Reconstituted IV solution

Systematic review of eradicating B. pertussis from the nasopharynx found short-term antibiotics (azithromycin for three to five days, or clarithromycin or erythromycin for seven days) were as effective as long-term (erythromycin for 10 to 14 days) (risk ratio (RR) 1.01; 95% CI 0.98 to 1.04), but had fewer side effects (RR 0.66; 95% CI 0.52 to 0.83). Effective treatment regimens included 3 days azithromycin (10 mg/kg as a single dose) (2 trials); and 5 days azithromycin (10 mg/kg on the first day and 5 mg/kg once daily on day two to five) (2 trials).¹

The Centers for Disease Control and Prevention recommend oral azithromycin as the preferred agent for post-exposure prophylaxis (PEP) and treatment in infants younger than 1 month of age.² Azithromycin has the advantage of once daily dosing and shorter duration of therapy. In infants 1 month of age and older, CDC recommends erythromycin, clarithromycin and azithromycin as preferred agents for the treatment of pertussis. For infants 2 months of age and older, an alternative to macrolides is trimethoprim-sulfamethoxazole. Recommended azithromycin dose for both treatment and PEP is the same for infants <6 months of age: 10 mg/kg/day once a day for 5 days (only limited safety data are available)²
Treatment of chlamydial conjunctivitis and pneumonia

C. trachomatis infection in neonates is most frequently recognised by conjunctivitis that develops 5–12 days after birth. C. trachomatis also can cause a subacute, afebrile pneumonia with onset at ages 1–3 months. There are limited data on the efficacy of azithromycin regimens in newborns. Hammerschlag 1998 reported oral azithromycin 20 mg/kg/day single dose resulted in 2 of 5 treatment failures and oral azithromycin 20 mg/kg/day single dose for 3 days resulted in 1 of 6 treatment failures.³ However, azithromycin has been extensively trialled for eradication of C. trachomatis in populations including infants and children.^4-6 Use of azithromycin for prevention of bronchopulmonary dysplasia provides some safety data in premature infants (see below).

Recommendation: The Centers for Disease Control and Prevention (CDC) recommend oral erythromycin 50 mg/kg per day given orally in four divided doses for 14 days for either chlamydial conjunctivitis or pneumonia. An alternative regimen is azithromycin 20 mg/kg/day once daily for 3 days. Topical antibiotic therapy alone is inadequate and is unnecessary when systemic treatment is administered.⁷

A systematic review of antibiotics for community-acquired lower respiratory tract infections secondary to Mycoplasma pneumoniae in children found no difference in clinical response between children randomised to a macrolide antibiotic and children randomised to a non-macrolide antibiotic for infants in whom a diagnosis of mycoplasma or chlamydia pneumonia was not made. In one controlled study of children with recurrent respiratory infections, whose acute LRTI was associated with Mycoplasma, Chlamydia or both, by polymerase chain reaction and/or paired sera, 100% of children treated with azithromycin had clinical resolution of their illness compared to 77% not treated with azithromycin at one month.⁸

Recommendation of the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America: Parenteral: Intravenous azithromycin 10 mg/kg on days 1 and 2 of therapy; transition to oral therapy if possible. Enteral: Azithromycin 10 mg/kg on day 1, followed by 5 mg/kg/day once daily on days 2–5.⁹
Prevention of bronchopulmonary dysplasia in preterm infants

Nair et al conducted a systematic review of azithromycin and other macrolides on the incidence of bronchopulmonary dysplasia (BPD) in preterm infants. Macrolides when used prophylactically, did not show significant reduction in BPD (risk ratio, RR, 0.88, 95% CI, 0.75–1.03), death (RR 0.89, 95% CI 0.79–1.01) or in the composite outcome of BPD/death. Similarly, there was no significant reduction in BPD (RR 0.64, 95% CI 0.31–1.31) or the composite outcome of BPD/death (RR 0.41, 95% CI 0.05–3.13), when macrolides were used in Ureaplasma-positive infants. However, prophylactic azithromycin therapy (3 studies) was associated with significant reduction in BPD (RR 0.83, 95% CI 0.71–0.97; number needed to treat, 10) and of BPD or death (RR 0.86, 95% CI 0.77–0.97; NNT 10). Dose regimens were 10 mg/kg/day for 7 days (2 studies) and 10 mg/kg/day for 7 days followed by 5 mg/kg/day for further 7 days (one study).

Conclusion: Although prophylactic azithromycin therapy was associated with a reduction in BPD and BPD/death in preterm infants, there is limited information on pharmacokinetics and potential harmful effects; further studies should be done before routine use of azithromycin in the neonatal population.¹¹
Eradication of Ureaplasma in preterm infants

A 3-day course of 20 mg/kg/day IV azithromycin commencing treatment within 72 hours of life in 24–28 weeks GA infants showed efficacy in eradicating Ureaplasma spp. from the preterm respiratory tract.¹² All post-treatment cultures were negative. Side effects reported in this study were related to prematurity. However, systematic review found no significant reduction in BPD (RR 0.64, 95% CI 0.31–1.31) or the composite outcome of BPD/death (RR 0.41, 95% CI 0.05–3.13), when macrolides were used in Ureaplasma-positive infants. Conclusion: The efficacy and safety of using macrolide antibiotics for eradication of Ureaplasma is unproven.¹¹