the challenge of c. difficile and multi-drug resistant organisms in long-term care
DESCRIPTION
Fred C. Tenover, Ph.D., D(ABMM) Vice President, Scientific Affairs Cepheid, Sunnyvale, CA, USA Consulting Professor of Pathology Stanford University School of Medicine Stanford, CA, USA Adjunct Professor of Epidemiology Rollins School of Public Heath Emory University, Atlanta, GA, USA. - PowerPoint PPT PresentationTRANSCRIPT
THE CHALLENGE OF C. DIFFICILE AND MULTI-DRUG
RESISTANT ORGANISMS IN LONG-TERM CARE
Fred C. Tenover, Ph.D., D(ABMM)Vice President, Scientific Affairs
Cepheid, Sunnyvale, CA, USA
Consulting Professor of PathologyStanford University School of Medicine
Stanford, CA, USA
Adjunct Professor of EpidemiologyRollins School of Public Heath
Emory University, Atlanta, GA, USA
Disclosures My salary and benefits are paid by
Cepheid, a molecular diagnostics company, and I am also a shareholder in Cepheid
Topics for Today Movement of MRSA in healthcare systems; setting the
stage Clostridium difficile
EpidemiologyInfection ControlLaboratory detection
Multidrug-resistant gram-negative bacilliEpidemiologyInfection ControlLaboratory detection
Conclusions
• Nursing homes play an important role in the spread and control of infectious pathogens, such as MRSA , in Orange County, CA hospitals.
• Data indicate that nursing homes: • Can multiply the effects of a hospital outbreak• Can originate outbreaks that in turn affect multiple
hospitals• Make it even more difficult to trace the source of an
outbreak. • Even if hospitals maintain effective infection control, even
a single nursing home with poor infection control can lead to hospital outbreaks.
Clostridium difficile - the Organism
Clostridium difficile is a Gram- positive, anaerobic, spore-forming bacillus.
Spore formation is critical to its prolonged survival in the environment and ability to spread.
Requires bleach for adequate disinfection
Alcohol hand gels not effective during outbreaks; requires soap and water
Pathogenicity Locus (PaLoc)
Binary Toxin (cdtA and cdtB) is an additional virulence factor; it is encoded at a different place on the chromosome
Two toxins, A and B, cause disease; some strains lack A and are still virulent; non toxigenic strains lack the PaLoc
Changing Epidemiology of Clostridium difficile Infection
C. difficile causes 3 million cases of diarrhea and colitis in US per year linked and is linked to >23,000 in-hospital deaths per year. It is surpassing MRSA as most common cause of healthcare-associated infection in the US
The incidence of CDI in U.S. hospitals nearly doubled from 2001 to 2010, with little evidence of recent decline
Outbreaks of severe disease caused by epidemic strain of C. difficile (027/NAP1/BI) with increased virulence and fluoroquinolone resistance have been seen worldwide.
Although elderly are still most frequently affected, more disease reported in “low-risk” persons, including healthy persons in community
Food may play a role in transmission
Frequency of C. difficile Outbreaks in U.S. Hospitals
Survey of 1714 Infection preventionists; reports from 289 hospitals, 386 outbreaks in prior 24 months
Top 5 pathogens (>65% ): Norovirus, Staphylococcus aureus, Acinetobacter spp., Clostridium difficile and Pseudomonas aeruginosa.C. difficile outbreaks mostly on medical and surgical
units (norovirus on behavioral and psychiatry units) Overall, outbreaks with top 5 organisms lasted
weeks to months C. difficile outbreaks were the longest
Rhinehart, E. 2012: Am J Infect Control 40:2-8
94%
6%
Diagnostic Methods- Reality Check
Clinical and laboratory characteristics of Clostridium difficile infection in patients with discordant diagnostic test results
(Kaltsas et al. JCM 2012) Tested for CDI in 2 time periods
56 samples positive by PCR only72 positive by direct cytotoxin and PCR. 72% of 027 strains detected by both methodsFor non- NAP1 strains, only 52% were positive by both
methods (p< 0.05), i.e., PCR more sensitive for non-027 No significant differences in CDI symptoms and
severity for 85% of cases positive by both assays and 84% of cases detected by PCR only
“Suggests that PCR is NOT an overly sensitive test in persons with clinical indications for C. difficile testing.”
Detection of C. difficile Infection (CDI): Impact of Test Method on Infection Control
Tenover FC et al. J. Molecular Diag. 2011 Nov;13(6):573-82.
TestMethod
Average Cost/ Test
SensitivityNo. of + Patients Missed
Spec-ificity
Patients in
isolation with CDI
Patients in
isolation without
CDI
Patients with CDI
not in Isolation*
GDH/EIA $18.00 55% 45 94% 55 54 45
NAAT $35.00 95% 5 96% 95 36 5
Assume 1000 patients are tested, 10% prevalence
*Is it worth spending more money in microbiology to treat these patients before they develop serious CDI and spread C difficile to others?
Does the Nose Know? The Diagnosis of Clostridium difficile-Associated Diarrhea by
Smell
Johansen et al. found that nurses were able to predict correctly the presence of Clostridium difficile disease in 31 of 37 cases (sensitivity, 84%; specificity, 77%), using a mixture of patient signs, symptoms, and history, including stool odor.
The positive and negative predictive values of the characteristic odor for CDAD were 77% and 82%, respectively.
Nurses are an important part of control strategies for C. difficile
Using PCR Only versus a GDH screen:Review of Published Data
Multiple recent studies (against toxigenic culture) show GDH sensitivity ranges from 42-98%, perhaps due to differences in strain types
Published PCR sensitivities ranges from 86-97% Major problem with the two-step algorithm, i.e.,
screening with GDH and testing GDH+/EIA- samples PCR:Misses 10-15% of positive samples upfront (i.e.,
those that are GDH-negative to start)These patients do not get treated and can continue to
infect other patients
Molecular methods superior to GDH-based algorithms for detecting CDI
(PCR vs GDH)
GDH screening decreases sensitivity of detection of CDI cases by 8-12%
CID 2007; 45:1266-73(BI=NAP1/027)
Used direct cytotoxin testing (sensitivity 70%) – was this also an issue?
InfectionControl
interventions
Northeast (174) South (82) Midwest (77) West (175)0%
5%
10%
15%
20%
25%
30%
35%
40%
Top 7 PCR Ribotypes in US by Region (2011-2013) Cepheid HAI Consortium Data (n=503)
027 014/020 106 053 001 002 056
Potential Value of 027/NAP1/BI Call-out at time of C. difficile Testing; Hospital A Data
Month 1 CDI Results Month 4 CDI Results
C.diff tox B+; 027 negative C.diff tox B+; 027 negative C.diff tox B+; 027 positive C.diff tox B+; 027 negative C.diff tox B+; 027 negative C.diff tox B+; 027 negative C.diff tox B+; 027 negative C.diff tox B+; 027 negative C.diff tox B+; 027 negative
C.diff tox B+; 027 negative C.diff tox B+; 027 positive C.diff tox B+; 027 positive C.diff tox B+; 027 positive C.diff tox B+; 027 positive C.diff tox B+; 027 negative C.diff tox B+; 027 positive C.diff tox B+; 027 positive C.diff tox B+; 027 positive
Would you find these data helpful in your hospital?
Dr. Dale Gerding’s Predictions for C. difficile Epidemiology
My pick is C
5th Decennial Conference on Healthcare Associated Infections, Atlanta 2010
Long Term Care Facilities often Serve as Reservoirs of MDROs
356 cases of KPC-producing Klebsiella pneumoniae in Los Angeles nursing homes
CDC Data on Carbapenem Resistant Enterobacteriaceae
http://www.cdc.gov/vitalsigns/hai/cre/
PAGE | 25
View of Beta-Lactamases (2013) The Road to Carbapenem Resistance
Class A TEM, SHV,
CTX-M, KPCs others
Class BMetallo-
enzymes, VIMNDM-1,others
Class CAmpCs, MIR, DHA,
FOX, and others
Class DOXA
ESBLS; Carba-
penemases OXA48, 162,
163, 181 carba-
penemases
Most are carba-
penemases
AmpC + porin change = carbapenem
resistance
More to detect than KPCs, but we must be able toDistinguish carbapenemase producers from porin changes
106Current #
212
142
14777
18113
363
3132
NDM 3a 9 NDM-1, NDM-2
8
48
Updated 9/5/13
The patient was a woman from the US who developed diarrhea during a Mediterranean cruise and was hospitalized in Greece
Klebsiella pneumoniae isolate with VIM-2 was resistant to all antimicrobials usually used to treat Klebsiella (no antibiogram given)
Facilities that have not identified cases of Carbapenem-resistant Enterobacteriaceae (CRE) should: Undertake periodic laboratory reviews to identify cases Patients with CRE should be managed using contact precautions Patients exposed to CRE patients (e.g., roommates) should be
screened with surveillance cultures
(VIM-1)
Multiple Broad-Spectrum Beta-Lactamase Targets for Comprehensive
Surveillance (Mangold et al. JCM Accepts 2013) Concern regarding frequent transfer of residents from long-term
acute care facilities (LTACHs) who are colonized with MDROs into hospitals.
Two-thirds of residents from two area LTACHs colonized with KPC producers.
Used active surveillance to identify patients with MDRO carriage, and contact tracing and PFGE to monitor for MDRO transmission
Surveillance included PCR for KPC, NDM, VIM, IMP, and CTX-M beta-lactamase genes performed on rectal swabs from residents of two (culture too slow)
Despite high colonization rated, to date, only one MDRO transmission to an existing hospital patient has been detected during nearly 4 years.
Alpha Evaluation of Xpert MDRO Rectal Swab Surveillance Assay
328 samples (5 hospitals; US and Spain)53 Xpert MDRO positive
○ 11 VIM positive results (10 DNA sequence +)○ 43 KPC positive results (42 DNA sequence +)○ 1 sample contained both VIM and KPC
276 Xpert MDRO negative○ 256 organisms susceptible to all carbapenems○ 20 organisms non-susceptible to at least one
carbapenem ○ All 20 negative by Check Points microarray for
carbapenemase genes
KPC
VIM
Control
KPC-Producing K. pneumoniae and VIM-Producing Pseudomonas
aeruginosa from Long-Term Care
CROs are much more widely disseminated than often perceivedThe reservoirs are huge.
Preventing Lethal Hospital Outbreaks of Antibiotic-Resistant Bacteria
MDROs are transmitted primarily on the hands of healthcare workers who do not practice effective hand washing after every contact with patients and the environment
“We urgently need screening media or real time genetic tests that can be deployed quickly to identify patients who are colonized with MDROs”
Antibiotic stewardship is a critical part of control
Sandora and Goldmann: New Engl J Med 2012:367:2168-70
Conclusions Long-term care facilities play a key role
in transmission and control of MDROs C. difficile continues to be an infection
control challenge in the US; tests with high sensitivity and specificity are crucial
Spread of carbapenem-resistant organisms is on the rise in the US but can be controlled with active surveillance
THANK YOU
Questions?