1. Antimicrobial Stewardship: Why Should I Care?
Edina Avdic, Pharm.D., MBA, BCPS, AQ-ID
Associate Director, Antimicrobial Stewardship Program
Program Director, Infectious Diseases Pharmacy Residency
The Johns Hopkins Hospital

2. Objectives
Discuss the rationale for implementation of antimicrobial stewardship program
List benefits of antimicrobial stewardship program to patients and health care facilities

3. Why Should You Care about Antimicrobial Stewardship?
Joint Commission requires it!
50% of hospitalized patients in the U.S. receive at least 1 antimicrobial
20-50% of prescribed antibiotics in U.S are unnecessary or inappropriate
Up to 28% of hospitalized patients experience antimicrobial-associated adverse events, including C. difficile infections
Antibiotic misuse contributes to antibiotic resistance
Development of new antibiotics is slow and expensive
According to 2011 CDC point prevalence survey: 33% receive at least one antimicrobial, 12% at least two, 5% at least 3.
Nursing homes 11% of patient are prescribed antibiotics
Patients who are unnecessarily exposed to antibiotics are placed at risk for serious adverse events with no clinical benefit.
Magill SS, et al. JAMA 2014;312(14): ;
; accessed 3/4/18

4. Joint Commission Requirement
8 elements of performance
1 removed: education of patients and their families about antibiotics and resistance
accessed 3/3/18

5. Antibiotic Stewardship
CDC Core Elements for
Antibiotic Stewardship
CDC had developed a Core Elements of Antibiotic Stewardship for hospitals in 2014, nursing homes in 2015, and more recently outpatients in The core elements provides a framework for antibiotic stewardship for clinicians and facilities that routinely provide antibiotic treatment. 

6. Prevalence of Antimicrobial Use in Acute Care Hospitals in U.S
One-day prevalence surveys were conducted in acute care hospitals in 10 states, 183 hospitals between May and September Patients were randomly selected from each hospital’s morning census on the survey date. 51% of hospital were small. 11, 282 patients were reviewed and 5,860 met criteria for évaluation.
Magill SS, et al. JAMA 2014;312(14): ;

7. Extent of Inappropriate or Unnecessary Antibiotic Use
5 center prospective study of post-prescription review
Cosgrove SE, et al. Infect Control Hosp Epidemiol 2012;33:374-80

8. Reasons for Inappropriate or Unnecessary Antibiotic Use
Reasons for recommending modified regimens (59%)
Organism not susceptible 9%
More appropriate agent
31%
Patient can take oral therapy 5%
Overlapping agents
15%
Reasons for recommending stopping antibiotics (41%)
Antibiotics not needed
28%
Inappropriate prophylaxis
13%
Cosgrove SE, et al. Infect Control Hosp Epidemiol 2012;33:374-80

9. Prescriber’s Perceptions and Knowledge
Single center survey of faculty and medical residents
94% agreed that antibiotics are overused nationally and 74% locally
62% agreed that doctors overprescribe antibiotics
13% agreed that they themselves overprescribe
Most would like more education about antibiotics and feedback about their antibiotic selection
Majority did not think antimicrobial stewardship programs are an obstacle to good patient care
Abbo L, et al. Infect Control Hosp Epidemiol 2011;32(7):

10. Causes Adverse Drug Events (ADE) in Hospitalized Patients
Data from 32 states
Antibiotics and anti-infectives were most common cause of ADE
23% present on admission
28% originated during hospital stay
C. difficile was the most common antibiotic-associated ADE
This is data from 2011, reported from 32 states participating in the Healthcare Cost and Utilization Project (HCUP). All numbers noted in the text and included in the tables are actual values, not estimates, because the data include a census of discharges rather than a sample of discharges.
Weiss AJ, et al. Statistical Brief #158, Jul 2013:

11. Antibiotic-Associated Adverse Events (ADE)
Retrospective chart review, single center (n=1488)
20% of patients experienced at least 1 ADE
97% considered clinically significant
27% resulting in prolonged hospitalization or ED/clinic visits
Gastrointestinal (42%), renal (24%), hematologic (15%)
20% of ADEs were attributable to antibiotics that were not indicated
73% occurred during hospitalization
4% developed CDI within 90-days of antibiotic initiation
6% developed an infection with a new MDRO within 90-days of antibiotic initiation
3% -prolonged hospitalization; 24%, additional clinic or emergency department visit; 9%, and additional laboratory tests, electrocardiograms,
or imaging 61%
Tamma PD, et al. JAMA Intern Med 2017;177(9):

12. Antibiotics Cause Prolonged Alterations to Gut Flora
2 years!
Green: susceptible bugs
Purple: resistant bugs
Jernberg C, et al. Microbiology. 2010;156:

13. Antibiotic Consumption and Resistance
Urinary Tract Bacteria
Costelloe C, et al. BMJ. 2010;340

14. Antimicrobial Stewardship Challenges with New Antibiotics
Agent
Year
FDA Indication
Desired Indication
Cost/day AWP
Fidaxomicin
2011
CDAD
$441
Ceftaroline
ABSSSI, CABP
MRSA bacteremia, endocarditis, osteomyelitis $
Tedizolid
2014
ABSSSI,
VRE bacteremia, MRSA PNA $
Ceftolozane/
tazobactam
cIAI, cUTIs, Pylo
MDR pseudomonas PNA, bacteremia $
Dalbavancin
ABSSSI
MRSA bacteremia/ osteomyelitis, endocarditis
$5,523-course
Oritavancin
$3,480-course
Ceftazidime/
avibactam
2015
CRE bacteremia, PNA
$1,179
Meropenem/
vaborbactam
2017
cUTIs, Pylo
$1,188
complicated urinary tract infections (cUTI) including pyelonephritis caused by designated susceptible bacteria
SIVEXTRO is an oxazolidinone-class antibacterial drug indicated in adults for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by designated susceptible bacteria. (
Complicated Intra-abdominal Infections (cIAI), Complicated Urinary Tract Infections (cUTI), acute bacterial skin and skin structure infections (ABSSSI), .C. difficile-associated diarrhea (CDAD)

15. Benefits of Antimicrobial Stewardship Programs

16. Stewardship Influences Antibiotic Prescribing Practices
Cochrane systematic review of 29 RCTs found:
Evidence that interventions lead to more patients receiving appropriate treatment
Increase in compliance with guidelines/policies by 15%
Interventions reduced duration of antibiotics by 2 days
Moderate-certainty evidence that interventions reduce length of stay without increasing risk of death
LOS decreased by 1.12 days
The risk of death was 11% in both the intervention and control
Very low-certainty evidence about the effect of the interventions on reducing C. difficile infections, resistant Gram-negative and Gram-positive organisms
Majority of studies were from north America and Europe. Interventions: ”restrictive” and “enablement” techniques. This represents an increase from 43% to 58% which is pretty low.
Davey P, et al. Cochrane Database of Systematic Reviews 2017;2:CD003543

17. Stewardship Improves Patient Outcomes
Meta-analysis of 142 studies assessed the effect of AS objectives on patient outcomes (clinical outcomes, adverse effects, costs, bacterial resistance rates)
AS objectives
Impact on patient outcomes
Guidelines adherence
RRR for mortality was 35% (p<0.0001)
Decrease in LOS, decreased costs
Therapy de-escalation
RRR for mortality was 56% (p<0.0001)
Therapeutic drug monitoring
RRR for the rate of nephrotoxicity was 50% (p=0.02)
Bedside consultation
RRR for mortality for S. aureus bacteremia was 66% (p=0.008)
Quality of evidence is generally low and heterogeneity between studies is low to moderate. Mortality had moderate heterogenicity
RRR- relative risk reduction
RRR- relative risk reduction, LOS-length of hospital stay
Schuts EC, et al. Lancet Infect Dis 2016;16:847-56

18. Stewardship Reduces Resistance
Meta-analysis of 32 studies from 20 countries showed that stewardship interventions were associated with:
51% reduction of MDR GNR infection/colonization
48% reduction of ESBL-producing organisms
37% reduction of MRSA infection/colonization
32% reduction of C. difficile infections
No reductions of VRE
No reductions in aminoglycosides or fluoroquinolone-resistant GNR
Baur D, et al. Lancet Infect Dis. 2017;17(9):

19. Subgroup Analyses
Baur D, et al. Lancet Infect Dis. 2017;17(9):

20. Stewardship Reduces C. difficile Infections
National AS intervention was implemented in Scotland
Focused on reduction in use of 4C antibiotics:
Fluoroquinolones
3rd generation cephalosporins
Clindamycin
Amoxicillin/clavulanate
Other infection control and prevention strategies were also implemented (e.g. hand hygiene)
Use of 4C was reduced by 59% in hospitals and community during the stewardship interventions
Promotion of empiric guidelines recommending against the use of 4C antibiotics: FQ, clinda, cephalosporins, and amox-clav
Required approval to use 4C agents from a microbiologist or ID physician if not used for approved indications
Susceptibilities not provided in micro reports
Root cause analysis for all episodes of CDI
Proton pump inhibitor use guidelines 2010-
Substitute antibiotics: amoxicillin, piperacillin/tazobactam, aminoglycosides, trimethoprim/sulfmethoxazole
Lawes T, et al. Lancet Infect Dis. 2017;17:

21. Stewardship Reduces C. difficile Infections
CDI prevalence density decreased by 68% in hospitals and 45% in community
Graphs represent c. diff prevalence density
Dotted line indicates the start of the AS intervention
Lawes T, et al. Lancet Infect Dis. 2017;17:

22. Stewardship Decreases Costs
Standiford HC, et al. Infect Control Hosp Epidemiol. 2012; 33:338.

23. Audience Question #1
Which of following are true about rationale for antimicrobial stewardship program implementation?
A. Joint Commission Standard requires it
20-50% of antibiotic prescriptions in acute care hospitals are unnecessary or inappropriate
An increase in antibiotic consumption is associated with an increase in antibiotic resistance
All of the above

24. Audience Question #2
Antimicrobial Stewardship Programs can (select all correct answers):
A. Limit or decrease antibiotic resistance
B. Decrease hospital mortality
C. Optimize antimicrobial therapy and safety
D. Reduce or control the costs

25. Summary
Multidisciplinary stewardship programs should be implemented across all healthcare settings
There is an association between antibiotic consumption and resistance development
Antimicrobial stewardship interventions can improve antibiotic use, decrease duration of therapy and decrease costs
Antimicrobial stewardship is an effective approach for controlling antibiotic resistance and CDI
New antibiotics will need to be matched with effective antimicrobial stewardship to extend their lives