1. Antibiotic use and bacterial complications following upper respiratory tract infections: a population based study

2. Disclosure: the authors have nothing to disclose
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

3. 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

4. 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.

5. 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.

6. 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

7. Prospective cohort study:
PPPP
Prospective cohort study:
Outpatients with diagnosis acute otitis media, tonsillitis, sinusitis or acute upper respiratory tract infections of multiple and unspecified sites
AOM
Stratification
4 sub-cohorts
Tonsillitis
Acute sinusitis
Combination
Sinusitis + URTI
Unspecified
(children mainly)

8. Definition of episode Complication/ mastoiditis Closes episode
Dispensation
Respiratory tract
antibiotic
Recorded
AOM diagnosis
Recorded
AOM diagnosis
Index date
Recorded
AOM diagnosis
Recorded
AOM diagnosis
Index date
≥ 30 days
Episode of AOM
New episode of AOM

9. 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

10. 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)

11. 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)

12. 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.

13. 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)

14. Results AOM cohort study
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 non-exposed group
19 cases of mastoiditis and 5 cases of meningitis: AOM index date=recorded complication date

16. No antibiotic treatment
Treated with antibiotics
No of patients
No of complications
Risk per 10000
Mastoiditis after acute otitis media
0-4
45 473 6
1.32 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 -
7 809
1.28
Total1
81 864 10
1.22 46
1.06
Meningitis after acute otitis media
45 476 2
0.44
0.04
21 292
0.47
88 746
93 581
1.39
7 804 4
5.13
81 865
0.49 18
0.42

17. Conclusions
Severe bacterial complications related to URTIs, including mastoiditis and meningitis in relation to AOM, were infrequent (less than 1.5/ 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