Urinary tract infection (UTI) is the most common type of severe bacterial infection (SBI) in infants presenting with fever without a source (FWS). Several management protocols have been developed to assess children with FWS and identify those with a UTI.1–3 The overall prevalence of UTI in infants with FWS is around 5%.4–9 However, this prevalence is not homogeneous and can vary with age, sex, race, body temperature or circumcision status. For example, a UTI is found in a large proportion of febrile girls aged less than 24 months and febrile boys aged less than 12 months.

Infants that receive a diagnosis of UTI require special care. Most febrile infants with this diagnosis exhibit renal parenchymal involvement. This can lead to long-term health problems, including hypertension and diminished renal function. The risk of renal impairment is greater in infants, and the diagnosis may be challenging to clinicians. The signs and symptoms of a UTI are often nonspecific, and the definitive diagnosis requires testing of a noncontaminated urine sample collected by catheterization or suprapubic aspiration.10,11 An accurate diagnosis is important to identify, evaluate and treat children at risk of UTI and renal scarring and to avoid overdiagnosis and overtreatment in children who are not at risk.11,12 Nevertheless, there are still differences between clinical guidelines on how to identify infants with FWS in whom UTI has to be ruled out in the paediatric emergency department (PED).1,2,13–18 Most clinical guidelines recommend performing urinalysis in infants with a rectal temperature of 39°C or higher.

Currently, there are no data available on the prevalence of UTI in infants with high fever in the paediatric emergency department (PED) setting. Such data could help physicians in deciding which children require further diagnostic testing.13

The aim of our study was to determine the point prevalence of UTI in febrile boys aged less than 12 months and girls less aged less than 24 months with FWS greater than 39°C admitted to PEDs in Spain.

In this multicentre prospective study of febrile infants evaluated in 7 PEDs for FWS greater than 39°C, we found a higher point prevalence of UTI, 15.5%, compared to the prevalence reported in previous studies, especially in boys aged less than 6 months and girls aged less than 12 months. One difference between our study and previous studies is that we only included children with a high temperature. Other epidemiological patterns, such as differences in point prevalence by age, sex, signs and symptoms of disease and bacteria isolated in urine or blood culture, were similar to those previously reported in infants and young children diagnosed with UTI.

Several previous studies have assessed the prevalence of UTI. They have reported an overall prevalence of UTI in infants presenting with fever without an evident source based on the medical history and physical examination of approximately 5%.7,19,20 In a review and meta-analysis of 14 studies, Shaikh et al.13 found a slightly higher pooled prevalence of UTI of 7% (95% CI, 5.5–8.4%) in febrile children aged less than 24 months of both sexes, with or without additional symptoms of UTI. In boys, the prevalence was highest in the first 3 months of life and then exhibited a declining trend, whereas in girls the prevalence was highest in the first 12 months of life.9,13 Although the differences based on sex and age found in our study were consistent with data from previous epidemiological studies of UTI, the point prevalences we found in each age group were higher compared to those reported in the literature.8,21 We found the highest point prevalence in febrile male infants aged less than 3 months, with UTI diagnosed in 43% of them. Our findings are consistent with a series of studies performed by Bachur,21 Zorc22 and colleagues, which showed that high fever (rectal temperature>39°C) and uncircumcised status were associated with a greater probability of UTI. Uncircumcised status22 has been identified as an important risk factor for UTI and seems to have a greater impact on younger children.23–27 Although we did not document circumcision status in our study, due to cultural customs the population we serve is mostly uncircumcised, which might explain the high point prevalence found in male infants.

Previous studies13 have proposed criteria for clinical prediction rules that clinicians can use to select patients from whom they should collect urine samples for analysis or culture. Our findings suggests that clinicians need to carefully investigate the possibility of UTI in all boys aged less than 12 months and girls aged less than 24 months with unexplained fever higher than 39°C. Given the high point prevalences found in our study, it would be reasonable to consider obtaining a urine specimen from infants with FWS and temperatures below this value. Factors other than the temperature, such as sex, duration of fever, history of UTI or pre-existing renal or urological conditions, must be considered to rule out UTI in febrile infants. The duration of fever has not been previously reported as a factor to be considered to rule out UTI in febrile infants seen in the PED. In the present study, the UTI point prevalence was higher in children with a longer duration of fever, especially in those aged more than 1 year. Although additional studies are needed to confirm this finding, we believe that this factor should be taken into account in the evaluation of a febrile infant.

The definition of UTI in febrile infants is controversial and differences in the definition used may explain the variability in the prevalences reported in different studies. In our study, the diagnosis of UTI was based on the quantitative results of urine culture in addition to evidence of pyuria and/or bacteriuria. In this sense, our UTI definition was more restrictive than those used in most previous studies, which have generally only required a positive urine culture.7,8,10 Our approach is in line with the most recent guidelines from the American Academy of Pediatrics, which define UTI as the growth of more than 50000CFU/mL of a single bacterium in a urine culture together with positive urine test strip or microscopic examination results. These criteria reduce the probability of overdiagnosis of UTI in infants with asymptomatic bacteriuria or contaminated specimens. Contrary to the guidelines proposed by the American Academy of Pediatrics guidelines for UTI, but in line with several other authors,14,18,28,29 we opted for a conservative threshold of 10000CFU/mL to consider a urine culture positive in order to avoid the risk of misdiagnosing real UTIs. Some factors, such as the urine collection method, can lead to a low bacterial count. A substantial proportion of infants with bacterial growth in urine culture of between 10000 and 50000CFU/mL and with a normal urinalysis results may have asymptomatic bacteriuria; we therefore considered urinalysis results to attempt to distinguish between acute infection and asymptomatic bacteriuria in infants with low bacteria counts.14,30,31

Quantitative urine culture is the gold standard for diagnosis of UTI, but unfortunately this method usually requires a period of up to 48h for results to become available. Dipstick urinalysis is a more attractive option in the ED setting as it is cheaper, quicker and easier to perform and interpret than microscopy or culture. However, urinalysis cannot just be substituted for urine culture to document the presence of UTI, but has to be used in conjunction with culture. Although dipstick urinalysis allows rapid testing, there is some doubt about its use in infants and young children.32–34 In our study, 19 children with positive urine cultures from samples collected with sterile technique and without pyuria were classified as possible cases of UTI. These patients were not included, therefore, in the global UTI point prevalence. In Spain, there is still a wide variability in the management of patients with normal urine test strip and positive urine culture results. Some authors suggest that patients with normal urine test strip results and a positive urine culture might have asymptomatic bacteriuria, and the source of the fever could be a viral infection.35 Once the results of urine culture are available, the management of these patients should be individualised.

There are several limitations to this study. First, we did not reach the initially estimated sample size for male infants; however, we were able to recruit 85% of the required number of males, so the results may be representative of the entire population. Second, by including only infants with FWS greater than 39°C we may have overestimated the point prevalence of UTI in the overall population of febrile infants. Nevertheless, we consider that the point prevalence of UTI reported by our study may be useful to emergency paediatricians who routinely use this temperature as the cut-off point to rule out this type of infection. Third, we did not recruit all the infants with FWS greater than 39°C managed in the participating hospitals, as we only needed a minimum of 80% of the total for the study. It is possible that our sample included patients at greater risk of having an UTI, which would have led to an overestimation of the actual point prevalence of UTI. Still, we believe our response rate of 80% of children eligible for the study minimises the effect of sampling bias and that the high point prevalence rate found in our study is attributable to other factors already discussed. Finally, although there is a specific definition for the concept of FWS, it is still a subjective one that can therefore vary between hospitals. This could limit the applicability of our results to other health settings where different diagnostic criteria are applied. Nevertheless, we ought to note that the point prevalences observed in the different hospitals were all similar and close to the overall point prevalence.

The point prevalence found in infants with FWS of more than 39°C was higher in our study compared to previous studies on the prevalence of UTI, especially in male infants aged less than 6 months and female infants aged less than 12 months. Our findings suggest that clinicians need to make a thorough assessment of UTI in all boys aged less than 12 months and girls aged less than 24 months with unexplained fever of more than 39°C.

The point prevalence in infants aged less than 12 months was highest in girls. On the other hand, the point prevalence in febrile male infants aged less than 3 months is twice that in female infants of the same age.