Use of Azithromycin in Children with Non-Cystic Fibrosis Bronchiectasis or Chronic Suppurative Lung Disease

Transcription

1 Use of Azithromycin in Children with Non-Cystic Fibrosis Bronchiectasis or Chronic Suppurative Lung Document ID CHQ-GDL Version no. 2.0 Approval date 28/08/2015 Executive sponsor Executive Director Medical Services Effective date 28/08/2015 Author/custodian Director, Infection Management and Prevention service Review date 28/08/2017 Supercedes 1.0 Applicable to All CHQ staff Authorisation Executive Director Hospital Services Purpose This Guideline provides recommendations for the use of azithromycin as prophylaxis in paediatric patients with non-cf bronchiectasis or chronic suppurative lung disease. Scope This Guideline provides information for Children s Health Queensland (CHQ) staff caring for paediatric patients with non-cf bronchiectasis or chronic suppurative lung disease. Related documents Procedures, Guidelines, Protocols CHQ Procedure_01035 Antimicrobial Restriction Procedure CHQ Antimicrobial Restriction list CHQ Paediatric Respiratory Antibiocard - Empirical antimicrobial therapy for patients with Cystic Fibrosis and Non-CF Bronchiectasis

2 Background Early and effective management reduces short and long-term morbidity in people with bronchiectasis.[1,2] In children, airway injury is superimposed upon the physiological changes involving lung growth and development.[3] Appropriate use of antibiotics is one of the key treatment principles. Use of maintenance antibiotics should be restricted to selected children with bronchiectasis and when doing so, the child should be closely monitored with consideration to cease these antibiotics after a period of 6-24 months. Azithromycin is a macrolide antibiotic with anti-inflammatory and immuno-modulatory properties. Evidence in Indigenous children indicate that 12 to 24 months of continuous azithromycin decreased the frequency of exacerbations in children with non-cystic fibrosis (non-cf) bronchiectasis or chronic suppurative lung disease (CSLD) by 50% (95% CI 35%, 71%, p<0 0001).[4] Data have also shown that use of the prolonged courses of macrolides (6-12 months) improves lung function and health-related quality of life in adults with non-cystic fibrosis bronchiectasis (summarised in [5]), Furthermore, despite the development of macrolide resistance in the resident nasopharyngeal microbiota, the use of antibiotics for non-pulmonary infections was significantly lower in the children who received azithromycin compared to those on placebo (incidence rate ratio 0 50; 95% CI ; p=0 005).[4] There are however, significant concerns around macrolide use and antibiotic resistance, with a consistent association with long-acting macrolide use and increased population-level macrolide resistance rates for several types of respiratory bacteria, including S pneumoniae (both invasive and clinical isolates) and S pyogenes, in many different countries. Although twice daily macrolides (e.g., clarithromycin) have also been implicated in increases in macrolide resistance rates, azithromycin has been most strongly associated in most investigations, with erythromycin least.[5] More worryingly macrolides also have a strong selection pressure for other multidrug resistant (MDR) pathogens, including increased risk of penicillin resistance[6] or community acquired MRSA[7]. The direct clinical consequences of macrolide resistance are difficult to quantify, and few data are available, however the global rise of all classes of antibiotic resistance is of great concern, thus judicious use of azithromycin is necessary. Based on current evidence, a trial of azithromycin therapy for 6-24 months to reduce respiratory exacerbations in carefully selected children with non-cf bronchiectasis can be justified under the circumstances presented below [8,9]. Guideline Guideline for Azithromycin prophylaxis in children with non cystic fibrosis (non-cf) bronchiectasis or chronic suppurative lung disease (CSLD) Prior to initiation of azithromycin as maintenance therapy, the following are required: Presence of bronchiectasis or CSLD Child has had 3 exacerbations and/or 2 hospitalisations in previous 12 months Child has been reviewed by a respiratory consultant Child has failed a trial of long term non-macrolide antibiotics (such as trimethoprim/ sulfamethoxazole) for a period of at least three months - 2 -

3 Previous documented absence of non-tuberculous mycobacteria in the lower airways. If child can produce sputum, culture the sputum for acid fast bacilli. Child is regularly followed up with other standard therapies for non-cf bronchiectasis optimised Consider doing liver function test and ECG if other risk factors are present. Exclusion criteria Patients with microbiological evidence of non-tuberculous mycobacterial infection Allergy to macrolides Abnormal liver function tests Clinically significant drug interaction with existing therapy (eg QT prolongation in patients receiving antiarrhythmics, neurotoxicity in patients receiving Vinca-alkaloids (CyP3A4 interaction). At follow-up (minimum at 6 months post initiation) Review effect of azithromycin on frequency of exacerbations and other clinical aspects Consider repeating liver function test Repeat sputum (if sputum can be obtained) Azithromycin prophylaxis dosing schedule Patient less than 25kg weight : 30mg/kg per week (may be given in divided doses on a daily basis, three times weekly or as a single weekly dose) Patient 25-40kg weight: 250mg/dose three times weekly Patient >40kg weight: 500mg/dose three times weekly Assessing benefit Patients requiring azithromycin for more than 6 months will require 6 monthly review and assessment of ongoing benefit and safety monitoring. Formal review by a Paediatric Respiratory Consultant at 12 months to assess benefit: o Reduction in frequency and/or severity of exacerbations, wet cough or sputum o Improvement in respiratory function o Improvement in general well-being (eg weight gain, school loss, behaviour) o Patient or family demonstrated capacity for regular review while on long term therapy o Surveillance of macrolide resistance patterns on microbiology results (if sputum can be obtained) Ceasing azithromycin after 6 to 24 months (or earlier) Not tolerating the medication - 3 -

4 No clinical benefit demonstrated after a 6 month trial of the antibiotic Anticipated spontaneous clinical improvement based upon prior history (e.g. over summer) Discontinue azithromycin for a trial 3 to 6 month period after 24 months of continuous use, since there is limited long-term safety and efficacy data and the condition frequently shows improvement over time. If after a trial of cessation (3 to 6 months off azithromycin), the child fulfils the criteria of deterioration ( 3 exacerbations and/or 2 hospitalisations in previous 12 months, pro-rata), azithromycin may be recommenced for up to 6 months, with formal review by a Paediatric Respiratory Consultant to assess benefit at 6 months. Consultation Key stakeholders who reviewed this version: Paediatric Respiratory Consultant Team Paediatric Infectious s Consultant team Antimicrobial Stewardship Pharmacist Definition of terms Term Definition Source Chronic suppurative lung disease (CSLD) Bronchiectasis A clinical syndrome of respiratory symptoms and/or signs. Symptoms of chronic endobronchial suppuration are a continuous, wet or productive cough for more than 8 weeks, with or without other features, such as exertional dyspnoea, symptoms of reactive airway disease, recurrent chest infections, growth failure, clubbing, hyperinflation or chest wall deformity. Refers to CSLD with the presence of radiological features on a chest high-resolution computed tomography. References and suggested reading Thoracic Society of Australia and New Zealand and Australian Lung Foundation Position Statement. Med J Aust 2010; 193: Thoracic Society of Australia and New Zealand and Australian Lung Foundation Position Statement. Med J Aust 2010; 193: Murray MP, Turnbull K, Macquarrie S, Hill AT. Assessing response to treatment of exacerbations of bronchiectasis in adults. Eur Respir J 2009; 33: Kapur N, Masters IB, Chang AB. Longitudinal growth and lung function in pediatric non-cf bronchiectasis - what influences lung function stability? Chest 2010; 138: Chang AB. Pediatric Cough: Children Are Not Miniature Adults. Lung 2010; 188: S Valery PC, Morris PS, Byrnes CA, Grimwood K, Torzillo PJ, Bauert P, Masters IB, Diaz A, McCallum GB, Mobberly C, Tjhung I, Hare KM, Ware RS, Chang AB. Long term azithromycin for Indigenous children with non

5 cystic fibrosis bronchiectasis or chronic suppurative lung disease (Bronchiectasis Intervention Study): a multicentre, double-blind randomised controlled trial. Lancet Respir Med 2013; 1: Serisier DJ. Risks of population antimicrobial resistance associated with chronic macrolide use for inflammatory airway diseases. Lancet Respir Med May;1(3): doi: /S (13) Epub 2013 Mar Garcia-Rey C, Aguilar L, Baquero F, Casal J, Dal-Ré R. Importance of local variations in antibiotic consumption and geographical differences of erythromycin and penicillin resistance in Streptococcus pneumoniae. J Clin Microbiol 2002; 40: Schneider-Lindner V, Delaney JA, Dial S, Dascal A, Suissa S. Antimicrobial drugs and community-acquired methicillinresistant Staphylococcus aureus, United Kingdom. Emerg Infect Dis 2007; 13: Goyal V, Grimwood K, Chang AB. Bronchiectasis: the arrival of better evidence. Lancet Respir Med 2014; 2: Chang AB, Bell SC, Byrnes CA, Grimwood K, Holmes PW, King PT, Kolbe J, Landau LI, Maguire GP, McDonald MI, Reid DW, Thien FC, Torzillo PJ. Bronchiectasis and chronic suppurative lung disease (CSLD) in children and adults in Australian and New Zealand: Thoracic Society of Australia and New Zealand and Australian Lung Foundation Position Statement. Med J Aust 2010; 193: Guideline revision and approval history Version No. Modified by Amendments authorised by Approved by 1.0 Infectious s Consultant (CHQ) 2.0 Paediatric Respiratory Consultant team (CHQ) Medicines Advisory Committee (MAC) Infectious s Consultant team (CHQ) Executive Director of Medical Services EDMS, Chair medicines Advisory Committee Keywords Accreditation references Azithromycin, macrolide, non-cystic fibrosis bronchiectasis, non-cf, chronic suppurative lung disease, CSLD, antimicrobial stewardship, antimicrobial resistance NSQHS Standards (1-10): Standard 3 Preventing and Controlling Healthcare Associated Infections - 5 -