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Danielle F. Wurzel, PhD; Julie M. Marchant, PhD; Stephanie T. Yerkovich, PhD; John W. Upham, PhD; Anne B. Chang, PhD
Author and Funding Information

FINANCIAL/NONFINANCIAL DISCLOSURES: See earlier cited article for author conflicts of interest.

aQueensland Children’s Medical Research Institute, Brisbane, QLD, Australia

bQueensland Children’s Health Service, Brisbane, QLD, Australia

cQueensland Lung Transplant Service, Prince Charles Hospital, Brisbane, QLD, Australia

dSchool of Medicine, The University of Queensland; School of Medicine, Griffith University, Gold Coast, QLD, Australia

eMurdoch Childrens Research Institute and The Royal Children’s Hospital, Melbourne, VIC

fChild Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia

CORRESPONDENCE TO: Danielle F. Wurzel, PhD, Murdoch Childrens Research Institute, Melbourne, VIC, 3052, Australia


Copyright 2017, American College of Chest Physicians. All Rights Reserved.


Chest. 2017;151(4):940-941. doi:10.1016/j.chest.2016.12.030
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We thank Sacco et al for their interest in our study on children with protracted bacterial bronchitis (PBB), which described high PBB recurrence rates. Further, at 2-year follow-up, those diagnosed with bronchiectasis were significantly more likely to have had recurrent episodes (> 3 per year) and Haemophilus influenzae in their BAL at initial diagnosis. We agree with Sacco et al's suggestion that antibiotic adherence should be closely monitored and that the presence of biofilm in the lower airways of these children is likely important. However, although we had previously described biofilms in the airways of children with bronchiectasis (without Pseudomonas aeruginosa), currently this remains a postulate for PBB.

There is little doubt that biofilms interfere with antibiotic penetration and host immune responses, and in vitro studies show that subinhibitory concentrations of beta-lactam antibiotics promote the formation of nontypeable H influenzae-associated biofilms, an effect also seen with aminoglycosides and P aeruginosa. Although higher doses and indeed longer durations of antibiotic therapy may reduce biofilm formation and recurrence of PBB, there are currently no clinical studies to support this. The need for studies evaluating the optimal duration of antibiotics was highlighted in our recent article.

The dose of amoxicillin-clavulanate used in the present study (22.5 mg/kg/dose twice daily) was based on our previous studies, including a randomized controlled trial. The concern with increasing dosing frequency from two to three times per day is that this may detrimentally impact adherence. In addition to promoting biofilms, poor adherence can lead to emergence of bacterial resistance, another potential cause of treatment failure. In the interim, parent education highlighting the importance of adherence to antibiotic regimens is required.

Sacco et al also referred to our previous study that described a relationship between airway inflammation and impaired interferon response to nontypeable H influenzae-specific stimulation in children with chronic suppurative lung disease. However, irrespective of airway inflammation, vaccination with a protein D (from nontypeable H influenzae) conjugate vaccine improved cell-mediated and humoral immunity to nontypeable H influenzae in these children.

Thus, several factors likely contribute to the high rates of PBB recurrence, and there is little doubt that more interventional studies relating to PBB and other suppurative airway diseases in children are needed.

References

Sacco O. .Capizzi A.F. .Silvestri M. .et al Recurrence of protracted bacterial bronchitis in children: what can we do? Chest. 2017;151:940- [PubMed]journal
 
Wurzel D.F. .Marchant J.M. .Yerkovich S.T. .et al Protracted bacterial bronchitis in children: natural history and risk factors for bronchiectasis. Chest. 2016;150:1101-1108 [PubMed]journal. [CrossRef] [PubMed]
 
Marsh RL, Thornton RB, Smith-Vaughan HC, et al. Detection of biofilm in bronchoalveolar lavage from children with non-cystic fibrosis bronchiectasis [published online ahead of print March 18, 2014].Pediatr Pulmonol.http://dx.doi.org/10.1002/ppul.23031.
 
Costerton J.W. .Stewart P.S. .Greenberg E.P. . Bacterial biofilms: a common cause of persistent infections. Science. 1999;284:1318-1322 [PubMed]journal. [CrossRef] [PubMed]
 
Hoffman L.R. .D'Argenio D.A. .MacCoss M.J. .et al Aminoglycoside antibiotics induce bacterial biofilm formation. Nature. 2005;436:1171-1175 [PubMed]journal. [CrossRef] [PubMed]
 
Chang A.B. .Upham J.W. .Masters I.B. .et al Protracted bacterial bronchitis: the last decade and the road ahead. Pediatr Pulmonol. 2016;51:225-242 [PubMed]journal. [CrossRef] [PubMed]
 
Marchant J. .Masters I.B. .Champion A. .et al Randomised controlled trial of amoxycillin clavulanate in children with chronic wet cough. Thorax. 2012;67:689-693 [PubMed]journal. [CrossRef] [PubMed]
 
Claxton A.J. .Cramer J. .Pierce C. . A systematic review of the associations between dose regimens and medication compliance. Clin Ther. 2001;23:1296-1310 [PubMed]journal. [CrossRef] [PubMed]
 
Hare K.M. .Grimwood K. .Chang A.B. .et al Nasopharyngeal carriage and macrolide resistance in indigenous children with bronchiectasis randomized to long-term azithromycin or placebo. Eur J Clin Microbiol Infect Dis. 2015;34:2275-2285 [PubMed]journal. [CrossRef] [PubMed]
 
Pizzutto S.J. .Yerkovich S.T. .Upham J.W. .et al Improving immunity to Haemophilus influenzae in children with chronic suppurative lung disease. Vaccine. 2015;33:321-326 [PubMed]journal. [CrossRef] [PubMed]
 

Figures

Tables

References

Sacco O. .Capizzi A.F. .Silvestri M. .et al Recurrence of protracted bacterial bronchitis in children: what can we do? Chest. 2017;151:940- [PubMed]journal
 
Wurzel D.F. .Marchant J.M. .Yerkovich S.T. .et al Protracted bacterial bronchitis in children: natural history and risk factors for bronchiectasis. Chest. 2016;150:1101-1108 [PubMed]journal. [CrossRef] [PubMed]
 
Marsh RL, Thornton RB, Smith-Vaughan HC, et al. Detection of biofilm in bronchoalveolar lavage from children with non-cystic fibrosis bronchiectasis [published online ahead of print March 18, 2014].Pediatr Pulmonol.http://dx.doi.org/10.1002/ppul.23031.
 
Costerton J.W. .Stewart P.S. .Greenberg E.P. . Bacterial biofilms: a common cause of persistent infections. Science. 1999;284:1318-1322 [PubMed]journal. [CrossRef] [PubMed]
 
Hoffman L.R. .D'Argenio D.A. .MacCoss M.J. .et al Aminoglycoside antibiotics induce bacterial biofilm formation. Nature. 2005;436:1171-1175 [PubMed]journal. [CrossRef] [PubMed]
 
Chang A.B. .Upham J.W. .Masters I.B. .et al Protracted bacterial bronchitis: the last decade and the road ahead. Pediatr Pulmonol. 2016;51:225-242 [PubMed]journal. [CrossRef] [PubMed]
 
Marchant J. .Masters I.B. .Champion A. .et al Randomised controlled trial of amoxycillin clavulanate in children with chronic wet cough. Thorax. 2012;67:689-693 [PubMed]journal. [CrossRef] [PubMed]
 
Claxton A.J. .Cramer J. .Pierce C. . A systematic review of the associations between dose regimens and medication compliance. Clin Ther. 2001;23:1296-1310 [PubMed]journal. [CrossRef] [PubMed]
 
Hare K.M. .Grimwood K. .Chang A.B. .et al Nasopharyngeal carriage and macrolide resistance in indigenous children with bronchiectasis randomized to long-term azithromycin or placebo. Eur J Clin Microbiol Infect Dis. 2015;34:2275-2285 [PubMed]journal. [CrossRef] [PubMed]
 
Pizzutto S.J. .Yerkovich S.T. .Upham J.W. .et al Improving immunity to Haemophilus influenzae in children with chronic suppurative lung disease. Vaccine. 2015;33:321-326 [PubMed]journal. [CrossRef] [PubMed]
 
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