Erythromycin is commonly used in the treatment of pneumonia in children. However, the pharmacokinetic properties of azithromycin, including its prolonged serum half-life of 11 to 14 hours, sustained tissue concentrations, prolonged serum concentration after completion of therapy and high intracellular concentrations make it a suitable alternative. These properties allow once-daily dosing and only five days of treatment for pneumonia compared with erythromycin, which is usually given three to four times daily for 10 days. Intracellular concentrations of azithromycin remain above the mean inhibitory concentration for many common respiratory pathogens for more than seven days after the drug is discontinued. Harris and associates conducted a multicenter, double-blind study to compare the safety and efficacy of a five-day course of azithromycin with a 10-day course of amoxicillin or erythromycin in the treatment of community-acquired pneumonia in children.
Children from six months to 16 years of age with radiologic findings of an acute infiltrate and the presence of tachypnea accompanied by either fever or an elevated white blood cell count were eligible to receive one of the study medications. Patients in the azithromycin group received 10 mg per kg of the drug on the first day, followed by 5 mg per kg on days 2 through 5. Depending on their age, patients in the conventional therapy group received either amoxicillin or erythromycin oral suspension in a dosage of 40 mg per kg per day in three divided doses. Patients were evaluated at baseline, once during days 2 through 5 of the study period, once during days 15 through 19 of the study period and once four to six weeks after therapy. Culture or polymerase chain reaction testing was done at baseline and at days 15 to 19 for bacteria, Chlamydia pneumoniae and Mycoplasma pneumoniae. Serology for C. pneumoniae and M. pneumoniae was done at baseline and four to six weeks posttherapy.
Data from 420 patients were evaluated. There were 285 patients in the group receiving azithromycin and 135 in the group receiving conventional treatment. The clinical presentation of pneumonia was similar in both groups at baseline. Clinical success (defined as the percentage of patients who experienced clinical improvement or cure) at the primary evaluation (days 15 to 19) and at four to six weeks posttherapy was also similar across groups. Treatment failures were highest among children under five years of age. This finding was independent of treatment group. Treatment-related side effects occurred significantly less often in the group receiving azithromycin. Vomiting and diarrhea were the most common side effects, followed by rash in children younger than five years and abdominal pain in those older than five years.
The authors conclude that the five-day course of azithromycin is just as effective in the treatment of community-acquired pneumonia in children as the conventional 10-day regimen with either amoxicillin or erythromycin. Patients taking azithromycin experienced significantly fewer side effects than patients taking either amoxicillin or erythromycin. Treatment with azithromycin appears to be appropriate in children six months of age or older. The significantly higher failure rate in children younger than five years may have been caused by a higher number of cases of pneumonia of viral etiology in this age group.