1. Strategies and Implementation: Pre-authorization vs. Post-prescription
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
State one advantage and one disadvantage for each pre-authorization and prospective audit and feedback review strategy

3. The Johns Hopkins Hospital (JHH)
Tertiary academic medical center
1,194 beds
205 pediatric beds
Adult patient care
6 adult ICUs
Oncology center
Organ transplant
Multiple surgical and medicine services and subspecialties
OB/GYN
Training
Residency and fellowship training in various disciplines

4. Antimicrobial Stewardship Program at The Johns Hopkins Hospital
Adult Program
0.75 ID physician, 1ID pharmacist
2014-second ID pharmacist
2016-second ID physician
Additional support
Clinical pharmacy specialists-2002
ID fellows-2002
ID pharmacy resident-2007
Clinical pharmacists-2014
Collaborators
Hospital epidemiology & infection control
Microbiology laboratory
Pharmacy
ID division
Medicine and surgery departments

5. Stewardship Strategies
Revision and publication of Antibiotic Guidelines
Pre-authorization (PPA)
Post-prescription review with feedback (PPRF)
IV to PO conversion
Dose optimization
Syndrome interventions
Rapid diagnostics interventions
Pharmacy-driven interventions
Education and research

6. Formulary Restrictions and Pre-Authorization (PPA) at JHH
Pre-authorization-implemented in 1980s by ID division
Authorized prescriber pages “antibiotic approval pager” between 8 am-10 pm 7 days per week
In 2002 responsibility and oversight was transferred to ASP
ID pharmacist and clinical pharmacy specialists answer pager from 8 am-4 pm M-F
3 ID pharmacists answer pager during the day M-F as of 2015
Clinical pharmacy specialists grant approvals for their services
Evenings and weekends ID fellows answer pager
>30 restricted antimicrobials
Selected antimicrobials require approval by ASP team member 24/7
All non-formulary agents require approval

7. Why Did We Want to Compare Two Core ASP Strategies?
Both strategies have been effective in reducing antibiotic use in the healthcare setting
Each strategy has its pros and cons
No study comparing the two strategies head-to-head
Most of our stewardship resources were dedicated to pre-authorization
Post-prescription review with feedback was not routinely performed by ASP
We were curious to see which strategy was more effective in our hospital
-This also leads to unnecessary antibiotic use and ADEs

8. Study Setting 4 medicine firms (internal medicine services)
Assistant Chief of Service (ACS) is attending for the entire year
Internal medicine housestaff assigned to the same firm throughout residency
Dedicated internal medicine clinical pharmacy specialists
Approve restricted antimicrobials & recommend de-escalation
ASP: 1 ID pharmacist and 0.75 ID physician
Grants approval for ASP restricted antimicrobials, back up for clinical pharmacy specialist
Patients
General internal medicine problems
Always admitted to the same firm
Tamma PD, et al. Clin Infect Dis 2017;64(5):

9. Study Participants
Adult inpatients on general wards admitted to 1 of the 4 medicine “firm” services
Timing: September 2013 to June 2014
Patients were included if they were receiving antimicrobial therapy
Exclusions:
Chronic prophylactic antimicrobials
Antimicrobials used for non-infectious reasons
Patients who were on firm service <24 hours
Tamma PD, et al. Clin Infect Dis 2017;64(5):

10. Antibiotics and Restrictions
AmBisome*
Ceftriaxone
Linezolid*
Amikacin*
Cephalexin
Meropenem*
Amoxicillin
Ciprofloxacin*
Metronidazole
Amoxicillin/clavulanate
Clarithromycin
Micafungin*
Amphotericin B decoxicolate
Clindamycin
Moxifloxacin
Ampicillin
Colistin*
Nitrofurantoin
Ampicillin/sulbactam
Dapsone
Norfloxacin
Azithromycin
Daptomycin**
Oxacillin
Aztreonam*
Doxycycline
Penicillin
Cefazolin
Dicloxacillin
Piperacillin/tazobactam*
Cefepime*
Ertapenem
Rifampin
Cefotetan
Ethambutol
Tigecycline*
Cefpodoxime
Fluconazole*
Trimethoprim/sulfamethoxazole
Ceftaroline**
Fosfomycin*
Tobramycin
Ceftazidime*
Gentamicin
Vancomycin*
*Restricted to standard approval; **Restricted to ASP approval 24/7

11. Study Design Tamma PD, et al. Clin Infect Dis 2017;64(5):537-543
We conducted a qua- si-experimental, crossover trial of PPA and PPRF in 4 medical wards at The Johns Hopkins Hospital (JHH) to compare these 2 antibiotic stewardship strategies in the acute-care setting.
Tamma PD, et al. Clin Infect Dis 2017;64(5):

12. Intervention Pre-authorization arm Post-prescription arm
Approvals granted by firm
pharmacist/ID fellow
Post-prescription arm
All restrictions were removed
At hours ASP team (ID physician and ID pharmacist) visited team in person to provide feedback M-F, including a printed description of the case with recommendations
Recommendations were not documented in the chart
Clinical specialties refrained from commenting on antimicrobial therapy
If results of diagnostic data were not yet available, recommendations were made once this information was known. If the patient was being seen by the infectious diseases consult service at the time of PPRF, the ASP discussed its recommendations with the consult service prior to making recommendations to the firm.
Tamma PD, et al. Clin Infect Dis 2017;64(5):

13. Results: Antibiotic Indications
Most Common Indications on Day 3
PPA
N=473
PPRF
N=447
 P-value
Urinary tract infection
24.9%
23.5
0.71
Skin and soft tissue infection
16.7%
13.3%
0.26
Community-acquired pneumonia
11.9%
14.4%
0.41
Osteoarticular infection
10%
9.1%
0.68
Clostridium difficile infection
7.8%
8.5%
0.77
COPD exacerbation
7.4%
7.9%
0.88
Intra-abdominal infection
6.8%
5.9%
0.74
Healthcare-associated pneumonia
6.3%
5.1%
0.60
Aspiration pneumonia
2.6%
4.2%
0.39
As adjudicated by ASP team
Top 3 indications were present on day 1
PPA-pre-authorization; PPRW-post-prescription review with feedback
Tamma PD, et al. Clin Infect Dis 2017;64(5):

14. Results: Antibiotic Therapy
Day 1
Day 3
PPA
N=778
PPRW
N=730
P-value
Antibiotic regimen inappropriate
33.7%
41.1%
<0.01
57.3%
36.4%
Antibiotic therapy not indicated
17.7%
22.1%
0.04
35.5%
23.6%
No bacterial infection
15.7%
19.3%
0.07
30.7%
16.0%
Antibiotic therapy too broad
14.5%
17.9%
0.08
20.9%
12.3%
Unnecessarily broad GN coverage
4.2%
6.7%
6.2%
4.1%
0.17
PPA-pre-authorization; PPRW-post-prescription review with feedback
Tamma PD, et al. Clin Infect Dis 2017;64(5):

15. Results: Days of Antibiotic Therapy
PPA
Median LOT in PPA and PPRF was 7 and 5 days (p<0.01)
PPRF
PPRF
Time series analysis
PPA
Tamma PD, et al. Clin Infect Dis 2017;64(5):

16. Results: Clinical Outcomes
There were no differences in CDI episodes, duration of hospital stay or in-hospital mortality between the two study arms
CDI episodes: 4% in PPA vs. 3% in PPRF (p=0.4)
Median duration of hospital stay: 3 days in both groups (p=0.99)
In-hospital mortality: 11% in PPA vs. 14% in PPRF (p=0.44)
Tamma PD, et al. Clin Infect Dis 2017;64(5):

17. Audience Question #4
Which of the following statements is FALSE about pre-authorization and prospective audit and feedback?
Pre-authorization is a real time resource intensive in comparison to prospective audit and feedback
Neither intervention effective in reducing antibiotic use
Pre-authorization optimizes empiric antibiotic choices
Prospective audit and feedback optimizes de-escalation and duration of therapy

18. Conclusions
Pre-authorization can significantly reduce inappropriate therapy on day 1
Influencing unnecessary antibiotic starts and unnecessary broad spectrum gram-negative coverage
Post-prescription review can significantly reduce inappropriate therapy on day 3
Influencing antibiotic discontinuation when no infection has been identified and de-escalating broad spectrum antibiotics
Post-prescription can significantly reduce overall antibiotic duration of therapy
Combination of both type of interventions would be ideal for antimicrobial stewardship programs

19. Questions ?
Thank you!

20. Results: Antibiotic Therapy
Day 1
Day 3
PPA
N=778
PPRW
N=730
P-value
Antibiotic regimen inappropriate
33.7%
41.1%
<0.01
57.3%
36.4%
Antibiotic therapy not indicated
17.7%
22.1%
0.04
35.5%
23.6%
No bacterial infection
15.7%
19.3%
0.07
30.7%
16.0%
Treatment course completed
1.2%
1.5%
0.65
2.9%
5.8%
0.03
Prophylaxis not indicated
0.9%
0.62
1.9%
1.7%
1.0
Antibiotic therapy too broad
14.5%
17.9%
0.08
20.9%
12.3%
Unnecessary redundant-coverage
2.2%
0.57
1.1%
0.28
Unnecessary MRSA coverage
5.0%
4.9%
1.00
6.5%
3.7%
0.06
Unnecessary broad GN coverage
4.2%
6.7%
6.2%
4.1%
0.17
Unnecessary GN coverage
1.8%
0.69
3.8%
Unnecessary GP coverage
0.6%
0.4%
0.73 1% 0%
n/a
Unnecessary anaerobic coverage
0.16
0.59
Antimicrobial therapy too narrow
0.7%
0.43
Equally effective, more cost-effective options existed
0.3%
0.68
0.2%
PPA-pre-authorization; PPRW-post-prescription review with feedback; GN-gram negative; GP-gram positive
Tamma PD, et al. Clin Infect Dis. 2017;64(5):