Antibiotic use and bacterial complications following
upper respiratory tract infections: a population based
study
Thomas Cars, pharmacist1, Irene Eriksson, pharmacist1, 2, Anna
Granath, ENT surgeon3, Björn Wettermark1, 2, associate professor in
pharmacoepidemiology, Jenny Hellman, pharmacist4, Christer
Norman, general practicioner4, Anders Ternhag, consultant in
infectious diseases2, 4
1
Department of Healthcare Development, Public Healthcare Services
Committee, Stockholm County Council, Stockholm, Sweden
2 Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
3 Department of Clinical Science, Intervention and Technology, Karolinska
Institutet and Ear, Nose and Throat Clinic Karolinska University Hospital,
Stockholm, Sweden
4 Public Health Agency of Sweden, Solna, Sweden
Disclosure: the authors have nothing to disclose
Objectives
• Method for continuous monitoring of incidence of upper
respiratory tract infections (URTIs), antibiotic use and
frequency of complications due to concerns on safety of
restrictive antibiotic guidelines (AOM, tonsillitis, sinusitis)
• (MIRA- measures and indicators of good rationales in antibiotic use)
• Ecologic and prospective cohort study
Setting
• Primary care, outpatient specialist and inpatient care in Stockholm
County, Sweden (2.2 million catchment area, approximately 23% of
Swedish population)
• Collection and analyses of administrative healthcare data on
consultations, diagnoses and dispensed prescription medicines from
January, 2006, to January, 2016.
Main outcome measures
• Ecological study: 10 year trend analyses of incidence of URTIs,
bacterial infections/complications and respiratory antibiotic
use
• Prospective cohort study: Incidence of bacterial complications
following URTIs in antibiotic-exposed and non-exposed
patients.
Antibiotic exposure to respratory tract antibiotics
• Exposed  prescription dispensed within the episode
• Not exposed  no prescription, or the first antibiotic
prescription dispensed on the same day as a recorded bacterial
complication
Prospective cohort study:
Outpatients with diagnosis acute otitis media, tonsillitis,
PPPP
sinusitis or acute upper respiratory tract infections of multiple
and unspecified sites
Stratification
4 sub-cohorts
AOM
Tonsillitis
Acute sinusitis
Combination
Sinusitis + URTI
Unspecified
(children mainly)
Definition of episode
Complication/
mastoiditis
Closes episode
Recorded
AOM diagnosis
Dispensation
Respiratory tract
antibiotic
Recorded
AOM diagnosis
Index date
Recorded
AOM diagnosis
Index date
Recorded
AOM diagnosis
≥ 30 days
Episode of AOM
New episode of AOM
Exclusion criteria
• Episodes with the first diagnosis recorded in inpatient setting
• Episodes with incomplete data follow up
• Episodes with primary infection and complication recorded the
first day
Databases
• The regional healthcare data warehouse of Stockholm County
(VAL) and the Swedish Prescribed Drug Register.
• VAL: comprehensive administrative healthcare data for all
Stockholm County residents (encrypted data)
Demographics and prescribed antibiotics
• From VAL : demographic data (age, gender), diagnoses (ICD-10)
in primary care, outpatient specialist- and inpatient care ,
consultation dates , hospital admission and discharge dates,
migration and death records.
• From the Swedish Prescribed Drug Register data on dispensed
antibiotics (ATC codes)
Results ecological study
• Total utilization (for all URTIs) of respiratory tract antibiotics decreased
by 32% (12<10 DDD/1000 inhabitants/day) (p<0.0001)
• Proportion of patients treated with antibiotics for AOM declined from
88% to 81%
• No increased trend for mastoiditis (p=0.0933) was observed.
Results ecological study
• No increased trend for mastoiditis (p=0.0933) was observed.
• Decline in number of diagnosed AOM episodes, meningitis and
complicated sinusitis in children (ethmoidal origin, periorbital
cellulitis)
Results AOM cohort study
• 82 582 individuals diagnosed with AOM without prescription
of antibiotics (16%), and 435 362 individuals were treated with
antibiotics (84%)
• No difference in risk for mastoiditis or meningitis for the nonexposed group
• 19 cases of mastoiditis and 5 cases of meningitis: AOM index
date=recorded complication date
No antibiotic treatment
No of patients
Treated with antibiotics
No of complications
Risk per 10000
No of patients
No of complications
Risk per 10000
Mastoiditis after acute otitis media
0-4
45 473
6
1.32
243 141
23
0.95
5-14
21 294
3
1.41
88 741
13
1.46
15-64
12 676
1
0.79
93 582
9
0.96
65+
2 412
0
-
7 809
1
1.28
Total1
81 864
10
1.22
4 33 273
46
1.06
Meningitis after acute otitis media
0-4
45 476
2
0.44
243 151
1
0.04
5-14
21 292
1
0.47
88 746
0
-
15-64
12 676
1
0.79
93 581
13
1.39
65+
2 412
0
-
7 804
4
5.13
Total1
81 865
4
0.49
433 286
18
0.42
Conclusions
• Severe bacterial complications related to URTIs, including
mastoiditis and meningitis in relation to AOM, were infrequent
(less than 1.5/10 000 episodes
• Restrictive use of antibiotics for common URTIs  no increase
of severe bacterial complications
• Many complications occur at the index date implying
aggressive course of infections