Antibiotic Stewardship
in Era of MDR
sepsis
Underlying Mortality with Mortality without P-value
disease appropriate therapy appropriate therapy
therapy on mortality
Alvarez-Lerma,1996 Initial adequate
therapy
Rello, 1997
Initial inadequate
Kollef, 1999 therapy
Kollef, 1998
Ibrahim, 2000
Luna, 1997
Harbarth, 2003
therapy
non-ESBL ESBL
Delay in Rx 0 10 20 30 40 50 60
Mortality pOR=1.85
JAC 2007
Spread in the community
Copyright: YEHUDA CARMELI 2014
9
No. of cases of ESBL-EC/UHABSIs per
7.87
8
6.93
7
10, 000 admissions
6
6 5.57
5 4.53
3.83
4
2.94
3
0
2003 2004 2005 2006 2007 2008 2009
Year
20
15
10
5
0
340 ESBL
isolates were
reported:
87% E. coli
Type varied
by region
Ben-Ami R.
CID 2009.
YEHUDA CARMELI_ISAR2014
Risk factors for infection with ESBL-producing
Enterobacteriaceae in non-hospitalized patients -
metasynthesis
appropriateness of therapy
Standard Rx Guidelines
Ibrahim EH. Crit Care Med 2001
YEHUDA CARMELI_ISAR2014
Mortality among 97 patients with
adequate empiric therapy
60
50
50
Mortality (%)
40
30 25
20 12
10 3
0
FQ (16) Amino (20) Bla/bli (33) Carbapenem
(28)
Antimicrobial treatment
Tumbarello 07
Imipenem
Quinolones
Paterson
Endiamini
0 10 20 30 40 50 60 70 80
Half-life
AUC
on PK/PD parameters
41 + 0.03 0.75
PK/PD breakpoint for ciprofloxacin ESBL – data from Edmiston CE, JAC 2005
400mg bid is 0.25 * ESBL+, Israeli ESBL Study
* Frei C, JAC 2008
Copyright: YEHUDA CARMELI 2014
AAC 2013
175
Copyright: YEHUDA CARMELI 2014
150
125
100
%
75
50
imipenem
Cephalosporins
25 ESBL
Imp-R-PA
0
1995 1996
Year
Adapted from Rahal JJ. JAMA 1998
YEHUDA CARMELI_ISAR2014
6
Group 2 carbapenem
5
4
3
2
1
0 20 40 60 80
carb2
6
Group 1 carbapenem
4
2
0
0 20 40 60
erta
Carmeli Y. DMID 2010 95% CI predicted imprpa
Copyright: YEHUDA CARMELI 2014
JAC 2011
Risk stratification
Copyright: YEHUDA CARMELI 2014
stewardship programs
Pathogen Syndrome
Treatment
Antibiotic treatment
Copyright: YEHUDA CARMELI 2014
intervention
of antibiotic stewardship
• OPAT is used to discharge patients early or
even avoid hospitalization
– cost saving, reduces hospital associated
complications
– improves patients satisfaction
• Overusing OPAT may be costly
– 56 patients were denied OPAT: antibiotic
stopped or switch to oral
– saving $ 215,000 ($ 3847 per patient)
– One treatment failure, required IV antibiotics
Conant MM. JAC 2014