Is urinary tract infection in infants and children a serious bacterial infection? Dr. Quinonez, chief of pediatrics at San Antonio Children’s Hospital and associate professor of pediatrics at Baylor College of Medicine, recently discussed this controversial issue, as reported in MedscapePediatrics.
Old and New Views on Diagnosing Urinary Tract Infections in Children
Over the years, Jaskiewicz and Bachur et al. have published studies on fever in children in Pediatrics. They have argued that urinary tract infections in infants and children should be taken seriously enough and their severity should be considered as “severe bacterial infections” along with bacteremia and meningitis, and these studies are historical landmarks. Zhang Lei, Department of Pediatric Surgery, Qilu Hospital, Shandong University
However, as more insight into the long-term prognosis of children with urinary tract infections has been gained, there has been ongoing controversy regarding the prevention of urinary tract infections, and several other recent studies have questioned the need for aggressive diagnosis of urinary tract infections in children.
For example, a review of relevant studies by Newman et al. in 2013 analyzed the following topical issues: the incidence of urinary tract infections in infants and children, the risk of progression to sepsis, the correlation between urinary tract infections and renal scar formation, and the question of whether subsequent prevention of urinary tract infections and possible formation of renal scarring mitigates the development of potential long-term adverse sequelae such as hypertension or renal failure.
Urinary tract infections are relatively common in infants and children less than 18 months of age with unexplained fever, with rates of approximately 2-7.5% reported in the literature. And what is the proportion of children with urinary tract infections who have sepsis?
A population-based survey showed that sepsis from urinary tract infections or pyelonephritis occurs in less than 1 in 20 children, most of whom (more than 70%) are infants and children, and about half have urinary tract abnormalities. The mortality rate in these cases of urinary sepsis was 3.7%, significantly lower than the rate of sepsis due to other etiologies in the pediatric population.
The debate over the relevance of active treatment to long-term adverse outcomes
The American Academy of Pediatrics (AAP) guidelines recommend that children with confirmed and suspected urinary tract infections should be treated as early as possible to reduce the development of renal scarring and secondary chronic kidney disease (CKD). However, numerous clinical randomized controlled trials (RCTs) and observational studies have confirmed that treatment does not reduce the development of renal scarring.
Notably, the results of not all relevant studies are consistent. A prospective RCT of 287 children found that 30% of children with urinary tract infections developed renal scarring regardless of whether they were treated with antibiotics early or late in the course of the fever.
In contrast, another observational study of 230 children with their first fever of urinary tract infection found that a delay of more than 4 days between the onset of fever and the initiation of treatment increased the rate of renal scarring in children with and without urinary reflux.
What is clear from the available evidence is that urinary tract infections are indeed associated with secondary renal scar formation. However, does scar formation necessarily increase the risk of adverse long-term prognostic outcomes (e.g., hypertension and CKD)? Two RCTs and a systematic review study have addressed this question.
The results of the first RCT, published in 1996, followed 111 women with urinary tract infections for a mean of 15 years. Its results showed no clinically significant differences in glomerular filtration rate (GFR) or incidence of hypertension in the moderate-to-severe renal scarring group compared with healthy controls.
The second RCT followed over 1200 children with symptomatic urinary tract infections for a mean of 25 years, and among the 57 subjects with complete long-term follow-up data, repeat scans with mercaptosuccinic acid (DMSA) revealed permanent renal scarring in the vast majority (93%). However, there were no statistically significant differences in GFR or hypertension onset between the observation and healthy control groups.
A systematic review study of 1500 patients with CKD analyzing the correlation between their childhood urinary tract infections and secondary CKD found that no cases developed as a direct result of a urinary tract infection. The authors of the study also researched information on patients with CKD of unknown etiology from a regional database in Finland and found that no patients appeared to have developed the disease as a result of a urinary tract infection.
Another reason for the “aggressive diagnosis of urinary tract infection” opinion is that it would allow for the timely detection of children with vesicourethral reflux (VUR), which is treatable with medication or surgery. Two relevant clinical trials are the recently conducted Randomized Intervention in Children with Vesicoureteral Reflux (RIVUR) study and the previously conducted Prevention of Recurrent Urinary Tract Infections (PRIVENT) trial in children with vesicoureteral reflux (normal renal structure).
The results of both studies confirmed that prophylactic treatment of recurrent urinary tract infections with antibiotics did prevent their recurrence (8 cases requiring treatment in the RIVUR study and 14 cases requiring treatment in the PRIVENT study), but treatment in both clinical trials did not prevent renal scar formation.
In addition, these trials also question whether the presence of VUR affects antibiotic prophylaxis of urinary tract infections; for example, the PRIVENT trial included children with VUR and children without VUR, and antibiotic efficacy did not differ between the two groups. In contrast, in both clinical trials, a higher proportion of bacteria resistant to common antibiotics appeared in the prophylactic group than in the control group.
It appears that prophylactic administration to children with and without VUR can prevent urinary tract infections, so VUR has little effect on the formation of renal scarring and the prevention of urinary tract infections. If the child is known to have VUR, surgical treatment is at least possible for severe cases. Currently, there is no evidence to support that surgical treatment can prevent adverse outcomes such as CKD.
Debate over the association of urinary tract infections with other diseases in children
Previous studies have shown a correlation between urinary tract infections and apparent life-threatening events (ALTE) and respiratory syncytial virus (RSV) bronchiolitis.
Some of these studies suggesting a correlation with RSV were conducted prior to the release of the AAP 2011 guideline diagnostic criteria (new diagnostic criteria required positive urine culture and urinalysis for pus urine).
However, a later study found that the previously found correlation was again absent when calculating the rate of urinary tract infections in children with RSV using the old and new diagnostic criteria. Similarly, all studies showing an association between urinary tract infection and ALTE used the old criteria for diagnosing urinary tract infection (requiring only a positive urine culture), and the reliability of the results has yet to be tested.
The incidence of asymptomatic bacteriuria in children in these early studies was similar to the rate of urinary tract infection detection. Therefore, it is likely that the findings of these studies are unreliable and that the cases of so-called urinary tract infections they found were actually bacterial colonization.
Summary
1. Urinary tract infections in children rarely progress to sepsis.
2. Early treatment of urinary tract infections does not appear to affect prognostic outcomes.
3. Urinary tract infection is not a major predisposing factor for CKD.
4. Pharmacological or surgical treatment of VUR is not effective in improving the outcome of urinary tract infection.
5. The findings of correlation studies between urinary tract infection and other diseases are often not very reliable.
Is urinary tract infection in infants and children a serious bacterial infection?
The results of studies published by Newman et al. and others later showed that urinary tract infections in infants and children are not serious bacterial infections. Indeed, it is undeniable that treating a clearly diagnosed urinary tract infection can largely alleviate the patient’s symptoms and promote recovery, which can be of value to the patient himself or his family.
However, the management of urinary tract infections in infants and children should be approximated to that of a disease such as otitis media, rather than being overemphasized and placed on a par with bacteremia or meningitis, thus challenging the need for aggressive diagnosis of urinary tract infections.
The above analysis suggests that when dealing with pediatric febrile cases, it is advisable to suspend the decision before active medical treatment and to discuss the treatment decision with the parents of the child after fully communicating with them about the above situation.