Extended Amoxicillin-Clavulanate Not Curative for Suspected Protracted Bacterial Bronchitis Among Children

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Researchers conducted a randomized controlled trial to determine the effectiveness of a 4-week course of oral amoxicillin-clavulanate in children with suspected protracted bacterial bronchitis.

An extended course of amoxicillin-clavulanate for children with chronic wet cough resulted in a longer cough-free period but did not lead to a clinical cure for possible protracted bacterial bronchitis, according to the results of a study published in Lancet Respiratory Medicine.

Children (N=106) with suspected protracted bacterial bronchitis were recruited for this 2-arm, parallel-group, double-blind, placebo-controlled randomized trial from 4 centers in Australia between 2017 and 2019. Stratified by age, children were randomly assigned to receive 4 weeks of active therapy (n=52) or 2 weeks of active therapy and 2 weeks of placebo (n=54). Children received amoxicillin 25 to 35 mg/kg twice daily. At 28 days, children were assessed for clinical cure, which was defined as a greater than 75% improvement in cough scores or an absence of cough for at least 3 days. Recurrence and Parent-proxy Cough-Specific Quality-of-Life (PC-QoL) were assessed at 6 to 7 months.

The median ages of children in the 4- and 2-week groups were 2.2 years (interquartile range [IQR], 1.3-4.1) and 1.7 years (IQR, 1.2-3.8), respectively; 64% and 57% were boys, 14% and 9% were of Indigenous ethnicity, cough had been present a median of 21.4 (IQR, 9.2-39.8) and 15.1 (IQR, 8.6-30.0) weeks, and 40% and 54% had used antibiotics for their cough, respectively.

Among children who were assessed for culprit bacterial strain, Moraxella catarrhalis (n=7), Streptococcus pneumoniae (n=4), Staphylococcus aureus (n=2), Methicillin-resistant S aureus (MRSA; n=1), and Haemophilus influenzae (n=1) were detected.

Clinical cure at day 28 was achieved by 62% of participants in the 4-week cohort and by 70% of the participants in the 2-week cohort (adjusted relative risk [aRR], 0.87; 95% CI, 0.60-1.28; P =.49).

At day 28, S aureus (n=3), MRSA(n=5), M catarrhalis (n=4), and S pneumoniae (n=1) were still present among some children.

Time to exacerbation of wet cough was a median of 150 days (IQR, 38-181) for the longer treatment and 36 days (IQR, 15-181) for the shorter antibiotic course (adjusted hazard ratio [aHR], 0.47; 95% CI, 0.25-0.90; P =.02). Recurrence at 6 months was noted among 53% of participants in the 4-week group and 74% of participants in the 2-week treatment group (aOR, 0.39; 95% CI, 0.14-1.04; P =.07).

At day 28, the PC-QoL was significantly improved from baseline by 1.9 points (IQR, 1.1-3.1) and 2.1 points (IQR, 1.3-3.1) for the long and short antibiotic courses, respectively. At 7 months, PC-QoL scores were unchanged (aRR, 0.1; 95% CI, -1.0 to 1.2; P =.91).

A total of 104 children reported adverse events, which did not differ on the basis of antibiotic course (P =.57). Some children did not complete the trial due to adverse events (n=8) and poor response to treatment (n=4).

This study may have been limited by differences among the cohorts, in which the children in the 4-week group tended to be older and fewer had been previously treated with antibiotics. These factors may indicate that these children had more severe disease, which would influence their response to treatment.

The study authors concluded that a longer course of amoxicillin-clavulanate did not lead to more clinical cures among children with chronic wet cough and suspected protracted bacterial bronchitis.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Ruffles TJC, Goyal V, Marchant JM, et al. Duration of amoxicillin-clavulanate for protracted bacterial bronchitis in children (DACS): a multi-centre, double blind, randomised controlled trial. Lancet Respir Med. 2021;S2213-2600(21)00104-1. doi:10.1016/S2213-2600(21)00104-1