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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://jamanetwork.com/journals/jama/fullarticle/2814287

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

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
More common in long-course group (not statistically significant)					Adverse
Rare in both groups					Adverse

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)

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

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

Content summarized and formatted by NeuroTrials.ai.

KIDS-DOTT

(2022)

Objective

6 weeks of anticoagulation versus 3 months for treating provoked VTE in patients younger than 21 years.

Study Summary

• A 6-week anticoagulation course was noninferior to 3 months for preventing recurrent VTE and major bleeding, supporting shorter treatment in eligible pediatric patients.

Intervention

Anticoagulant therapy for 6 weeks vs. 3 months. All patients initially received LMWH or UFH, then transitioned to LMWH, fondaparinux, VKA, or DOAC. Randomization required partial thrombus resolution and absence of antiphospholipid antibodies at 6 weeks.

Inclusion Criteria

Patients <21 years with provoked VTE confirmed radiologically within 30 days, no prior VTE, no antiphospholipid antibodies or severe thrombophilia. Only those with partial or resolved thrombus at 6 weeks were randomized.

Study Design

Arms: 6 Weeks vs. 3 Months of Anticoagulation

Patients per Arm: 6 Weeks: 207, 3 Months: 210 (per-protocol: 154 and 143)

Outcome

• Primary (recurrent VTE at 1 year): 0.66% vs. 0.70%, absolute difference −0.04%.• Primary (clinically relevant bleeding): 0.65% vs. 0.70%, absolute difference −0.05%.• All-cause mortality: 1.9% in both groups; none treatment-related.• Composite (VTE or chronic venous insufficiency at 1 year in limb DVT): 30.0% vs. 29.6%.• Adverse events: 26% vs. 32%, most common was fever.• Serious adverse events: 2 bleeding cases in 3-month group.• Postthrombotic syndrome risk similar across groups.

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.

Study Design

Study Type: Multicenter, open-label, randomized noninferiority trial
Randomization: Yes
Blinding: Open-label
Sample Size: 451
Follow-up: 28 days post-randomization
Centers: 36
Countries: United States

Primary Outcome

Definition: Composite of clinical deterioration, relapse, or death within 28 days

Control	Intervention	HR/OR	P-value
18.6% (42/226)	17.3% (39/225)	- (–8.9% to 6.5%)	<0.001 (for noninferiority)

Limitations & Criticisms

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

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

View Original Publication →

KIDS-DOTT

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

Clinical Question

Bottom Line

Major Points

Design

Inclusion Criteria

Exclusion Criteria

Arms

Outcomes

Subgroup Analysis

Criticisms

Funding

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