A 28-day-old uncircumcised male infant presents to the emergency department with fever of 38.9° C, decreased feeding, and irritability. The physical examination is normal with the exception of the irritability and your assessment of mild dehydration. The infant undergoes a sepsis work-up. The CBC is remarkable for a WBC of 16,500/mm3 with 44% neutrophils, 52% lymphocytes, and 4% monocytes. Platelet count is normal. Cerebrospinal fluid (CSF) shows no white or red blood cells with normal glucose and protein. The urinalysis (UA) has a positive 1+ leukocyte esterase (LE) with 10 WBC per high-power field (HPF), but negative nitrite and 1+ bacteria microscopically. The child is admitted to the hospital for empiric antibiotics pending blood, urine, and CSF cultures. What are the chances that a urinary tract infection (UTI) is the origin of the febrile presentation?
UTIs are currently the most common serious bacterial infection (SBI) in < 2-year-old febrile children without an apparent source of fever (Pediatrics 2011;128:595-610). Since 2000, the prevalence of UTIs in all febrile infants and young children without an apparent source is unchanged, being approximately 5%. The rate of UTIs in fever-without-apparent-source presentations at < 90 days of age is higher, ranging from 6%-15% in different studies.
Meanwhile bacteremia, sepsis, meningitis, and other previously common SBIs, mostly caused by Haemophilus influenzae type b (Hib) or pneumococcus, have decreased. We recognize these reductions as effects of universal implementation of Hib (mid-1990s) and pneumococcal (2000 and 2010) conjugate vaccines.
Given the case above, other pertinent facts are that uncircumcised males have more UTIs in the first months of life (J. Pediatr. 1996;128:23-7) and approximately 5% of young infants with UTIs also are concurrently bacteremic (Pediatrics 1999;104:79-86;J. Pediatr. 1994;124:513-9)
The elephant in the room is the fact that we also need to be cognizant of asymptomatic bacteriuria (AB). AB is colonization of the lower urinary tract without infection. Patients with AB may meet culture criteria for UTI (whether we consider > 50,000 or > 100,000 colony-forming units/mL), but there is no evidence of true infection, that is no inflammation or mucosal injury. So children with AB are not at risk for renal injury or later renal damage and do not require antibiotic treatment.
But when AB patients develop fever, for example with an enterovirus infection, their urine cultures (together with the fever) can do a good imitation of a UTI, unless we focus on the UA results. It not only remains critical to detect true UTIs in infants < 90 days old, such as the one in our case above, but also to distinguish UTI from AB.
The 1999 American Academy of Pediatrics’ UTI guidelines (Pediatrics 1999;103:843-52) included UA results as suggestive of UTI. They stated that a positive LE or nitrite test or > 5 WBC/HPF in a spun urine, or bacteria visualized in unspun gram-stained specimen suggest, but cannot be diagnostic of a UTI. Recommendation five in the guidelines states that UTI diagnosis required 100,000 CFU/mL in culture of sterilely obtained catheterized urine as the threshold criterion (strength of evidence: strong). However, AB was not fully considered because, in part, data defining AB was incomplete in 1999.
The 1999 guidelines also stated, “The urinalysis … can be valuable in selecting individuals for prompt initiation of treatment while waiting for the results of the urine culture.” So, UA was considered adjunctive. UA’s main function was to allow empiric therapy of sufficiently ill children, given positive results for LE, nitrites, or microscopic visualization of > 5 WBC/HPF or bacteria in the spun urine.
In the 2011 AAP guidelines for UTI, things have changed (Pediatrics 2011;128:595-610). The third action statement tells us that both the UA and culture taken together are necessary for UTI diagnosis. To paraphrase: The diagnosis of UTI requires urinalysis results suggesting infection (pyuria or microscopic bacteriuria) plus > 50,000 CFU/mL of a uropathogen in urine from catheterization or suprapubic aspiration. But remember that these guidelines do not apply specifically to the youngest of infants, that is < 2 months old.
Both of these criteria were changes from the 1999 UTI guidelines. Previously pyuria or microscopic bacteriuria were not considered necessary to diagnose UTI, and >100,000 CFU/mL rather than > 50,000 CFU/mL of a single pathogen species was the critical diagnostic result for catheterized urine. For suprapubic aspiration urine samples, > 10,000 CFU/HPF were considered adequate for UTI diagnoses in 1999.
Now, a recent study of children < 90 days of age (including those < 2 months of age) reports that pyuria (> 3 WBC/HPF) plus > 50,000 CFU/mL are the keys to diagnosing UTI (Pediatrics 2015;135:965-71). One caveat is that the study population was febrile infants < 90 days old with concurrent bacteremia (bacteremic UTI). Bacteremic UTI was studied to reduce as much as possible the chance that AB patients might be inadvertently included in the study. One other conclusion of this new study is that microscopic bacteriuria did not add significantly to the either sensitivity or specificity.