Wise Use of Antibiotics

Diagnosing and Treating Pediatric Urinary Tract Infections – What’s New?

Column Editor: Rana El Feghaly, MD, MSCI | Director, Clinical Services | Director, Outpatient Antibiotic Stewardship Program | Associate Professor of Pediatrics, UMKC School of Medicine

Urinary tract infections (UTIs) are among the most common reasons for antibiotic prescribing in outpatient settings. New data are emerging that support shorter antibiotic courses in children and early transition from intravenous to oral antibiotics in young children with pyelonephritis. The Evidence Based Practice Team at Children’s Mercy recently developed new Clinical Practice Guidelines to help providers diagnose and treat children with UTIs.

Which children should I evaluate for a UTI?

• Children with high-grade fever (≥39°C), lasting ≥48 hours without a clear source, particularly those with risk factors (girls ≤12 months of age, boys ≤6 months of age especially if uncircumcised, immunosuppression, vesicoureteral reflux, posterior urethral valves or other ureteral or renal abnormalities, neurogenic bladder, bladder catheterization, and constipation).
• Children with referrable urinary tract symptoms (such as urinary frequency, urgency, dysuria, nausea/vomiting, incontinence, abdominal/flank pain, hematuria or foul-smelling urine).

What sample should I obtain?

The collection method should take into consideration age and toilet-training.

• A sterile urethral catheterization is the ideal sample in non-toilet-trained children. Although suprapubic aspiration provides an excellent sample, it is invasive and painful, thus recommended only if a catheterized sample cannot be obtained.
• A bagged specimen should not be sent for culture; contamination rates as high as 63% make culture results unreliable in most cases.¹ If used as an initial screen for a urinalysis (UA), a subsequent catheterized sample should be obtained if culture is required.
• In toilet-trained children, a midstream clean-catch urine is recommended. Contamination rates remain somewhat elevated (up to 34%), likely due to poor collection techniques,^2,3 so appropriate education on collection technique (particularly obtaining a true midstream sample) is paramount when using this method.

How do I diagnose a UTI?

A fresh urine specimen (less than one hour after voiding with maintenance at room temperature, or less than four hours after voiding with refrigeration) should ideally be analyzed using dipstick and microscopy. To establish a diagnosis of UTI, the patient should have BOTH an abnormal UA AND a urine culture.

• Urinalysis: A positive nitrite test is 99% specific for UTI (positive predictive value of 86%, and negative predictive value of 89%). On the other hand, the leukocyte esterase (LE) test is less specific, albeit more sensitive. Having both a positive nitrite and LE brings up the positive predictive value to 93% and the negative predictive value to 94%. A test that is negative for LE and nitrites is excellent in ruling out UTI. Pyuria (≥5 WBC/HPF) and bacteriuria are not specific for UTI.^3-5
• Urine culture: Cut-offs are slightly different based on the collection technique; UTI is confirmed with growth of ≥50,000 colony forming unit/mL of a uropathogen from a catheterized sample, and ≥100,000 colony forming unit/mL of a uropathogen from a clean-catch. The presence of mixed growth typically indicates contamination. Common uropathogens include enteric gram-negatives (such as E. coli, Klebsiella spp, Proteus spp, Enterobacter spp, Citrobacter spp), Enterococcus spp and Candida spp.⁵

Which antibiotics are best to use?

• Parenteral antibiotics are recommended for patients who appear toxic, or who cannot tolerate oral intake.⁵ Most patients with UTI can be managed with oral antibiotics.
• If a patient has a previous history of UTI, use previous cultures to make antibiotic decisions.
• Based on our local antibiogram showing >95% of urine E. coli, Proteus mirabilis and Klebsiella pneumonia are susceptible to cefazolin, we suggest initiating cefazolin (intravenous), or cephalexin (oral), unless there is a risk factor for a more resistant organism.
• Alternate therapies include amoxicillin/clavulanate and cefixime. Nitrofurantoin could be used in uncomplicated UTI in children >2 years of age. Because data suggest poor urinary excretion of cefdinir in children, we do not recommend using it as a first-line agent. Quinolones should be reserved for children with severe penicillin allergy or history of resistant organisms.
• Once susceptibility is available, antibiotics should be adjusted.

Is prolonged intravenous antibiotic necessary for all infants with UTI?

A recent systematic review evaluated 18 studies with over 16,000 infants ≤90 days of age. The review found no significant difference in the adjusted 30-day recurrence between infants with UTIs receiving a short intravenous (IV) course of antibiotics (less than or equal to three days for non bacteremic UTIs, and less than or equal to seven days for bacteremic UTIs) and those with a more prolonged IV course.⁶ Another systematic review focusing on infants <2 months of age found no increased risk of recurrence with a short (less than or equal to three days) IV course compared to a longer one regardless of bacteremia status.⁷ If bacteremia clears, fever resolves, and the infant responds to therapy, a short IV course followed by oral antibiotics to complete seven to 10 days is perfectly reasonable in young infants with UTI. In fact, the American Academy of Pediatrics Guidelines for management of febrile infants offer the option of oral antibiotics for the well-appearing older infant (≥29 days) without elevated inflammatory markers and an abnormal UA with oral antibiotics only.⁸

How long should I treat?

A recently published large retrospective cohort analysis of patients 2-17 years of age with new-onset UTI from 2013 to 2015 found that, of the 7,698 patients included, almost half received 10 days of antibiotics although 85% of their cases were diagnosed with cystitis. Recurrence occurred in 5.5% children. The analysis did not show a significant association between duration of antimicrobials and treatment recurrence.⁹ Preliminary data from the SCOUT study (Short Course Therapy for Urinary Tract Infections in Children), a multicenter randomized double-blind placebo-controlled study of five days of antibiotics followed by five days of placebo versus 10 days of antibiotics in children 2-10 years of age with UTIs, reported treatment success rates of 96% (322/336) for the short course compared to 99% (326/328) for the 10-day course.¹⁰

Based on the current available evidence, we propose treatment duration of:

• Three days for adolescent girls (≥13 years of age) and adults with cystitis.
• Five days for girls 2-12 years, and boys ≥2 years of age with cystitis.
• Seven to 10 days for children 2-24 months old, and those with complicated and febrile UTIs.

Antimicrobial prophylaxis is ineffective in preventing recurrence of febrile UTI/pyelonephritis in most children and is therefore rarely recommended.⁵

Visit the links below to access the Children's Mercy Clinical Practice Guidelines for UTI:

• Urinary Tract Infection - Diagnosis
• Urinary Tract Infection - Management
• Urinary Tract Infection - Renal Imaging
• Urinary Tract Infection CPG Synopsis

References:

1. Al-Orifi F, McGillivray D, Tange S, Kramer MS. Urine culture from bag specimens in young children: are the risks too high? J Pediatr. 2000;137(2):221-226.
2. Stein R, Dogan HS, Hoebeke P, et al. Urinary tract infections in children: EAU/ESPU guidelines. Eur Urol. 2015;67(3):546-558.
3. Tosif S, Baker A, Oakley E, Donath S, Babl FE. Contamination rates of different urine collection methods for the diagnosis of urinary tract infections in young children: an observational cohort study. J Paediatr Child Health. 2012;48(8):659-664.
4. Millner R, Becknell B. Urinary tract infections. Pediatr Clin North Am. 2019;66(1):1-13.
5. Roberts KB; Subcommittee on Urinary Tract Infection Steering Committee on Quality Improvement and Management. Urinary tract infection: clinical practice guideline for the diagnosis and management of the initial UTI in febrile infants and children 2 to 24 months. Pediatrics. 2011;128(3):595-610.
6. Hikmat S, Lawrence J, Gwee A. Short intravenous antibiotic courses for urinary infections in young infants: a systematic review. Pediatrics. 2022;149(2).
7. Nama N, Donken R, Pawliuk C, et al. Treatment of UTIs in infants <2 months: a living systematic review. Hosp Pediatr. 2021;11(9):1017-1030.
8. Pantell RH, Roberts KB, Adams WG, et al. Evaluation and management of well-appearing febrile infants 8 to 60 days old. Pediatrics. 2021;148(2).
9. Afolabi TM, Goodlet KJ, Fairman KA. Association of antibiotic treatment duration with recurrence of uncomplicated urinary tract infection in pediatric patients. Ann Pharmacother. 2020;54(8):757-766.
10. Zaoutis T, Bhatnagar S, Black SI, et al. 639. Short course therapy for urinary tract infections (SCOUT) in children. Open Forum Infect Dis. 2020;7:S380.