mdros of public health importancepublichealth.lacounty.gov/acd/docs/ip2daycoursebasicsip...mdros of...
TRANSCRIPT
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MDROs of Public Health Importance
James McKinnell, MD
Infectious Disease Specialist
Los Angeles County Department of Public Health
Associate Professor at the David Geffen School of Medicine, UCLA
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Disclosures
• None relevant to this presentation
The opinions expressed here are my own and do not reflect
the Los Angeles County Department of Public Health
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US Causes of Death
2013 Deaths
1 Heart Disease 611,000
2 Cancer 584,000
3 Accidents 130,000
4 Stroke 129,000
5 Healthcare Associated Infections 100,000
6 Alzheimer’s Disease 83,000
http://www.cdc.gov/nchs/fastats/leading-causes-of-death.htm Accessed 4/22/2015, rounded
to the nearest thousand deaths.
http://www.cdc.gov/HAI/pdfs/hai/infections_deaths.pdf Accessed 4/22/2015.
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Infection Prevention Nosocomial
Infections• Hand Hygeine
• Isolation Precautions
• Contact
• Airborne
• Biohazard
• Personal Protective Equipment
• Cleaning of the Environment
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Insanity is
repeating the same mistakes
and
expecting different results.
-Narcotics Anonymous 1981
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Number of
annual
cases
Cost Number of annual
deaths
Hospital-onset, hospital
acquired (HO-HA)165,000 $ 1.3 B 9,000
Community-onset hospital
acquired (CO-HA)
[4 weeks of hospitalization]
50,000 $ 0.3 B 3,000
Nursing home-onset 263,000 $ 2.2 B 16,500
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CDI: Impact
25,000 HCA Deaths
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US Causes of Death
2013 Deaths
1 Heart Disease 611,000
2 Cancer 584,000
3 Accidents 130,000
4 Stroke 129,000
5 Healthcare Associated Infections 100,000
6 Alzheimer’s Disease 83,000
http://www.cdc.gov/nchs/fastats/leading-causes-of-death.htm Accessed 4/22/2015, rounded
to the nearest thousand deaths.
http://www.cdc.gov/HAI/pdfs/hai/infections_deaths.pdf Accessed 4/22/2015.
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Valiquette, et al. Clin Infect Dis. 2007;45:S112-21
Draconian Infection Control Measures
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CDI Pathogenesis
Admitted to
healthcare facility
C. difficile
Exposure
Colonized
no symptoms
Infected
Symptomatic
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Serum IgG Antibodies Against C. difficile Toxins
Are Prevalent in the General Population
IgG anti-toxin A
IgG anti-toxin B
Viscidi R, et al. J Infect Dis. 1983;148:93-100.
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CDI case
28 (10%)
271 enrolled
Hospital-acquired
47 (17%)
Colonized at
Admission
37 (14%)
CDI case
19 (7%)
Carrier
19 (7%)
Carrier
18 (7%)
Nosocomial C. difficile infection
& asymptomatic carriage are common
Hospital patients
(Acute medical ward)
LOS > 2 days
Receiving antibiotic
Kyne et al N Engl J Med 2000;342:390
Colonized by
C. difficile
84 (31%)
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3-month study in LTCF with 73 residents
Five (7%) patients had CDI
35 (51%) were asymptomatic carriers (nine had a prior history of CDI)
Asymptomatic carriers associated with significantly higher rates of skin
(61% vs. 19%) and environmental contamination (59% vs. 24%) than
non-carriers
Asymptomatic carriers are a potential source for
transmission of Clostridium difficile
Riggs et al Clin Infect Dis 2007 45:8, 992-8
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CDI Pathogenesis
Admitted to
healthcare facility
Antimicrobial
Treatment
C. difficile
Exposure
Colonized
no symptoms
Infected
Symptomatic
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Valiquette, et al. Clin Infect Dis. 2007;45:S112-21
Targeting High-Risk Antibiotics Reduces CDI
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Antibiotics and CDI
Risk of CDI compared to
resident on 1 antibiotic
Risk of CDI compared to
resident on ATBs for
<4 days
15. Epson,E. Orange County CDI Prevention Collaborative: Antimicrobial Stewardship. CDPH. November 5, 2015. Permission granted for use of this slide by Dr. Erin Epson. Original slide reference: Stevens,et al. Clin Infect Dis. 2011;53(1):42-48
Number of
ATBs
2 ATBs 3-4 ATBs 5+ ATBs
2.5 times
higher
3.3 times
higher
9.6 times
higher
Days of Antibiotic
4-7 days 8-18 days >18
days
1.4 times
higher
3 times
higher
7.8
times
higher
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• Incidence of C. difficle in UK dropped by 80% after 2006
• Decline was due to multiple interventions
• However, Fluoroquinolone reduction is thought to be the
primary driver for change
Dingle et al. Lancet ID. 2017
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One Third of What You Learned in Medical School is
Wrong.
The Trick is Figuring Out Which Third
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Dr. McKinnell’s Notes on Antibiotic Duration
•CAP 7-10
•HAP/VAP 10-14
•Pyelonephritis 10-14
•Cellulitis 7-10
•Bacteremia 14-42
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• Several RCTs 7-8 days equal to 10-15 days
• Reduced emergence of resistance
• MRSA and Pseudomonas infections may
require longer therapy
Capellier et al. PLoS One 2012:7:e41290; Chastre et al. JAMA 2003
290:2588-98; Kalil et al. CID 2016 63:e61-e111
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HCAP/VAP7 DAYS
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Short Course Therapy!!!!
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Diagnosis Short (d) Long (d) Result
CAP 3 or 5 7, 8, or 10 Equal
HAP 7 10-15 Equal
VAP 8 15 Equal
Pyelo 7 or 5 14 or 10 Equal
Intra-abd 4 10 Equal
AECB <5 >7 Equal
Cellulitis 5-6 10 Equal
Osteo 42 84 Equal
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MDRO of Public Health Importance
• Clostridium difficile
Pay Attention to Duration of Treatment
Avoid Ciprofloxacin and Levofloxacin
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• CDC Report, Antibiotic Resistance Threats in the US 2013
• One of only three pathogens with an URGENT Threat
Level
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The French Grammar Lesson
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Family Genus Species
Enterobacteriacea
Citrobacter freundii,koseri,amalonaticus
Enterobacter cloacae,aerogenes,sakasakii
Esherichia coli,albertii
Klebsiella pneumoniae,oxytoca,granulomatis
Morganella marganii
Proteus mirabilis,vulgaris
Providencia stuartii,rettgeri
Serratia marcescens
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Spread of CRE in US Reported to CDC in
2006
http://www.cdc.gov/hai/organisms/cre/Trackin
gCRE.html
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Growing Spread of CRE Reported to
CDC in 2018
http://www.cdc.gov/hai/organisms/cre/Tracking
CRE.html
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Steady Increase in CRE Cases in US
Schneider et al., SHEA 2017. Thaden et al. ICHE. 2014. Lodise et al., AAC 2017. Bartsch et al., Clin Microbiol Infect
2017.
CR
E H
osp
italizati
on
Total Cases (2009-2015) =
227,828
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• Novel Antibitiotics (Ceftazidime-Avibactam, Imipenem-
Relebactam, Meropenem-Vaborbactam and Plazomicin)
have reduced mortality from 50% to <20% in most studies
Crackle 2, Tango, Care
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Two Forms of Carbapenem-Resistant
Enterobacteriaceae
Carbapenemase
producing
(CP-CRE)
Non-carbapenemase
producing
(Non-CP-CRE)
Sub-type
KPC
NDM, IMP, VIM
OXA 23, 48Sub-type
AMP-C, ESBL
Additional mechanism
Porin mutation
Efflux pump
KPC=K. pneumoniae carbapenemase, NDM=New Delhi metallo-betalactamase, IMP=Imipenemase,
VIM=Verona integraon-encoded metallo-betalactamase, OXA=oxacilinase
+
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Non-KPC CRE on the Rise
• Los Angeles 2015-2017
• 1,000 CRE isolates
• 20% non-KPC
• Vancouver 2008–2017
• >3,500 CRE isolates
• 703 CP organisms
• 90% non-KPC
Bhaurla, S. et al. LA County Department of Public Health, IDWeek 2017. Hoang, L. BC Center for Disease Control Public
Health Laboratory. West Region ARLN EpiTalks Meeting, Sept. 2017.
http://www.cdc.gov/hai/organisms/cre/TrackingCRE.html
NDM Enzyme
Reported
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• 31 clinical labs since 2015
• 1,263 isolates collected
• 77% of CRE in LA County are CP
• 34 Non-KPC CP Producers
• 16 OXA (first detected 2015)
• 11 NDM (first detected 2015)
• 6 VIM (first detected 2016)
• 1 IMP (first detected 2017)
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Ongoing CRE Surveillance in LA
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“How are CRE and Other MDROs spreading so
effectively?”
The Pig Pen Principle
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The Pig Pen Principle
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• Relatively enclosed
• Ocean to West
• Forest to East
• Undeveloped land to South
• Traffic to North
Orange County, CaliforniaIdeal Virtual Laboratory
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Orange County
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• 32 Acute Care Hospitals
• 6 Long-Term Acute Care Hospitals (LTACs)
• 2 Dedicated Children’s Hospitals
• 71 nursing homes
• Serves population of 3.1 million
(6th largest US county)
• >320,000 admissions annually
Huang SS et al. Infect Control Hosp Epidemiol 2010. 31(11):1160-9
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Hospitals Share Patients – Direct
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Huang SS et al. Infect Control Hosp Epidemiol 2010. 31(11):1160-9
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Hospitals Share Patients-Indirect
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Huang SS et al. Infect Control Hosp Epidemiol 2010. 31(11):1160-9
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Sharing Patients – 10 Patients
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Lee BY et al. Plos ONE. 2011;6(12):e29342
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MDRO of Public Health Importance
• Clostridioides difficile (Clostridium difficile )
Pay Attention to Duration of Treatment
Avoid Ciprofloxacin and Levofloxacin
• CRE
Activity with last line agents not guranteed
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LA County Antibiogram
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• Acinetobacter baumanii
61% Carbapenem Resistant
Minocycline and Tigecycline are challenging
• Pseudomonas aeruginosa
20% Carbapenem Resistant
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Ceftazidime-Avibactam & Ceftolozane-Tazobactam for
P. aeruginosa Resistant to:
Ceftazidime, Meropenem, & Pip-Tazobactam
# ≤0.25 0.5 1 2 4 8 16 32 >32
Ceftazidim
e-
Avibactam
330 0.3 1.5 15.2 45.1 71.8 87.9 93 100
Ceftolozan
e-
Tazobacta
m
175 12.6 39.4 68.6 85.1 89.7 92 100
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Cumulative % inhibited at an MIC of:
Sader HS et al. Antimicrob Agents Chemother 2015;59:3656-3659. Table 1
Farrell DJ et al. Antimicrob Agents Chemother 2013;57:6305-6310. Table 3
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Ceftazidime-Avibactam Versus Ceftolozane-
Tazobactam for P. aeruginosa Resistant to:
Ceftazidime, Meropenem, & Pip-Tazobactam*
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Number of
IsolatesCaz/Avi C/T
Humphries 105 29% 52.4%
Grupper 103 54% 79%
Sader 47 70.2% 72.3%
*Buehrle et al and Gonzalez et al excluded due to too few isolates for BLR resistance phenotype
Humphries et al. Antimicrobial agents and chemotherapy. 2017 Dec 1;61(12):e01858-17.
Grupper et al. Antimicrob Agents Chemother. 2017 Sep 22;61(10). pii: e00875-17. doi:
10.1128/AAC.00875-17. Print 2017 Oct.
Sader et al. J Antimicrob Chemother. 2018 Jul 27. doi: 10.1093/jac/dky279. [Epub ahead of print]
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MDRO of Public Health Importance
• Clostridioides difficile (Clostridium difficile )
Antibiotic Stewardship
• CRE
Activity with last line agents is not guaranteed
• CRO (CRAB, CRP)
Activity with last line agents is not guaranteed
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“How can we control spread of CRO?”
The Pig Pen Principle
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“Many Believe that Decolonization is the
Answer”
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Hygeine
•Many Patient are Dependent on HCW for Personal
Hygeine
•Bathing Frequency and Efficacy is Highly Variable
•Patient Hand Hygeine Programs are Uncommon
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Mody JAMA Intern Med. 2013; 173(10):853-4.
SHEA/APIC Guideline. ICHE 2008; 29(9):785-814.
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Skin Cleansing
•Use of topical antiseptics to clean patients
•Chlorhexidine (CHG) for skin and wound bathing
•Mupirocin or iodophor for nasal use
•CHG and iodophor used in healthcare for 60+ years
with strong safety record
Standard of Care when we want to prepare patients
for Surgery.
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SHIELD ORANGE COUNTYIMPACT OF REGIONAL DECOLONIZATION
JAMES A. MCKINNELL, MD
ASSOCIATE PROFESSOR OF MEDICINE
DAVID GEFFEN SCHOOL OF MEDICINE AT UCLA
LUNDQUIST INSTITUTE AT HARBOR-UCLA
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• Collaborative: CDC, California, and OC county public
health
• Coordinated by UC Irvine and Harbor UCLA
• 38-facility decolonization intervention (NH, LTAC,
Hospitals)
• Recruitment based on patient sharing networks
• Outcomes
• Point prevalence MDROs
• Countywide MDRO burden (clinical cultures)
SHIELD OC Regional Collaborative
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Characteristics of SHIELD OC
Facilities
NH LTACH Hospital
N Facilities 18 3 17
Mean age 76 72 47
% Male 40% 53% 42%
Mean Licensed Beds 133 83 247
Average Daily Census 115 63 141
Mean LOS 69.3 30.6 4.1
Elixhauser Comorbidity
Score3.8 2.9 1.9
% Diabetes 36% 13% 12%
% Chronic Lung Disease 22% 21% 11%
% Renal Failure 21% 23% 8%
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https://www.cdc.gov/hai/research/cdc-mdro-project.html
SHIELD OC Intervention
• NH and LTAC – Decolonize all patients
• Hospitals – Decolonize patients in contact
precautions
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https://www.cdc.gov/hai/research/cdc-mdro-project.html
SHIELD OC Intervention
• NH and LTAC – Decolonize all patients
– CHG on admission and for all routine bathing
• Hospitals – Decolonize patients in contact
precautions
– CHG Daily
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https://www.cdc.gov/hai/research/cdc-mdro-project.html
SHIELD OC Intervention
• NH and LTAC – Decolonize all patients
– CHG on admission and for all routine bathing
– Nasal iodophor on admission and every other week
• Hospitals – Decolonize patients in contact
precautions
– CHG daily
– Nasal iodophor for 5 days on admission
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8%
4%
0.00
0.20
0.40
0.60
0.80
1.00
1.20
1.40
1.60
1.80
Non-Intervention (7) SHIELD (15) Late Start (3)
Ca
se
s p
er
1,0
00
pa
tie
nt d
ays
Rates of Adults Acute Care Hospital Inpatient Healthcare Onset MDROs in
Orange County:Pre- and Post- Intervention
Pre Post
11%
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0
0.01
0.02
0.03
0.04
0.05
0.06
0.07
0.08
0.09
0.1
Non-Intervention (7) SHIELD (15)
Ca
se
s p
er
1,0
00
pa
tie
nt d
ays
CRE Hospital Onset Rates in OC Hospitals,
Pre- and Post- Intervention
Pre Post
105%
6%
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Long Term Acute Care Hospital MDRO Rates,
Pre- and Post-Intervention
20%
23%16%
20%
Cases p
er
1,0
00 P
atient
Days
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MDRO of Public Health Importance
• Clostridioides difficile (Clostridium difficile )
Antibiotic Stewardship
• CRE
Infection Control and Decolonization
• CRO (CRAB, CRP)
Infection Control and Decolonization?
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MRSA-the most important pathogen?
• 40% of all Healthcare Infections Worldwide
• High mortality, particularly for Bloodstream Infections
• Emerging resistance to last line agents-Daptomycin and
Vancomycin
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https://www.cdc.gov/vitalsigns/staph/index.html
Released March 5, 2019
CDC US Burden of MRSA and MSSA
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AN INDIVIDUAL RANDOMIZED CLINICAL TRIAL
OF EDUCATION VS DECOLONIZATION OF MRSA+
PATIENTS DISCHARGED FROM HOSPITALS TO REDUCE
POST-DISCHARGE INFECTION
Funded by AHRQ; clinicaltrials.gov: NCT01209234
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What is CLEAR?
• Changing Lives by Eradicating Antibiotic Resistance
• CLEAR, which was recently published in the NEJM, was a post-discharge trial of MRSA carriers who were randomized to education alone vs education plus repeated decolonization for 6 months post-discharge and followed for infection outcomes for 1 year
Huang SS NEJM 2019; 380(7):638-
650
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• 2,121 inpatients, ~535,000 days of follow up
• Two Arms
Arm 1: Education
Arm 2: Education + Serial Decolonization
• Inclusion Criteria
>18 years old
Hospitalized within the past 30 days
MRSA+ culture within 30 days of hospitalization
The Project CLEAR Trial
Huang SS NEJM 2019; 380(7):638-
650
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• 5-day regimen twice monthly for 6 monthsTwice daily 2% nasal mupirocin
Twice daily 0.12% chlorhexidine oral rinse
Daily 4% rinse-off chlorhexidine bath/shower
• 1-year follow upBody swabs and surveys
Months 1, 3, 6, 9 post-recruitment
Phone exit survey at month 12
Serial Decolonization
Huang SS NEJM 2019; 380(7):638-
650
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• In the year following discharge, decolonization:
reduced MRSA infection and hospitalization by
30%
reduced all-cause infection and hospitalization
by 17%
• Number needed to treat to prevent an infection or
a hospitalization is less than 35Huang et al. NEJM
2019
Project CLEAR Evidence Summary
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“Chlorhexidine Bathing with Nasal
Decolonization for six months post
hospitalization should be considered for all
MRSA carriers”
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• LA DPH program for hospitals with high MRSA rates
• Program: Provide hospitalized MRSA carriers with a
decolonization kit at discharge
• Why participate?
Be part of a collaborative
Collectively reduce MRSA prevalence
Reduce MRSA infections & readmissions
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What is CLEAR LA?
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MDRO of Public Health Importance
• Clostridioides difficile (Clostridium difficile )
Antibiotic Stewardship
• CRE
Infection Control and Decolonization?
• CRO (CRAB, CRP)
Infection Control and Decolonization?
• MRSA
Decolonization
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Invasive C. auris Infections
• Half of clinical cases are bloodstream infections
• Half of patients with C. auris bloodstream infections
die during that hospitalization
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Substantial Antifungal Resistance
Among C. auris
• 41% isolates multidrug resistant
• 4% resistant to all three classes
1 2 3
93% resistant to fluconazole
54% resistant to voriconazole
35% resistant to
amphotericin B
7% resistant to
echinocandins
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C. auris Cases Reported by State —
United States, 2013–August 2016
0
2
4
6
8
10
12
14
16
13-May 15-Jul 16-Apr 16-May 16-Jun 16-Jul 16-Aug
Nu
mb
er o
f cl
inic
al c
ases
New York New Jersey Maryland Illinois
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C. auris Cases Reported by State —
United States, 2013–December 2016
0
2
4
6
8
10
12
14
16
13-May 15-Jul 16-Apr 16-May 16-Jun 16-Jul 16-Aug 16-Sep 16-Oct 16-Nov 16-Dec
Nu
mb
er o
f cl
inic
al c
ases
New York New Jersey Maryland Illinois
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C. auris Cases Reported by State
United States, 2013–2017
Solid: Confirmed case Striped: Probable case
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MDRO of Public Health Importance
• Clostridioides difficile (Clostridium difficile )
Antibiotic Stewardship
• CRE
Infection Control and Decolonization
• CRO (CRAB, CRP)
Infection Control and Decolonization?
• MRSA
Decolonization
• Candida auris
Infection Control, Containment and
Decolonization
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