Early Administration of Azithromycin and Prevention of Severe Lower Respiratory Tract Illnesses in Preschool Children with a History of Such Illnesses: A Randomized Clinical Trial

Conner Mansfield, Mercer University College of Pharmacy

It is estimated that severe lower respiratory tract illnesses (SLRTI) in children younger than 5 years old accounted for almost 15 million hospitalizations globally in 2010. Those hospitalizations were thought to have led to 265,000 deaths. [1]

Azithromycin is thought to decrease inflammation through its immunomodulatory effects in cells that include bronchial epithelial cells. This is in addition to its apparent action against common respiratory bacteria: S. pneumoniae, H. influenzae, and atypicals. [2]

The significant morbidity and mortality caused by lower respiratory tract illnesses (LRTI) in children and azithromycin’s multiple therapeutic actions in respiratory tract illnesses (RTIs) encouraged researchers to conduct the following study:

Early Administration of Azithromycin and Prevention of Severe Lower Respiratory Tract Illnesses in Preschool Children With a History of Such Illnesses: A Randomized Clinical Trial
Design Randomized, double-blind, placebo-controlled trial; N = 607
Objective To determine if early administration of azithromycin can prevent the progression of RTIs to LRTI
Study Groups Patients were randomized to receive either azithromycin 12 mg/kg or placebo for 5 days at the first sign of RTI defined as the guardian-perceived first sign of LRTI.
Methods Patients were 12 to 71 months old and experienced recurrent wheezing secondary to LRTI. Recurrent wheezing must have required systemic corticosteroids, an unscheduled physician office visit, an emergency department visit, or hospitalization. Patients that required more than 4 courses of systemic corticosteroids, 1 hospitalization, or required the use of 8 months or more of a controller medication for asthma in the last 12 months were excluded. All patients were to receive albuterol inhalations four times daily for the first two days of an RTI and as needed thereafter in addition to azithromycin or placebo. At randomization, patients could receive successful early treatment for a maximum of three RTIs. This was increased to four RTIs after follow-up duration was increased from 52 to 78 weeks due to a lower than expected RTI rate.
Duration April 2011 to December 2014
Primary Outcome Measure The number of treated RTIs not progressing to severe LRTIs among patients who experienced at least one treated RTI.
Baseline Characteristics   Patients assigned to azithromycin with at least one treated RTI; n = 223 Patients assigned to placebo with at least one treated RTI; n = 220
Mean age — months (standard deviation) 42.5 (16.4) 40.2 (16.6)
Male sex (%) 139 (62.3) 135 (61.4)
Black race (%) 47 (21.1) 42 (19.1)
White race (%) 141 (62.3) 149 (67.7)
Physician-diagnosed asthma (%) 127 (57.0) 121 (55.0)
Results   Azithromycin; n = 223 Placebo; n = 220 p-value
Number of treated RTIs 473 464
Number of SLRTIs 35 57
Adjusted hazard ratio 0.64 0.04
Adverse Events Common Adverse Events:   Azithromycin Placebo
Gastrointestinal symptoms (%) 4 (1.8) 3 (1.4)
Serious Adverse Events: None noted
Percentage that Discontinued due to Adverse Events: None
Study Author Conclusions Azithromycin started at the earliest signs of an RTI was effective in significantly reducing the risk of experiencing progression to severe LRTI. Azithromycin therapy was well tolerated, with low rates of treatment-related adverse effects.

Azithromycin administered at the first sign of RTI appears to decrease the development of LRTIs. However, these findings do not seem to be generalizable to the most severely ill patients presumably at greatest risk for hospitalization and death since they were excluded. Additionally, widespread implementation would increase antibiotic exposure among children, possibly leading increased side effects and resistance to azithromycin. Nonetheless, azithromycin might have a future role in preventing LRTIs.

  1. Nair H, Simões EA, Rudan I, et al. Global and regional burden of hospital admissions for severe acute lower respiratory infections in young children in 2010: a systematic analysis. Lancet. 2013;381(9875):1380-90.
  2. Sivapalasingam S, Steigbigel N. Macrolides, Clindamycin, and Ketolides. In: Bennett J, ed. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 3rd ed. Philadelphia, PA: Saunders; 2015:358-376.
  3. Bacharier LB, Guilbert TW, Mauger DT, et al. Early Administration of Azithromycin and Prevention of Severe Lower Respiratory Tract Illnesses in Preschool Children with a History of Such Illnesses: A Randomized Clinical Trial. JAMA. 2015;314(19):2034-44.
Advertisements

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s