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. 
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. 
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.
- 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.
- 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.
- 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.