This large prospective cohort study of young children presenting with a febrile illness to an emergency department in Australia has shown that urinary tract infection, pneumonia, and bacteraemia occur in about 7% of illnesses in children who present with fever, but in only 66-81% of cases are the children administered antibiotics at the time of their first presentation.
Our study has shown that the low rate of antibiotic administration is not caused by failure to consider the diagnosis of serious bacterial infection. Urinary tract infection, pneumonia, and bacteraemia were almost always considered as possible causes of febrile illness, as shown by the ordering of the appropriate tests in approximately 95% of children with serious bacterial infection. Nor is the lack of treatment the result of the symptoms and signs elicited by physicians in this setting having poor diagnostic value. We found that many clinical features widely considered to be indicative of serious bacterial infection—such as overall appearance of the child, urinary symptoms for urinary tract infection, and cough for pneumonia—were highly discriminatory for both ruling in and ruling out infection.
We identified two major, potentially correctable, difficulties in the current diagnostic decision making process. Firstly, in combining the demographic items and clinical symptoms and signs related to febrile illness, the physicians tended to underestimate the likelihood of serious bacterial infection. There are too many relevant signs and symptoms for doctors to assimilate effectively; instead, they tended to discount the information and underestimate the probability of serious disease. As such, the full diagnostic value of current clinical tests was often not reached. Secondly, where near patient tests were available, such as urinalysis for urinary tract infection and chest radiograph for pneumonia, errors in interpretation meant that serious bacterial infection was left untreated at the initial presentation.
It is likely that in some cases physicians correctly identified pneumonia on the chest radiograph or urinary tract infection using the urinalysis results but decided not to treat the child with antibiotics. Consolidation on chest radiograph in association with viral symptoms, for example, may have been considered indicative of viral pneumonia by the treating physician. In suspected urinary tract infection, the importance of collecting an uncontaminated specimen of urine means that some practitioners routinely delay the prescription of antibiotics until the culture result is known. Within an emergency department setting, this approach is not unreasonable and all children are referred back to their local healthcare provider. However, we found that about two thirds of children who were not treated at their first presentation were subsequently prescribed antibiotics; therefore, early antibiotic administration would be expected to shorten the duration of the febrile illness and prevent unnecessary re-presentations.
One third of children with serious bacterial infection appeared to recover spontaneously without antibiotics. This finding could be explained by some degree of misclassification in our definitions of urinary tract infection and pneumonia, the two infections responsible for most cases in this study. Some level of misclassification is inevitable because no definition will encompass every possible variant of either of these infections; however, our definitions were based on published information and clinical consensus, and are clearly reported. There is evidence that between 28% and 40% of adult women with urinary tract infection are cured within 7 days without having received treatment,26 27
which suggests that our rate of spontaneous cure is not unprecedented.
Our data suggest that two interventions could be used to improve clinical decision making with respect to children who present with fever. Firstly, a computer assisted diagnostic decision tool such as that developed in this study could be used to determine the likelihood of serious bacterial infection. Doctors in the emergency department would enter the clinical findings into a computer program and the risk calculation would be generated for them. On the basis of the level of risk, treatment could commence or be withheld until further information is available. The model developed in our study could be calibrated to a low threshold of diagnosis (high sensitivity), for example, which should result in more children with serious bacterial infection receiving antibiotics and at an earlier stage of their illness. The trade-off would be a lower specificity, however, resulting in additional testing and treatment for children who do not have serious bacterial infection. Secondly, for urinary tract infection, where urinalysis can assist diagnostic decision making, and for pneumonia, where chest radiograph is available as the reference standard, better understanding of the results and the use of decision rules with lower decision thresholds than are currently used could improve rates of antibiotic prescription on initial presentation to emergency departments.
Strengths and limitations of study
Our study has a number of important features. The eligibility criteria were based on a common reason for presentation—a febrile illness rather than a specific disease—which enabled us to evaluate the accuracy of clinical symptoms and signs for the main types of relevant bacterial infections. The size of the study provided sufficient power to allow us to develop a robust and reasonably precise model to discriminate between the most common serious bacterial infections (urinary tract infection, pneumonia, and bacteraemia) rather than having to consider them as a single group of “serious bacterial infections,” which is critical given that the treatment for each is different. Validation of the model in a different group of patients showed that the performance of the model was very stable for both pneumonia and urinary tract infection, the most common serious bacterial illnesses
We collected data on the decision making steps after the initial assessment of a febrile child—including physician estimates of the probability of serious bacterial infection on the basis of initial assessment, test ordering, and antibiotic administration—and not simply on the final diagnosis for each child. We also used a final diagnosis committee to verify probable cases of bacterial infection, members of which were blinded to other clinical data like the reference test results, which minimised possible random and systematic error in the classification of children. Finally, we were able to follow up and verify the diagnosis in 93% of children.
We believe the findings of this study are generalisable to other acute paediatric settings because the prevalence of serious bacterial infection in this research is very similar to that in other studies17 28 29
and the frequency of antibiotic administration is also similar.30 31
Our study does have some potential limitations. We did not have microbiological and radiological verification in all children, so we may not have detected some bacterial infections that spontaneously resolved. This would have required urine, blood, and chest radiography in all children up to 5 years of age, which was not justifiable clinically or ethically. Instead, in keeping with standards for the evaluation of diagnostic tests where applying the reference standard test in all patients is not feasible, we used a double reference standard.32 33
Children were classified as “negative” for serious bacterial infection if all reference standard tests that were done were negative (which was the case in about 25% of eligible children) and if, on follow-up, a parent reported resolution of the child’s illness by days 10-14. Any cases of serious bacterial infection missed because no tests were done and that resolved spontaneously within the follow-up time frame would not greatly benefit from earlier antibiotic administration. In addition, the validity of the physician estimates of disease may be uncertain, particularly at this early stage of assessment, and the estimates had no influence on subsequent clinical care decisions.
Comparison with other studies
The evaluation of young febrile children is a major management dilemma worldwide and has attracted considerable research and policy attention. This is reflected in the recently published National Institute for Health and Clinical Excellence (NICE) guidelines for the assessment and initial management of febrile illness in children under 5 years.34
These guidelines summarise the existing clinical assessment scales that combine multiple signs and symptoms in this setting. The guideline authors conducted a literature review and identified two scoring systems: the Yale observational scale12
and the young infant observational scale.11
Problems in the development of each scale were detected, however, and neither scale was considered sensitive for the detection of serious bacterial infection. Furthermore, the review of studies of individual signs and symptoms noted that most of the data were in infants younger than 6 months of age but authors concluded it was reasonable to extrapolate to older children.
The NICE group subsequently developed a “traffic light” assessment tool that can be used to classify children into low risk, intermediate risk, and high risk of serious infection; however, the tool has not yet been evaluated. The elements in the assessment tool do have considerable overlap with fields collected in the current study, with omission only of some comparatively rare and specific events: status epilepticus, swelling of limb (non-weight bearing), bile stained vomit, and “new lump.”
Diagnostic decision making has received little attention compared with therapeutics, despite the universally accepted “medical mantra” of the importance of history taking and physical examination for all patients. Given the complexity of this process and the sheer number of clinical symptoms and signs elicited (including multiple thresholds at multiple and varying times during the illness), it is highly likely that errors in judgment occur when combining these clinical features. In many situations, inefficiencies, costs, and harms may occur by the needless ordering of additional tests and by overtreatment or undertreatment. By combining routinely collected clinical information into a statistical model, we have demonstrated that a clinical diagnostic model may improve the care of children presenting with fever who have suspected serious bacterial illness.
Urinary tract infection, pneumonia, and bacteraemia occur in about 7% of children who present to an emergency department with a febrile illness, but only 70-80% of such children are prescribed antibiotics on initial consultation and 20% of children without an identified bacterial infection are probably overtreated with antibiotics. Combining physician elicited symptoms and signs into a statistical model presented as a computer assisted diagnostic decision system provides scope to improve sensitivity compared with physician judgment, thereby improving early treatment.
What is already known on this topic
- In children with fever, it can be difficult to distinguish serious bacterial infections from viral infections
- Current diagnostic processes and clinical scoring systems are inadequate in an acute setting and lead to a substantial proportion of children with serious bacterial infection not being treated with antibiotics when they first present
- There is a need for an accurate acute clinical decision making tool that takes into account all the signs and symptoms associated with serious causes of febrile illness
What this study adds
- Urinary tract infection, pneumonia, and bacteraemia occur in about 7% of children who present to an emergency department with a febrile illness, but only 70-80% of such children are prescribed antibiotics on initial consultation
- Our computerised diagnostic model successfully combined clinical history, signs, and symptoms to provide a high to moderately accurate estimate of the risk of serious bacterial infection in children presenting with febrile illness
- Our clinical diagnostic model outperformed clinical judgment for the diagnosis of fever in young children