1. Antibiotic Stewardship
Katherine Shea, Pharm.D., BCPS-AQ-ID
Theresa Jaso, Pharm.D. BCPS-AQ-ID
Clinical Pharmacy Specialists, Infectious Diseases
Seton Healthcare Family

2. Objectives
Understand the rationale and importance of antibiotic stewardship
Identify key points from the antimicrobial stewardship guidelines
Recognize the necessary components of a stewardship program
Identify key strategies for implementation of an antibiotic stewardship program

3. Antibiotic Stewardship
“Good Antibiotic Stewardship is a
practice that ensures the optimal selection,
dose, and duration of an antimicrobial
therapy that leads to the best clinical
outcome for the treatment or prevention of
an infection while producing the fewest
toxic effects and the lowest risk for
subsequent resistance.”
-Dale N. Gerding, MD
Gerding DN. Jnt Comm J Qual Improv 2001; 27:

4. Multi-drug Resistant Organisms (MDROs): “ESCAPE”
Enterococcus faecium (VRE)
Staphylococcus aureus (MRSA)
Clostridium difficile
Acinetobacter baumanni
Pseudomonas aeruginosa
Enterobacteriaceae (ESBLs)
Carbapenem resistant Enterobacteriaceae is on the rise!
Peterson LR. Clin Inf Dis 2009;49:

5. Risk Factors for MDROs Prior antibiotic exposure
History of MDRO or exposure to other colonized patients
Recent or prolonged duration of hospital stay
Long-term care residence
Immunosuppressive disease
Dialysis
Comorbidity/Dependency (need for contact care)
High frequency of antibiotic resistance in the community
Drinka P, et al. JAMDA 2011; June editorial:
Muto CA, et al. Infect Control Hosp Epidemiol 2002;23:
Muto CA, et al. Infect Control Hosp Epidemiol 2003;24:
Ostrowsky et al. N Engl J Med 2001;344:

6. Antibiotic Use Linked to MDROs
Collateral Damage:
Use of antimicrobial results in colonization or infection with resistant organisms
3rd gen cephalosporins and fluoroquinolones
Linked to multi-drug resistant (MDR) organisms:
VRE, MRSA, ESBL-producing organisms, C. difficile,
Enterobacteriaceae, CRE (fluoroquinlones)
Clindamycin: C.difficile infection (CDI)
Choi et al. Antimicrob Agents Chemother. 2008;52: Chow et al. Ann Intern Med. 1991;115:
Nauciel et al. Presse Med. 1985;23: Pai et al. Antimicrob Agents Chemother. 2004;48:
Paterson. Clin Infect Dis. 2004;38:S 6

7. Impact of Resistant Organisms
Delay in appropriate antibiotic therapy
Up to 30-44% increase in mortality
Increased length of stay by up to 18 days
Increased attributable hospital cost per case: $9,000-$72,000
Dellit et al. Clin Infect Dis. 2007;44:
Mauldin et al. Antimicrob Agents Chemother 2010;54:
Obritsch et al. Pharmacotherapy 2005;25(10):

8. Resistance Impact: CDC National Summary
Clostridium difficile

9. 2013 CDC Antibiotic Resistance Threats

10. CDI Risk Factors Advanced age (> 64 y/o)
Duration of hospitalization
Exposure to antimicrobial agents
Including single-dose surgical prophylaxis
Longer duration = higher risk
Highest risk agents: fluoroquinolones, clindamycin, 2nd & 3rd generation cephalosporins
Chemotherapy
GI surgery or tube feeding
Acid suppressive agents
Cohen SH, et al. Infect Control Hosp Epidemiol 2010;31. Loo VG, et al. N Engl J Med 2005;353:
King RN, et al. Pharmacotherapy 2011;31(7): Owens RC. Pharmacotherapy 2006;26:

11. No Antibiotics in Development for Gram-negatives in the Next 10 yrs
Infectious Diseases Society of America (IDSA) Campaign in
2004: Bad Bugs, No Drugs New Antibiotics by 2020
                                                                 
No Antibiotics in Development for Gram-negatives in the Next 10 yrs
2004, 2 approved: telvancin & ceftaroline. 7 in development for MDR GNs

12. Antibiotics in the Pipeline
Antibiotics approved since 2004:
Tigecycline
Doripenem
Telavancin
Ceftaroline
Tidezolid
Dalbavancin

13. CDC Core Preventative Actions
Stop inappropriate
antibiotic use
Use antibiotics safely
& appropriately
Diagnosis
Choice
Dose
Duration

14. Antimicrobial Stewardship
Extending the life of antimicrobials requires appropriate use
Maximize therapeutic impact
Minimize unintended consequences
Toxicity
Selection of pathogenic organisms
Emergence of resistance
Prescribe only when appropriate diagnosis
Appropriate treatment: drug, dose and duration
Streamline therapy
Dellit et al. Clin Infect Dis. 2007;44:
Shlaes et al. Clin Infect Dis. 1997;25: 14

15. Antibiotic Stewardship
Component of patient safety
Up to 50% antibiotic use = Inappropriate
Inappropriate use = ’d selection of resistance
Programs shown to ↓ antibiotic use by 22-36%
Annual savings $ ,000
Successful decrease in multi-drug resistant organisms w/in 3-5yrs
Guidelines supported by AAP, ASHP, IDSA, SIDP
Delit et al. Clin Infect Dis 2007; 44.

16. CDC Get Smart Campaign
Antibiotics do not fight viral illness like colds.
Taking antibiotics for colds can be harmful to your child’s health –
In fact, unnecessary antibiotics can make future infections harder to treat

17. Stewardship Core Requirements
Multi-disciplinary team
ID-trained pharmacist
ID physician
Clinical microbiologist
Infection preventionist
Information systems specialist
Dellit et al. Clin Infect Dis. 2007;44:

18. Core Implementation Strategies
Prospective audit with feedback
ID physician or pharmacist with ID training
Formulary restriction with pre-authorization
Dellit et al. Clin Infect Dis. 2007;44:

19. Supplemental Strategies
Education
Guidelines & clinical pathways
Antimicrobial order forms
Avoidance of antimicrobial cycling & routine combination therapy
Streamlining or de-escalation of therapy
Dose optimization
IV to PO
Utilization of technology (CPOE, eMAR)
Dellit et al. Clin Infect Dis. 2007;44:

20. Barriers to Implementing
IDSA guidelines focus on the development of hospital-based programs
Lack of resources
Funding
Personnel (physician, ID trained pharmacist)
Data & outcomes management
Creation of antimicrobial stewardship tools
Lack of physician participation
Drew RH. J Manag Care Pharm 2009;15:S18-23.

21. Resources: How to implement a program
AHRQ Toolkits
Abx Stew:
Decreasing CDI through Abx Stew:
Joint Commission Toolkit
Regional susceptibility info
National Society of Infectious Diseases Guidelines

22. Antimicrobial Stewardship Long-term Care Facilities (LTCFs)

23. Epidemiology ~ 16,000 nursing homes in the U.S.
~ 1.5 million residents
Infection incidence rates:
/ 1000 resident days
Most commonly reported infections:
urinary tract infections (UTIs), pneumonia, skin infections, and gastroenteritis
Accessed July 11, 2014.
Smith PW, et al. SHEA APIC Guideline. Am J Infect Control 2008;36:
Rhee M, et al. Infect Dis Clin N Am 2014;28:

24. Epidemiology
Infection most common cause for transfer to an acute care hospital
Antibiotics among most frequently prescribed medications in LTCFs and have second highest adverse drug event rate
Estimated inappropriate antibiotic use rates range: % (depends on definition used)
Rhee M, et al. Infect Dis Clin N Am 2014;28:
Antipsychotics most commonly associated with ADEs

25. Antimicrobial Challenges for LTCFs
Distinguishing colonization from infection
Prevalence asymptomatic bacteriuria (ASB):
Noncatheterized: %
Long-term urinary catheters: 100%
Elderly: ASB associated with pyuria 90% cases
Symptomatic UTIs may present atypically
Rhee M, et al. Infect Dis Clin N Am 2014;28:

26. Antimicrobial Challenges for LTCFs
Lack of resources:
Clinical providers may be offsite
Therapy decisions based on staff clinical assessments
Limited diagnostic testing services
Rhee M, et al. Infect Dis Clin N Am 2014;28:

27. Implementing Antimicrobial Stewardship in LTCFs
SHEA/APIC guidelines encourage infection prevention programs to include a component antimicrobial stewardship
No consensus on specific components
Hampered by limited resources
Smith PW, et al. SHEA APIC Guideline. Am J Infect Control 2008;36:
Nicolle L. Antimicrobial Resistance and Infection Control 2014;3:6.

28. Implementing Antimicrobial Stewardship: LTCFs
Consider stepwise approach
Engage key leadership
Medical director
Director of nursing
Infection prevention coordinator
Consultant pharmacist
Representatives from medical & nursing staff
Rhee M, et al. Infect Dis Clin N Am 2014;28:

29. Implementing Antimicrobial Stewardship: LTCFs
Assess baseline antimicrobial usage if possible (engage pharmacist)
Monitor antibiotic resistance and C. difficile infection rates
Educate providers/ staff regarding appropriate antibiotic use
Educate/ train staff on proper clinical assessments (especially important if clinical providers offsite)
Rhee M, et al. Infect Dis Clin N Am 2014;28:

30. Implementing Antimicrobial Stewardship: LTCFs
Develop LTCF diagnostic & treatment guidelines based on currently published national guidelines
Focus on most common LTCF infections; e.g. UTIs, pneumonia
Consider restricting broad spectrum antimicrobials; e.g. fluoroquinolones (levofloxacin, ciprofloxacin), carbapenems (e.g. meropenem) based on usage criteria
Rhee M, et al. Infect Dis Clin N Am 2014;28:

31. UTI Treatment Guideline: Process Example
Collaborate with physician champion, pharmacist, and lead nurse
Review current national UTI treatment guidelines
Develop institution-specific diagnosis & treatment guideline
Utilize institution pathogen (e.g. E. coli) susceptibility data (if available)
May also use regional (Texas) susceptibility data

32. National Treatment Guidelines

33. UTI Treatment Guideline: Process Example
Collaborate with physician champion, pharmacist, and lead nurse
Review current national UTI treatment guidelines
Develop institution-specific diagnosis & treatment guideline
Utilize institution pathogen (e.g. E. coli) susceptibility data (if available)
May also use regional (Texas) susceptibility data

34. Center for Disease Dynamics, Economics & Policy

35. UTI Treatment Guideline: Process Example
Educate staff and clinical providers
Ensure guidelines easily accessible
Measure antimicrobial usage improvement
Report post implementation outcomes to clinical providers and staff
Antibiotic usage
C. difficile infection rate
Delit et al. Clin Infect Dis 2007; 44.

36. Resources: How to implement a program
AHRQ Toolkits
Abx Stew:
Decreasing CDI through Abx Stew:
Joint Commission Toolkit
Regional susceptibility info
National Society of Infectious Diseases Guidelines

37. Seton Healthcare Family (SHF) Antibiotic Stewardship Program

38. Seton Healthcare Family
12 hospital network in Central Texas
Two of the largest medical centers
Level I trauma academic hospital (381 bed)
Community hospital (473 bed)
Limited clinical pharmacy specialists dispersed throughout the network

39. Implementation Development of antimicrobial stewardship team (AST)
Assessed for implementation of core strategies
Identify key physician groups
Infectious diseases (ID), hospitalists, intensivists, emergency medicine
Identify key goals for the program
Develop pertinent site-based treatment guidelines or initiatives
Gain support from key physician groups
Develop & disseminate education

40. Network Multi-disciplinary AST
ID physicians
Total of 10 throughout the network
Network ID pharmacists (3 Co-chairs)
Two adult and one pediatric
Network Director of Infection Prevention
Network Microbiology Clinical Manager

41. Core Strategies: Formulary Restriction
ID consult/approval required for specific IV antimicrobials
Developed based on antimicrobial spectrum, availability, & cost (additions & modifications as needed)
Gram-positive agents: Daptomycin, ceftaroline, linezolid,
tigecycline, quinupristin/dalfopristin
Gram-negative agents: meropenem, amikacin
Antifungals other than fluconazole
Others: acyclovir, trim/sulfa

42. Core Strategy: Prospective Audit (began FY2009)
Two network ID pharmacists dedicated to largest 2 sites
ID pharmacists audit daily: IV antibiotic report & microbiology culture report
Streamlining/de-escalation
Dose-optimization
IV to PO (including non-policy medications)
ID pharmacists: microbiology laboratory & infection prevention resource for resistant organisms

43. SHF Supplemental Strategies
Education (annual presentations):
Hospitalists, family medicine, emergency medicine
Automatic pharmacy policies:
IV dose optimization
IV to PO policy
Review of all order sets containing antibiotics by ID pharmacists
Modification of order sentences within physician order entry & pharmacy system by ID pharmacists

44. Identification of Key Physician Groups
Identification of all network order sets containing antibiotics (specialty specific)
Reviewed by ID pharmacist
Identification of stakeholder physician groups for treatment guidelines during development
Hospitalists/Internal Medicine
Pulmonologists
Emergency Department

45. SHF Stewardship Goals Appropriate antibiotic therapy for core measures
Reduce overall use of fluoroquinolones, ceftriaxone, and clindamycin
Increase cefazolin utilization for community-acquired Gram-negative infections based on antibiogram
Increase usage of SHF treatment guidelines
Appropriate empiric & streamlined therapy
Appropriate duration of therapy
Optimize dosing based on pharmacokinetics & pharmacodynamics

46. Joint Commission and Antimicrobial Stewardship
Surgical Care Improvement Project (SCIP)
Antimicrobial surgical prophylaxis
Guideline developed & order set review to ensure correct antibiotic, weight-based dosing, timing of pre- op dose, and duration
Pneumonia Core Measure (CAP)
Patient’s should receive antibiotic regimens based on national guidelines
Guideline & order sets developed consistent with SHF treatment guideline

47. SHF Stewardship Goals Appropriate antibiotic therapy for core measures
Reduce overall use of fluoroquinolones, ceftriaxone, and clindamycin
Increase usage of SHF treatment guidelines
Appropriate empiric & streamlined therapy
Appropriate duration of therapy
Increase cefazolin utilization for community-acquired Gram-negative infections based on antibiogram
Optimize dosing based on pharmacokinetics & pharmacodynamics

48. Antibiotic Stewardship to Prevent C.difficile Infection (CDI)
Minimize the frequency, duration, and number of antimicrobial agents prescribed
Limit utilization of high risk agents:
Fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin)
2nd generation cephalosporins (e.g., cefoxitin, cefotetan)
3rd generation cephalosporins (e.g., ceftriaxone, cefotaxime)
IP interventions pre-stewardship = staff education, strict isolation for patients with diarrhea prior to assay available, dedicated equipment with disposable rectal thermometers, environmental cleaning with bleach
Cohen SH, et al. Infect Control Hosp Epidemiol 2010;

49. Antibiotic Stewardship to Prevent C.difficile Infection (CDI)
Programs implementing restriction criteria or reduced utilization measures
Reduction in use of high risk agents
Reduction in nosocomial CDI
One program reduced high risk agent utilization by 54% corresponding with a 60% reduction in CDI3
Also limited duration of therapy (pneumonia, abdominal infection)
IP interventions pre-stewardship = staff education, strict isolation for patients with diarrhea prior to assay available, dedicated equipment with disposable rectal thermometers, environmental cleaning with bleach
Aldeyab MA, et al. J Antimicrob Chemother 2012;67:
Cohen SH, et al. Infect Control Hosp Epidemiol 2010;
(3) Valiquette L, et al. Clin Infect Dis 2007;45:S

50. SHF Stewardship Goals Appropriate antibiotic therapy for core measures
Reduce overall use of fluoroquinolones, ceftriaxone, and clindamycin
Increase usage of SHF treatment guidelines
Appropriate empiric & streamlined therapy
Appropriate duration of therapy
Increase cefazolin utilization for community-acquired Gram-negative infections based on antibiogram
Optimize dosing based on pharmacokinetics & pharmacodynamics

51. Institution-Based Treatment Guidelines
Assess disease states associated with potential for greatest impact related to program goals
SHF: Urinary tract infections (UTIs) had the largest inpatient utilization of fluoroquinolones (ciprofloxacin) and ceftriaxone
Assess antibiogram susceptibilities of narrowest spectrum agents
Perform literature review
Identify key stakeholders (hospitalists, intensivists, emergency department)

52. Hospital Antibiogram Cefazolin susceptibility > 85-90%
Adequate activity for empiric community-acquired Gram-negative therapy vs. agents with collateral damage

53. Antibiogram: Clinical Pearls
Pros
Assists in guiding empiric therapy
Assess resistance trends
Cons
All isolates
Community vs hospital acquired
Not site specific (ie. urine)
Institution specific
“S” may not equal optimal antimicrobial activity
Not able to see incremental increases in resistance

54. Seton Healthcare Family Antibiotic Stewardship Results

55. SHF Reduction in Use of Antibiotics Associated with Collateral Damage:
Days of Therapy (DOT)/1000 patient days

56. Fluoroquinolone Use Implementation of treatment guidelines mid-FY09
Hospitals w/Antibiotic Stewardship
70-80% reduction
3- 4 times lower than other hospitals
DOT/1000 patient days
Targeted education began at Hospital #1 & 2
Implementation of treatment guidelines mid-FY09

57. Ceftriaxone Use Implementation of treatment guidelines mid-FY09
Hospitals w/Antibiotic Stewardship
38-60% reduction
~2 times lower than other hospitals
DOT/1000 patient days
Targeted education began at Hospital #2
Implementation of treatment guidelines mid-FY09

58. Clindamycin Use Hospitals w/Antibiotic Stewardship 37-40% reduction
DOT/1000 patient days
Hospitals w/Antibiotic Stewardship
37-40% reduction

59. Ciprofloxacin Pseudomonas Non-Susceptibility

60. Pseudomonas – Ciprofloxacin Non-Susceptible Trend

61. C.difficile Infection (CDI)

62. CDI Cases/1000 Patient Days

63. Current CDI Rates: CMS Publicly Reported
National 1
Texas
0.812
UMCB
0.728
SMCA
0.601
SMCH
0.649
SMCW
0.788

64. SHF Antibiotic Stewardship Program Cost Savings

65. Total Antibiotic Expenditure
45-50% reduction in total antibiotic expenditure
UMCB ~ 45% reduction, SMCA ~ 50%
*FY10: purchase reports unavailable

66. Site-based Total Antibiotic Cost/Adj Patient discharge
40% reduction in total antibiotic expenditure

67. Conclusion: Antibiotic Stewardship
Important component of patient safety
Associated with a in costly & high mortality resistant organisms
Key implementation strategies
Form antibiotic stewardship team
Identify goals and areas for opportunity
Identify & gain support from key physician groups
Utilization of treatment guidelines can be an instrumental component for implementation
Provide results & feedback
Positive results are motivating to key physician groups!

68. Antibiotic Stewardship
System-wide implementation of antibiotic stewardship initiatives led to the following:
Decreased antibiotic utilization of agents associated with collateral damage
Formal stewardship programs at both a community & academic setting were associated with:
Lower utilization of broad spectrum agents
Lower CDI rates
40% lower cost/adjusted patient discharge
Results presented to leadership and resources allotted (additional pharmacy specialists) to further spread to other sites

69. Antibiotic Stewardship:
Katherine Shea, Pharm.D., BCPS-AQ-ID
Theresa Jaso, Pharm.D. BCPS-AQ-ID
Clinical Pharmacy Specialists, Infectious Diseases
Seton Healthcare Family