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Published on: July 27, 2022
Antibiotic Cocktail for Pediatric Acute Severe Colitis and the Microbiome: The PRASCO Randomized Controlled Trial
Dan Turner1, Jason Bishai2, Leah Reshef3
1Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Israel.
Insights
Quadruple antibiotic therapy combined with intravenous corticosteroids improved acute severe colitis (ASC) in children. This approach showed better disease activity by day 5 compared to IVCS alone, though long-term outcomes require further study.
Area of Science:
- Gastroenterology
- Pediatric Inflammatory Bowel Disease
- Microbiome Research
Background:
- Inflammatory bowel disease (IBD) is linked to alterations in the gut microbiome.
- Acute severe colitis (ASC) in children requires effective treatment strategies.
- This study investigates a quadruple antibiotic cocktail alongside intravenous corticosteroids (IVCS) for ASC.
Purpose of the Study:
- To evaluate the effectiveness of a quadruple antibiotic cocktail plus IVCS in pediatric ASC.
- To assess the impact on disease activity and microbiome composition in children with ASC.
Main Methods:
- A pilot randomized controlled trial involving hospitalized children with ASC (pediatric ulcerative colitis activity index [PUCAI] ≥65).
- Two arms: IVCS plus antibiotics (amoxicillin, vancomycin, metronidazole, doxycycline/ciprofloxacin) vs. IVCS alone for 14 days.
- Primary outcome: PUCAI at day 5. Microbiome analysis via 16S rRNA gene and metagenome sequencing.
Main Results:
- The IVCS plus antibiotics group showed a significantly lower mean day-5 PUCAI (25) compared to the IVCS-only group (40.4) (P = 0.037).
- Colectomy rates were similar between groups over 1 year (3 vs. 2 children).
- Decreased microbiome diversity at admission was associated with day-5 response in the IVCS-only arm.
Conclusions:
- Quadruple antibiotic therapy in addition to IVCS improved disease activity in children with ASC by day 5.
- ASC is associated with microbiome alterations, including reduced diversity and predominant bacterial species.
- Larger studies are needed to confirm long-term benefits of this combined therapy.
Background:
Alterations in the microbiome have been postulated to drive inflammation in IBD. In this pilot randomized controlled trial, we evaluated the effectiveness of quadruple antibiotic cocktail in addition to intravenous-corticosteroids (IVCSs) in acute severe colitis (ASC).
Methods:
Hospitalized children with ASC (pediatric ulcerative colitis activity index [PUCAI] ≥65) were randomized into 2 arms: the first received antibiotics in addition to IVCS (amoxicillin, vancomycin, metronidazole, doxycycline/ciprofloxacin [IVCS+AB]), whereas the other received only IVCS for 14 days. The primary outcome was disease activity (PUCAI) at day 5. Microbiome was analyzed using 16S rRNA gene and metagenome.
Results:
Twenty-eight children were included: 16 in the AB + IVCS arm and 12 in the IVCS arm (mean age 13.9 ± 4.1 years and 23 [82%] with extensive colitis). The mean day-5 PUCAI was 25 ± 16.7 vs 40.4 ± 20.4, respectively (P = 0.037). Only 3 and 2 children, respectively, required colectomy during 1-year follow-up (P = 0.89). Microbiome data at time of admission were analyzed for 25 children, of whom 17 (68%) had a predominant bacterial species (>33% abundance); response was not associated with the specific species, whereas decreased microbiome diversity at admission was associated with day-5 response in the IVCS arm.
Conclusion:
Patients with ASC have alterations in the microbiome characterized by loss of diversity and presence of predominant bacterial species. Quadruple therapy in addition to IVCS improved disease activity on day 5, but larger studies are needed to determine whether this is associated with improved long-term outcomes (clinicaltrials.gov NCT02033408).
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