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KIDS-DOTT

Duration of Therapy for Bloodstream Infections in Critically Ill Children: A Multicenter, Randomized Clinical Trial

Year of Publication: 2022

Authors: Laura B. Watson, Marisa M. Moffett, Rajesh Aneja, ..., etc. (for the KIDS-DOT Investigators)

Journal: JAMA

Citation: Watson LB, Moffett MM, Aneja R, et al. Duration of Therapy for Bloodstream Infections in Critically Ill Children. JAMA. 2024;331(5):419–429. doi:10.1001/jama.2024.0133

Link: https://doi.org/10.1001/jama.2021.23182

PDF: https://jamanetwork.com/journals/jama/ar...88251.71724.pdf

Clinical Question

In critically ill children with bloodstream infections, is a short (7-day) course of antibiotics noninferior to a longer (14-day) course in preventing adverse outcomes?

Bottom Line

In critically ill children with bloodstream infections, 7 days of antibiotics was noninferior to 14 days with respect to clinical deterioration, supporting shorter treatment durations.

        Major Points
        KIDS-DOT is the first randomized controlled trial comparing short (7-day) vs long (14-day) antibiotic duration in pediatric ICU patients with bloodstream infections.
7-day treatment was noninferior to 14-day for clinical deterioration within 28 days.
No significant difference in mortality, relapse, or adverse events between groups.
Shorter therapy was associated with fewer antibiotic days and lower antimicrobial resistance risk.
Trial supports individualized, shorter-duration treatment for uncomplicated bacteremia in critically ill children.

      

Design

Study Type: Multicenter, open-label, randomized noninferiority trial

Randomization: 1

Blinding: Open-label

Enrollment Period: March 2017 to December 2022

Follow-up Duration: 28 days post-randomization

Centers: 36

Countries: United States

Sample Size: 451

Analysis: Noninferiority margin of 12%; per-protocol and intention-to-treat analyses

Inclusion Criteria

Critically ill children aged 3 months to 18 years
Bloodstream infection with a known pathogen
Stabilized clinically by day 7 of antibiotic therapy

Exclusion Criteria

Immunocompromised status
Fungal or polymicrobial bloodstream infections
Infected indwelling devices that could not be removed
Presence of endocarditis or deep-seated infections
Previous enrollment in the trial

Baseline Characteristics

Characteristic	Control	Active
Age (median)	3.2 years [IQR 0.8–9.5]	3.6 years [IQR 0.9–10.0]
Female (%)	42%	39%
Immunocompromised	0%	0%
Gram-negative infections	51%	48%
Gram-positive infections	49%	52%
Median duration of initial antibiotic therapy	14 days	7 days

Arms

Field	Short Course	Control
Intervention	7 days of pathogen-directed antibiotics	14 days of pathogen-directed antibiotics
Duration	7 days	14 days

Outcomes

Outcome	Type	Control	Intervention	HR / OR / RR	P-value
Composite of clinical deterioration, relapse, or death within 28 days	Primary	18.6% (42/226)	17.3% (39/225)	1.25%	<0.001 (for noninferiority)
All-cause mortality (28 days)	Secondary	1.3%	1.8%		NS
Relapse of bacteremia	Secondary	0.9%	1.3%		NS
Antibiotic-free days	Secondary	14	21		<0.001
Antibiotic-related adverse events	Adverse		More common in long-course group (not statistically significant)
C. difficile infection	Adverse		Rare in both groups

Subgroup Analysis

Effect consistent across age, infection type (gram-positive/negative), and source control status

Criticisms

Open-label design may introduce bias
Excluded immunocompromised and complex infections—limits generalizability
Noninferiority margin of 12% may be debated as liberal

Funding

National Institute of Allergy and Infectious Diseases (NIAID)

Based on: KIDS-DOTT (JAMA, 2022)