cases/yr
Baylor St. Luke’s (main group) 200 cases/yr
Texas Children’s hospitals (Tor Savidge) 100 cases/yr
UT Memorial Hermann (Cesar Arias) 50 cases/yr
Ben Taub Hospital (Robert Atmar) 50 cases/yr
MD Anderson (Javier Adachi) 200 cases/yr
VA Medical Center (Dan Musher) “C diff alley”
UH COP (us)
UT SPH (Herbert DuPont)
iiiiii V @ Cleveland
Todd Mission Moss Hill G
Magnolia
Hardin
d Dais
Dayton Liberty
Brookshire Katy Anahuac
Baytown ®
Rosenberg
I Alvin
Needville Texas City
® I
®
@
/ _
Thanks to the systemization of health-systems, HCA, and some buddies, we have an active surveillance system that covers Houston
Ru11oso
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Juan Aldama
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Midland
Od~ssa o
Sig S~ring
COAHUILA
ijj Abilene
Sani;.ngelo
-t
J-
TEXAS
t Plano
0
Dallas Fort Wortho 0
• v
Roun~ Rock
Austin 0
Waco 0
San ~arcos
1
' I
San Antonio 0
Roctport
f"l"\ r r•11 1C f"hric-tl
ijj
ijj
f
Tex~~kane
ijj El C
ijj
Ty~er
Loniview Shreveport _ o 'J:J
Naco~ches
The Woo~ands
Beaumont Lake ~harles
Houston 0
0 Pasadena
Galv~ston
0 0 01a-r,ge
…and thanks from funding from the TX Dept of State Health Services we have a network of hospitals all over TX sending us samples
Fort Worth Plano Texarkana
Dallas
El Paso
Bryan
San Antonio
Galveston Webster
Corpus Christi McAllen Brownsville
We have been able to collect a lot of C diff samples around Texas!
City Total Amarillo 195 Austin 194 Corpus Christi 187 Dallas 180 El Paso 194 Fort Worth 190 Galveston 162 Laredo 192 Lubbock 175 San Antonio 185 Total 1896
�
50
Active surveillance of C. diff in Texas
Ribotypes
0
5
10
15
20
25
30
35
40
45
F014-020 F027 F106 F002 F001 Other (n=48)
Ribotypes
001
PCR ribotyping is commonly used worldwide
Ribotype Houston Australia Belgium Europe
014/020 15% 26% 20% 12%
002 11% 11% 8% 3%
106 12% NR 6% 2.5%
027 14% 1.6% 4.2% 12%
4% NR NR 9%
Congratulations, Houston! We have our own unique C. difficile ribotype!!
Collins et al. Pathology 2017:309-13 Neely et al. J Hosp Infect 2017; 394-9 Freeman et al. Clin Microbiol Infect 2015:248e9-e16
We can likely detect the next emerging strain
2011 2012 2013 2014 2015 2016 2017 2018
RT027 28 22% 63 28% 91 27% 12 22% 49 20% 266 15% 226 14% 22 14%
RT014-020 23 18% 42 19% 56 17% 16 29% 39 16% 301 17% 265 16% 22 14%
RT106 16 12% 21 9% 36 11% 5 9% 33 13% 175 10% 236 15% 18 12%
RT002 12 9% 22 10% 37 11% 5 9% 20 8% 149 9% 139 9% 16 10%
RT001 13 10% 8 4% 14 4% 1 2% 11 4% 57 3% 54 3% 5 3%
RT078-126 9 7% 13 6% 21 6% 3 6% 12 5% 40 2% 23 1% 0 0%
RT255 0 0% 0 0% 0 0% 0 0% 2 1% 77 5% 80 5% 10 7%
RT054 2 2% 7 3% 10 3% 4 7% 11 4% 45 3% 37 2% 9 6%
RT053-163 4 3% 6 3% 4 1% 2 4% 12 5% 43 3% 26 2% 3 2%
RT017 3 2% 10 4% 10 3% 1 2% 7 3% 44 3% 34 2% 1 1%
ubMeel • ribotype 255 I Create RSS Create alert Advanced
Fonnat: Summary• Sort by: Most Recent • Per page: 20 •
Search results Items: 11
Send to •
D Circulation of Hign!Y. Drug-Resistant Clostrid ium difficile RibO!Y.Jles 027 and 001 in Two Tertia [Y.-Care 1. HOSP-ita ls in Mexico.
Martinez-Melendez A , Tijerina-Rodriguez L, Morfin-Otero R, Camacho-Ortiz A, Villarreal-Trevino L, Sanchez-Alanis H, Rodriguez-Noriega E, Baines SD, Flores-Trevino s, Maldonado-Garza HJ, GarzaGonzalez E. Microb Drug Resist. 2018 May;24(4):386-392. doi: 10.1089/mdr.2017.0323. Epub 2018 Feb 27.
PMID: 29485939 Similar articles
D Clostrid ium difficile PCR ribOtY.P.es 001 and 176 - tne common denominator of C. difficile infection 2. § P.idemiologY. in the Czecn Rei;1ublic, 20 14.
Krutova M, Matejkova J, Kuijper EJ, Drevinek P, Nye o ; Czecn Clostrid ium difficile study group. Euro Surveill. 2016 Jul 21;21(29). doi: 10.2807/1560-7917.ES.2016.21.29.30296.
PMID: 27484171 Free Article Similar articles
We can then link these findings back to the rest of the world
18
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180
160
140
120
100
80
60
40
20
0 Leaves
� Total Samples
C.difficile
� Toxigenic C. difficile
One Health meets C. diff Fig. 1: Isolation of Clostridium difficile from park tree leaves
Fig. 2: Ribotypes of Clostridium difficile from park tree leaves
We can also use these tool to impact patient care
• In 2016, we were consulted on an increased number of CDIcases at a nursing home (n=4). One patients was originallysymptomatic with three subsequent cases developing over the next month. This was the first case of CDI occurring atthis nursing home ever!
• ALL STOOL SAMPLES WERE POSITIVE FOR RIBOTYPE 027 • Environmental samples also positive to ribotype 027 • Based on these results, the nursing home underwent an
institution-wide terminal clean • We then performed a follow-up environmental sampling
study
� �
Proportion of positive environmental samples before and after facility-wide terminal clean with 10% bleach solution
P<0.001
P=0.17
43%
5%
30%
3% 0%
5%
10%
15%
20%
25%
30%
35%
40%
45%
50%
Prop
ortio
n of
sam
ples
pos
itive
for C
. diff
icile
P=0.76
Before terminal clean (n=50 samples) After terminal clean (n=50 samples) Patient care rooms (30 swabs from each sampling period) Non-patient care room (20 swabs from each sampling period)
70
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� Community environmental (n=344) � Hospital environmental (n=74)
� Clinical isolates (n=6 l 5)
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Clostridioides difficile – Focus on ribotype 027
• Global pandemic of CDI began in the early 2000’s and was caused by the ribotype 027 strain
• Epidemiological studies in Houston indicates RT027 is still one of the most prominent ribotypes in the hospital/clinic
Pubmed search term: “clostridium difficile
ribotype 027”
Alam MJ, et al. OFID 2017
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Figure 1 Phylogeny of C. d1lf1C1le 0271BI/N l!Pl bas.ed on '.he genotype .al co,e genom! SNPs. (a) G:Obal phylogeny ( n "' 151 isolates). Colored nodes mdc.:1tc t he geog.:i,ph ic !;Ource o f the ,~ l.:t.t c~. ( b} Phyl c,seny of U K i ~ l~c~ ( n - 188) col orcd .:11ce0td,ng t o gcos,,1,ph ,e !:aOur ec. In :i,, the pv.;, tio n of the 1nlend root Is 1n:ticat ed by a MShed line. ai d dashed ou1I1nes in a,b eRclose the isolates w it h t he gyrA mutation enC-Odmg p. lhr82IIe associat ed wi th l luaoqumotone r~sistance. Blac,k arrows show the msertlon of selected mobi le eleme� ls.
Tn6103 R20291 (FOR2)
Ribotype 027: the man, the myth, the PANDEMIC legend
• WGS of 151 worldwide RT027s identified 2 distinct lineages that diverged independently (denoted FQR1 and FQR2)
• Both lineages emerged in North America with high probability
• Both epidemic lineages inherited the same gyrA mutation, but different transposable elements (Tn6192 and Tn6105)
• FQR2 strains spread more widely in Europe, therefore, <20 FQR1 strains sampled in this study
• Little is known about the emergence and spread of FQR1
He M, et al. Nature Genetics 2013
•• •• •• •• •• •• •• •• •• •• •• •••
•• •• •• •• •• •• •• •• •• •• •• ••
Goal: Provide a better understanding of the emergence and dissemination of the ribotype 027 strain in the USA
• Objective 1: WGS US strains and identify SNPdifferences amongst RT027’s
• Objective 2: Determine the gene differencesbetween US and world wide strains
• Objective 3: Conduct phylogeographic analyses
Garey Lab Biobank
•• •• •• •• •• •• •• •• •• •• •• •••
•• •• •• •• •• •• •• •• •• •• •• ••
Goal: Provide a better understanding of the emergence and dissemination of the ribotype 027 strain in the USA
• Objective 1: WGS US strains and identify SNPdifferences amongst RT027’s
• Objective 2: Determine the gene differencesbetween US and world wide strains
• Objective 3: Conduct phylogeographic analyses
Garey Lab Biobank
SLIDES embargoed
• The next set of slides are embargoed while they are going through the peer review process for publication
1·,,
Some amazing data can come out of active surveillance programs • FQR1 and FQR2 lineages are present in Houstonin equal proportionsNovel SNPs identified may lend insight into changesin metronidazole responsiveness
• Presence or absence of genes/transposableelements are lineage-specific with some uniquestrain-specific exceptionsFQR1 strains have more antimicrobial resistance thanFQR2 strains
• Emergence of RT027 lineages was associatedwith FDA approval of first fluoroquinolones in early1980’sTexas-wide RT027 lineages originated from Houston
Defending the need for active surveillance
• In a short amount of time, our C diff surveillance efforts have: – Been able to inform circulating ribotypes • Confirmed CDC reports on emergence of 106 strain • Identified the R255 emerging strain
– Able to confirm successful eradication of the epidemic 027 strain in a LTC facility
– Enabled global (and state-wide) surveillance ofepidemic strains
• Pretty cool, eh!!
I ~ Centers for Disease Control and Prevention I SEARCH . CDC 24/7: Saving Lives, Protecting People™
Fungal Diseases
Fungal Diseases
Types of Fungal Diseases
Who Gets Fungal Infections?
Outbreaks
CDC at Work
Global Fungal Diseases
Antifungal Resistance
+
+
+
+
Think Fungus: Fungal Disease + Awareness Wee
Candida auris
D CI D Candida auris is an emerging fungus that presents a serious global healt h threat. CDC is
concerned about C auris for three main reasons:
1. It is often multidrug-resistant, meaning that it is resistant to multiple antifungal drugs
commonly used to treat Candida infections.
2. It is difficult to identify with standard laboratory methods, and it can be misidentified in labs
without specific technology. Misidentification may lead to inappropriate management.
I
CANDIDA AURIS
..,.
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C. auris first reported in Japan in 2009
Many of these slides are courtesy of Snigdha Vallabhaneni (CDC/OID/NCEZID)
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Countries from which C. auris cases had been reported by 2016
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Num
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ical
cas
es
0
5
10
15
20
25
30
CDC issued a
C. auris clinical cases reported by state — United States, June 2016 M
ay-1
3
Jun-
15Ju
l-15
Aug-
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p-15
Oct
-15
Nov
-15
Dec-
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n-16
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May
-16
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-17
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Nov
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New York
--- - T T T T T T T =---1�� 1 I I T T T T T T T T
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Num
ber o
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ical
cas
es
C. auris clinical cases reported by state — United States, 2013–December 201630
25
20
15
10
5
0
May
-13
Jun-
15Ju
l-15
Aug-
15Se
p-15
Oct
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Nov
-15
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n-16
Feb-
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ar-1
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r-16
May
-16
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p-16
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Nov
-16
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r-17
May
-17
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r-18
New York New Jersey Maryland Illinois
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C. auris clinical cases reported by state — United States, 2013–April 2018
25
30
~300 clinical cases ~800 clinical + screening cases
May
-13
Jun-
15Ju
l-15
Aug-
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p-15
Oct
-15
Nov
-15
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New York New Jersey Maryland Illinois California Massachusetts Oklahoma Indiana Florida Connecticut Texas
Solid: Confirmed case Striped: Probable case
---------
Eleven cases linked to healthcare abroad
Patients from India, Pakistan, South Africa, and Venezuela
Identified weeks to two years after hospitalization in that country
WGS showed isolates were related to those from the countries where patients received healthcare
Isolates were from all different body sites
-------
Healthcare abroad is risk factor for C. auris Majority of US cases don’t have links to healthcare abroad US C. auris cases are a result of introductions from abroad followed by
local transmission
Why is Candida auris a public health threat? Highly drug-resistant yeast Causes invasive infections associated with high mortality Spreads easily in healthcare settings
� �
Antifungal Resistance, C. auris isolates United States, 2013-2018
89% 30% 3% 4% 3% 4%350 300 250 200 150 100
50 0
Not Resistant Resistant
Causes invasive infections
40-50% of clinical cases are bloodstream infections
40% in-hospital mortality in BSI cases
Risk factors for C. auris
Multiple healthcare stays (LTCFs) Tracheostomy/Ventilator PEG tubes Central venous catheters On antibiotics and antifungals Being colonized with another MDRO is
a risk factor for C. auris colonization Receipt of healthcare abroad
A Ventilator/Trach Floor March 2017 C. auris PPS Results
0 0QOO O a -a o a -
0
C. auris colonization prevalence=l.5% (1/69)
• C. auris positive O Screened negative for C. auris 0 Not tested for C. auris (refused or not in room)
Slide courtesy of Chicago Department of Public Health.
0
vSNF A Ventilator/Trach Floor January 2018 C. auris PPS Results
--- - -0 0 0 ... .. -
u
C. auris colonization prevalence=43% (29/67)
• C. gJJ[jj_ positive 0 Screened negative for C. gJJ[jj_ 0 Not tested for C. ~ (refused or not in room)
•
Slide courtesy of Chicago Department of Public Health.
0
vSNF A Ventilator/Trach Floor January 2018 CPO and C. aJJClli PPS Results
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• • i"h• •• o- . .?
C. auris and CPO colonization
• C. ffi!J1§, • C. QIJL/§, and KPC
e KPC or CRE with unknown mechanism of resistance
• C. auris, KPC, and NDM
C. auris, VIM -CRPA, and KPC
• C. QIJL/§, and KPC-CRPA
O Screened negative for C. auris, but not
tested for CRE
O Screened negative for CRE and C. ~
Slide courtesy of Chicago Department of Public Health.
Patients are colonized for the long term
In NY, of ~300 patients being followed with C. auris, only 16 have “cleared” colonization
C. auris in the Hospital Environment
0 0
Other places where C. auris has been cultured from:
Temperature probe
C > ,___ ______ __
Challenges with identification
C. auris can be misidentified as:
Candida haemulonii
Candida famata
Candida sake
Candida catenulata
Candida guilliermondii
Candida lusitaniae
Rhodotorula glutinis,
Candida spp. after a validated method of Candida identification attempted.
Mizusawa et al. 2017 JCM
Method
Vitek 2 YST
API 20C
BO Phoenix yeast ident ifi cat ion system
M icroSca n
Rap ID Yeast Plus
Organism C auris can be misidentified as
Candida haemulonii Candida duobushaemulonii
Rhodotorula glutinis (character istic red color not present )
Candida sake
Candida haemulonii Candida catenulata
Candida famata Candida guilliermondi( Candida /usitaniae" Candida parapsilosis"
Candida parapsilosis *
For the clinical lab experts
Continuing challenges with identification
Half of clinical cases in the U.S. have been from non-bloodstream isolates (e.g., urine, bile, wounds) Initial culture site of C. auris
clinical cases (n = 150)
Species from non-sterile isolates often not identified
Controlling the spread of C. auris
DETECT TREAT INFECTION CONTROL
Challenges Detection/Identification Lack of decolonization/ source control strategies Environmental disinfection
Decolonization/source control Chlorhexidine? Antifungals? Remove pressure of antibiotics and antifungals?
Chlorhexidine activity
• C. auris was effectively inhibited by ch lorhexidine (Hibiscrub, Ecolab, UK) in vitro at concentrations below 2 and 4% for skin decolonization.
• Iodinated povidone (Videne, UK) demonstrated an even greater activity much below the average 10% concentration used as antiseptic.
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All UK outbreak chlorhexidine wipes (Sage, Geneva, Switzerland) and wash cloth (Clinell , Gama healthcare, Watford, UK) after 18-48 hours incubation at 30 ± 2°c.
kK:reased inhbi6on zone C. a.11fa 1003 1062 {1ndia)
A11£rage ff1 ibi6on zone C. a.lhcan.s ATCC 10231
a Sage w ipes b Cli t1ell cloth
In vitro data on chlorhexidine looks good
Schelenz, Federation of Infection Societies Poster, 2017
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 CHG bathing
� C. albicans DC. glabrata ~ C.auris D MRSA 7
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Environmental disinfection
Cadnum et al. 2017
l'lgure I!. 6 .enniddal Adimy agaimst C. ,iruri.s, C. ,alfm:nru:, aoo 5. QUn!'U5
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Environmental disinfection
Rutala et al, ID Week 2017
• Exposure of H20 2 vapour was 96.6-100% effective in killing C. auris isolates in a total of three separate experiments.
• A ll non-C. auris Candida species were 100% killed by H20 2 vapour.
C. gur/s n•30
ATCC Candida na4
lx106CFU/ml
Rl'MI reconstitution r,.
SDA ,ubculture
H HJ ' :: ~
- O _ O Exposure
vaporiied H10,
Environmental disinfection – Hydrogen Peroxide
In vitro studies promising Need real world
assessments
Schelenz, Federation of Infection Societies Poster, 2017
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� Cand ida au ris � Candida albicans � Candida glabrata KIi Clostridium d iffici le � MRSA
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Components of an active surveillance system: C. auris
Clinical data
Clinical or environmental
sample
Candida growth and confirmation
Biobank / long-term storage Regrowth QA
DNA extraction
WGS
Long-term storage
Candida auris surveillance
• Details – 1-2 year evaluation of Candida bloodstream
isolates from 2 health systems – WGS for clonal relatedness and identification of C.
auris (if it is present in Houston) – Outreach to the Houston medical community for
evaluation of Candida outbreaks or difficult to identify isolates
Facilities work together to protect patients.
� Patients can be transferred back and forth from facilities for treatment without all the communication and necessary Infection control actions In place.
Independent Efforts (Still not enough)
� Some facllltles work Independently to ,enhance Infection control but arre not often alerted to antilblotic-resrstant or C. dlfflcile gel'ms oomingr from other facili1!1es or outbreaks in the area.
� Ladle of sharred information from otlher facilities means that rnecessary infect1lon ,control actfons are not always talk.em and germs are spread to other patients.
~ Coordinated Ap1proach (Needed)
� Publlc health departments track and alert health care facllltles to antlblotlcreslstant or C. difficile germs coming from other facllltles and outbreaks in the area.
� Facllltles and public health authorities share Information and implement shared infection contro l actions to stop spread of germs ~rom facillty to facility.
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Future: XDRO registry
CDC Vital Signs, August 2015 www.cdc.gov/vitalsigns/stop-spread
XDROregistry Extensively drug resistant organism registry Citations Help Login
The XDRO registry is a product of collaboration between IDPH, Medical Research Analytics and Informatics Alliance (MRAIA), and the Chicago CDC Prevention Epicenter.
Carbapenem-resistant Enterobacteriaceae (CRE) are extensively drug resistant organisms
(XDROs) that have few treatment options and high mortality rates. CRE are increasingly
detected among patients in Illinois, including in acute and long term care healthcare
facilities.
In response to the CRE public health threat, the Illinois Department of Public Health (IDPH)
has guided development of an infection control tool called the XDRO registry. The purpose
of the XDRO registry is two-fold:
1. Improve CRE surveillance: The first CRE-positive culture per patient stay must be
reported to the XDRO registry.
2. Improve inter-facility communication: Healthcare facilities can query the XDRO
registry to see whether a patient has been previously reported as CRE-positive.
For access to the XDRO registry, click here
UPDATES
As of April 2017, IDPH is entering carbapenemase-producing Pseudomonas aeruginosa cases into the XDRO registry. Link: [CDC Pseudomonas aeruginosa in Healthcare Settings ]
As of January 2017, IDPH is entering Candida auris cases into the XDRO registry. Links: [ CDC C. auris Questions and Answers ][CDC Interim Recommendations ]
IL CRE Detect and Protect Campaign. More ...
CRE are reportable to IDPH via the XDRO registry. Links: [IDPH letter to facilities, September 2013 H Reportinq rule l
Electronic Public Health Registry of Extensively Drug-Resistant
Organisms, Illinois, USA William E. Trick, Michael Y. Lin, Robynn Cheng-Leidig, Mary Driscoll , Angela S. Tang,
Wei Gao, Erica Runningdeer, M. Allison Arwady, Robert A. Weinstein
lltJr:IMINMid·ffiMi·,@
Illinois Department Of Public Health change facility
XDRO culture infomiation
_. °"9~nl.:Sm name genus s ·•
_. S cdmeo source P'••tie St-ttol Sptcimtn: •
XDRO Report
* >CORO crit~ri• (select ell that apply)
RCPSllloa ode 8 Molecular test (4'.9. PCR) specific for
c..-b~nemase 0 Phenotyplc test (4'.g. Modified Hodg4')
specific for carbap4'f1ef'MSC production For E. coli and Klebsiella spp. only: Rwm,ILL Jrd91- ca,,halo...,. ·• ....., aod ~r-or-imcabapo,wn.iw-e~m.
• Date (culture acquisition)
EJILil mi:::
• lte<hanrsm of resrrunce _Pltl_!t Selltce Mlt<i't!n~::.!.J c-••rt•st-itldJ
Facility infomiation
Faclllty name • Pa Uent l'IRN • Oat" of admission/ Encounter oa,., jiin""OG Otpa1n"ltnt0t Publre Hea.lfl E:]/ E:::;/ m:C]
Cultlre obtained as outpllltient
Patient demographics
_. First name Middle name(if applicable) I 1
• Gender • Dat e of bl rth(mm/ dd/ yyyy) • ,.._, • l'emale E:] / E:) / ~
Race EthnicityIP'•• .. s.1tc<0nt: • l 0 Hispanic or Lallno
O Not Hi.sp.¥1ic or t.atiro ,., Ci ,..•.,Cs-"t.i""t"-• --...,,.., • Zip code
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XDRO registry: Texas style! Automated
admission feed
XDRO registry
ELR feed
XDRO notification
Acknowledgements
Funding: NIH (NIAID 1UO1 AI24290-01)
Houston Dept of Health and Human Services
TX Dept of State Health Services
TMC Public Policy Institute
Merck & Co, Summit PLC
