Philip C.

Carling, MD
Professor of Clinical Medicine,
Boston University School of Medicine
APUA Webinar
July 2, 2013
 How the problem developed

A Basic Approach to Healthcare Antimicrobial

Stewardship

Four Elements:
1. Measure IV antibiotic use
2. Optimize IV to oral switch
3. Teach the core concepts of antibiotic use
4. Measure success and escalate the program

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Sir Alexander Fleming

The time may come when

penicillin can be bought by
anyone in the shops. Then there
is the danger that the ignorant
man may easily under dose
himself and, by exposing his
microbes to non-lethal quantities
of the drug, educate them to
resist penicillin.
-Nobel lecture, 1945

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 Achieve optimal clinical outcomes
Minimize toxicity and other adverse events
Minimize development of antimicrobial resistance

May also reduce excessive costs attributable to:

inappropriate/unnecessary therapy
suboptimal outcomes
toxicity and other adverse events
antimicrobial resistance

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What would Duke have
said about our nave
optimism about
antibiotic use over the
past 60 years?

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Coming to a
hospital near you!

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9 Isolates
K. pneumoniae (5), E. coli (2), Enterobacter cloacae (1),
Salmonella (1)
Resistant to all lactams + carbenipenems,
all aminoglycosides, all quinolones
Colistin sens. Tygecycline variable
All isolates also carried other resistance genes

8 Patients hospitalized in India or Pakistan (none medial tourists)

15 countries and 5 continents
North Africa France this spring

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18
16
14
12
10
8
6
4
2
0
1983-1987 1988-1992 1993-1997 1998-2002 2003-2007 2008-2011

Adapted from Spellberg B et al. Clin Infect Dis. 2004;38:1279-86.

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 Only 15-16 antibiotics are in development
Only 8 of these have activity against key Gram negative
bacteria
None have activity against bacteria resistant to all current
drugs

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 FDA Review

Phase III

Phase II
Phase 1
Pre-clinical

0 1 2 3 4 5 6 7 8 9 10
Discovery

IND NDA Product

Filing Filing Launch

Development time (years)

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 March 2010 | Volume 58
Editorial

An obituary- On the Death of antibiotics!

Abdul Ghafur K
Consultant in Infectious Diseases, Apollo Hospital, Chennai

The art of war is deception, that is deceiving the enemy.

But in the war against microbes we have deceived
ourselves by misusing, under using and overusing
antibiotics.Why should we Indians worry? We can
always depend on honey, yoghurt and cows urine.

http://www.japi.org/march_2010/article_01.html

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You can achieve incredible progress if you
set a clear goal and find a measure that will
drive progress toward that goal.

Wall Street Journal - January 26, 2013

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Four Elements:
1. Measure IV antibiotic use
2. Optimize IV to oral switch
3. Teach the core concepts of antibiotic use
A. Dont treat unnecessarily
B. Higher dose shorter duration
C. Consult ID early and often
4. Measure success and escalate the program

P. Carling 2011 SHEA / CDC Course

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 Hospital purchase data
Easiest data to obtain
All Pharmacies know their COSTS

Pharmacy dispensing data from billing records

Closer to actual use
Are pharmacy returns counted?

Antibiotic administration data

Most difficult to get
Presumably represents true antibiotic use

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 600
Hundred thousand dollars

550

500

450

400
1988 1989 1990

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The equation was
simple
A. More expensive antibiotics
were being used.
B. Costs were going down.

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29
The hospital was
shrinking!!
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DDD/1000 PTD
31
 30
Defined Dose Days / 1000 PT DAYS

25

20

15

10
> 200 % increase
5

1988 1989 1990 1991

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 5

0
PERCENT CHANGE

-5

-10

-15

-20
1991 1992 1993
DDD / 1000 PT DAYS COST / 1000 PT DAYS MEDICARE CASE MIX INDEX

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 Impact of the Program
20

10
PERCENT CHANGE

-10

-20

-30

-40
1991 1992 1993 1994 1995 1996 1997 1998
DDD / 1000 PT DAYS COST / 1000 PT DAYS MEDICARE CASE MIX INDEX

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 ANTIBIOTIC COSTS / 1000 PT DAYS
40 IN 14 ACUTE CARE HOSPITALS

30

20

10
Percent

-10

-20

-30

-40
A B C D E F G H I J K L M N

GROUP A GROUP B

Carling PC, Fung T, Coldiron JS.

Clin Infect Dis. 1999 Nov;29(5):1189-96.
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 Defined daily dose (DDD): the usual daily dose for adults as
defined by the World Health Organization (WHO)
Vancomycin DDD = 2 grams.
A patient receives 2 grams/day for 5 days; total use (10 grams) DDD (2
grams) = 5 DDDs
A hospital uses 1000 grams of vancomycin (e.g., purchases, dispenses,
administers) in the 1st quarter of 2010, for a total of 4500 patient days, then:
[1000 grams/2 grams /4500 patient days] X 1000 = 111 DDD/1000 patient
days

Days of therapy (DOT): 1 DOT is administration of a single

agent at least once that day
If a patient receives 2 agents, she receives one DOT for each
Normalize to 1000 patient days

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Four Elements:
1. Measure IV antibiotic use
2. Optimize IV to oral switch
A. Pick the low-hanging fruit
B. IV treatment is not needed
3. Teach the core concepts of antibiotic use
A. Dont treat unnecessarily
B. Higher dose shorter duration
C. Consult ID early and often
4. Measure success and escalate the program

P. Carling 2011 SHEA / CDC Course

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A. Pick the low hanging fruit
IV Quinolones:
Often begun empirically in the ED
Patient improves Why change Rx?
Because PO = IV blood levels
PO costs 25% as much!!

Linezolid
Empiric use varies between hospitals
PO = IV blood levels
Both cost > $200. / day
IV is more costly

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B. IV treatment is not needed
PO often very effectiveespecially when you dont
really need to continue antibiotic therapy

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B. IV treatment is not needed

PO often very effectiveespecially when you dont

really need to continue antibiotic therapy
Good News:
80 % of the cost savings in our program came from stopping unnecessary
antibiotic therapy

Bad news:
It takes work, education and some time (varies)

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Four Elements:
1. Measure IV antibiotic use
2. Optimize IV to oral switch
3. Teach the core concepts of antibiotic use
A. Dont treat unnecessarily
B. Higher dose shorter duration
C. Consult ID early and often
4. Measure success and escalate the program

P. Carling 2011 SHEA / CDC Course

42
A. Dont treat unnecessarily

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Most Common Reasons for
Unnecessary Days of Therapy

30% of 1941 antimicrobial days of

therapy deemed unnecessary
250

200 192 187

Days of therapy

150
94
100

50

0
Duration of therapy Noninfectious or Treatment of
longer than nonbacterial colonization or
necessary syndrome contamination

Hecker MT et al. Arch Intern Med. 2003;163:972-978.

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A. Dont treat unnecessarily
Empiric treatment should be for evident serious
infection in hospitalized patients.pneumonia,
occult sepsis, documented meningitis, urosepsis.

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A. Dont treat unnecessarily
Empiric treatment should be for evident serious
infection in hospitalized patients.pneumonia,
occult sepsis, documented meningitis, urosepsis.

Use positive non-culture testing:

CASE STUDY

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 56 y.o. man, no meds, moderate alcohol, smoker
1wk. - fevers, myalgias, cough
3d. - PCP visit 102 fever, CXR ? +, moderate diarrhea
Rxd - Levofloxacin
1d. - Fever to 103, worse SOB
PE - 103.4, R 32, Toxic appearing
- Chest - Poor breath sounds RA SaO2 82%
- WBC 10.7 - 82p 15B
- Na+ 127 k+ 3.4 Cl- - 85 HC03 25.6
- Cr 1.4 UA SG 1.30, 5-10 WBC, 10-15 RBC

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Differential Diagnosis Extensive
Viral pneumonia Influenza, Adenovirus Rhinovirus, Severe sepsis
with evolving respiratory failure
Evolving bacterial pneumonia on top of preceding viral pneumonia
Legionnaire's disease
Pneumocystis pneumonia
New Coronavirus (SARS)

Antibiotic Therapy
Ticaricillin-sulbactam, Levofloxacin,Tamiflu and bactrim

Rapid antigen testing implemented

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 Course
Intubated with
progressive pneumonia
x6d
ARF necessitating
dialysis x2 wk.
Gradual Improvement
D/C after 3wk.
hospitalization

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Your Answer?

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Your Answer?

Urine Legionella Antigen positive

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A. Dont treat unnecessarily
Empiric treatment should be for evident serious
infection in hospitalized patients.pneumonia,
occult sepsis, documented meningitis, urosepsis.

Use positive non-culture testing:

Legionella urine Ag.
Urine Pneumococcal Ag
Influenza rapid diagnostic tests
(Stay tunedlots more coming)

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B. Think - Higher dose Shorter duration
Higher doses are safewith exceptions
Continuous IV Rx Beta Lactams gaining acceptance

Shorter Duration
CAP 3d. = 8d.
VAP 8d. = 15d.
Cellulitis 5d. = 10d.
Cystitis 3 to 5d. Fine in many studies
Pyelonephritis 5 to 7 d.

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C. Consult ID early and often
Providers who try to use antibiotics need support!
Share the worry
Different perspectives are valuable
Education is pragmatic not didactic
Provides for next step planning of treatment
Share the liability risk
It is CHEAP
the cost of a dose of newer IV antibiotics

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Four Elements:
1. Measure IV antibiotic use
2. Optimize IV to oral switch
3. Teach the core concepts of antibiotic use
A. Dont treat unnecessarily
B. Higher dose shorter duration
C. Consult ID early and often

4. Measure success and escalate the program

P. Carling 2011 SHEA / CDC Course

56
 Put antimicrobial use / cost front and center for the medical
staff and administrationits a win / win proposition
As Bill Gates saidobjective measurement is the basic
element
Celebrate success and use the $$$ saved to enhance the
depth of the program

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Questions Comments? Philip.Carling.MD@steward.org

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