Principal findings
Three out of four children diagnosed with AOM in Danish general practice were prescribed antibiotics. The inter-practice variation was considerable. Among patient characteristics, fever, poor general condition, and purulent ear secretion were associated with antibiotic prescribing. Furthermore, the practice’s rates of prescribing antibiotics for RTIs in general and specifically for AOM in children were closely associated with prescription of antibiotics to the individual child. Parent request for antibiotics was not significantly associated with antibiotic prescribing in any of the models.
Comparison to other studies
The clinical findings associated with the AOM diagnosis were similar to findings in other studies; purulent ear secretion, ear pain, abnormal tympanometry, and fever having the strongest associations (Supplementary table 1) (2-4). Only 52% of children diagnosed with AOM had a tympanometry performed, even though 55 out of 60 participating practices performed at least one tympanometry, indicative of having access to tympanometry.
We found an antibiotic prescribing rate of 74%, similar to a Danish study from year 2012 with a prescribing rate of 73% for AOM (12), an Australian study from 2017 (79%) (23), and a Swedish study from 2016 (75%) (24).
We found that penicillin V was prescribed for 60% of cases, and amoxicillin for 22%. In Denmark, the prevalence of penicillin-resistant Streptococcus pneumoniae is low, and since penicillin V is a narrow-spectrum antibiotic and has relatively few side effects, compared to other antibiotics, it is recommended as the first-choice antibiotic for children with AOM (25, 26). In most other western countries, amoxicillin is the first-choice antibiotic (4, 27).
This study demonstrated large variations in Danish practices’ antibiotic prescribing rates for RTIs (Figure 2) and specifically for AOM in children (Figure 1). Similar variations were found in an American paediatric primary care network, indicating that unintended variation may be a general problem (28).
In this study fever, purulent ear secretion, and poor general condition were statistically significantly associated with antibiotic prescribing. Multiple studies suggest these findings to be indicative of an antibiotic prescription (2-4). In addition, a Danish study from 2013 found type B tympanometry and a red eardrum associated with antibiotic prescribing (15). In this study, having a tympanometry performed was not statistically significantly associated with antibiotic treatment (Table 3). The waste majority of performed tympanometries were abnormal. It is likely that most of the children without a tympanometry would have had abnormal findings if it had been performed. Performance of a tympanometry was included in the analyses as an effort to equalize the validity of the AOM diagnoses.
In our study, even though recommended indicative of antibiotic treatment neither symptom duration ≥ 3 days nor symptom worsening was statistically associated with antibiotic treatment (2-4). Regarding symptom duration the statistical insignificance may be explained by underpowering of the analyses. However, most likely GPs value the present state of the child much higher than the disease history when deciding whether to prescribe antibiotics.
Though likely to influence the GP, parent’s request for antibiotics was not associated with prescribing in this study. GPs may misinterpret parent’s expectations. An Australian study from 2019 found that 86% of parents disagreed that they expected antibiotics for their child, though the GP interpreted the parent as wanting a prescription (29).
In this study, the most significant predictor of antibiotic prescribing was the practice’s antibiotic prescribing rate for RTIs and for children with AOM in particular. In line with this finding, a Danish study from 1997 showed that GPs with a high over-all prescription rate are also more likely to prescribe antibiotics (13). Some GPs may tend to follow a set pattern were AOM is treated with antibiotics regardless of whether the criteria for prescribing are met. A reason may be poor knowledge of the guidelines for AOM. However, a conservative approach has been recommended since 1981 (30). In this study the GPs gender and sex was not significantly associated though suggested to be by other studies (31), Other reasons for variation in prescribing rates may be differences in the GP’s workload (32) and in the socioeconomic status of the listed patients (33). However, in theory none of the latter should be allowed to influence the indications for antibiotic prescribing. This study does not present the final explanation for this variation.
Strengths and limitations
The main strengths of the study are the consecutive in situ recording of all consulting children with AOM and the GP and staff’s familiarity with the recording method reducing selection and information bias (14).
A shortcoming is the cross-sectional study design, which impairs assessments of causality; i.e. some of the specific assessments of the children including the AOM diagnosis may in some cases have been done and certainly recorded after deciding to prescribe antibiotics and thus be influenced by the decision to treat and not the other way around.
The study has a risk of selection bias. GPs’ choice to participate in the audit may depend on workload and degree of interest in RTIs, antibiotics, and quality improvement in general. A 2009 study done in Sweden showed that GPs who chose to enrol in medical audits had significantly lower antibiotic prescription patterns for RTIs compared to their non-participating colleagues (34), indicating that the real prescribing rate in Denmark may be higher than our 74% estimate. However, the aim of the study was not to assess the absolute rate of antibiotic prescriptions, but rather to analyse factors associated with antibiotic prescribing, an aim less likely to be biased by selection. The findings of the study are applicable to other Danish GPs and likely GPs in other countries with similar health care systems. The participating GPs were comparable to the rest of the Danish GP population in the three regions (Table 1), and our main finding, the large variation in antibiotic prescribing have been shown in the UK (35) and explicitly regarding paediatric patients in the US (28).
A potential limitation is the exclusion of patients for whom it was not the first visit for the current disease. This hinders evaluation of the ‘Watchful waiting’ approach. It is however speculative whether this influences our results, considering the lack of association between antibiotic prescribing and ‘Symptom duration ≤ 3 days’ in the analyses.
The study is restricted by reporting of age in whole years instead of in months. Children below six months of age diagnosed with AOM should always be treated with antibiotics according to national guidelines (2). This age group could not be specifically accounted for. Furthermore, the GPs were not requested to register otoscopy findings nor bilateralism of AOM resulting in lacking information on bulging and redness of the tympanic membrane. The lack of recording bilateralism is somewhat concerning, because this parameter is also indicative of prescribing antibiotics (2). Bulging, redness and bilateralism might account for some use of antibiotics in the study. However, the explanatory factor might be hidden in other variables in the regression (e.g. bilateralism might result in poor general condition (36)). But is very unlikely to affect the practices’ antibiotic prescribing rates for children with AOM, and possibly could not interfere with the prescription rates for all patients due to comparably few cases of AOM.
Implications for clinical practice and further research
Overprescribing of antibiotics for children diagnosed with AOM is evident and concerning. The inter-practice variation is large and independent of the patients’ signs, symptoms, and request for antibiotics. In order to support prudent prescribing of antibiotics for AOM, interventions should target high-prescribing practices and further research should investigate more detailed practice-related factors associated with overprescribing of antibiotics to AOM.