Diagnosis and Management of UTI in Febrile Infants Age 0–2 Months: Applicability of the AAP Guideline

Urinary tract infections (UTIs) are the most common bacterial infection and one of the most common reasons for hospitalization in young infants.^1,2 The American Academy of Pediatrics (AAP) has published several clinical practice guidelines for the evaluation and management of febrile children ages 2-24 months with first-time UTIs, most recently in 2011 and affirmed in 2016.³ These guidelines do not provide recommendations for infants aged <2 months, which leads to uncertainty regarding the diagnosis and management of UTIs for infants in this age group. We assess the applicability of the AAP UTI Guideline’s action statements for infants aged <2 months presenting with first-time UTIs, with an emphasis on recent evidence. Because the considerations for bacterial infections differ for febrile infants aged <2 months compared with older infants, we do not discuss action statements one and two (determination of the likelihood of UTIs and decision to test urine) and statement seven (medical evaluation for fever after first UTI).³ Additionally, because concomitant bacteremia and meningitis are more common in this age group than in older infants, we review some of the controversies surrounding the diagnosis and treatment of these disease entities.

“Action Statement 3: To establish the diagnosis of UTI, clinicians should require both urinalysis results that suggest infection (pyuria and/or bacteriuria) and the presence of at least 50,000 colony-forming units (CFUs) per mL of a uropathogen cultured from a urine specimen obtained through catheterization or SPA.”³

To distinguish asymptomatic bacteriuria or contamination from a true UTI, the AAP Guideline requires both a positive urinalysis (UA) and culture for a diagnosis of a UTI.³ Historically, the UA was considered to be poorly sensitive for infections in young infants, with older studies reporting sensitivities ranging from 40% to 82% using urine culture as the gold standard.^4-7 Thus, infants aged <2 months with positive urine cultures and negative UAs are often treated as having true UTIs, though this practice varies by institution.⁸ Possible explanations for the low UA sensitivity in this population include rapid bladder emptying, immature immune systems, and inability to concentrate urine. However, a negative UA plus a positive urine culture could also represent a “true negative” UA and a “false positive” culture, a finding that may be more common in young infants in whom sterile urine obtainment is often challenging.

Two recent studies have addressed this issue by evaluating the UA sensitivity in patients with bacteremic UTIs, as growth of the same pathogenic organism from the blood and urine almost certainly represents true infection.^9,10 In a retrospective study of 203 infants aged <3 months with bacteremic UTIs, the presence of any leukocyte esterase (LE) or pyuria (>3 white blood cells per high-powered field [WBC/HPF]) had a sensitivity of 99.5% (95% CI: 98.5%-100%) and specificity of 93.9% (95% CI: 87.8%-93.2%).⁹ In a prospective, multicenter study of 4,147 febrile infants aged ≤60 days, of whom 27 infants had bacteremic UTIs, a positive UA (any LE, >5 WBC/HPF, or nitrite) had a sensitivity and specificity of 1.00 (95% CI: 0.87-1.00) and 0.91 (95% CI: 0.90-0.91), respectively.¹⁰ Although screening tests may appear to have higher sensitivity in more severely diseased populations (“spectrum bias”),¹¹ it is not clear that infants with bacteremic UTIs are definitively sicker than infants with nonbacteremic UTIs (see “bacteremic UTI” section below). Additionally, this study found similarly excellent sensitivity (0.94 [95% CI: 0.90-0.96]) and specificity (0.91 [95% CI: 0.90-0.91]) of the UA among infants with nonbacteremic UTIs, including infants <28 days old.¹⁰

UA sensitivity (using urine culture as the gold standard) may be lower for non-Escherichia coli UTIs.^9,10,12 In a retrospective study that included 90 infants <2 months old with UTIs, urine cultures yielding Pseudomonas aeruginosa, Enterococcus, or Klebsiella species were significantly less likely (odds ratio [95% CI]: 0.19 [0.06-0.60]; 0.14 [0.07-0.28]; 0.34 [0.17-0.68], respectively) to have pyuria (≥5 WBC/HPF) or LE (1+ or greater) than urine cultures yielding E. coli.,¹² though an alternative explanation for this finding is that these organisms may be more likely to cause asymptomatic bacteriuria or contamination.¹³

The appropriate CFU/mL threshold to define a UTI and the extent that this threshold should vary by urine collection methods are still unclear. In the aforementioned bacteremic UTI study,⁹ 12 patients with E. coli bacteremia had urine cultures with <50,000 CFU/mL plus pyuria (WBC or LE) in the UA, indicating that true UTIs may occur with <50,000 CFU/mL.

Based on these recent studies, we believe that the recommendation to incorporate UA results into the diagnoses of UTIs can be applied to infants <2 months old, as well as consideration for a UTI for colony counts of ≥10,000 CFU/mL if the UA is positive. For infants with positive urine cultures and negative UAs who have not received antibiotics, we suggest repeating both studies if treatment is being considered. For those who have started antibiotics, the pretest probability of a UTI, initial illness severity, and risks and benefits of continuing treatment should be considered.