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BEST-1 confirms preferred antibiotic regimen for children with bronchiectasis
New data from the BEST-1 trial indicated that amoxicillin-clavulanate is more effective than placebo in resolving non-severe exacerbations in children with bronchiectasis unrelated to cystic fibrosis.
Notably, azithromycin was also associated with some improvement in exacerbation resolution and duration compared with placebo, but it was not deemed statistically superior to placebo and was also linked to an increase in antibiotic-resistant bacteria, according to the researchers.
For the study, Vikas Goyal, FRACP, from the department of respiratory and sleep medicine at Queensland Children’s Hospital in Brisbane, and colleagues randomly assigned 197 children to oral suspensions of amoxicillin-clavulanate 45 mg/kg daily plus placebo azithromycin (n = 63), azithromycin 5 mg/kg daily plus placebo amoxicillin-clavulanate (n = 67) or both placebos (n = 67) for 14 days.
The double-dummy study, which was conducted at four pediatric centers in Australia and New Zealand, included children aged 1 to 18 years with confirmed bronchiectasis unrelated to cystic fibrosis who had experienced at least two exacerbations in the previous 18 months. The proportion of patients with exacerbation resolution within 14 days served as the primary endpoint, with a threshold for statistical significance of P < .0245. Patients, caregivers, study coordinators and investigators were all masked to treatment.
Amoxicillin-clavulanate superior to placebo
At 14 days, exacerbations had resolved in 65% of children in the amoxicillin-clavulanate group, compared with 43% of children in the placebo group, with an RR for resolution of 1.5 (95% CI, 1.08-2.09; P = .015) and a number needed to treat of five. In the azithromycin group, the proportion of children who had exacerbation resolution by day 14 (61%) also exceeded that of placebo group, but the difference did not meet the predefined threshold for statistical significance (RR = 1.41; 95% CI, 1.01-1.97; P = .042; number needed to treat = 6).
Additionally, the median duration of exacerbation was longer in the placebo group vs. the amoxicillin-clavulanate group (10 vs. 7 days; P = .018) but was not significantly different from that in the azithromycin group (8 days).
Although Goyal and colleagues found no differences in bacteria isolated from nasal swabs on day 1 of treatment, they identified potentially pathogenic bacteria in significantly fewer patients assigned amoxicillin-clavulanate (P < .0001) and azithromycin (P < .001), compared with those assigned placebo, on day 14. However, there was an increase in the azithromycin group, there was an increase from day 1 to day 14 in azithromycin-resistant bacteria. In contrast, the proportion of antibiotic-resistant bacteria did not change significantly over the course of treatment in the amoxicillin-clavulanate or placebo groups.
The rate of adverse events was 30% in the amoxicillin-clavulanate group, 30% in the azithromycin group and 21% in the placebo group, with no severe or life-threatening events occurring in any group.
“The results suggest that amoxicillin–clavulanate should remain the first-line oral
antibiotic for the treatment of non-severe exacerbations of bronchiectasis in children, with once-daily azithromycin reserved for those with genuine penicillin hypersensitivity or for situations in which directly observed therapy is feasible in settings of poor treatment adherence,” Goyal and colleagues wrote.
Important evidence
In a linked comment, Brian O’Sullivan, MD, from the Geisel School of Medicine at Dartmouth in Hanover, New Hampshire, agreed that these data confirm current recommendations for the use of amoxicillin-clavulanate to treat non-severe exacerbations in children with bronchiectasis and build on findings from the previous BEST-2 trial.
He also noted, however, that the high proportion of children in the placebo group achieving exacerbation resolution at day 14 raises questions about whether antibiotic treatment is warranted for all exacerbations. Nevertheless, treatment of mild exacerbations before they progress is important and without a way to identify which patients will resolve without antibiotic therapy, clinicians should forge ahead with treatment based on what is known, including findings from BEST-1 and BEST-2, O’Sullivan added.
“The two studies by Goyal and colleagues support our current understanding of outpatient treatment of non-serious exacerbations of bronchiectasis: antibiotics shorten the duration and increase the proportion of children attaining resolution of their exacerbations by day 14; and either amoxicillin–clavulanate or azithromycin could be used in these situations, although amoxicillin–clavulanate might be more efficacious and lead to less antibiotic resistance than does azithromycin. More work is needed in the field of bronchiectasis, which can no longer be considered an orphan disease,” he wrote. – by Melissa Foster
Disclosures: This study was funded by the National Medical Health and Research Council of Australia and Cure Kids in New Zealand. The authors report no relevant financial disclosures. O’Sullivan reports no relevant financial disclosures.