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One Health and the control and prevention of antimicrobial resistance: Perspectives from human medicine
One Health, One Planet 2019Phipps Conservatory and Botanical GardensPittsburgh, PA14 March 2019
Cornelius J. Clancy, M.D.Chief, Infectious Diseases
VA Pittsburgh Healthcare System
Director, XDR Pathogen Lab and
Mycology Research Unit
University of Pittsburgh
An illustrative case, 2019
65 y/o woman; double lung transplant for COPD.
Fever; shortness of breath. On admission required ventilation. 0 10 20 30 40 50 60DAY
Pneumonia
Meropenem
Septic shock Altered mental
status
C-R K. pneumoniae
TREATMENT
LAB RESULT
Ceftazidime-avibactam
2 types of ESBLK. pneumoniae
ESBLK. pneumoniae
C-R & ESBLK. pneumoniae
Meropenem
Persistent hypotension and pneumonia
New feverspersistent pneumonia CTB
Meropenem+ Gentamicin
*Carbapenem Resistant Enterobacteriaceae
The rise of CRE* superbugs
*Carbapenem Resistant Enterobacteriaceae
The rise of CRE* superbugs
*Carbapenem Resistant Enterobacteriaceae
The rise of CRE* superbugs
10 million deaths due to drug-resistant infections per year in 2050
Review on Antimicrobial Resistance, Wellcome Trust and UK Department of Health
An illustrative case, 2019
65 y/o woman; double lung transplant for COPD.
Fever; shortness of breath. On admission required ventilation. 0 10 20 30 40 50 60DAY
Pneumonia
Septic shock Altered mental
status
C-R K. pneumoniae 2 types of ESBLK. pneumoniae
CTB
$728,035DAY 25 DAY 54
An illustrative case, 2019
65 y/o woman; double lung transplant for COPD.
Fever; shortness of breath. On admission required ventilation. 0 10 20 30 40 50 60DAY
Pneumonia
Septic shock Altered mental
status
C-R K. pneumoniae 2 types of ESBLK. pneumoniae
CTB
$728,035DAY 25 DAY 54
Lost global production due to antimicrobial resistance 2016-2050:$100 trillion
Review on Antimicrobial Resistance, Wellcome Trust and UK Department of Health
CDC: Antibiotic Resistance Threats in the US, 2013 (http://www.cdc.gov/drugresistance/threat-report-2013/index.html)
Antibiotic resistance threats
History of penicillin resistance
“… the thoughtless person playing with penicillin is morally responsible for the death of the man who finally succumbs to infection with the penicillin-resistant organism.” 26 June, 1945
Clin Infect Dis 2007; 44:159-77
“Surveys of hospitals have found that practices to improve antimicrobial use are frequently inadequate and not routinely implemented”
Clin Infect Dis 2004; 38:1279-86
Clin Infect Dis 2007; 44:159-77
“Surveys of hospitals have found that practices to improve antimicrobial use are frequently inadequate and not routinely implemented”
CDC Core Elements of AMSHospitals
Nursing homesOutpatient
Mandates for Antimicrobial Stewardship (AMS)
Core elements of AMS programs
• Leadership commitment– Human, financial, IT resources
• Accountability– Single leader (M.D.) responsible for program
outcomes
• Drug expertise– Single leader (Pharmacist) responsible for
improved antibiotic use
• Action– Implementing at least one recommended action
• Tracking– Monitoring prescribing and resistance
• Reporting– Regular reporting on antibiotic use and resistance
• Education– Optimal prescribing and resistance
AMS Program
1. Leadership Commitment
2. Accountability
3. Drug Expertise
4. Action5. Tracking
6. Reporting
7. Education
E. Friestrom, E. McCreary
AMS Program
Core Team
Infectious Disease
Physicians
Clinical Infectious Disease
Pharmacist
Clinical Microbiologists
Hospital Nursing Staff
Hospital Epidemiologist/
Infection Preventionist
Hospital Administration & Staff Leadership
Core AMS team
E. Friestrom, E. McCreary
“There is no single template for a program to optimize antibiotic prescribing”
• 38 studies, 6 AMS intervention types
• Reduced utilization (11%-38%), lowered costs (US$5-10/patient-day), shortened duration of treatment, reduced inappropriate use and adverse events/toxicity
• Not associated with increased nosocomial infection rates, lengths of stay, or mortality
• Interventions beyond >6 mos were associated with reduced resistance
Does AMS work?
1585
1131
626
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800
1000
1200
1400
1600
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Total Antibiotic Prescriptions
Baseline (Jan - Apr2016)
Intervention (Jan -Apr 2017)
Post-Intervention(Jan - Apr 2018)
61.4%
7.9%
9.9%
20.8%
Baseline(Jan - Apr 2016)
40.0%
8.3%19.2%
32.5%
Intervention(Jan - Apr 2017)
45%
5%11%
39%
Post-Intervention(Jan - Apr 2018)
Antibiotic Not Indicated
Guideline-discordant Agent
Guideline-discordant Duration
Optimally Prescribed
AMS: Still a lot of work to do
Brooke Decker, MD
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Fluoroquinolones utilization over time
CIPROFLOXACIN
MOXIFLOXACIN
LEVOFLOXACIN
All quinolones
Initiation of UPMC AMS
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Clindamycin utilization over time
Initiation of UPMC AMS
AMS: Still a lot of work to do
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Per
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scep
tib
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UPMC Presbyterian campus K. pneumoniae
Ciprofloxacin Cefepime Pip/tazo Meropenem
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Per
cen
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scep
tib
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UPMC Presbyterian campus E. coli
Ciprofloxacin Cefepime Pip/tazo Meropenem
M. Hong Nguyen, MD
Boqvist, Acta Vet Scand 2018
McEwen, Microbiol Spectrum 2018
Boqvist, Acta Vet Scand 2018
Health
Antibiotic resistance: World on cusp of 'post-antibiotic era'By James GallagherHealth editor, BBC News website
19 November 2015
One Health AMR Case Study 1: Colistin
Health
Antibiotic resistance: World on cusp of 'post-antibiotic era'By James GallagherHealth editor, BBC News website
19 November 2015
One Health AMR Case Study 1: Colistin
• China, Brazil, Europe (certain countries)• Administered orally to pigs, poultry,
calves for treatment, prophylaxis, metaphylaxis of diarrhea, and/or as growth promoter
• Vastly exceeds use in humans (12,000 tonnes in China)
• Phenotypic resistance testing is technically difficult• Not included in routine surveillance of
animals, environment, food, humans
Liu YY et al. Lancet Infect Dis. 2016 Feb;16(2):161-8. Du H Lancet Infect Dis. 2016 Jan 29. Yao X et al. Lancet Infect Dis. 2016 Jan 29, Bloomberg. AAC 2016 May 26 online; doi:10.1128/AAC.01103-16
Nov Q1
2015 2016
Mcr-1 resistance plasmid found in carbapenem-resistant Enterobacteriaceae
Mcr-1 found in CRE + NDM-9 E. coli
mcr-1 gene found in at least 19 countries
Q1 Q2 Q3 MayQ4Q4
First report of transmissible colistin mcr-1 resistance gene
Q2
MDR E. coli harboring mcr-1 and blaCTX-M genes detected – first human case in US
Second US case reported in June
Five new mcr-like genes have arisen globally: mcr-2 through mcr-5, icr-Mo
CRE: Our last line of defense is breached
Case Study 2: Azole-R Aspergillus
Case Study 2: Azole-R Aspergillus
Azole antifungals
Chowdhary Plos Pathogens 2013
Case Study 2: Azole-R Aspergillus
Azole antifungals
Chowdhary Plos Pathogens 2013
Crop protection, wood preservation, fruit and vegetablemildew and rust
Case Study 2: Azole-R Aspergillus
>25% clinical isolatesazole-R in the Netherlands
~2-6% in U.S.
Berger Frontiers Micro 2017
TR34/L98H mutation
Case Study 3: AMS in the poultry industry
• Ceftiofur was administered to eggs or day-old hatchery chicks as prophylaxis against E. coli or egg yolk infections
– Canadian Integrated Program for Antimicrobial Resistance Surveillance
• High rates of ceftiofur resistant Salmonellla
• Ceftriaxone cross-resistance
McEwen, Microbiol Spectrum 2017; CPIARS 2009
Case Study 3: AMS in the poultry industry
McEwen, Microbiol Spectrum 2017; CIPARS 2009
Case Study 3: AMS in the poultry industry
• Japan, 2012– Voluntary withdrawal of ceftiofur use in hatcheries
• Decrease in cephalosporin-R E. coli in broilers
• Canada, 2014– Ceftiofur voluntary ban by Canadian poultry industry
http://www.chickenfarms.ca/wjat-we-do/antibiotics/faq/
• Europe– Label claim for ceftiofur use in day-old chicks withdrawn
• U.S.– Off-label use of 3rd generation cephalosporin banned
McEwen, Microbiol Spectrum 2017
One Health strategies against AMR• Drug classification
– Limit use of medically important antibiotics
One Health strategies against AMR
• AMS– Align medical, animal, agricultural activities– Regulatory
• Antimicrobials in animal growth promotion• Extra-label fluoroquinolone, 3rd generation cephalosporin use in
animals• Prescription-only antibiotics for veterinary use
• Surveillance and research• Improved sanitation, hygiene and infection
prevention• New therapeutics, diagnostic tests, vaccines
One Health strategies against AMR
• Communication, education, and training
– Views on moral implications of antibiotic use
• Physicians, Veterinarians
– Limit inappropriate use and resistance (“do no harm”)
• Poultry industry leaders
– Responsibility to business and employees
– Interviews with farmers in India indicated that antibiotics are viewed as vitamins and feed supplements
• Human medicine needs to get its own act together
One Health strategies against AMR
• Communication, education, and training
– Views on moral implications of antibiotic use
• Physicians, Veterinarians
– Limit inappropriate use and resistance (“do no harm”)
• Poultry industry leaders
– Responsibility to business and employees
– Interviews with farmers in India indicated that antibiotics are viewed as vitamins and feed supplements
• Human medicine needs to get its own house in order
Acknowledgments
UPMC AMS• M. Hong Nguyen MD (Director)
• Ryan Bariola MD (System AMS)
• Brian Potoski PharmD,
• Ryan Shields PharmD
• Erin McCreary PharmD, Rachel Marini PharmD, Tina Khadem PharmD, Greg Eschenauer PharmD, Bonnie Falcione PharmD, Ryan Rivosecchi Pharm D
• Ghady Haidar MD, EJ Kwak MD, Alex Viehman MD
• Lloyd Clarke, Diana Pakstis, Ellen Press
UPMC XDR Pathogen Lab• Binghua Hao PhD, Shaoji Cheng PhD
VAPHS AMS• Brooke Decker MD (Director)
• Deanna Buehrle PharmD
• Jae Hong, MD
UPMC AMS and XDR Pathogen LabVAPHS AMS
Worldwide emergence of fungal disease and antifungal-R
Fisher, Science 2018
