Number of Daily Doses Does Not Affect Compliance with Flucloxacillin Prescriptions

doi:10.4236/ijcm.2013.49069

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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.

Email: *[email protected]

Received July 5th, 2013; revised August 6th, 2013; accepted August 16th, 2013

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%

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%

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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