ORIGINAL ARTICLE

Prescribed medications and pharmacy interventions for

acute respiratory tract infections in Swiss primary care
K. E. Hersberger* PhD, A. Botomino* PhD, R. Sarkar* PharmD, P. Tschudi MD, H. C.
Bucher MD MPH and M. Briel MD
*Institute of Clinical Pharmacy, University of Basel, Klingelbergstr, Basel, Institute for Primary Care
Medicine, University Hospital Basel, Basel and Basel Institute for Clinical Epidemiology, University
Hospital Basel, Basel, Switzerland
SUMMARY
Background and objectives: Symptomatic medica-
tions are often not considered in clinical studies
assessing interventions to reduce prescribing of
antibiotics for acute respiratory tract infections
(ARTI). Our study objectives were to examine
prescribing patterns of antibiotics and symptom-
atic medications for ARTI in Swiss primary care
and to monitor pharmacists interventions during
the prescription-dispensing process.
Methods: Medical records of 695 patients partici-
pating in a clinical trial which was designed to
reduce use of antibiotics for ARTI in primary
care, were linked to their prescriptions. Matching
of prescribed and dispensed medications enabled
the assessment of interventions by community
pharmacists.
Results: On average, 24 different drugs were
prescribed per patient (in total 142 antibiotics,
1599 symptomatic medications, and 56 non-ARTI-
medication). Most patients (80%) were treated
only with symptomatic medications. Most
frequently prescribed symptomatic ARTI-
medications were nasal decongestants (39%),
cough suppressants (36%), and mucolytics (31%).
Patients with prescribed antibiotics received
signicantly fewer symptomatic medications
(odds ratio, 024; 95% condence interval
016037). Over 20%of prescriptions prompted at
least one intervention by a pharmacist in the
dispensing process. A discrepancy between pre-
scribed and dispensed medications was seen in
19% of patients.
Conclusions: Prescription rates of antibiotics for
ARTI in this trial were low and patients were
treated mainly with non-antibiotic symptomatic
medications. Efforts to reduce antibiotic pre-
scribing may induce higher rates of use of
medications for intensive symptomatic treatment.
Considerable differences between prescribed and
dispensed medications were noted.
Keywords: antibiotic therapy, community
pharmacy services, prescription quality, primary
care, respiratory tract infections, symptomatic
treatment
BACKGROUND
Acute respiratory tract infections (ARTI) are among
the most frequent reasons for seeking ambulatory
care (1). Excessive prescription of antibiotics is
common and constitutes a serious public health
problem in particular due to increasing antibiotic
resistance by common bacteria (2). Accordingly,
guidelines for the treatment of ARTI focus more on
recommendations about antibiotic prescribing than
on symptomatic therapy (3). Delaying antibiotic
prescriptions and adequate symptomatic treatment
have been recommended to reduce unnecessary
antibiotic prescribing for ARTI (4). However, the
efcacy of frequently prescribed symptomatic
medications for ARTI (e.g. cough suppressants or
mucolytics) is not supported by evidence, and
studies examining prescribed antibiotics together
with symptomatic ARTI-medication in primary
Received 24 June 2008, Accepted 10 September 2008
Correspondence: PD Dr K. E. Hersberger, Institute of Clinical
Pharmacy, University of Basel, Pharmazentrum (0059), Klingel-
bergstrasse 50, 4056 Basel, Switzerland. Tel.: +41 61 2671426;
fax: +41 61 2671428; e-mail: kurt.hersberger@unibas.ch
Journal of Clinical Pharmacy and Therapeutics (2009) 34, 387395 doi:10.1111/j.1365-2710.2009.01049.x
2009 The Authors. Journal compilation 2009 Blackwell Publishing Ltd 387
care are few (5). One exception is the French AIR II
study which reports that symptomatic medications
(analgesics and or antipyretics, antitussives,
mucomodiers, corticosteroids or bronchodilators)
were twice as numerous as prescriptions of anti-
biotics in French primary care (6, 7). Thus, the rst
objective of the present study was a comprehensive
analysis of prescribing of antibiotics and all
symptomatic medications for ARTI, as part of a
Swiss primary care trial.
When dispensing prescribed medications, Swiss
community pharmacies are requested by law to
check each prescription (e.g. drug-drug interac-
tions, plausibility of dosage regimen). They doc-
ument all dispensed medicines and receive a
remuneration based on each prescription. Modi-
cations of the original prescriptions are possible
(e.g. generic substitution, change of dosage form);
some, however, require consultation with the
prescribing physician. Prescription modications
and interventions in pharmacies can be used as a
quality indicator in the drug therapy process and
evaluation of modications has been shown to
contribute positively to the quality of pharmaco-
therapy (8). Studies from North America (9), the
UK (10) and the Netherlands (11) report pharmacy
intervention rates of 15%. In a recent Swiss study
pharmacists reported an intervention rate of 27%
per patient (12). The Dutch study identied illeg-
ibility and incompleteness of prescriptions as the
main reasons for interventions by pharmacists.
Since these studies focused mainly on drug-
related problems and data on interventions were
only based on pharmacists self-report, our second
objective of the present study was to retro-
spectively monitor pharmacists interventions
including all alterations during the prescription-
dispensing process for ARTI-medications.
METHODS
Setting and design
Prescriptions used for this study were collected in
a cluster randomized trial (ISRCTN57824788) (13).
This trial failed to show any effect of training
general practitioners (GPs) in communication
skills on the prescription rate of antibiotics for
ARTI in primary care. We invited all GPs
(n = 345) in two cantons in the Northwest of
Switzerland, where GPs were not allowed to sell
drugs directly to patients (self-dispensing), to
participate in the trial; 45 gave written informed
consent and were recruited. GPs were random-
ized either to communication training plus the
provision of evidence-based guidelines for the
management of ARTI or guidelines alone. A
second control group consisted of GPs receiving
no intervention at all, to blind the physicians in
the other two groups to the true comparison. We
obtained baseline data on all eligible GPs from
the registry of the Swiss Medical Association to
control whether the sample of GPs participating
in trial was representative for Swiss GPs. Between
January and May 2004 study GPs screened con-
secutive patients aged 18 years or older, with a
rst consultation for an acute infection of the
respiratory tract (symptoms rst experienced
within the previous 28 days) for inclusion into the
trial. Possible diagnoses were common cold,
rhinosinusitis, laryngo-pharyngitis, exudative
tonsillitis, otitis media, bronchitis, exacerbated
chronic obstructive pulmonary disease (COPD)
and inuenza. For patients included in the trial
GPs used standardized forms to collect patient
baseline data on signs, symptoms and co-mor-
bidity, and to record their diagnostic procedures,
diagnoses, and prescribed medication. The pre-
scriptions from each of these consultations were
labelled and could easily be recognized by com-
munity pharmacies. All pharmacies (n = 213) in
the two cantons received written instructions to
fax all prescriptions with study labels to the study
centre. Swiss pharmacies are obliged to document
on the prescriptions exact specications (name,
dosage, size, price and date of dispensing) of all
dispensed medicines. In addition to the usual
prescription checks and counselling, pharmacists
were asked to document their interventions and
prescription modications. A reminder was sent
out to all pharmacies during the study to ensure
a continuously high level of collaboration.
Pharmacists interventions during prescription
processing
We dened any activity during the dispensing
process that altered or complemented the original
prescription as an intervention and distinguished
four categories:
2009 The Authors. Journal compilation 2009 Blackwell Publishing Ltd, Journal of Clinical Pharmacy and Therapeutics, 34, 387395
388 K. E. Hersberger et al.
Addition of missing specications in a prescription
to allow unambiguous dispensing of a drug
in the correct dose, dosage form and package
size.
Modication of the original prescription is
dened as: (i) dispensing of a drug in a different
dosage, dosage form, package size; (ii) change in
the number of packages; (iii) exchange of the
prescribed drug within the same drug class
(therapeutic substitution); and (iv) decision not
to dispense a drug at all.
Substitution is dened as any substitution of the
prescribed drug: the original brand with a
generic drug, a generic with another generic, or a
generic with the original brand.
Contacting of the prescribing physician, as
annotated by the pharmacist.
Prescription analysis
We retrieved all prescriptions (antibiotics and
symptomatic medications) from fax-copies and
entered them into a prescription analysis data-
base (14). An electronic version of the Swiss
article master of registered drugs was stored in
the same database to exactly assign and docu-
ment prescribed drugs with ATC-code (Anatomical
Therapeutic Chemical classication by WHO),
dosage form, original or generic brand and price.
During prescription processing, pharmacists are
obliged to document in detail each dispensed
item; this information is then automatically
printed on the back of the prescription. Thus, for
each prescription, the prescribed and the dis-
pensed drug could be identied and compared.
This comparison enabled us to assess post-hoc, all
additions of specications, modications, or
substitutions and specic annotations by the
pharmacists after contacting the prescribing
physician.
Prescribed drugs were divided into seven
groups of antibiotics, 15 different groups of
symptomatic ARTI-medication specied by ATC-
code, one group of various symptomatic
ARTI-medication (e.g. vitamins, minerals, mois-
turizing nose preparations), and a group of
non-ARTI-medication. We agged symptomatic
ARTI-medication with a higher risk for drug-drug-
interactions, side effects, or contra-indications
[cough suppressant (R05D), systemic nasal
decongestant (R01B), NSAID (M01A), paracetamol
combination (N02BE51), and salicylic acid deriva-
tive (N02BA)]. The selection of these potentially
hazardous symptomatic ARTI-medication was
based on the Swiss labelling as prescription only
medicine, or as pharmacy medicine rather than
over-the-counter drugs available in drugstores or
supermarkets. In case of problems with the
assessment of interventions or missing data, the
relevant pharmacy was contacted by phone.
To compare the number and type of symp-
tomatic treatment used by patients prescribed an
antibiotic and those who were not, we tted the
data to generalized linear mixed models with the
GP as a random effect, and with trial group and
patient baseline characteristics (age, gender,
degree of discomfort, days with restrictions
before consultation) as xed effects. To compare
the quality of documentation of prescribed items
we tted a three-level generalized linear mixed
model with patient and GP as random effects, i.e.
the model accounts for the fact that prescriptions
are clustered by patients and patients are
clustered by GPs. We used SPSS

(V.13) and
Stata 92 (Stata Corp, College Station, TX, USA)
for data analysis.
RESULTS
Study sample
Data from the Swiss Medical Association suggests
that participating GPs were similar to all eligible
GPs in the two cantons with respect to characteristics
recorded by the association (13). The median age of
the 45 participating GPs was 52 years (interquartile
range, IQR, 11); 18% were female; 53% and 33%
were board approved in General Medicine and
Internal Medicine, respectively, with a median of
92 years (IQR 30) of post-graduate training and
of 14 years (IQR 15) of experience in private
practice.
Study GPs consecutively recruited 837 patients
with ARTI into the trial and issued a prescription in
771 cases (92%). Pharmacies sent fax-copies of
prescriptions from 695 patients, i.e. 90% of pre-
scriptions were captured. Baseline characteristics of
patients with captured prescriptions were similar
to those of all patients recruited into the trial
(Table 1).
2009 The Authors. Journal compilation 2009 Blackwell Publishing Ltd, Journal of Clinical Pharmacy and Therapeutics, 34, 387395
Prescriptions for ARTI 389
Prescribing and dispensing patterns of acute
respiratory tract infections medications
From the 695 patients we identied a total of 1797
prescriptions (142 antibiotics, 1599 symptomatic
ARTI-medications, 56 non-ARTI-medications). The
number of medications ranged from one to six per
patient (mean 24, SD 12). The overall antibiotic
prescription rate was 204%; the highest rate
(769%) was observed in patients with exacerbated
COPD, while only about 2% of patients diagnosed
with common cold received an antibiotic. Overall,
acetylcysteine was the most frequently prescribed
drug (286%), and 253%of patients treated with an
antibiotic additionally received acetylcysteine. The
most frequently prescribed groups of symptomatic
ARTI-medications were topical nasal deconges-
tants (390%), cough suppressants (363%) and
mucolytics (311%). Non-steroidal anti-inamma-
tory drugs (NSAID) and paracetamol were each
prescribed for about a quarter of the patients. Non-
ARTI-medication was prescribed for 81% of all
patients. Cardiovascular and central nervous
system medication were the most frequent non-
ARTI drugs. Prescription only medicines accoun-
ted for 276% of all symptomatic medications.
Table 2 shows antibiotics and symptomatic ARTI-
medications according to ARTI-diagnosis. Mean
total costs for antibiotics and symptomatic ARTI-
medication per prescription was 28 Euro. Costs for
symptomatic ARTI-medication accounted for 74%
of total medication costs (Table 2).
Adjusted for prognostic factors, patients with
antibiotic treatment received signicantly less
symptomatic ARTI-medication (mean 18 vs. 25
items; Table 3). Moreover, patients with antibiotic
treatment were less likely to receive potentially
hazardous symptomatic ARTI-medications (415%
vs. 642% of patients; Table 3).
Pick-up date of most prescriptions was the same
day (83%), or the day following the consultation
(11%) with a range of 12 days.
Pharmacy interventions and prescription quality
Almost all prescriptions (973%) were handwritten
on standard blank physician order sheets; only
27% were printed. The intervention rate for
prescriptions was 216% (symptomatic ARTI-
medication: 221%, antibiotics: 162%). Addition of
specications to unclear or not sufciently speci-
ed prescriptions accounted for 537%, modica-
tion of prescriptions for 390%, substitution by
generic and or original drug for 62%, and
contacting the prescribing physician for 10%of all
interventions (Table 4). At least one discrepancy
between prescribed and dispensed drugs (modi-
cation and or generic substitution) was seen in 131
(188%) of all patients. Of all prescribed symp-
tomatic ARTI-medications, 86 (52%) were not
dispensed. Most common reasons for modications
of prescribed drugs were supply problems (out of
stock, temporarily not available), drugs not reim-
bursed by the health insurance, and patients
declaring that they had the prescribed drug at
home already.
According to the ofcial Swiss article master
list, generic prescription was possible for 493%
of all prescribed antibiotics (70 out of 142). Of
those, GPs prescribed the cheaper generic in 63
(90%) of the cases. For the remaining seven cases,
none of the pharmacies dispensed a cheaper
generic.
Table 1. Patient baseline characteristics
Study
patients
(with
captured
prescriptions)
Initially
recruited
patients
n = 695 n = 837
Age, median (IQR) 425 (270) 415 (265)
Women, n (%) 404 (581) 481 (575)
Days with restricted
activities, median (IQR)
4 (4) 4 (4)
Degree of discomfort
(scale 110), median (IQR)
5 (3) 5 (3)
Diagnosis
Common cold, n (%) 233 (335) 307 (367)
Acute rhinosinusitis, n (%) 137 (197) 152 (182)
Acute laryngo-
pharyngitis, n (%)
90 (129) 109 (130)
Exsudative tonsillitis, n (%) 40 (58) 41 (49)
Acute otitis media, n (%) 17 (24) 17 (20)
Acute bronchitis, n (%) 112 (161) 129 (154)
Inuenza, n (%) 53 (76) 69 (82)
Exacerbated COPD, n (%) 13 (19) 13 (16)
IQR, interquartile range.
2009 The Authors. Journal compilation 2009 Blackwell Publishing Ltd, Journal of Clinical Pharmacy and Therapeutics, 34, 387395
390 K. E. Hersberger et al.
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0

0
0

0
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0
1

2
C
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r
t
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m
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c
(
H
0
2
)
0

4
0

0
0

0
0

0
0

0
1

8
0

0
1
5

4
0

7
2009 The Authors. Journal compilation 2009 Blackwell Publishing Ltd, Journal of Clinical Pharmacy and Therapeutics, 34, 387395
Prescriptions for ARTI 391
The rate of additional specications, a measure
of documentation quality of prescriptions, was
227% (158 out of 695). Additions were less likely
for antibiotics when compared with symptomatic
ARTI-medications (odds ratio from multi-level
model 020; 95% condence interval, 008048)
indicating that the quality of recording of pre-
scriptions was better for antibiotics (Table 3). The
statistical model suggests that the GP accounted for
about 40%of the variance in relation to the additions
(intraclass correlation).
DISCUSSION
Given the high incidence, and mostly self-limiting
nature of ARTI, physicians should generally aim
for judicious use of medications when treating such
patients. Our study found that ARTI were mainly
treated with non-antibiotic, symptomatic medications.
Cough suppressants and mucolytics were among T
a
b
l
e
2
.
(
c
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n
1
0

3
1
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3
1
6

7
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1
7

6
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5
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-
A
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m
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n
9

4
5

8
8

9
1
0

0
.
0
9

8
3

8
7

7
8

1
N
u
m
b
e
r
o
f
A
R
T
I
-
m
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d
i
c
a
-
t
i
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n
s
p
e
r
p
a
t
i
e
n
t
(
m
e
a
n
)
2

5
2

6
2

6
2

3
2

5
2

4
2

4
2

5
2

5
N
u
m
b
e
r
o
f
s
y
m
p
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a
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n
s
(
m
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a
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)
2

5
2

3
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1

6
2

1
2

1
2

3
1

8
2

3
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e
a
n
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a
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t
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f
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m
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d
i
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a
t
i
o
n
s
(
E
u
r
o
)
2
2

8
3
2

2
2
3

4
3
4

0
3
7

2
3
5

0
2
1

1
4
6

3
2
8

0
M
e
a
n
c
o
s
t
o
f
s
y
m
p
t
o
m
a
t
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A
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m
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d
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c
a
t
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o
n
s
(
E
u
r
o
)
2
1

9
1
8

5
2
1

0
1
2

2
1
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7
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4

9
2
0

4
1
9

4
2
0

8
A
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T
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,
a
c
u
t
e
r
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s
p
i
r
a
t
o
r
y
t
r
a
c
t
i
n
f
e
c
t
i
o
n
s
;
A
T
C
,
A
n
a
t
o
m
i
c
a
l
T
h
e
r
a
p
e
u
t
i
c
C
h
e
m
i
c
a
l
c
l
a
s
s
i

c
a
t
i
o
n
s
b
y
W
H
O
.
Table 3. Predictors for symptomatic treatment
Predictors
Odds ratio (95% condence
interval) n = 619
a
No. of
symptomatic
medications
(0,1,...,6)
Potentially
hazardous
symptomatic
medication
b
(yes no)
Antibiotic prescribed 024 (016037) 044 (027070)
Degree of discomfort
(110)
107 (098116) 115 (104128)
Days with restrictions 099 (095103) 095 (091101)
Age (per 10 years) 109 (099121) 106 (094120)
Gender (men) 110 (081150) 118 (081171)
Treatment group of GPs
Control 100 (reference) 100 (reference)
Guidelines 047 (019120) 166 (083331)
Guidelines +
communication
training
074 (029189) 157 (078317)
GPs, general practitioners.
a
Multivariate mixed models for ordinal (left column) and binary
(right column) outcomes with the GP as a random effect.
Missing values led to a reduced sample.
b
Medications with a higher risk for drug-drug-interactions, side
effects, or contra-indications [coughsuppressant (R05D), systemic
nasal decongestant (R01B), NSAID (M01A), paracetamol
combination (N02BE51), and salicylic acid derivative (N02BA)].
2009 The Authors. Journal compilation 2009 Blackwell Publishing Ltd, Journal of Clinical Pharmacy and Therapeutics, 34, 387395
392 K. E. Hersberger et al.
the most frequently prescribed symptomatic ARTI-
medications in our study (35% and 31%, respec-
tively, of all patients). The frequent use of these
symptomatic medications, however, is not sup-
ported by evidence and needs to be questioned (5,
1517). Studies from France (7) and Germany (18)
reported even higher prescription rates for muco-
lytics (both about 60%) but lower rates for cough
suppressants (both about 20%).
In our study, drug expenses for symptomatic
ARTI-medication varied only very little between
ARTI diagnoses. The 72% of the drugs could also
be purchased in a pharmacy without a prescription.
Given the high incidence of ARTI and the consid-
erable costs for symptomatic treatment, these
mostly self-limiting infections impose a great eco-
nomic burden (19). This raises a question about the
extent to which non-medical self care is a rational
option, given that a great majority of adults with a
cold do not visit a doctor (20). There is a need for
more research on symptomatic and supportive
treatment options in ARTI (21). Such treatments
should also be studied when assessing interven-
tions to reduce antibiotic use.
In our study, the pharmacist intervention rate of
216% for all prescriptions was high compared to
ndings of other studies with reported rates of
19%(9), 27%(12) or 43%(11). However, we used
a more comprehensive denition of intervention
than is usual, and included any activity that altered
or complemented the original prescription in order
to capture all actions of pharmacists with potential
clinical or economic consequences. If we exclude all
additions, which could be considered as being
mainly administrative interventions, and all pre-
scriptions which were not dispensed, as done in the
other studies, the intervention rate declines to 10%
and 48%, respectively. The high intervention rate
may also be due to the high proportion of non-
prescription drugs seen in our study. These drugs
are usually not considered in the few studies on
pharmacist interventions. Furthermore, we retro-
spectively compared prescribed with dispensed
medications independently from pharmacy self-
reports and we found a considerable discrepancy
between prescribed and dispensed medications for
19%of patients. This result is relevant with respect
to electronic patient records, which apparently give
an incomplete image of what patients actually
receive as prescribed therapy. In a study with
HIV-positive patients, that also compared pre-
scribed with dispensed items independently of
Table 4. Pharmacists interven-
tions. Interventions picked up as
differences between prescribed and
dispensed prescriptions and or as
comments by the pharmacies
Intervention
a
Symptomatic
medication
n = 1655 (100%)
Antibiotics
n = 142
(100%)
Total
n = 1797
(100%)
Addition of specications
Dosage 22 (13) 5 (35) 27 (15)
Dosage form 168 (102) 0 168 (93)
Package size 12 (073) 2 (14) 14 (077)
Total additions 202 (122) 7 (49) 209 (116)
Modication
Dosage 1 (006) 0 1 (006)
Dosage form 16 (095) 1 (070) 17 (095)
Package size 14 (085) 1 (070) 15 (083)
Number of packages 8 (048) 1 (070) 9 (050)
Other 9 (054) 2 (14) 11 (061)
Change of drug (therapeutic
substitution)
12 (073) 0 12 (067)
Not dispensed prescriptions 86 (52) 1 (070) 87 (48)
Total modication 146 (88) 6 (49) 152 (85)
Substitution 14 (085) 10 (70) 24 (13)
Contact to prescribing physician 4 (024) 0 4 (022)
Total interventions 366 (221) 23 (162) 389 (216)
a
Denitions are given in the Methods section.
2009 The Authors. Journal compilation 2009 Blackwell Publishing Ltd, Journal of Clinical Pharmacy and Therapeutics, 34, 387395
Prescriptions for ARTI 393
pharmacy self-reports, an even larger number of
discrepancies (55%) was observed (22). Thus,
physicians should be aware of potentially signi-
cant differences between prescribed and dispensed
items when necessary specications are missing on
prescriptions. Such errors of omission, and similar
patterns of interventions on dispensed items, have
been reported by Westein (23), Hawksworth (10)
and Buurma (11). In our study, prescriptions were
mostly handwritten and therefore electronic pre-
scribing may decrease the high rate of additional
specications. Further research is needed to
explore the clinical and economic relevance of the
predominantly administrative interventions and
the reasons for the high rate of prescriptions not
dispensed.
Although during the trial (13) none of the
participating GPs and pharmacists was aware of
the fact that the issued prescriptions would be used
for this sub-study, we acknowledge that GPs and
pharmacists might have behaved differently when
monitored in the setting of a trial (Hawthorne effect
(24). This may limit the external validity of our
results. Furthermore, evidence-based guidelines for
ARTI given to two thirds of the GPs in the trial may
have inuenced physicians behaviour in their
prescribing. However, the evidence-based guide-
lines focused on the appropriate use of antibiotic
therapy rather than on appropriateness of symp-
tomatic treatment. Moreover, the trial intervention
was designed to reduce antibiotic use and
ultimately failed to do so resulting in a low average
antibiotic prescription rate of 204%. This is
consistent with the known low rate of use of anti-
biotics among outpatients in Switzerland com-
pared to those of other European countries (25).
However, we also noted a high rate of prescribing
of new broad-spectrum antibiotics (macrolides,
cephalosporins) reecting the trends seen in many
other European countries (26). Since no further
action of pharmacists was necessary for us to assess
interventions like additions, modications, or sub-
stitutions, and since contacts with physicians were
rare, we consider it unlikely that the labelling of
prescriptions caused the relatively high pharmacist
intervention rate in our study. Other strengths of
this study are a high rate of captured prescriptions
(>90%), data from prescriptions linked to clinical
data from GPs, the inclusion of antibiotics and of
all prescribed symptomatic ARTI-medications, and
an estimate of the discrepancies between pre-
scribed and actually dispensed prescription items.
International comparisons of rates of use of
symptomatic ARTI-medication are hampered by
the differences in health insurance systems and
funding policies. Nevertheless, the high prescrip-
tion rates of symptomatic or supportive treatment
in our study (mean of 23 items per patient)
appear similar to those found in the French AIR II
study (mean of 20 items per patient) (7) and in a
German study (mean of 13 symptomatic medica-
tion items per patient ignoring NSAID and
paracetamol) (18).
In conclusion, this analysis of prescriptions,
captured from a clinical trial which was designed
to reduce antibiotic prescribing, suggests that pre-
scribing of symptomatic medications was frequent
and that reducing antibiotic prescribing for
patients with ARTI may further increase the use of
such medications. Future studies of antibiotic pre-
scribing for ARTI should take account of symp-
tomatic treatments. Evidence-based guidelines
should not only argue for rational antibiotic pre-
scribing but also for judicious symptomatic treat-
ment. The considerable differences between
prescribed and dispensed items require further
investigation.
ACKNOWLEDGEMENTS
We thank the participating general practitioners
and their patients as well as all community
pharmacists who thoroughly captured prescrip-
tions and provided us with further information
about their interventions.
FINANCIAL SUPPORT
Swiss National Science Foundation (project
3200B0-102137), and Novartis Foundation, Basel,
Switzerland. The funding sources had no role in
study design, data collection, data analysis, data
interpretation, or writing of the manuscript.
REFERENCES
1. Schappert SM, Burt CW (2006) Ambulatory care
visits to physician ofces, hospital outpatient
departments, and emergency departments: United
States, 20012002. Vital and Health Statistics, 13, 166.
2009 The Authors. Journal compilation 2009 Blackwell Publishing Ltd, Journal of Clinical Pharmacy and Therapeutics, 34, 387395
394 K. E. Hersberger et al.
2. Goossens H, Ferech M, Vander Stichele R, Elseviers
M (2005) Outpatient antibiotic use in Europe and
association with resistance: a cross-national database
study. The Lancet, 365, 579587.
3. Gonzales R, Bartlett JG, Besser RE et al. (2001)
Principles of appropriate antibiotic use for treatment
of acute respiratory tract infections in adults:
background, specic aims, and methods. Annals of
Internal Medicine, 134, 479486.
4. Spurling GK, Del Mar CB, Dooley L, Foxlee R (2004)
Delayed antibiotics for symptoms and complications
of respiratory infections. Cochrane Database Systematic
Reviews, CD004417.
5. Irwin RS, Baumann MH, Bolser DC et al. (2006)
Diagnosis and management of cough executive
summary: ACCP evidence-based clinical practice
guidelines. Chest, 129, 1S23S.
6. Raherison C, Peray P, Poirier R et al. (2002)
Management of lower respiratory tract infections by
French general practitioners: the AIR II study.
European Respiratory Journal, 19, 314319.
7. Raherison C, Poirier R, Daures JP et al. (2003) Lower
respiratory tract infections in adults: non-antibiotic
prescriptions by GPs. Respiratory Medicine, 97,
9951000.
8. Buurma H, De Smet PAGM, Leufkens HGM, Egberts
ACG (2004) Evaluation of the clinical value of
pharmacists modications of prescription errors.
British Journal of Clinical Pharmacology, 58, 503
511.
9. Rupp MT, DeYoung M, Schondelmeyer SW (1992)
Prescribing problems and pharmacist interventions
in community practice. Medical Care, 30, 926940.
10. Hawksworth G, Corlett A, Wright D, Chrystyn H
(1999) Clinical pharmacy interventions by community
pharmacists during the dispensing process. British
Journal of Clinical Pharmacology, 47, 695700.
11. Buurma H, de Smet PAGM, van den Hoff OP,
Egberts ACG (2001) Nature, frequency and deter-
minants of prescription modications in Dutch
community pharmacies. British Journal of Clinical
Pharmacology, 52, 8591.
12. Krahenbuhl JM, Kremer B, Guignard B, Bugnon O
(2008) Practical evaluation of the drug-related problem
management process in Swiss community pharma-
cies. Pharmacy World and Science, 30, 777786.
13. Briel M, Langewitz W, Tschudi P, Young J,
Hugenschmidt C, Bucher HC (2006) Communication
training and antibiotic use in acute respiratory tract
infections. A cluster randomised controlled trial in
general practice. Swiss Medical Weekly, 136, 241247.
14. Sarkar R (2004) Analysis of prescriptions for patients
with acute respiratory tract infections (ARTI) in
primary care. In: Diploma thesis in pharmaceutical
sciences. University of Basel, Basel.
15. Schroeder K, Fahey T (2002) Systematic review of
randomised controlled trials of over the counter
cough medicines for acute cough in adults. BMJ, 324,
329.
16. Morice AH, Widdicombe J, Dicpinigaitis P, Groenke L
(2002) Understanding cough. European Respiratory
Journal, 19, 67.
17. Taverner D, Latte J (2007) Nasal decongestants for
the common cold. Cochrane Database Systematic
Reviews, CD001953.
18. Fischer T, Fischer S, Kochen MM, Hummers-Pradier E
(2005) Inuence of patient symptoms and physical
ndings on general practitioners treatment of
respiratory tract infections: a direct observation
study. BMC Family Practice, 6, 6.
19. Fendrick AM, Monto AS, Nightengale B, Sarnes M
(2003) The economic burden of non-inuenza-related
viral respiratory tract infection in the United States.
Archives of Internal Medicine, 163, 487494.
20. McIsaac WJ, Levine N, Goel V (1998) Visits by adults
to family physicians for the common cold. Journal of
Family Practice, 47, 366369.
21. Turnidge J (2001) Responsible prescribing for upper
respiratory tract infections. Drugs, 61, 20652077.
22. de Maat MM, Frankfort SV, Mathot RA et al. (2002)
Discrepancies between medical and pharmacy
records for patients on anti-HIV drugs. Annals of
Pharmacotherapy, 36, 410415.
23. Westein MP, Herings RM, Leufkens HG (2001)
Determinants of pharmacists interventions linked to
prescription processing. Pharmacy World and Science,
23, 98101.
24. Eccles M, Grimshaw J, Campbell M, Ramsay C
(2003) Research designs for studies evaluating the
effectiveness of change and improvement strategies.
Quality and Safety in Health Care, 12, 4752.
25. Filippini M, Masiero G, Moschetti K (2006)
Socioeconomic determinants of regional differences
in outpatient antibiotic consumption: evidence from
Switzerland. Health Policy, 78, 7792.
26. Goossens H, Guillemot D, Ferech M et al. (2006)
National campaigns to improve antibiotic use.
European Journal of Clinical Pharmacology, 62, 373379.
2009 The Authors. Journal compilation 2009 Blackwell Publishing Ltd, Journal of Clinical Pharmacy and Therapeutics, 34, 387395
Prescriptions for ARTI 395