Use and safety of azithromycin in neonates: a systematic review

Coral Smith, Oluwaseun Egunsola, Imti Choonara, Sailesh Kotecha, Evelyne Jacqz-Aigrain, Helen Sammons, Coral Smith, Oluwaseun Egunsola, Imti Choonara, Sailesh Kotecha, Evelyne Jacqz-Aigrain, Helen Sammons

Abstract

Objectives: To identify the use and adverse drug reactions associated with azithromycin in neonates.

Setting: Databases MEDLINE (1948-August 2015), EMBASE (1980-August 2015) and Pubmed (August 2015) were searched for studies on azithromycin in neonates.

Participants: All studies involving neonates (<28 days old) who have received at least a single dose of azithromycin for which safety was evaluated.

Primary and secondary outcome measures: The primary outcome was adverse event (AE) associated with use of azithromycin. Use of azithromycin in neonates was the secondary outcome.

Results: A total of 11 articles involving 473 neonates were identified. 371 AEs were reported. Adverse events were mainly respiratory (358/1000 neonate), neurological (273/1000 neonates) and gastrointestinal (196/1000 neonates) in origin. Azithromycin significantly reduced the risk of bronchopulmonary dysplasia (BPD) in extremely premature neonates (RR=0.83, 95% CI 0.71 to 0.98, p=0.02). There was no significant difference in the incidence of elevated liver enzymes between the azithromycin and placebo group (p=0.76). There were four cases of infantile hypertrophic pyloric stenosis (IHPS).

Conclusions: Azithromycin significantly reduces the risk of BPD in preterm neonates. The relationship between azithromycin and IHPS requires further investigation.

Keywords: CLINICAL PHARMACOLOGY; NEONATOLOGY.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Figures

Figure 1
Figure 1
Summary of risk of bias.
Figure 2
Figure 2
Flow chart of included articles.
Figure 3
Figure 3
Relative risks of BPD in azithromycin and untreated/placebo treated preterm neonates. BPD, bronchopulmonary dysplasia.
Figure 4
Figure 4
Funnel plot to determine publication bias.
Figure 5
Figure 5
Relative risk of elevated transaminase in azithromycin and placebo treated neonates.

References

    1. Clavenna A, Bonati M. Differences in antibiotic prescribing in paediatric outpatients. Arch Dis Child 2011;96:590–5. 10.1136/adc.2010.183541
    1. Franchi C, Sequi M, Bonati M et al. . Differences in outpatient antibiotic prescription in Italy's Lombardy region. Infection 2011;39:299–308. 10.1007/s15010-011-0129-1
    1. Grijalva CG, Nuorti JP, Griffin MR. Antibiotic prescription rates for acute respiratory tract infections in US ambulatory settings. JAMA 2009;302:758–66. 10.1001/jama.2009.1163
    1. Zuckerman JM. Macrolides and ketolides: azithromycin, clarithromycin, telithromycin. Infect Dis Clin North Am 2004;18:621–49. 10.1016/j.idc.2004.04.010
    1. Heads of Medicines Agencies. Azithromycin part II. (accessed 18 Feb 2014).
    1. Langtry HD, Balfour JA. Azithromycin. A review of its use in paediatric infectious diseases. Drugs 1998;56:273–97. 10.2165/00003495-199856020-00014
    1. Joint Formulary Committee. British National Formulary (online). London: BMJ Group and Pharmaceutical Press; (accessed 17 Jul 2013).
    1. Medicine and healthcare products regulatory agency. Azithromycin 500 mg powder for infusion. (accessed 17 Jul 2013).
    1. Summary of product characteristics: Azyter 15 mg/g eye drops. (accessed 19 Jul 2013).
    1. Full prescribing information: AzaSite®. (accessed 19 Jul 2013).
    1. Ruuskanen O. Safety and tolerability of azithromycin in pediatric infectious diseases: 2003 update. Pediatr Infect Dis J 2004;23(2 Suppl):S135–9. 10.1097/01.inf.0000112528.75956.41
    1. Ray WA, Murray KT, Hall K et al. . Azithromycin and the risk of cardiovascular death. N Engl J Med. 2012;366:1881–90. 10.1056/NEJMoa1003833
    1. FDA drug safety communication. Azithromycin (Zithromax or Zmax) and the risk of potentially fatal heart rhythms. (accessed 9 Jul 2013).
    1. Taylor-Robinson D, Bébéar C. Antibiotic susceptibilities of mycoplasmas and treatment of mycoplasmal infections. J Antimicrob Chemother 1997;40:622–30. 10.1093/jac/40.5.622
    1. Koh E, Kim S, Kim IS et al. . Antimicrobial susceptibilities of Ureaplasma urealyticum and Mycoplasma hominis in pregnant women. Korean J Clin Microbiol 2009;12:159–62. 10.5145/KJCM.2009.12.4.159
    1. Wang EL, Ohlsson A, Kellner JD. Association of Ureaplasma urealyticum colonization with chronic lung disease of prematurity: results of a metaanalysis. J Pediatr 1995;127:640–4. 10.1016/S0022-3476(95)70130-3
    1. Schelonka RL, Katz B, Waites KB et al. . Critical appraisal of the role of Ureaplasma in the development of bronchopulmonary dysplasia with metaanalytic techniques. Pediatr Infect Dis J 2005;24:1033–9. 10.1097/01.inf.0000190632.31565.83
    1. Tiwari T, Murphy TV, Moran J. Recommended antimicrobial agents for the treatment and postexposure prophylaxis of pertussis: 2005 CDC Guidelines. MMWR Recomm Rep 2005;54(RR-14):1–16.
    1. Cochrane bias method group: Assessing risk of bias in included studies. . (accessed 10 Jul 2013).
    1. Ballard HO, Shook LA, Bernard P et al. . Use of azithromycin for the prevention of bronchopulmonary dysplasia in preterm infants: a randomised, double-blind, placebo controlled trial. Pediatr Pulmonol 2011;46:111–18. 10.1002/ppul.21352
    1. Ballard HO, Anstead MI, Shook LA. Azithromycin in the extremely low birth weight infant for the prevention of bronchopulmonary dysplasia: a pilot study. Respir Res 2007;8:41 10.1186/1465-9921-8-41
    1. Gharehbaghi MM, Peirovifar A, Ghojazadeh M et al. . Efficacy of azithromycin for prevention of bronchopulmonary dysplasia (BPD). Turk J Med Sci 2012;42:1070–5.
    1. Dong Z. Efficacy of azithromycin in the treatment of Chlamydia trichomatis conjunctivitis in neofant. Chin J Antibiot 2005;30:428–9.
    1. Friedman DS, Curtis CR, Schauer SL et al. . Surveillance for transmission and antibiotic adverse events among neonates and adults exposed to a healthcare worker with pertussis. Infect Control Hosp Epidemiol 2004;25:967–73. 10.1086/502328
    1. Hammerschlag MR, Gelling M, Roblin PM et al. . Treatment of neonatal chlamydial conjunctivitis with azithromycin. Pediatr Infect Dis J 1998;17:1049–50. 10.1097/00006454-199811000-00020
    1. Eberly MD, Eide MB, Thompson JL et al. . Azithromycin in early infancy and pyloric stenosis. Pediatrics 2015;135:483–8. 10.1542/peds.2014-2026
    1. Viscardi RM, Othman AA, Hassan HE et al. . Azithromycin to prevent bronchopulmonary dysplasia in ureaplasma-infected preterm infants: pharmacokinetics, safety, microbial response, and clinical outcomes with a 20-milligram-per-kilogram single intravenous dose. Antimicrob Agents Chemother 2013;57:2127–33. 10.1128/AAC.02183-12
    1. Hassan HE, Othman AA, Eddington ND et al. . Pharmacokinetics, safety, and biological effects of azithromycin in extremely preterm infants at risk for ureaplasma colonization and bronchopulmonary dysplasia. J Clin Pharmacol 2011;51:1264–75. 10.1177/0091270010382021
    1. Tessema E, Warrier I, Lulic-Botica M et al. . Pharmacokinetics (PK) of intravenous azithromycin in preterm newborns. Neonatology 2007;92:279–95. 10.1159/000107709
    1. Zayas J. A 5 week old male presenting with infantile hypertrophic pyloric stenosis following azithromycin therapy: a case report. J Investig Med 2010;58:415.
    1. Nair V, Loganathan P, Soraisham AS. Azithromycin and other macrolides for prevention of bronchopulmonary dysplasia: a systematic review and meta-analysis. Neonatology 2014;106:337–47. 10.1159/000363493
    1. Kallapur SG, Kramer BW, Jobe AH. Ureaplasma and BPD. Semin Perinatol 2013;37:94–101. 10.1053/j.semperi.2013.01.005
    1. Welsh L, Gaydos C, Quinn T. In vitro evaluation of activities of azithromycin, erythromycin, and tetracycline against Chlamydia trachomatis and Chlamydia pneumoniae. Antimicrob Agents Chemother 1992;36:291–4. 10.1128/AAC.36.2.291
    1. Peeters T, Matthijs G, Depoortere I et al. . Erythromycin is a motilin receptor agonist. Am J Physiol 1989;257:G470–4.
    1. Cooper WO, Griffin MR, Arbogast P et al. . Very early exposure to erythromycin and infantile hypertrophic pyloric stenosis. Arch Pediatr Adolesc Med 2002;156:647–50. 10.1001/archpedi.156.7.647
    1. Maheshwai N. Are young infants treated with erythromycin at risk for developing hypertrophic pyloric stenosis? Arch Dis Child 2007;92:271–3. 10.1136/adc.2006.110007
    1. Broad J, Sanger GJ. The antibiotic azithromycin is a motilin receptor agonist in human stomach: comparison with erythromycin. Br J Pharmacol 2013;168:1859–67. 10.1111/bph.12077
    1. Klein JO. History of macrolide use in paediatrics. Pediatr Infect Dis J 1997;16:427–31. 10.1097/00006454-199704000-00025
    1. Zuckerman JM, Qamar F, Bono BR. Review of macrolides (azithromycin, clarithromycin), ketolids (telithromycin) and glycylcyclines (tigecycline). Med Clin North Am 2011;95: 761–91. 10.1016/j.mcna.2011.03.012
    1. Sørensen HT, Skriver MV, Pedersen L et al. . Risk of infantile hypertrophic pyloric stenosis after maternal postnatal use of macrolides. Scand J Infect Dis 2003;35:104–6. 10.1080/0036554021000027010
    1. Howard PA. Azithromycin-induced proarrhythmia and cardiovascular death. Ann Pharmacother 2013;47:1547–51. 10.1177/1060028013504905
    1. Tilelli JA, Smith KM, Pettignano R. Life-threatening bradyarrhythmia after massive azithromycin overdose. Pharmacotherapy 2006;26:147–50. 10.1592/phco.2006.26.1.147
    1. Stramba-Badiale M, Nador F, Porta N et al. . QT interval prolongation and risk of life-threatening arrhythmias during toxoplasmosis prophylaxis with spiramycin in neonates. Am Heart J 1997;133:108–11. 10.1016/S0002-8703(97)70255-2
    1. Ulrich TJ, Ellsworth MA, Carey WA et al. . Heart-rate-corrected QT interval evolution in premature infants during the first week of life. Pediatr Cardiol 2014;35:1363–9. 10.1007/s00246-014-0937-z

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