International Journal of Clinical Medicine, 2013, 4, 384-387
http://dx.doi.org/10.4236/ijcm.2013.49069 Published Online September 2013 (http://www.scirp.org/journal/ijcm)
Number of Daily Doses Does Not Affect Compliance with
Flucloxacillin Prescriptions
Elisabeth Rönnbäck1, Sofia Kälvemark Sporrong1,2*, Anders Österlund3
1Department of Pharmacy, Uppsala University, Uppsala, Sweden; 2Department of Pharmacy, University of Copenhagen, Copenhagen,
Denmark; 3Department of Communicable Disease Control and Prevention, Norrbotten County Council, Luleå, Sweden.
Received July 5th, 2013; revised August 6th, 2013; accepted August 16th, 2013
Copyright © 2013 Elisabeth Rönnbäck et al. This is an open access article distributed under the Creative Commons Attribution Li-
cense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
Objective: To achieve optimal effect with beta-lactam antibiotics, regimens with frequent dosages have been found nec-
essary. However, if compliance is negatively influenced by more frequent dosages, this might hamper the effect of the
treatments. Therefore, we have studied whether the numbers of daily dosages influence the compliance with prescribed
flucloxacillin regimens. Design: A prospective interview stud y of patients with different dos ing regimens of flucloxacil-
lin. Setting: In the study, 200 patients with different dosing regimens of flucloxacillin underwent structured telephone
interviews in order to reveal their compliance with the medication. Of these, 13 were prescribed twice-daily doses, 163
three times daily and 24 patients four times daily regimens. Results: There were no statistically significant differences
between missed doses and prescribed numbers of daily doses. There was, however, a significant difference in the num-
ber of daily doses and experiences associated with the medication. Conclusions: This study shows th at patients comply
well with regimens of up to four daily do ses of flucloxacillin, d espite experiencing increasin g difficulties with reg imens
of more frequent dosages.
Keywords: Antibiotics; Compliance; Flucloxacillin; Treatment; Sweden
1. Introduction
Compliance with antibiotic regimens is important, not
only to get optimal effect from the drug, but also to pre-
vent bacterial resistance [1]. Non-compliance can be in-
tentional or unintentional; the latter can for example be
due to forgetfulness or shortcomings in communication
between patient and health care provider [2]. Lack of
compliance has been identified as one contributor to un-
successful antibiotics therapies, predominantly due to
forgetfulness, adverse effects and patients determining
themselves that they have been cured [3-5].
Earlier studies have shown compliance with antibiotics
to be connected with dosing, with better adherence to
regimens of fewer doses per day [6-8]. On the other hand,
it is well known that for beta-lactam antibiotics, regimens
with more frequent dosages have been found necessary
to reach blood concentrations in sufficient time above
MIC (minimum inhibitory concentration) to achieve op-
timal effect [9,10].
Norrbotten County Council, responsible for healthcare
in the northernmost part of Sweden, has since 2011 rec-
ommended four daily doses of beta-lactam antibiotics in
order to optimize efficacy. However, this could influence
the compliance and thus the recommendation could be
counteractive. Thus, this study was done to compare pa-
tient experiences of different prescribed doses of flu-
cloxacillin, and to reveal whether bad compliance with
more frequent dosages could hamper the effect of the
treatments.
2. Material and Methods
All patients who obtained flucloxacillin during the study
time, 1st of April - 15th of May and 1st of September -
15th of October in 2011, at five pharmacies in the county
of Norrbotten, Sweden, were asked by pharmacy staff to
participate in the study. The five largest pharmacies in
the county, responsible for dispensing 64% of all flu-
cloxacillin prescriptions in 2010, were enrolled in the
study. Inclusion criteria for patients were: fluency in
Swedish, collecting a prescription for oneself or one’s
own children, and written consent to an interview about
the treatment after the course had ended. Two patients
*Corresponding a uthor.

Number of Daily Doses Does Not Affect Compliance with Flucloxacillin Prescriptions 385
who terminated their course after one and three days re-
spectively were excluded as they were viewed as not
having had enough experience. The patients that were
enrolled in the study were not informed about that the
main purpose of the interview was to collect data con-
cerning compliance to the prescribed doses. Structured
telephone interviews were conducted with the patient a
few days after estimated end of course. The questions
were predominantly retrospective. The choice of method,
i.e. telephone interviews, was to try to counteract any
memory bias that might occur, as the respondent can
expand on answers, e.g. communicate that they are un-
certain, and the interviewer can prompt answers to get as
correct data as possible [11].
Questions included whether the respondent had not
taken the medicine any day; if so why, and how the re-
spondent experienced taking the medicine several times
per day.
The Statistical Package for Social Sciences (SPSS)
was used for the statistical analysis. Answers to open-
ended question were collected into broad categories.
To get informed consent, patients were given written
information and if they accepted they were to give the
pharmacy staff their phone numbers, as well as preferred
times for interviews. The interviewer also collected in-
formation from the prescription, including age, sex, date
of dispensing, dosage, package size, diagnosis and length
of course.
Ethical approval was applied for at the regional ethical
review board in Uppsala, which stated that no ethical
approval was needed, but all the same declared no ethical
obstacles.
3. Results
In total 325 patients (160 women and 165 men) were
asked to participate in the study. Of those, 230 patients
(112 women and 118 men) accepted. The interviewer
finally succeeded in contacting 200 patients, 99 women
(mean age 49 years) and 101 men (mean age 51 years).
Flucloxacillin was mainly prescribed for the treatment
or prevention of skin and soft tissue infections (see Table
1). Three different dosage regimens were used; twice,
three times, and four times daily. Three times daily was
the predominant regimen used (see Table 2). Despite the
somewhat small sample, it was evident that the self-es-
timated compliance with the different dosage regimens
did not differ significantly (see Figure 1). However, it
was just as clearly shown that the patients found it
gradually more prob lematic to take more daily d oses (see
Figure 2).
Out of the 200 patients 58 (29%) reported that they
had missed doses. Among these 58 patients 25 (43%) had
forgotten only one or two doses. Forgetfulness was the
main reason for missing doses; 36 (77%) had missed as a
Table 1. Indications for flucloxacillin treatments.
Indication No of Patients (proportion)
Skin or soft tissue infections 155 (78%)
Prophylaxis after minor surgery24 (12%)
Bone or joint infections 9 (5%)
Other infections 5 (3%)
Unknown 7 (4%)
Table 2. Prescribed doses of flucloxacillin to interviewed
study patients.
Prescribed dose of flucloxacillin No of Patients (proportion)
Twice daily 13 (6.5%)
Three times dai ly 163 (82%)
Four times dail y 24 (12%)
92%
67%
79%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
t wice dail yt hree t i m es dail yfour tim es dail y
Prescribed dose
Proportion of patients who did not
m iss a single d o se
Figure 1. Proportion of patients who reported that they did
not miss a single dose. Bars showing 95% confidence inter-
vals.
85%
64%
42%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
t wice dail yt hree t im es dai l yfour ti m es dail y
Prescribed dose
Proportion of patients who did not experience
pro blems w i th taki n g th e prescribed d osag e
Figure 2. Proportion of patients who reported that they did
not experience any problems with taking the prescribed
dosage of antibiotics. Bars showing 95% confidence inter-
vals.

Number of Daily Doses Does Not Affect Compliance with Flucloxacillin Prescriptions 386
result of that. Missing doses was mainly due to changes
in daily routines, such as going back to work. Adverse
events were reported from three (6%) patients (see Table
3).
4. Discussion
During the past decade, there has been an increasing
awa reness of adhering to pharmacodynamic principles [9]
in antibiotic treatments. Thus, the importance of doses
being administered more frequently for the time-de-
pendent antibiotics, such as the beta-lactams, has become
evident [10]. The finding that more frequent daily dosing
has led to poor compliance with the prescriptions [3,11]
has thus been though t to be an obstacle to op timal antibi-
otic dosing. However, recently Eide and co-workers pub-
lished data from a study on antibiotic treatment in pri-
mary health care in Norway which showed no significant
differences in compliance between antibio tic regimens of
three and four daily doses [12]. The results of our study
further strengthen their findings that it is not evident that
more doses lead to poorer compliance. Furthermore, our
data show no differences in compliance to dosage regi-
mens of twice, three times, or four times daily, despite
reports from the patients that they find it increasingly
difficult with more daily doses.
However, our data show that patients seem to find it
more problematic to take more doses per day. As flu-
cloxacillin is often u sed under a short period of ti me, this
might be an obstacle that is fairly easily overcome.
Communication between prescriber and patient, and phar-
macy staff and patient, in order to encourage patients to
put up with these inconveniences should be highlighted.
The results of this stud y are based on the answer s from
patients during interviews. To reduce the risk of inter-
viewer’s bias, all interviews are carried out in a system-
atic way by the same interviewer. However, there is still
a risk that missed doses are under-reported in the inter-
views. Furthermore, only 200 out of the 325 patients
(62%) that get flucloxacillin dispensed at the pharmacies
participate in the study. Despite the risk of under-re-
porting and a slight selection, there are no reasons to be-
lieve that patients are more prone to be biased in respect
to certain dosing regimens. As this is a real life study,
differences in number of patients per regimen are inevita-
ble.
These results might reflect the intens ive focus on anti-
biotic consumption an d resistant bacteria in Swedish me-
dia during the past year. As a consequence, patients may
have become more aware that unnecessary consumption
of antibiotics might be harmful, an d that compliance with
the prescribed dosages is impo rtant for maximal effect in
those circumstances where antibiotics are needed. Also,
prescribers and pharmacy staff might have been more
pro n e to motivate patients with four doses, as this regimen
Table 3. Answers to the question of “What was the reason
for missing the dose/doses?”
Reason No of Answers (proportion)
I forgot 36 (77%)
I ran out of medicine 2 (4%)
Child with difficulties taking the
medicine 2 (4%)
Inconvenient due to activities 4 (9%)
Adverse reaction 3 (6%)
is fairly new to them as well.
5. Acknowledgements
We thank the staff at the Apoteket AB pharmacies in
Norrbotten, Sweden, includ ing Blåklo ckan in Sund erbyn,
Manhem in Kalix, Lejonet in Luleå, Laxen in Boden, and
Renen in Piteå. The project was performed with a grant
from Norrbotten County Council, Sweden.
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