Antimicrobial Resistance Surveillance in Hospital and
Community-Issues for Human Population Medicine
Kurt B. Stevenson MD ...
Disclosures
 No financial disclosures or conflicts of interest
relative to this presentation.
2
Time Magazine-Feb 25, 1966
 “Nearly all experts agree that (by the year 2000)
bacterial and viral diseases will have been...
Rene Dubos-1941
 “...the readiness with which microorganisms
selectively change their enzymatic constitution in
response ...
Critical impact of antimicrobial resistance
““If we do not act to address the problem of AR, weIf we do not act to address...
Antimicrobials present unique management
challenges
 200-300 million antibiotics are prescribed
annually
 45% for outpat...
7
Science 2008;321:356-361
8
Science 2008;321:356-361
Resistant Strains
Rare
xx
Resistant Strains
Dominant
Antimicrobial
Exposure
xx
xx
xx
xx
xx
Selection for antimicrobial-
re...
ESKAPE pathogens
 Enterococcus faecium (VRE)
 Staphylococcus aureus (MRSA)
 Klebsiella pneumonia (ESBL-producing)
 Aci...
Emerging antimicrobial resistance of
importance in human medicine
 Methicillin-Resistant Staphylococcus aureus
(MRSA)
 M...
Emerging antimicrobial resistance of
importance in human medicine
 Epidemic strains of C. difficile
 Vancomycin-resistan...
Definitions of antimicrobial resistance
MDRO=multidrug resistant organisms
 Resistant to more than one class of antimicro...
Definitions of antimicrobial resistance
MDRO=multidrug resistant organisms
 Facility specific parameters
 First isolate,...
15
Clin Microbiol Infect 2012:18:268-281
Abbreviations
 MDR=multidrug-resistant
 XDR=extensively drug-resistant
 PDR=pandrug-resistant
16
17
Clin Microbiol Infect 2012:18:268-281
18
Multi-Drug
Resistant
Organism
s
(MRSA)
Epidemiologic and
risk factor data
Geographic
links
Social network
analysis
Geno...
Methicillin-resistant S. aureus (MRSA)
 A group of anti-penicillinase antibiotics were
developed in the 1960s to treat pe...
MRSA
 Historically, MRSA has been isolated almost
exclusively in healthcare settings, suggesting
that transmission has oc...
Community-associated MRSA
 Increasing reports of MRSA occurring in patients
with little or no direct contact with the hea...
22
 Hospital-acquired
 Large SCCmec A (types
I,II,III)
 Multi-drug resistance
 Multiple risk factors for
contact with ...
Multi-Drug
Resistant
Organism
s
(MRSA)
Epidemiologic and
risk factor data
HA-MRSA
CA-MRSA
Geographic
links
Social network
...
24
 Ohio State Health Network
Infection Control
Collaborative
 Objectives:
 To compare clinical
characteristics and
mol...
OSUWMC IW
(Honest Broker)
OSHNICC
IW de-
identifies
the data,
sends a
code back
to the
hospital for
each case
ODH Lab
OSUW...
Web portal-Outreach Hospital
Study Design
 Retrospective analysis of OSUMC banked isolates
(projected ~450 isolates) Study period 1/1/07-10/31/08
 En...
28
Emerg Infect Dis 2012;18:1557-1565
Results
 Among 1286 MRSA isolates collected as part of
the MRSA surveillance project there were 78
(6%) isolates that wer...
ST 239
 Demonstrated epidemic/outbreak potential-
caused a 2 year ICU outbreak in London
 Healthcare-associated with pul...
31
Emerg Infect Dis 2012;18:1557-1565
32
Emerg Infect Dis 2012;18:1557-1565
Pseudomonas aeruginosa
 Gram-negative, non-fermenting bacillus
 Common environmental pathogen, especially in
water
 Res...
Clinical Infections
 Bacteremia in neutropenic patients; more
common in the 1980’s, decreasing in past
decade
 Cystic fi...
Imipenem-resistant Pseudomonas
aeruginosa
 University of Pennsylvania
 1991 to 2000, significant increase in imipenem
re...
Extended spectrum β-lactamases
 K. pneumoniae, E. coli
 Also reported with Salmonella, Proteus,
Enterobacter, Citrobacte...
ESBLs
 Phenotype: resistance to 3rd
generation
cephalosporins and monobactams
 Their proliferation is a global concern a...
38
Clin Infect Dis 2006;42:S153
39
Clin Infect Dis 2006;42:S153
Carbapenemases
 Carbapenemases are enzymes which can
inactivate a wide range of antibiotics including
the carbapenem clas...
KPC
 96 isolates from 10 Brooklyn hospitals
 All resistant to carbapenems and most other
antibiotics
 About 50% suscept...
NDM-1 strain
 New Delhi metallo-beta-lactamase-1
 Klebsiella pneumoniae and Escherichia coli.
 NDM-1 has been reported ...
44
Lancet Infect Dis 2010;10:597-602
45
Lancet Infect Dis 2010;10:597-602
46
Lancet Infect Dis 2010;10:597-602
Acinetobacter baumannii
 Acinetobacter baumannii (Ab) is a ubiquitous
encapsulated, aerobic, nonfermentive gram-
negative...
Acinetobacter baumannii (Ab)
 Major risk factors include invasive procedures
such as using mechanical ventilation, centra...
MDR Ab outbreaks across geographic
distances
 Citywide clonal outbreak of MDR-Ab; involved 15
hospitals in Brooklyn (base...
Colistin
 Mixture of cyclic polypeptides (polymixin A and
B); polycationic with both hydrophilic and
lipophilic moieties
...
Colistin resistance
 265 isolates of Acinetobacter from 2 Korean hospitals
 Categorized into 3 subgroups:
 Subgroup I (...
Emerging antimicrobial resistance of
importance in human medicine
 Methicillin-Resistant Staphylococcus aureus
(MRSA)
 M...
Emerging antimicrobial resistance of
importance in human medicine
 Epidemic strains of C. difficile
 Vancomycin-resistan...
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  • Once resistant strains of bacteria are present in a population, exposure to antimicrobial drugs favors their survival.
    Reducing antimicrobial selection pressure is one key to preventing antimicrobial resistance and preserving the utility of available drugs for as long as possible.
  • Traditional analysis of MDRO such as MRSA focused on epidemiological risk factors to differentiate HA-MRSA from CA-MRSA. However, new epidemiological tools such as genotyping, geocoding, and social network analysis can improve identification of transmission links inter and intra facility
  • Traditional analysis of MDRO such as MRSA focused on epidemiological risk factors to differentiate HA-MRSA from CA-MRSA. However, new epidemiological tools such as genotyping, geocoding, and social network analysis can improve identification of transmission links inter and intra facility
  • OSU Information Warehouse set up web portal for Outreach Hospitals. Patients were de-identified. OSU IW represents honest broker and de-identify information such as address, names, medical record numbers. OSU invsestigators are only able to visualize de-identified data.
    Detailed Method –presented Poster 505, abstract 2440
  • Dr. Kurt Stevenson - Antimicrobial Resistance Surveillance and Management in Hospital and Community Settings - Issues for Human Population Medicine

    1. 1. Antimicrobial Resistance Surveillance in Hospital and Community-Issues for Human Population Medicine Kurt B. Stevenson MD MPH Division of Infectious Diseases November 13, 2012
    2. 2. Disclosures  No financial disclosures or conflicts of interest relative to this presentation. 2
    3. 3. Time Magazine-Feb 25, 1966  “Nearly all experts agree that (by the year 2000) bacterial and viral diseases will have been wiped out. Probably arteriosclerotic heart disease will also have been eliminated.” 3
    4. 4. Rene Dubos-1941  “...the readiness with which microorganisms selectively change their enzymatic constitution in response to change in the environment may … be of importance in determining the pathology of infectious diseases.” 4
    5. 5. Critical impact of antimicrobial resistance ““If we do not act to address the problem of AR, weIf we do not act to address the problem of AR, we may lose quick and reliable treatment ofmay lose quick and reliable treatment of infections that have been a manageable probleminfections that have been a manageable problem in the United States since the 1940s.in the United States since the 1940s. DrugDrug choices for the treatment of common infectionschoices for the treatment of common infections will become increasingly limited andwill become increasingly limited and expensive - and, in some cases, nonexistentexpensive - and, in some cases, nonexistent.”.” -A Public Health Action Plan to Combat Antimicrobial Resistance-A Public Health Action Plan to Combat Antimicrobial Resistance CDCCDC Underline added 5
    6. 6. Antimicrobials present unique management challenges  200-300 million antibiotics are prescribed annually  45% for outpatient use  25-40% of hospitalized patients receive antibiotics  10-70% are unnecessary or sub-optimal  5% of hospitalized patients who receive antibiotics experience an adverse reaction  Antibiotics are unlike any other drugs, in that use of the agent in one patient can compromise its efficacy in another (“Societal Drugs”)  Slide courtesy of Sara Cosgrove, MD Johns Hopkins University 6
    7. 7. 7 Science 2008;321:356-361
    8. 8. 8 Science 2008;321:356-361
    9. 9. Resistant Strains Rare xx Resistant Strains Dominant Antimicrobial Exposure xx xx xx xx xx Selection for antimicrobial- resistant Strains Campaign to Prevent Antimicrobial Resistance in Healthcare Settings
    10. 10. ESKAPE pathogens  Enterococcus faecium (VRE)  Staphylococcus aureus (MRSA)  Klebsiella pneumonia (ESBL-producing)  Acinetobacter baumannii  Pseudomonas aeruginosa  Enterobacter species 10 Rice LB. J Infect Dis 2008;197:1079-81
    11. 11. Emerging antimicrobial resistance of importance in human medicine  Methicillin-Resistant Staphylococcus aureus (MRSA)  Multi-drug resistant gram-negative bacilli  “SPACE” organisms (Serratia, Pseudomonas, Acinetobacter, Citrobacter, Enterobacter)  Ciprofloxacin resistance  AmpC/inducible beta-lactamases  Extended spectrum beta-lactamases (ESBLs)  Carbapenem-resistance  Now with colistin resistance 11
    12. 12. Emerging antimicrobial resistance of importance in human medicine  Epidemic strains of C. difficile  Vancomycin-resistant Enterococcus ssp. (VRE)  Vancomycin-intermediate Staphylococcus aureus (VISA)  Vancomycin-resistant Staphylococcus aureus (VRSA) 12
    13. 13. Definitions of antimicrobial resistance MDRO=multidrug resistant organisms  Resistant to more than one class of antimicrobial agent (IOM, 1998)  Although this definition suggests resistance to only one class, most of the pathogens discussed are resistant to multiple classes  May use more explicit definitions  Epidemiologically important  Known to be transmitted in the healthcare environment  Modifiable risk factors  Effective infection control interventions 13
    14. 14. Definitions of antimicrobial resistance MDRO=multidrug resistant organisms  Facility specific parameters  First isolate, newly introduced  Increasing in frequency  Limited treatment options  Associated with poor patient outcomes 14
    15. 15. 15 Clin Microbiol Infect 2012:18:268-281
    16. 16. Abbreviations  MDR=multidrug-resistant  XDR=extensively drug-resistant  PDR=pandrug-resistant 16
    17. 17. 17 Clin Microbiol Infect 2012:18:268-281
    18. 18. 18 Multi-Drug Resistant Organism s (MRSA) Epidemiologic and risk factor data Geographic links Social network analysis Genotyping PFGE Sequence-based typing MLST Multi-Drug Resistant Organisms (MDRO)
    19. 19. Methicillin-resistant S. aureus (MRSA)  A group of anti-penicillinase antibiotics were developed in the 1960s to treat penicillin- resistant staph (methicillin, nafcillin, oxacillin)  MRSA contains mecA gene which encodes for a modified penicillin-binding protein with reduced binding of methicillin, oxacillin, or nafcillin  Also resistant to cephalosporins  mecA gene is housed within the staphylococcal chromosomal cassette (SCC) which also houses multiple resistance genes 19
    20. 20. MRSA  Historically, MRSA has been isolated almost exclusively in healthcare settings, suggesting that transmission has occurred primarily in this environment  Typically, nosocomial MRSA have multi-drug resistance patterns  Risk factors for healthcare-associated MRSA acquisition include hospitalization, antimicrobial exposure, device utilization, hemodialysis, nursing home, open wounds  Healthcare-associated MRSA results in infections at many different clinical sites 20
    21. 21. Community-associated MRSA  Increasing reports of MRSA occurring in patients with little or no direct contact with the healthcare system  Interpretation of these reports are complicated by lack of consistent definitions  Phenotypic definition: lack of multi-drug resistance profile  Genotypic definition: presence of type IV SCCmec gene cassette  Typically younger patients and most often associated with skin and soft tissue infections 21
    22. 22. 22  Hospital-acquired  Large SCCmec A (types I,II,III)  Multi-drug resistance  Multiple risk factors for contact with the healthcare system  Infections at many sites (blood, lung, skin, etc)  USA 100, 200, 500, 600, 800 PFGE types (2003)  Community-acquired  Small SCCmecA (Type IV)  Typically resistant only to beta-lactam drugs  No risk factors for contact with healthcare system  Younger patients  Skin and soft tissue infections  Toxin-producing strains  USA 300, 400 PFGE types MRSA
    23. 23. Multi-Drug Resistant Organism s (MRSA) Epidemiologic and risk factor data HA-MRSA CA-MRSA Geographic links Social network analysis Genotyping PFGE RepPCR Spa Typing MLST SCCmecA MRSA
    24. 24. 24  Ohio State Health Network Infection Control Collaborative  Objectives:  To compare clinical characteristics and molecular genotypes of MRSA isolates  Use a network of a tertiary medical center and 7 referring community hospitals  To characterize transmission of CA- and HA-MRSA between these facilities. MRSA Surveillance Study Funded by CDC Prevention Epicenter Program 7 Outreach hospitals 27 to 121 miles from OSU Wexner Medical Center (OSUWMC)
    25. 25. OSUWMC IW (Honest Broker) OSHNICC IW de- identifies the data, sends a code back to the hospital for each case ODH Lab OSUWMC Clinical Micro Lab (REP-PCR, Storage of Specimens) OSU Epicenter MRSA Database MRSA Project Process Flow Each hospital collects data and PHI on +MRSA cases and sends to: Each hospitals sends +MRSA micro samples with assigned de-identified code to: OSU lab sends micro samples using assigned de-identified code for PFGE testing to: IW stores all data in: ODH sends PFGE results back to OSU lab Data Analysis Epicenter reports back de-identified data to OHSNICC and publishes results OSU lab sends PCR and PFGE results using assigned de- identified code to IW Web-Based Data Entry Portal Potential for MLST and spa typing
    26. 26. Web portal-Outreach Hospital
    27. 27. Study Design  Retrospective analysis of OSUMC banked isolates (projected ~450 isolates) Study period 1/1/07-10/31/08  Endemic clonal distribution/molecular typing  Geographic distribution  Epidemiologic and Risk factors  Social Networking analysis-social relatedness of cases  Concurrent analysis of OSHNICC hospitals (~1300 isolates) Study period 11/01/08 to 6/30/10  All cases at outreach hospitals  All cases at OSUMC from outreach hospital catchment areas  Sampling of other OSUMC cases  Collect all of the same data elements 27
    28. 28. 28 Emerg Infect Dis 2012;18:1557-1565
    29. 29. Results  Among 1286 MRSA isolates collected as part of the MRSA surveillance project there were 78 (6%) isolates that were sequence typed as ST- 239  ST-239 has a history of successful dissemination in many regions but had not been noted to play a predominant role in the US 29
    30. 30. ST 239  Demonstrated epidemic/outbreak potential- caused a 2 year ICU outbreak in London  Healthcare-associated with pulmonary and central venous catheter associated bloodstream infections in Korea and China  Highly drug resistant beyond methicillin  Resistant to clindamycin, TMP-SMX, moxifloxacin, gentamicin. 30
    31. 31. 31 Emerg Infect Dis 2012;18:1557-1565
    32. 32. 32 Emerg Infect Dis 2012;18:1557-1565
    33. 33. Pseudomonas aeruginosa  Gram-negative, non-fermenting bacillus  Common environmental pathogen, especially in water  Reservoirs for infection can develop, even in intensive care units  One of the most serious causes of ventilator- associated pneumonia (VAP) 33
    34. 34. Clinical Infections  Bacteremia in neutropenic patients; more common in the 1980’s, decreasing in past decade  Cystic fibrosis Science 2000:288:1251  Healthcare-associated infections (VAP, bacteremia) Am Surg 1999;65:706 Arch Int Med 1985;145:1621 Crit Care Med 1999;27:887  Community-acquired infections (hot tub folliculitis) J Clin Microbiol 1986;23:655 34
    35. 35. Imipenem-resistant Pseudomonas aeruginosa  University of Pennsylvania  1991 to 2000, significant increase in imipenem resistance (p<0.001)  Only independent risk factor for acquisition was prior fluoroquinolone use  Resistant infections resulted in longer hospital stay (15.5 vs 9 days, p=0.02) and increased costs ($81,330 vs $48,381)  Increased mortality rate (31.1 vs 16.7%) Lautenbach E et al. Infect Cont Hosp Epidem 2006;27:893-900 35
    36. 36. Extended spectrum β-lactamases  K. pneumoniae, E. coli  Also reported with Salmonella, Proteus, Enterobacter, Citrobacter, Serratia, and Pseudomonas  Plasmid-mediated enzymes able to hydrolyze most penicillins and cephalosporins  Mutated from native β-lactamases, particularly TEM-1, TEM-2, and SHV-1; heterogenous group of enzymes also derived from other β- lactamases-now CTX-M 36 Clin Infect Dis 2006;42:S153
    37. 37. ESBLs  Phenotype: resistance to 3rd generation cephalosporins and monobactams  Their proliferation is a global concern and results in serious limitations in treatment options  Usually carbapenems are the best and only treatment option 37
    38. 38. 38 Clin Infect Dis 2006;42:S153
    39. 39. 39 Clin Infect Dis 2006;42:S153
    40. 40. Carbapenemases  Carbapenemases are enzymes which can inactivate a wide range of antibiotics including the carbapenem class, thus rendering the bacteria highly resistant to most treatment modalities  Two current classes noted:  KPC: class A  NDM-1: class B 40
    41. 41. KPC  96 isolates from 10 Brooklyn hospitals  All resistant to carbapenems and most other antibiotics  About 50% susceptible to aminoglycosides and 90% to polymixin B; all susceptible to tigecycline.  Therapeutic options: colistin, tigecycline 42 JAC 2005;56:128
    42. 42. NDM-1 strain  New Delhi metallo-beta-lactamase-1  Klebsiella pneumoniae and Escherichia coli.  NDM-1 has been reported in >37 states within the United States, including Ohio 43
    43. 43. 44 Lancet Infect Dis 2010;10:597-602
    44. 44. 45 Lancet Infect Dis 2010;10:597-602
    45. 45. 46 Lancet Infect Dis 2010;10:597-602
    46. 46. Acinetobacter baumannii  Acinetobacter baumannii (Ab) is a ubiquitous encapsulated, aerobic, nonfermentive gram- negative coccobacillus  It is capable of causing both community and healthcare-associated infections involving pulmonary system, urinary tract, bloodstream, and surgical wounds  These organisms have a high propensity to accumulate mechanisms of drug-resistance; large HAI outbreaks with pan resistant strains have been reported 47 Clin Infect Dis 2006;42:692-699
    47. 47. Acinetobacter baumannii (Ab)  Major risk factors include invasive procedures such as using mechanical ventilation, central venous or urinary catheters, and exposure to broad spectrum antimicrobials  The organisms exist in the environment in both wet and dry conditions and can survive for months on clothing, bedrails, ventilators, and other surfaces 48 Clin Infect Dis 2006;42:692-699 J Clin Microbiol 1996;34:2881-2887 Principles and Practices of Infectious Diseases 2000:2339-2344
    48. 48. MDR Ab outbreaks across geographic distances  Citywide clonal outbreak of MDR-Ab; involved 15 hospitals in Brooklyn (based on ribotyping)  Interhospital transfer of MDR-Ab among 4 hospitals in Johannesburg, South Africa (based on PFGE) 49 Arch Intern Med 2002;162:1515-1520 Am J Infect Control 2004;32:278-281
    49. 49. Colistin  Mixture of cyclic polypeptides (polymixin A and B); polycationic with both hydrophilic and lipophilic moieties  Disrupts cell membrane  Active against gram negative bacteria esp Pseudomonas and Acinetobacter  Previous concerns for neurotoxicity and nephrotoxicity  Resistance currently has been generally rare 50
    50. 50. Colistin resistance  265 isolates of Acinetobacter from 2 Korean hospitals  Categorized into 3 subgroups:  Subgroup I (142 isolates [53.6%])  Subgroup II (54 [20.4%])  Subgroup III (18 [6.8%])  Forty-eight isolates (18.1%) and 74 isolates (27.9%) were resistant to polymyxin B and colistin, respectively. 51 J Antimicrob Chemother. 2007 Aug 29
    51. 51. Emerging antimicrobial resistance of importance in human medicine  Methicillin-Resistant Staphylococcus aureus (MRSA)  Multi-drug resistant gram-negative bacilli  “SPACE” organisms (Serratia, Pseudomonas, Acinetobacter, Citrobacter, Enterobacter)  Ciprofloxacin resistance  AmpC/inducible beta-lactamases  Extended spectrum beta-lactamases (ESBLs)  Carbapenem-resistance  Now with colistin resistance 52
    52. 52. Emerging antimicrobial resistance of importance in human medicine  Epidemic strains of C. difficile  Vancomycin-resistant Enterococcus ssp. (VRE)  Vancomycin-intermediate Staphylococcus aureus (VISA)  Vancomycin-resistant Staphylococcus aureus (VRSA) 53

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