Strengths and limitations
A major strength of the study is the large number of patient records. This minimises the probability that the results are based on chance, and lack of power plays no role in the non-significant related variables.
The study did not look for any relation between (working) diagnosis and antibiotic prescription. This is based on the fact that GPs make diagnostic transfers to diagnoses that justify their antibiotic prescription.18 Therefore, these diagnoses are ultimately related to the signs and/or symptoms of the presenting febrile child. Therefore, investigating the relation between alarm signs and/or symptoms and antibiotic prescription seems more appropriate.
The GPs did not record the signs and symptoms in a fully structured way. Therefore, when a characteristic was not recorded, it is possible that the variable was absent and that the GP did not write it down, or that the GP did not look for that particular sign or symptom. This problem was discussed in a consensus meeting including specialists in family medicine and paediatrics. It seems legitimate to consider some signs (for example, unconsciousness) as being absent when the GP did not report this, since if that sign had been present the GP would always notice and record it. This is especially so since the Dutch guideline specifically advises to look for the various alarm signs and/or symptoms when assessing a febrile child.5
Comparison with existing literature
In the present study, the amount of prescribed antibiotics (36.5%) is similar to the 36.3% prescribed in a previous study.4 Although this latter study was performed in younger children, overall it is similar to the present one with regard to the setting, study population, and clinical guidelines used. When selecting the same age category in the present study, 35.0% of children aged 3 months to 6 years were prescribed antibiotics, that is, a rate very similar to the earlier report.
Surprisingly, increasing age was significantly related to antibiotic prescription. This was unexpected since younger children are more at risk of a serious infection, and therefore more cautious management (that is, more antibiotic prescriptions) could be expected. However, since febrile illnesses in young children can deteriorate quickly, the GP may take even more precautions than simply prescribing antibiotics. For example, in this earlier study,4 children referred to secondary care were significantly younger than those included in the analyses: median age 1.6 years (interquartile range [IQR] = 0.6 to 3.6 versus 2.4 years, IQR = 1.1 to 4.7) (Mann–Whitney U test <0.01). Perhaps the consideration of prescription of antibiotics is less important in younger children than the consideration of whether or not to immediately refer them to secondary care. A similar explanation may apply to the negative associations found between antibiotic prescription and neurological signs and vomiting and/or diarrhoea. Children with these signs are also more often referred to secondary care (data not shown). Another explanation for the findings related to children with vomiting and/or diarrhoea is that it is not reasonable to administer antibiotics in children with these alarm signs, since the risk of bacterial infection is considered to be low.19
Compared with other European countries, GPs in the Netherlands have one of the lowest overall rates of antibiotic prescription.20,21 Nevertheless, in the present study more than one out of three children were prescribed antibiotics. Although other studies also reported antibiotic prescription rates, they were performed in different study populations (for example, only children with acute otitis media, not solely febrile children),21–24 making comparison with the present results difficult.
The GP cooperative out-of-hours setting was chosen because a high number of consultations concerning fever was expected. One in five consultations at a GP cooperative out-of-hours service concerns children (aged 3 months to 5 years), and in almost half of these children, fever is the reason for encounter (unpublished data). Patient characteristics like sociodemographic status are expected to be similar to those of children seen during regular hours, since the region for the out-of-hours care, and the regular hours care is the same. However, at the GP cooperative, triage is performed to select the children that need immediate assessment, and those that can wait until regular hours. Therefore, the children in the present study might be more seriously ill compared with those seen during regular hours and, therefore, may have had more alarm signs and/or symptoms and have been more eligible for antibiotic treatment. However, if this was the case, the explained variation in antibiotic prescription should be even higher, since alarm signs and/or symptoms are thought to be indicative of the severity of disease.
Furthermore, in the Netherlands, GPs are not familiar with the patients assessed at the out-of-hours service, and follow-up of these patients is performed by another physician. This may make it more difficult to provide adequate safety netting. Ultimately, this may lead to more defensive management and to more antibiotic prescription.
The present study shows that only a small proportion of the antibiotic prescriptions is explained by the related alarm signs and symptoms. This is not surprising, since other clinical features may also contribute to considering whether to prescribe antibiotics (for example, otorrhoea, bulging tympanic membrane).25–28 Unfortunately, information on these clinical features was not available in this study, and could therefore not be included in the analyses. The explained variation of antibiotic prescriptions might have been higher, if these variables could have been added. This assumption was confirmed by the previous study in a similar setting, in which it was shown that variables like signs of throat infection or earache are also related to antibiotic prescription.4 In that study, multivariate analysis explained 26% of the proportion of variation. Hypothetically, in the most positive perspective, 45% of the variation in antibiotic prescription is explained by the two studies; however, this is not actually the case, since there is some overlap in the signs and symptoms (for example, ill appearance). This indicates that in ≥55% of the prescribed antibiotics, other (unknown) factors contribute to the GP’s decision to prescribe antibiotics. Earlier studies found that non-medically based considerations may also contribute to the GP’s decision to prescribe antibiotics, for example, assuming that the patient or the parents expect antibiotics.29–31 However, these assumptions are not always valid,32–34 and GPs may need to reconsider their management of febrile children.
Bacterial resistance to antibiotics is a growing problem.20 Since overuse of antibiotics contributes to this problem, prevention of unnecessary prescription is important.20,35 Since ≥50% of the prescribed antibiotics do not appear to be based on medical considerations, strategies to diminish antibiotic prescription should focus on this aspect. Cals et al reported that point-of-care testing of C-reactive protein (CRP) and training in communication skills significantly reduced antibiotic prescribing for lower respiratory tract infection, without compromising patients’ recovery and satisfaction with care.36 However, the role of CRP in febrile children in primary care needs further elucidation.37 It may be useful to investigate whether a negative CRP can reassure both patients and GPs in the decision-making process, and thereby diminish antibiotic prescription.
In the present study, ill appearance, being inconsolable, shortness of breath, increasing temperature, and longer duration of fever were significantly and positively related to antibiotic prescription. All of these signs and/or symptoms are suggested to be related to serious infections, mostly in secondary care settings.2 Prescribing antibiotics in these children suggests that GPs may be concerned about the (future) course of the febrile disease, and therefore want to treat or prevent potential complications of a serious bacterial infection. However, although oral antibiotics are helpful in some serious bacterial infections like pneumonia, UTI, or acute tonsillitis (prevention of peritonsillar abscess),27–28,38,39 they are not useful in the initial treatment of rare serious bacterial infections like meningitis or sepsis. In addition, antibiotics frequently cause side effects. Therefore, the disadvantages of antibiotics should be weighed against their limited benefits in treating and preventing serious bacterial infections.
Signs of UTI were significantly related to less antibiotic prescription; this is surprising because a UTI is a clear indication for antibiotics.39 However, this result can be explained by the fact that this variable is composed of several signs, including pollakiuria, dysuria, and abdominal pain without diarrhoea or other focus of the fever (Appendix 1). This may explain the lack of a significant relation between signs of UTI and antibiotic prescription. Another, more disturbing, explanation may be that GPs do not endorse the signs and/or symptoms of a possible UTI. Recognition and treatment of UTIs in children is important since they can cause transient or permanent kidney damage.40,41