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Antibiotic policy to prevent
resistance development
Inga Odenholt
Associate professor
Department of Infectious Diseases, Malmö
Lund University, Sweden
Antibiotic Resistance
-THE RESULT OF A GLOBAL
FAILURE
Antibiotic
resistance
New treatment
options
Introduction of New Antibiotic Classes
Oxazolidinones
Trimetoprim
Streptogramins
Quinolones
Lincosamides
Chloramphenicol
Cephalosporins
Tetracyclines
Macrolides
Glycopeptides
Aminoglycosides
Penicillins
Sulphonamides
1930´s
1940´s
1950´s
1960´s
1970’s
1980´s
1990´s
2000´s
How to combat the increasing
resistance?
STRAMA
Swedish Strategic programme
for The Rational use of
Antimicrobial Agents and
Surveillance of Resistance
www.strama.org
How it all started
• Increasing incidence of Pc-resistant pneumococci
(PRP) in Southern Sweden from ~2% to 8-15%
in early 1990s
• Deterring international experiences
• Who is responsible for action?
• Discussion between competent authorities and
professional organizations resulted in the
formation of a national network for the combat of
antibiotic resistance (1994)
STRAMA National Group
Swedish Medical Association
Swedish Institute for Infectious Disease Control
National Board of Health and Welfare
Medical Products Agency
National Corporation of Swedish Pharmacies
Swedish Society for Hospital Hygiene and
Infection Control
The Swedish Federation of County Councils
Corporation of County Medical Officers
Swedish Association of Local Authorities
The Swedish Network of Pharmacoepidemiology
National Veterinary Institute
The Swedish Board of Agriculture
STRAMA Primary objectives
1.To create a cross-sectorial national forum to
- share information
- formulate national strategies
- support an initiate research activities
- collaborate with media
2. To stimulate the formation of regional
STRAMA - groups in every county
STRAMA
1995-1999 Voluntary basis
2000-2002 Supported by the Swedish
Government with 320.000 EUR yearly
2003 Funding increased to 800.000 EUR
Examples of Goals for
STRAMA (out-patients)
1. To follow the usage of antibiotics and the
pattern of resistance at the national/regional levels
2. To implement therapeutic guidelines and
intervention programmes
3. To give feed-back to prescribers
4. Cooperation with media
In order to reduce inappropriate antibiotic
use
Antibiotic consumption on a
national level
Swedish DiagnosisAntibiotic Prescribing study
2000 and 2002
• Five counties, 1.3 mil inhabitants
– chosen to reflect the country’s antibiotic
utilisation
• 140 primary care centres, 600 GPs
• One week in November
• Recruitment through local STRAMA
groups
• Anonymous
Antibiotics for urinary tract infections in the
2000 and 2002 STRAMA Diagnosis-antibiotic
prescribing study
100%
80%
60%
40%
20%
0%
3 18
8
59 =52
6
5
=
n
n
n= n=
0
2
0 02
0
00 200
0
0
2
2 I2
I TI
I
T
T
T
U rU
U
U
r
e pe
er er
p
p
p
w ow
o
U
U
L
L
No treatment
Referral
On treatment
Others
Quinolones
Trim+sulfa
Trimetoprim
Cefalosporines
Tetracyclines
Fosfomycin
Nitrofurantoin
Pivmecillinam
Antibiotic consumption
on a regional level Antibiotics in the county of Skåne
6
5
4
Tetracyclins
Amoxicillin
Penicillin V
Cephalosporins
Macrolids
3
2
DDD / 1000 inv o dag
1
0
1999
2000
2001
2002
År
2003
2004
2005
Antibiotics age group 0-6 years, municipalities in Sweden
with the highest and lowest consumption, 2002.
Resistance pattern
The resistance of E. coli in Sweden
25
20
Ampicillin
% resistens
15
Trimethoprim
Quinolones
Cefadroxil
Mecillinam
10
Nitrofurantoin
5
0
1995
1996
1997
1998
1999
2000
År
2001
2002
2003
2004
Feed-back to the prescribers
Consumption of fluoroquinolones in 4 districts Uppsala County
The effect of prescriber feed-back and educational outreach
(DDD/1000 inhabitants/day)
1,8
1,6
1,4
1,2
1995
1
1996 0,8
0,6
0,4
0,2
0
1
2
3
4
en
t
t
t
t
c
c
c
c
d
i
i
i
i
e
r
r
r
r
t
t
t
t
w
s
s
s
s
S
Di
Di
Di
Di
Consumption of fluoroquinolones in 4 districts Uppsala County
The effect of prescriber feed-back and educational outreach
(DDD/1000 inhabitants/day)
1,8
1,6
1,4
1,2
1995
1
1996
1997 0,8
0,6
0,4
0,2
0
1
2
3
4
en
t
t
t
t
c
c
c
c
d
i
i
i
i
e
r
r
r
r
t
t
t
t
w
s
s
s
s
S
Di
Di
Di
Di
Conclusions
• Knowing the national and regional use of
antibiotics and the national and regional resistance
pattern
Interventions e.g. Therapeutic guidelines,
education on a local level
• Continuous efforts have led to changes in
prescribing patterns (e. g. reduced use of
quinolones in uncomplicated UTI, decreased use
of of antibiotics in total; 20% in 8 years)
Treatment guidelines
STRAMA in hospitals
The point-prevalence study
• During 2 weeks in November 2003 and
2004 all patients in appr. 80% of the
hospitals in Sweden were registered
• 54 hospitals were included
• 434 departments
• 13536/11 348 patients
• 30.9/31.8 % of the patients were treated
with antibiotics
The point-prevalence study
• The aims of the study were to describe the
use of antibiotics in Swedish hospitals
–
–
–
–
–
Indications/Diagnoses
Choice of antibiotics. Correct or not?
Dose
Community-acquired or nosocomial infections
Infections related to foreign-body devices
Diagnoses
Central nervous system
Ophthalmic infections
Mouth and throat
Upper respiratory tract
Bronchitis
Pulmonary infections
Cardiovascular system
Gastrointestinal upper
Gastrointestinal lower
Gastrointestinal transmissible diseases
Liver/bile duct/pancreas/spleen
Skin and soft tissue
Bone and joint
Urinary bladder, cystitis
Kidney, pyelonephritis, febrile urinary tract
infection
Genitalia
Sepsis
Indication not specified
Indication unclear
The point-prevalence study
• Of all patients in the hospitals, antibiotic
treatment was initiated
– In 17% due to community-acquired infections
– In 9% due to nosocomial infections
– In 6% as prophylaxis
0%
Alla specialiteter
öron-näsa-hals
ögon
urologi
transplantations kirurgi
thoraxkirurgi
reumatologi
plastikkirurgi
ortopedisk kirurgi
onkologi
njurmedicin
neurologi
neurokirurgi
neuro rehab
neonatalavd
med rehab
lungmedicin
kärlkirurgi
kardiologi
infektionsklin
hudklinik
hematologi
handkirurgi
gynekologi
geriatrik
gastroenterologi
endokrinologi
BB/förlossning
barnmedicin
barnkirurgi
barnhabilitering
allm kirurgi
allm internmed
akutklinik
Andel behandlade/inneliggande patienter
Percentage of antibiotic treated patients per speciality; PPS 2003 och 2004.
2003: tot 4178 treated of 13 536 patients
2004: tot 3622 treated, of 11 348 ipatients
90%
80%
PPS 2003
PPS 2004
70%
60%
50%
40%
30%
20%
10%
What antibiotics were used?
Antibioticusedfortreatment andprophylaxis
1000
900
800
700
Noof terapies
600
Treatment
500
Prophylaxis
400
300
200
100
0
Cephalosporins
Isoxazolyl-pc
Quinolones
Ampicillin
Penicillins
Tetracyclins
bro
ad
sp
ec
Community aquired
Hospital aquired
im
ox
az
o le
im
eto
pr
im
Ot
he
rs
Flu
or
oq
u in
ol o
ne
s
Li n
co
sa
mi
de
s
Co
-tr
Tr
Ca
rb
ap
en
em
s
Ce
ph
a lo
sp
or
ins
lin
s
tru
m
Is o
xa
zo
ly l
pe
nic
il
Pe
nic
ill in
Number of DDD
PPS 2003
Urology, spectrum of used antimicrobials
12
10
8
6
4
2
0
PPS 2003
Urology
Treatment diagnoses
30
Number of therapies
25
20
15
10
5
0
Cystitis
Fever
Cl difficile
colitis
Genital
Lower GI-tract Upper GI-tract
Therapy, 62
Skin / soft
tissue
Prophylaxis, 37
Pneumonia
Pyelitis
Septicemia
Others
Too much quinolones and
cephalosporins!
CID, 2004;38 (suppl 4): 341-345
SANT-study
Swedish Antibiotic Nursing home Trial
Aims of the study
•To describe and evaluate the
treatment of infections in elderly
patients in nursing homes
Results of the registration
•
•
•
•
58 nursing homes with 2752 patients
890 infection registrations
Mean age of 86 years.
Appr. 2/3 were women
Results
• 43% of the patients had received antibiotics the past
3 months
• 33% had had the same infection the past 3 month
• Urinary tract infections was the most common
diagnosis (60 %). Thereafter skin- and soft tissue
infections (15 %), pneumonia (15 %) and others
(10 %).
• In 86 % of all registered infections antibiotics were
initiated
Treatment of UTIs
• 89 % of the patients received antibiotics
• >50% of the patients had got a UTI diagnosis the
past 3 month and > 50% had received antibiotics the
past 3 month
35
20
15
10
5
os
po
rin
s
Ce
ph
al
Ni
tro
fu
ra
nt
oi
n
Pi
vm
ec
i
llin
am
/s
ul
ph
a
Tr
im
ol
on
es
0
Q
ui
n
%
30
25
What did we learn?
• Earlier studies have shown that appr. 50%
of patients in nursing homes have
asymptomatic bacteriuria
• A majority of these patients receive
antibiotics, which is not recommended
Hospital-acquired infections
Percent hospital-acquired infections in relation to all admitted patients in some
Swedish counties
12,0
10,0
8,0
Postoperative infections
%
Device-related HAI
C. difficile enterocolitis
6,0
Other HAI
HAI from other hospitals
All
4,0
2,0
0,0
Jönköpings län, 808
Skåne län, 2116
Sweden, 11348
PPS2003
Hospital acquiredinfections, foreigndevices, 299 st
120
100
Number of treatments
80
60
40
20
0
CNS
Hart /
vascular
Cystitis
Upper GI-tr
Skin / soft
tissue
Liver / bile
Bone / joint
Pneunonia Pyelonefritis Septicemia
Others
Asymptomatic patients with or
without indwelling catheters
should not be treated with
antibiotics
Antibiotic prophylaxis
PPS 2003
All peri-operative prophylaxis in surgical departments
120
Number of therapies
100
80
60
40
20
0
Urology 40
Orthopaedics
212
Ear surgery 15
Prophylaxis single dose
General surgery Gynaecology 48 Other surgery 65
202
Prophylaxis 24 hours
Prophylaxis >24 hours
PPS 2003
Urology, length of peri-operative prophylaxis, 37 therapies
30
25
Number of therapies
20
15
10
5
0
Prophylaxis one dose
Prophylaxis one day
Prophylaxis >1 day
PPS 2003
Urology, spectrum of substances in peri-operative prophylaxis in DDD
18
16
14
Number of DDD
12
10
Prophylaxis one dose, 3,5
Prophylax one day, 7
8
Prophylaxis >1 day, 27,4
6
4
2
0
Penicillin
broadspectrum
Cephalosporins
Trimetoprim
Co-trimoxazole
Aminoglycosides Fluoroquinolones
Imidazoles
Too long prophylaxis!
• One dose before
–
–
–
–
–
Transurethral prostate resection
Transrectal prostate core biopsy
Surgery with bowel substitute
Opening of the urinary tract, i.e. radical
prostatectomy
Conclusions
• Too much quinolones and cephalosporins in the
hospitals
• Too much quinolones on not recommended
indications (e.g. lower UTIs in women)
• Too much antibiotic treatment for urinary tract
infections in asymptomatic patients
• Too much antibiotic treatment for urinary tract
infections in patients with catheters
• Too long prophylaxis in surgery
If we stop using one antibiotic,
can the resistance trend be
reversed?
The resistance of E. coli in Sweden
25
20
Ampicillin
% resistens
15
Trimetoprim
Nalidixinsyra
Cefadroxil
Mecillinam
10
Nitrofurantoin
5
0
1995
1996
1997
1998
1999
2000
År
2001
2002
2003
2004
Consumption of Trimethoprim in Kronoberg 1998-Jan 2005
A difficult balance
The global need
for
effective
antibacterial
treatment
The
best interests
of
the individual
Appropriate antibacterial
prescribing
Butler C et al. JAC 2001; 48:435–440