Comparison of the Respiratory Resistomes and Microbiota in Children Receiving Short versus Standard Course Treatment
M M Pettigrew1, J Kwon1, J F Gent2
1Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, USA.
Insights
Shorter antibiotic courses for pediatric pneumonia may reduce antibiotic resistance. A 5-day treatment lowered resistance genes in the respiratory microbiome compared to 10 days, suggesting shorter antibiotic durations are beneficial.
Area of Science:
- Microbiology
- Pharmacology
- Pediatrics
Background:
- Pediatric community-acquired pneumonia (CAP) is commonly treated with 10-day antibiotic courses.
- Shorter antibiotic durations may reduce antibiotic resistance, but their impact on the respiratory microbiome is not well understood.
- Antibiotic resistance is a significant global public health concern.
Purpose of the Study:
- To investigate the impact of short (5-day) versus standard (10-day) beta-lactam antibiotic treatment on the respiratory microbiome's antibiotic resistance gene abundance in children with CAP.
- To compare changes in the respiratory microbiome's resistome between short and standard antibiotic treatment groups.
Main Methods:
- A randomized controlled trial (SCOUT-CAP) involving 171 children (6-71 months) with CAP randomized to 5-day or 10-day beta-lactam therapy.
- Shotgun metagenomic sequencing of throat swabs collected at enrollment and study end.
- Analysis of beta-lactam and multidrug efflux resistance genes per prokaryotic cell (RGPC) and relative abundances of bacterial species.
Main Results:
- Children receiving 5-day treatment had significantly lower beta-lactam and multidrug efflux RGPC at study end compared to the 10-day group (P < 0.05).
- The respiratory microbiome's resistome significantly differed between groups, with higher relative abundances of commensals like Neisseria subflava in the standard group and Prevotella and Veillonella parvula in the short group.
- Effect sizes for reduced resistance genes were small to medium (r=0.15-0.23).
Conclusions:
- A 5-day beta-lactam therapy for pediatric CAP is associated with a significantly lower abundance of antibiotic resistance determinants in the respiratory microbiome compared to 10-day therapy.
- These findings support shorter antibiotic treatment durations to mitigate antibiotic resistance.
- The study provides evidence for reducing antibiotic use when clinically appropriate.
Abstract:
Pediatric community-acquired pneumonia (CAP) is often treated with 10 days of antibiotics. Shorter treatment strategies may be effective and lead to less resistance. The impact of duration of treatment on the respiratory microbiome is unknown. Data are from children (n = 171), ages 6 to 71 months, enrolled in the SCOUT-CAP trial (NCT02891915). Children with CAP were randomized to a short (5 days) versus standard (10 days) beta-lactam treatment strategy. Throat swabs were collected at enrollment and the end of the study and used for shotgun metagenomic sequencing. The number of beta-lactam and multidrug efflux resistance genes per prokaryotic cell (RGPC) was significantly lower in children receiving the short compared to standard treatment strategy at the end of the study (Wilcoxon rank sum test, P < 0.05 for each). Wilcoxon effect sizes were small for beta-lactam (r: 0.15; 95% confidence interval [CI], 0.01 to 0.29) and medium for multidrug efflux RGPC (r: 0.23; 95% CI, 0.09 to 0.37). Analyses comparing the resistome at the beginning and end of the trial indicated that in contrast to the standard strategy group, the resistome significantly differed in children receiving the short course strategy. Relative abundances of commensals such as Neisseria subflava were higher in children receiving the standard strategy, and Prevotella species and Veillonella parvula were higher in children receiving the short course strategy. We conclude that children receiving 5 days of beta-lactam therapy for CAP had a significantly lower abundance of antibiotic resistance determinants than those receiving standard 10-day treatment. These data provide an additional rationale for reductions in antibiotic use when feasible. IMPORTANCE Antibiotic resistance is a major threat to public health. Treatment strategies involving shorter antibiotic courses have been proposed as a strategy to lower the potential for antibiotic resistance. We examined relationships between the duration of antibiotic treatment and its impact on resistance genes and bacteria in the respiratory microbiome using data from a randomized controlled trial of beta-lactam therapy for pediatric pneumonia. The randomized design provides reliable evidence of the effectiveness of interventions and minimizes the potential for confounding. Children receiving 5 days of therapy for pneumonia had a lower prevalence of two different types of resistance genes than did those receiving the 10-day treatment. Our data also suggest that children receiving longer durations of therapy have a greater abundance of antibiotic resistance genes for a longer period of time than do children receiving shorter durations of therapy. These data provide an additional rationale for reductions in antibiotic use.
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