Approximately 60% of adults prescribed antibiotics for acute cough/lower respiratory tract infection did not adhere fully to the prescription, and some 40% reported taking none of the antibiotics prescribed at the index consultation. More than one in 10 patients reported taking antibiotics not prescribed for them at the index consultation, and more than a third of those who consumed antibiotics not prescribed at the index consultation reported having no subsequent consultations during the study period. Duration of symptoms prior to consulting, duration of antibiotic course, choice of antibiotic, and regional factors were all associated with differences in adherence. Adherence to antibiotics prescribed for acute cough/lower respiratory tract infection was not associated with difference in recovery.
Strengths and limitations
This prospective study of >2500 adults presenting with acute cough/lower respiratory tract infection in the community included 14 primary care networks in 13 European countries and allowed for meaningful descriptions of antibiotic prescribing and adherence. The multinational nature of the study increases generalisability of findings and allowed for comparisons between primary care networks.
As there was no experimental intervention, clinicians were asked to record their usual practice and patients recorded antibiotic consumption prospectively; as such, these results are likely to closely represent the usual behaviour of clinicians and patients. Patients recorded the names of all medication consumed, together with the days on which the medication was taken. Although pharmacists were allowed to change from a branded to a generic prescription in some networks, the comparisons were based on the active ingredient and, therefore, this would not have affected this study's findings. As a result, the study was able to assess whether patients took the same antibiotic that was prescribed for them and whether they took it for the recommended length of time. The fact that patients reported the day they felt recovered allowed the impact of adherence with prescribed antibiotics on recovery to be assessed.
There is a risk of response bias; diary return rates varied from 60% in the Cardiff network to nearly 100% in the Bratislava network. There are no data to inform assumptions about the rate of adherence in those who did not return their diaries, but it seems unlikely that those who did not follow instructions to return a research diary would be more likely to follow instructions to consume antibiotics compared with those who did return their diaries. Therefore, the adherence rate measured in this study may be an overestimate, rather than an underestimate, of actual adherence.
Ascertainment bias is also a possibility. Medication use was measured through self-report and, although the dosing frequency that was directed on the prescription was known, patients were only asked to record whether or not they consumed the medication on each day, and not how many times a day they took that medication. Electronic measurement of medication use may be more accurate than self-report. Leftover antibiotics were not counted but awareness that an electronic device is monitoring one's behaviour may, in itself, affect medication use. Furthermore, self-report by diary has been shown to have moderate-to-high concordance with measurement of adherence through objective measures.8
Conclusions about rates of recovery need to be interpreted with caution. As these are observational data, confounding by indication cannot be completely excluded.
Comparison with existing literature
A systematic review and meta-analysis of adherence to antibiotic therapies (for all indications) in the community, which used 51 estimates from 46 studies and included 29 291 participants, found an overall adherence rate of 62.2% (95% CI = 56.4 to 68.0).15
In the 14 estimates involving 7204 participants in whom antibiotics were prescribed for respiratory tract infections, the rate of adherence was slightly higher at 72.6% (95% CI = 65.5 to 79.7). However, there were studies included in this review that included only children,16–19
were conducted in resource-poor17,20,21
or secondary care settings,7
and/or included small numbers. Furthermore, a number of different methods of measuring and defining adherence were used.
In studies where adherence was assessed by patient-completed questionnaire, most of which defined adherence as completing the antibiotic course, the mean adherence rate was 55.3% (95% CI = 44.4 to 66.1).15
Adherence was also lower in studies of adults than in studies of children or studies of children and adults.15
The adherence rate of 44.2% is lower than all of these estimates, although the CIs overlap with other studies that used patient-completed questionnaires (use of diaries was not reported) and was higher than the adherence rate found in studies using the electronic Medication Event Monitoring System devices (30.0%; 95% CI = 18.0 to 41.9).
An observational study of antibiotic treatment of lower respiratory tract infection in outpatients found higher rates of adherence than found in the study: 55% adherence to 80% of the prescribed medication for those with thrice daily dosing and 87% for those prescribed an antibiotic with once daily dosing.7
However, those patients were recruited from a medical outpatient setting rather than primary care and, likely, had more severe illness. For example, 58% of participants in that study had exacerbations of COPD, compared with only 2.8% of participants in the current study.13
No previous observational study has measured adherence to antibiotics for acute cough/lower respiratory tract infection in adults in primary care.
A lower number of daily antibiotic doses has been associated with greater adherence,7,9,22–24
and this is consistent with evidence on adherence to non-antibiotic medication. A relationship between number of daily doses and adherence was not found in the current study. This may have been because antibiotic consumption was measured on a day-by-day basis rather than a dose-by-dose basis, or may have been because choice of antibiotic was included in the current model; this is closely correlated with the number of daily doses. The finding that those who had the longest duration of illness prior to consulting were more likely to adhere is not surprising; these individuals are more likely to be motivated to take treatment. However, waiting 1–3 weeks before consulting was not associated with greater odds of adherence.
It is not clear why greater adherence was found in those prescribed co-amoxiclav, quinolones, and spiramycin. Although the study controlled for symptom severity, there may have been some residual confounding, with those who had more severe symptoms being more likely to be prescribed these antibiotics and more likely to adhere. This study's finding that a longer duration of treatment was associated with lower adherence is consistent with other studies.25
Illness severity and poor communication within the consultation,25
country of residence, age, attitude to the doctor, and attitude to antibiotics have all been associated with differences in adherence to antibiotic prescriptions.26
Although no attempt was made to measure aspects of clinician–patient communication, there is some evidence that clinicians do not consistently provide clear communication in consultations for respiratory tract infections;27
this may contribute to poor adherence. An association was also shown in the current study between management in certain networks and adherence, with one network (Bratislava) being associated with worse adherence and two networks (Helsinki and Jönköping) being associated with better adherence. The reasons for these differences are not yet clear. However, it is interesting to note that, along with Tromsø (which was borderline significant), the three networks associated with greatest adherence are all in Nordic countries.
This study's finding that adherence to acute antibiotic prescriptions was not associated with faster recovery is consistent with the previous finding that antibiotic prescribing is not associated with differences in recovery at the primary care network level,6
as well as being consistent with evidence that there is little meaningful benefit from antibiotics for acute bronchitis.28
Those who were not prescribed antibiotics at the index consultation but ended up taking them during the study period had a significantly slower rate of recovery; this could be because those who were recovering more slowly may have been more likely to reconsult and be prescribed antibiotics at a subsequent consultation.
Taking antibiotics that have been prescribed for others or prescribed for a previous illness is common.3
A systematic review and meta-analysis of 18 estimates from 16 755 participants in nine studies reported a mean rate of leftover antibiotic use of 28.6% (95% CI = 21.8 to 35.4).15
A survey of 7120 members of the public in the UK found that 15.8% (95% CI = 14.3 to 17.4) reported keeping antibiotics at some point during the previous year.3
These data are consistent with this study's findings that antibiotic courses are frequently not adhered to, and that >10% of patients, more than one-third of whom had not reconsulted, consumed an antibiotic that had not been prescribed for them in the index consultation.
Implications for practice and research
These findings provide the most convincing evidence so far that adults frequently do not adhere to antibiotics that are prescribed for acute cough/lower respiratory tract infection in primary care settings. Duration of antibiotic course, choice of antibiotic, and regional factors all seem to be associated with differences in adherence, but the reasons why patients do not adhere remain unclear. The finding that the variation in consumption at a network level was less than the variation in prescribing suggests that patients may ‘vote with their feet’; that is, be less likely to take prescribed antibiotics in high-prescribing networks and more likely to take their prescribed antibiotic and/or obtain antibiotics subsequent to their initial consultation in low-prescribing networks. Patients may also stop taking antibiotics because they are starting to feel better or have an adverse reaction. Nevertheless, low levels of adherence suggest a degree of misunderstanding, miscommunication, or failure to reach common ground in these consultations, and may result in:
- worse health outcomes (if prescribed for appropriate indications);
- waste resources (if prescriptions are collected and not used);
- antibiotics being kept for future use (which may be used later for inappropriate indications); and
- a distortion of data on antibiotic use.
There is a need for further research, including both quantitative and qualitative studies, to better understand the reasons for these diverse behaviours.
The study found that antibiotic prescribing at the initial consultation for a presumed infectious episode is a crude indicator of antibiotic use; antibiotic consumption during the entire period of the usual illness course is a more meaningful consideration. This is important for research into the association between antibiotic prescribing and antimicrobial resistance.29
The finding that adherence to acute antibiotic treatment was not associated with improved recovery is consistent with increasing evidence that antibiotics do not benefit most adult patients with acute cough/lower respiratory tract infection who are otherwise well. This may be because most of these infections are caused by viruses and might not be expected to respond to antibiotic treatment. Clinicians do not yet have the tools to adequately identify patients with acute cough/lower respiratory tract infection who will, and will not, benefit from antibiotic treatment.
These data will have implications for GPs when considering the use of antibiotics for acute cough/lower respiratory tract infection. Communication in these consultations needs to encompass not only the likely effect of antibiotic treatment, but also issues about adherence, such as motivation to adhere, factors likely to impair adherence, strategies to improve adherence, and, in particular, the practice of storing and using leftover antibiotics.