Placebo was noninferior to azithromycin in reducing duration of fever and intensity of pain from group A streptococcal (GAS) pharyngitis in children, in a clinical trial which investigators assert challenges the common use of antibiotics at initial presentation.1
"It is commonly observed that when prescribing antibiotics for GAS pharyngitis, pediatricians are influenced by parental pressure and expectations for rapid symptom relief," remarked principle investigator, Klara Posfay-Barbe, MD, Division of General Pediatrics, Department of Pediatrics, Gynecology and Obstetrics, Geneva University Children's Hospital and University of Geneva, Geneva, Switzerland, and colleagues.
"Our study findings show a marginal impact of amoxicillin on the duration of fever and intensity of pain and could help moderate such prescribing practices," the investigators suggest.
Posfay-Barbe and colleagues identified 88 children presenting as outpatients with fever >8°C, clinical symptoms suggestive of pharyngitis, a McIsaac score ≥3, and a positive rapid antigen detection test for GAS.The size of the cohort fell short of the study target, however, as the investigators encountered a "significant reluctance by parents" for children to participate in a blinded trial against placebo; which was probably exacerbated by the ongoing COVID-19 pandemic.
The children were randomized to receive either amoxicillin 50mg/kg/day for 7 days (n=31 completed regimen) or placebo (n=34).Parents or caregivers were called on day 3 for a standardized assessment; and throat culture and clinical evaluation were repeated at 1 month.Follow-up phone calls were scheduled at 6- and 12-months to ascertain relapse, recurrence and late complications.
The investigators reported no significant difference in duration of fever between groups (2 hours in the per-protocol analysis and 2.8 hours in the intention-to-treat analysis).Pain intensity, a secondary measure of the study, also appeared to be similar with or without antibiotic; albeit with the small sample size underpowered to definitively differentiate this measure between groups.
The risk of treatment failure, however, marked by emergence of scarlet fever, acute otitis media, or retropharyngeal abscess, was higher without antibiotic treatment (RR 2.15; 95%CI 0.44-10.57).In addition, a positive throat culture for GAS at one month was found in more receiving placebo (n=6) than treated with antibiotic (n=3).
What You Need to Know
The study found that placebo was non-inferior to amoxicillin in reducing fever duration and pain intensity in children with group A streptococcal (GAS) pharyngitis, challenging the need for antibiotics at the initial presentation.
Although fever and pain duration were similar between groups, children who received a placebo had a higher risk of complications like scarlet fever and acute otitis media, indicating some benefit in using antibiotics for prevention.
The findings suggest a more cautious approach to prescribing antibiotics, particularly in well-resourced areas, as the study shows limited symptom relief from antibiotics, which could help moderate the tendency for immediate antibiotic prescription due to parental pressure.
To the first, the investigators argue that "these complications can generally be treated as soon as they occur."They acknowledge, however, that under-resourced regions with fewer treatment resources and greater risk conditions will continue to benefit from broader initial antibiotic treatment.
As for the greater number of persistent GAS positive throat cultures at 1 month in the group receiving placebo, the investigators note that all patients were asymptomatic and question whether this suggests greater risk for resurgence of invasive GAS infections.
"However, this finding must be carefully analyzed, especially in the context of the recent resurgence of invasive GAS infections, and suggests the need for close epidemiological surveillance," they indicate.
Regarding the potential sequelae of rheumatic fever, the investigators note it was notfound at the 12-month follow-up, and attribute reduced risk to a likely decrease in circulating rheumatogenic strains of GAS.They also discount risk of post-streptococcal acute glomerulonephritis without antibiotic treatment.
"Witholding antibiotic treatment is not expected to influence the risk of post-streptococcal acute glomerulonephritis, as previous studies have failed to demonstrate a preventive effect of antibiotic treatment on this immunologically mediated complication," they argue.
Reference
1.Gualtieri R, Verolet C, Mardegan C, et al. Amoxicillin vs placebo to reduce symptoms in children with group A streptococcal pharyngitis: A randomized, multicenter, double-blind, non-inferiority trial. Eur J Pediatr 2024; 183:4773-4782.
