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Drug Utilization Evaluation
of Vancomycin
at
King Khalid University Hospital
By:
Dina I. Fouda, M.Sc. Pharm. candidate
Supervised by:
Dr. Lamya AL Naim
Dr. Iman Zaghloul
Dr. Ahmed Albarraq
Major adviser
Faculty Co-advisor
External Co-adviser
Outline
 Introduction to Vancomycin
 Why Vancomycin?
 CDC Guidelines
 TDM
 Objectives
 Methodology
 Results & Discussion
 Limitations
 Recommendations
 Conclusion
Introduction
 Vancomycin is a glycopeptide antibiotic with
bactericidal activity against gram - positive
microorganisms.
 Approved by FDA in 1958.
Johnson S.V., et al. Pharmacotherapy. 1995
Introduction
 In the past, it was used as a 2nd or 3rd line
agent due to availability of:
• Equally efficacious
• Less toxic
alternatives
• Less expensive
Johnson S.V., et al. Pharmacotherapy. 1995
Why Vancomycin?
 Over the last 15–20 years, the utilization of
Vancomycin has increased because of the
dramatic increase in MRSA, MRSE and
Ampicillin resistant enterococci.
MRSA = methicillin-resistant Staphylococcus aureus
MRSE = methicillin-resistant Staphylococcus epidermidis
Johnson S.V., et al. Pharmacotherapy. 1995
Percentage of Nosocomial Enterococcal Infections in
United States
7.9%
0.3%
1988
1989
1990
1991
1992
1993
Year
CDC. Nosocomial enterococci resistant to vancomycin -- United States, 1989-1993. MMWR 1993
Why Vancomycin?
Problems:

The lack of available antimicrobial therapy for VRE infections
, because most VRE are also resistant to drugs previously used
to treat such infections (e.g., aminoglycosides and ampicillin).
 VRE therapy requires expensive & not readily available
antibiotics (e.g Linezolid & Teicoplanin).
 The possibility that the vancomycin-resistant genes present in
VRE can be transferred to other gram-positive microorganisms
(e.g., Staphylococcus aureus).
 Vancomycin has an important role in serious infections and we
do not want to loose its efficacy.
VRE=Vancomycin-resistant enterococci
Centers for Disease Control and Prevention. MMWR . 1995
Why Vancomycin?
resistant infections
morbidity
spread of
infection
Inappropriate use
of vancomycin
hospital stays
costs
Centers for Disease Control and Prevention. MMWR . 1995
Florida Department of Health. Guidelines for control of antibiotic resistant organisms. 1999
Why Vancomycin?
 In 1995, the Centers for Disease Control
and Prevention (CDC) published guidelines
for the use of vancomycin.
Centers for Disease Control and Prevention. MMWR.. 1995
Guidelines published by the Centers for Disease Control and
Prevention (CDC)
Situations in which the use of vancomycin is appropriate or acceptable
1.
2.
3.
4.
5.
For treatment of serious infections due to β-lactam resistant Grampositive microorganisms.
For treatment of infections because of Gram positive
microorganisms in patients with serious allergy to beta-lactam antimicrobials.
Prophylaxis, as recommended by the American Heart Association,
for bacterial endocarditis following certain procedures in high-risk
patients.
Prophylaxis for major surgical procedures involving implantation of
prosthetic materials or devices.
When antibiotic-associated colitis fails to respond to metronidazole
therapy or is severe and potentially life-threatening.
Centers for Disease Control and Prevention. MMWR.. 1995
Guidelines published by the Centers for Disease Control and
Prevention (CDC)
Situations in which the use of vancomycin should be discouraged
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
Routine surgical prophylaxis.
Treatment in response to a single blood culture positive for coagulase-negative
staphylococcus, if other blood cultures taken during the same time frame are negative.
Continued empiric use for presumed infections in patients whose cultures are negative
for β-lactam–resistant gram-positive microorganisms.
Empiric antimicrobial therapy for a febrile neutropenic patient.
Systemic or local prophylaxis for infection or colonization of indwelling central or
peripheral intravascular catheters.
Selective decontamination of the digestive tract.
Eradication of MRSA colonization.
Primary treatment of antibiotic-associated colitis.
Routine prophylaxis for very low-birth weight infants (i.e., infants who weigh<1,500 g).
Routine prophylaxis for patients on continuous ambulatory peritoneal dialysis or
hemodialysis.
Treatment (chosen for dosing convenience) of infections caused by β-lactam–
sensitive gram-positive microorganisms in patients who have renal failure.
Use of vancomycin solution for topical application or irrigation.
Centers for Disease Control and Prevention. MMWR . 1995
Guidelines published by National Comprehensive
Cancer Network (NCCN)
Indication consider appropriate at KKUH but NOT part of CDC
guidelines
1. Empiric anti-microbial therapy for a febrile neutropenic
patient, when there is strong evidence at the onset that the
patient has an infection because of Gram-positive
microorganisms.
National Comprehensive Cancer Network. NCCN,. 2005
Why Vancomycin?
 Vancomycin considered a restricted antibiotic .
 Antimicrobial advisory committee at KKUH noticed
a tremendous increase in vancomycin orders by non
Infectious Disease specialties.
KKUH = King Khalid University Hospital
Vancomycin Therapeutic Drug Monitoring
(TDM)
 The need for TDM in patients receiving Vancomycin is
remaining controversial.
 Vancomycin demonstrates concentration-independent
killing in its effect on bacteria.
 Measuring serum Vancomycin levels is to ensure an
adequate trough serum level for efficacy rather than to
predict or prevent toxicity.
Vancomycin Therapeutic Drug Monitoring (TDM)
 One large problem, however, remains for
vancomycin: the lack of standardized targets for
serum concentration monitoring.
 The ideal vancomycin dosing regimen:
Peak= 20 - 40 mg/L , Trough= 5 – 20 mg/L.
Vancomycin Therapeutic Drug Monitoring (TDM)
 One large problem, however, remains for
vancomycin: the lack of standardized targets for
serum concentration monitoring.
 The ideal vancomycin dosing regimen:
Peak= 20 - 40 mg/L , Trough= 5 – 20 mg/L.
 Vancomycin concentration sampling should be
repeated if there is a change in renal function or lack
of therapeutic response.
Nephrotoxicity
 Vancomycin alone has a low potential for causing
nephrotoxicity ( ≤5% ) in the absence of other factors
that can adversely affect renal function.
 The nephrotoxicity of Vancomycin is increased to
43% when it is co-administered with nephrotoxic
drugs.
Cantú TG et al. Serum vancomycin concentrations:reappraisal of their clinical value. 1994
Evaluate the appropriateness of vancomycin use
in KKUH in terms of
Main
objectives
Indications in
accordance
with
CDC guidelines
Appropriate
application
Of
TDM
Secondary
objectives
Incidence of
Nephrotoxicity
Estimated
acquisition cost
Methodology
Methodology
 Study Design and Population :
• A retrospective review of medical charts & computerized
databases of all patients who received a course of
vancomycin between January and June 2005 during there
admission to KKUH.
KKUH = King Khalid University Hospital
Methodology

Data Collection:
Data collection form was used to collect data.
Divided into 6 categories:
1.
2.
3.
4.
5.
6.
Demographic Data
Hospital departments
Appropriateness of therapy
Dosing regimen
Laboratory test
Cost
Methodology
 Statistical Analysis:
• The data was coded & entered into SPSS version 14.
• Descriptive statistics were used to evaluate most of the
parameters.
• Continuous variables were reported as a range.
• Paired t-test was used to compare some of the parameters before
and after the use of Vancomycin.
SPSS= Statistical Package for Social Sciences
S.D. = Standard Deviations
Results & Discussion
Six months period
222 patients
255 courses of vancomycin
176 adults
79 neonates & pediatric patients
Age
18 – 95 Years
Age
< 1 month – 17 years
Duration of course
1 – 74 days
Route of Administration
Intravenous
Intraperitoneal
Irrigation
249 courses
( 98%)
5 courses
(2%)
1 course
(<1%)
Type of Vancomycin Therapy
Empirical therapy
Specific therapy
Surgical prophylaxis
119 courses (47%)
90 courses (35%)
46 courses (18%)
Appropriateness of Vancomycin therapy
60%
51%
49%
50%
40%
30%
20%
10%
0%
Appropriate
Inappropriate
Appropriateness of Vancomycin therapy in different
DUE studies
80%
70%
72%
72%
60%
54%
60%
49%
50%
40%
32%
33%
35%
40%
Inappropriate
30%
20%
10%
0%
Sin
Ho
Ho
KS
US
US
US
Fra
US
ng
ng
A(
ga
A,
A,
A,
A,
nc
po
KK
e,
K
K
19
19
19
2
00
on
on
re,
94
95
96
19
UH
1
g,
g,
99
),
19
2
2
00
00
99
20
0
2
05
Categories of inappropriate Vancomycin use
Continued empiric use with
culture -ve
Routine surgical prophylaxis
Treatment of bacteria sensitive to Blactam Gm +ve in non allergic patients
12%
5%
3%
2% 1%1%
Routine empiric use for febrile
neutropenic patient
Treatment without evidence of
a resistant Gm+ve infection
13%
Single blood culture +ve to
staphylococcus epidermidis
14%
49%
Local prophylaxis for infection
peripheral intravascular catheter
Use of vancomycin solution
for irrigation
Eradication of MRSA colonization
Compare with Hong Kong study
Continued empiric use in patients whose culture negative
KKUH
49%
PWH
71%
Appropriateness of Vancomycin use by different
departments
60%
50%
ICU 55%
ICU 47%
40%
30%
Medical
25%
Surgical
28%
Medical
23%
Surgical
22%
20%
10%
0%
Appropriate
Inappropriate
Appropriateness of Vancomycin use by the type of ICU
CCU
37%
40%
NICU
31%
35%
30%
25%
20%
NICU
15%
PICU
19%
MICU
23%
CCU
PICU
20%
19%
MICU
15%
15%
SICU
6%
10%
5%
0%
Appropriate
Inappropriate
SICU
15%
Appropriateness of Vancomycin prescribing by medical
service
9%
10%
13.7%
14%
12%
8%
6%
Appropriate
Inappropriate
4%
2%
0%
y
log
ino
cr
do
En
gy
olo
ur
Ne
y
og
iol
rd
y
Ca
l og
e
ro
as
ph
ise
Ne
sd
ou
cti
fe
In
i ce
y
dic
er
rg
me
Su
re
ca
s
al
ric
iat
itic
Cr
ed
lp
ra
ne
Ge
y
l og
co
gy
On
olo
at
on
Ne
Appropriateness of Vancomycin prescribing by surgical
service
40%
35%
35%
30%
25%
25%
20%
15%
Appropriate
Inappropriate
10%
5%
0%
gy
lo
ro
U
s
tic
as
Pl
ic
ed
op
r
la
rth
O
cu
as
ov
di
ar
C
al
er
y
en
G
er
rg
su
ro
eu
N
Inappropriate use according to type of Vancomycin
therapy
80%
65%
70%
60%
50%
40%
Inappropriate
30%
19%
20%
16%
10%
0%
Specific therapy Empirical therapy
Surgical
prophylaxis
Compare with Hong Kong study
76%
80%
65%
70%
60%
50%
40%
30%
KKUH
PWH
19%
16%
20%
10%
19%
5%
0%
Specific therapy Empirical therapy
Surgical
prophylaxis
Inappropriate use of Vancomycin according to the type of therapy
Inappropriate use of Vancomycin classified by
microorganism
60%
50%
50%
40%
30%
19%
23%
20%
10%
Inappropriate
4%
4%
0%
O
o
er
th
us
s
m
is
an
rg
cc
co
ro
te
En
us
re
SA
R
au
M
us
cc
is
id
co
m
lo
er
hy
id
ap
ep
St
us
cc
co
lo
hy
ap
St
Order for Vancomycin serum level
Not
applicable
22%
Yes
69%
No 9%
Trough
81%
Peak&Trough
19%
Vancomycin serum level outcome
Subtherapeutic
level
57%
Toxic level
14%
Therapeutic
level
29%
Vancomycin
protocol
Vancomycin serum level outcome
18%
16%
Neonatology
Oncology
General pediatrics
Critical care medicine
Surgery
Infectious disease
Nephrology
Cardiology
14%
12%
10%
8%
6%
4%
2%
0%
Therapeutic
SubToxic Level
Level
therapeutic
Level
Response to non-therapeutic level
No
response
48%
No
appropriate
response
Appropriate
response
32%
20%
Failure
75%
Success
25%
Achievement of therapeutic level
after response
Nephrotoxicity
A decrease of >50 ml/min in creatinine clearance due
to Vancomycin use is considered nephrotoxic.
Estimated creatinine clearance (before and after
receiving Vancomycin)
t-test:
Difference is not significant (P>0.05).
Nephrotoxicity
1
10
Srcr before
mg/dl
0.4
2
12 *
0.4
0.5
218
143.8
3
20
0.5
1.6
209.7
63.9
4
23 *
0.6
3.4
169
28.9
5
33 *
1.3
5.1
83.7
21
6
33 *
1.2
5.6
86.8
19
7
56 *
1
3.3
75.1
21.9
8
61 *
0.6
1.1
122.5
69.8
9
64 *
0.7
1.5
105
49
10
70 *
0.6
2.5
97.4
24
Mean ±
S.D
-
0.73
± 0.32
2.51
± 1.8
137
± 57
57.9
± 47.4
Number of
patients
Age
(year)
Srcr after
mg/dl
0.5
Clcr befor
ml/min
203
Clcr after
ml/min
138
* Received Vancomycin with other nephrotoxic drugs.
P < 0.05
Compare with Hong Kong study
25
21
20
17
Number
of
patients
15
10
10
Nephrotoxicity
8
5
0
KKUH
PWH
Cost
 The cost of Vancomycin during the study period
47,901.44 SR.
 The cost / therapeutic course = 187.85 SR.
 The cost of Vancomycin in which inappropriately
used = 10,115 SR or (21%).
=
Conclusion
1)
Vancomycin was inappropriately used in
125 patients (49%).
2)
The most common situation in which the use of
Vancomycin was inappropriate is continuing
empirical use for presumed infections in patients
whose cultures were negative for β-lactam resistant
gram-positive organisms.
Conclusion
3)
ICU was the department with the highest
inappropriate use of Vancomycin (55%).
4)
Vancomycin serum level was sub-theraputic in
101 patients (57%).
5)
Nephrotoxicity was found only in 10 patients
(4.5%).
Limitations
•
•
•
Retrospective
Poor documentation
Covered short period
Recommendations
1)
Development & distribution of practical guidelines
for Vancomycin use.
2)
Adhere to Vancomycin guidelines.
3)
Implementation of programs:
•
Formal reassessment of therapy after 2-4 days.
•
Educational interventions & programs for physicians.
•
Computer-assisted prescribing of Vancomycin.
•
Clinical pharmacist in Infectious disease team.
Recommendations
4)
Continued evaluation of Vancomycin usage to
ensure that interventions for improving its use are
effective.
Even 50 years after Vancomycin’s discovery,
it remains an interesting and somewhat
controversial agent
Acknowledgements