1. Antibiotic Stewardship
James S. Lewis II, PharmD, FIDSA
ID Clinical Pharmacy Supervisor & Co-Director of Antibiotic Stewardship
Oregon Health & Science University
Departments of Pharmacy & Infectious Diseases

2. Objectives
Define the appropriate duration of therapy for pyelonephritis
Explain the appropriate duration of therapy for community acquired pneumonia
List common infections where shorter durations of therapy have been supported by recent evidence or guidelines

3. “We know all we need to know about antibiotics except for how much to give and how long to give them”
Lou Rice, M.D. - ICAAC 2007

4. “Assessment of Appropriateness of Antibiotics for…”
CAP
Skin & soft tissue infections
Urinary tract infections
Care of patients with C. difficile
“Guidelines for Antimicrobial Use in Adults & Pediatrics”

6. So What Do We Know?

7. “One thing we ID doctors know — that other clinicians simply don’t — is how long to treat a patient with antibiotics.”
Multiple of 5 (fingers of the hand) or 7 (days of the week).
Outpatient problem? Relatively mild? 
If so, <10 days. 
After application of rule 1, this should be 5 or 7 days.
Is it really mild? ABX probably not needed but clinician or patient insistent? 
Break the 5/7 rule and go with 3 days.  Ditto uncomplicated cystitis in young women.
Serious problem that occurs in the hospital or could end up leading to hospitalization?  
With the exception of CAP (5 or 7 days), 10 d minimum.
End of therapy & patient not doing better? 
Extend treatment, again using a multiple of 5 or 7 days.
Infection involve bone or heart valve? 
Four weeks (28 days) at least, often 6 weeks (42 days).
Note that 5 weeks (35 days) is not an option — here the 5’s and 7’s cancel each other out, and chaos ensues.

8. And most importantly
The following lengths of therapy are inherently weird, and should generally be avoided:  2, 4, 6, 8, 9, 11, 12, 13 days.  Also,   days. OR
Use a football score!

9. Infections for Which Short-Course Therapy Has Been Shown to Be Equivalent in Efficacy to Longer Therapy
Disease
Treatment, Days
Short
Long
Community-acquired pneumonia
3-5
7-10
Nosocomial pneumonia ≤8
10-15
Pyelonephritis
5-7
10-14
Intraabdominal infection 4 10
AECB & COPD ≤5
>7
Acute bacterial sinusitis 5
Cellulitis
5-6
Chronic osteomyelitis 42 84
Spellberg B, JAMA Intern Med 2016;176:1254-5

10. Barlam TF, et al. Clin Infect Dis 2016;62:e51-e77

11. Shorter Courses Do Not Affect Outcome
Sawyer RG, et al. NEJM 2015;372: ; Chastre J, et al. JAMA. 2003;290(19):
Sandberg T, et al. Lancet 2012;380: ; Moran GJ, et al. Lancet Infect Dis. 2014;14(8):

12. Clin Infect Dis 2007;44:s27-72

13. 312 patients – 4 teaching hospitals in Spain
Minimum of 5 days of antibiotics vs standard of care
Intervention arm stopped based on
Tmax < 37.8C for 48h
≤ 1 CAP associated sign of clinical instability – WHAT ARE THESE
JAMA Internal Medicine 2016;176:

14. CAP Associated Signs of Instability
No more than one of the following
SBP<90
HR >100/min
Respiratory rate >24/min
Arterial O2 saturation <90% or PaO2 <60mm Hg on room air
Recommended by IDSA/ATS in 2007 CAP guidelines
Weak evidence
Poor uptake of recommendation
How often do you still see days?
JAMA Internal Medicine 2016;176:

15. Outcomes
JAMA Internal Medicine 2016;176:

16. Results for Secondary Outcomes
Control group (n=137)
Intervention group (n=146)
P Value
Time, median (IQR), days
Taking antibiotics
10 (10-11)
5 (5-6.5)
<.001
Until clinical improvement
12 (8-18)
12 (7-15)
.41
Return to normal activity
18 (9-25)
15 (10-21)
.12
30 day mortality
3 (2.2%)
3 (2.1%)
>.99
30 day readmission
9 (6.6%)
2 (1.4%)
.02
Length of hospital stay, mean (sd)
5.5 (2.3)
5.7 (2.8)
.69
JAMA Internal Medicine 2016;176:

17. CID 2018;66:1333

18. Kalil AC, et al. Clin Infect Dis 2016;63:e61-e111

19. Short vs Long Courses: But What About…
Pseudomonas
Acinetobacter
Stenotrophomonas
“… no differences were observed for pneumonia recurrence (95% CI )
or mortality (95% CI )”
“…short courses of antibiotics reduce antibiotic exposure & recurrent pneumonia
due to MDR organisms.“
“…mortality not affected by duration of antibiotic therapy…”
Kalil AC, et al. Clin Infect Dis 2016;63:e61-e111

20. What About MRSA & Duration of Therapy
The 2016 HAP/VAP guidelines say…
MSSA
MRSA
The 2011 IDSA MRSA Guidelines say…
“IV vancomycin, linezolid, … recommended for 7-21 days depending on the extent of the infection.”
Kalil AC, et al. Clin Infect Dis 2016;63:e61-e111
Liu C, et al. Clin Infect Dis 2011;52:1-38

21. 2 Pages of Pure Genius
JAMA Internal Medicine 2015; epub 1/15/15

22. 7 vs 14 Days of Ciprofloxacin (Cip) for Pyelonephritis
Randomized, open-label and double-blind, placebo- controlled, non-inferiority trial
Cip for 7 days (n=73)
Cip for 14 days (n=83)
Age
46 (27-62)
41 (23-58
Recurrent UTIs
11 (15%)
10 (12%)
E. Coli
64 (88%)
79 (95%)
Positive blood cultures
16 (22%)
26 (32%)
Initial IV dose of cip
14 (19%)
Data are number (%) or median (IQR). All blood cultures grew Escherichia coli.
Sandberg T, et al. Lancet 2012;380:

23. 7 vs 14 Days of Ciprofloxacin (Cip) for Pyelonephritis
Cip 7 days
Cip 14 days
Difference
(90% CI)
Non-Inferiority
test P value
Cure
93%
-0.3% (-7.4 to 7.2)
0.015
Clinical failure
or recurrent UTI symptoms 7% -
The take home – quit treating pyelo for 14 days with quinolones!
Even bacteremic pyelo!
Questions when using non-quinolone agents
Sandberg T, et al. Lancet 2012;380:

24. Notice anything missing?
Cellulitis w/o systemic signs of infection – cover streptococci
Cellulitis with systemic signs of infection – cover streptococci and MSSA
Cellulitis associated with penetrating trauma, MRSA elsewhere, injection drug use, or SIRS - vancomycin
Stevens DL, et al. Clin Infect Dis 2014;doi: /cid/ciu296

25. Skin and Skin-Structure Infection Durations
Prokocimer P, et al. JAMA 2013;309:
Moran GJ, et al. Lancet Infect Dis 2014;14:

26. Ceftaroline prescribing information

27. 518 patients with complicated intraabdominal infection
Adequate source control
Antibiotics until 2 days after resolution of – max of 10 days
Fever
Leukocytosis
Ileus
Vs experimental group – 4 days of antibiotic therapy
Sawyer RG, et al. NEJM 2015;372:

28. Results No difference in: Major differences (p<0.01) in SSI rate
Recurrent IAI
Death
Major differences (p<0.01) in
Time to SSI or rIAI
Days of antibiotics
P=0.92
Sawyer RG, et al. NEJM 2015;372:

29. Conclusions Less is more The Joint Commission is coming!
Historical durations of therapy are largely based on…
Pneumonia, SSTI, and IAI can should all be <10 days
Clinical caveats