Duration of Antibiotic Therapy for the Management of Urinary Tract Infections in Newborns and Young Infants Aged Under 3 Months: A Living Systematic Review and Meta-analysis Using Crowdsourcing

Background: Urinary tract infections (UTIs) are the most common bacterial infections in infants < 3 months of age. However, there are no clear guidelines on the appropriate duration of antibiotics. To compare different durations of parenteral antibiotics (≤ 3 vs. >3 days) in newborn and young infants ( < 3 months) with UTIs, with regards to UTI recurrence. Secondary objective was to compare different durations of total antibiotic courses (≤ 10 vs. >10 days).

Methods: Searched databases included MEDLINE, EMBASE, CENTRAL, Web of Science, LILACS, Google Scholar, and grey literature, up to November 3rd, 2020. Citations were screened in triplicate using a crowdsourcing methodology. Eligible studies were randomized controlled trials or observational studies, targeting infants < 3 months with UTIs, and comparing different durations of antibiotics. This living systematic review and meta-analysis was registered (PROSPERO CRD42020167096). Outcomes were pooled in a meta-analysis via a random-effects model. The primary outcome of the study was UTI recurrence within 30 days of treatment.

Results: 10,131 citations were screened, and twelve eligible studies were identified. A total of 59/3,509 (1.7%) infants had a UTI recurrence within 30 days after short parenteral treatment (≤ 3 days), and 54/2,047 (2.6%) after longer courses. Pooled adjusted odds ratio for UTI recurrence with a short vs. long duration of parenteral antibiotics was 0.98 [95%CI: 0.62 — 1.54] (p=0.93) [GRADE level low]. There was no significant heterogeneity of treatment effects noted between studies (I2= 0%).
In a subgroup analysis, there was no significant difference in UTI recurrence with IV duration ≤ 3 days in bacteremic patients (pooled OR: 0.81 [95%CI: 0.19 — 3.39]; 4 studies; N= 411), and in non-bacteremic infants (pooled OR: 1.03 [95%CI: 0.64 — 1.66]; 8 studies; N= 4,777). Among neonates (≤1 month), UTI recurrence was 2.1%, with no significant difference according to duration of parenteral treatment (pooled OR: 1.19 [95%CI: 0.66 — 2.14]; 6 studies; N= 2,158).
The total duration of antibiotics (≤10 vs. >10 days) was compared in five studies with similar odds of recurrence (pooled OR: 1.05 [95%CI: 0.41 — 2.71]; N= 522).

Conclusion: Based on retrospective studies, short and long duration of parenteral antibiotics were associated with similar risk of UTI recurrence in infants < 3 months. Prospective trials may provide further support. Given the living nature of this systematic review, new studies will be incorporated rapidly in the evidence synthesis, using a novel crowdsourcing approach.