Am Fam Physician. 2008;77(6):838-842
Background: Levofloxacin (Levaquin) is not approved by the U.S. Food and Drug Administration for use in children, but historical data on fluoroquinolones in children suggest an adverse event rate similar to that found in adults. Growing resistance in some bacteria that commonly cause community-acquired pneumonia (CAP) in children has increased the need for alternative antibiotics. Because levofloxacin has a broad spectrum of activity against bacterial and atypical pathogens and because it has an acceptable safety profile in adults, Bradley and colleagues studied the safety and effectiveness of levofloxacin to treat CAP in children.
The Study: This randomized, multicenter, open-label study evaluated children six months to 16 years of age in seven countries, including the United States. Children were eligible to participate if they had a clinical diagnosis of CAP based on positive radiographic findings and the presence of two or more clinical findings of pneumonia (e.g., fever, dyspnea, cough, chest pain, abnormal white blood cell count, physical signs on examination). Children in outpatient and inpatient settings were included.
Children were excluded if they received systemic antibiotics for more than 24 hours immediately before enrollment, if they required antibiotics other than the study drugs, or if they had an infection suspected to be resistant to the study drugs. Children were not eligible to participate if they were residents of long-term care facilities, had recent hospitalization or presumed nosocomial pneumonia, or were suspected to have a central nervous system infection. Because musculoskeletal complications were the primary safety concerns with levofloxacin in children, any patients with a history of periarticular disease or with musculoskeletal signs or symptoms were also excluded to avoid confounding the safety evaluation.
Children were randomized to receive levofloxacin or a comparator antibiotic (that varied with patient age) at a ratio of 3 to 1, respectively. The randomization was stratified by age group and country to ensure balance between treatment groups. All antibiotics were prescribed for 10 days; dosing depended on patient age (see accompanying table). Patients were allowed to switch between intravenous and oral therapy within treatment arms.
| Group | Comparator drug and dosage | Levofloxacin dosage | ||
|---|---|---|---|---|
| Six months to younger than five years | 22.5 mg per kg amoxicillin/clavulanic acid [Augmentin] oral suspension twice daily (maximal dosage: 875 mg per day)* or 25 mg per kg ceftriaxone (Rocephin) IV every 12 hours (maximal dosage: 4 g per day) | 10 mg per kg oral suspension twice daily (maximal dosage: 500 mg per day) or 10 mg per kg IV every 12 hours (maximal dosage: 500 mg per day) | ||
| Five to 16 years of age | 7.5 mg per kg clarithromycin (Biaxin) oral suspension twice daily or 250-mg tablet twice daily (maximal dosage: 250 mg twice daily) or 25 mg per kg ceftriaxone IV every 12 hours (maximal dosage: 4 g per day) plus 10 mg per kg erythromycin IV every six hours (maximal dosage: 4 g per 24 hours) or 7.5 mg per kg clarithromycin oral suspension twice daily or 250-mg tablet twice daily (maximal dosage: 250 mg twice daily) | 10 mg per kg oral suspension once daily (maximal dosage: 500 mg per day) or 250-mg tablet once daily (for children weighing 49.6 to 60.6 lb [22.5 to 27.5 kg]) or two 250-mg tablets once daily (for children weighing more than 100.3 lb [45.5 kg]) or 10 mg per kg IV every 24 hours (maximal dosage: 500 mg per day) | ||
Symptoms and signs were assessed at presentation, three to five days into treatment, one to three days after completing treatment, and at a test-of-cure visit occurring 10 to 17 days after the last antibiotic dose. The primary end point was clinical cure rate at the test-of-cure visit and was based on resolution of clinical symptoms and signs of pneumonia and resolution or stabilization of radiographic findings. Microbiologic response was determined by sputum Gram stain and culture with sensitivities when available and by serum acute and convalescent titers for Mycoplasma pneumoniae and Chlamydia pneumoniae. Microbiologic eradication data were assessed with clinical cure rates.
Adverse events or symptoms were evaluated by investigators within 72 hours of onset and were designated by severity and the likelihood of an association with the study drug.
Results: The study met statistical criteria to detect a difference in effectiveness between levofloxacin and standard-of-care antibiotics. Both groups reflected a more than 90 percent cure rate for clinical and microbiologic resolution, which persisted across stratified risk groups. The levofloxacin and comparator groups also experienced similar rates and types of adverse events, including musculoskeletal symptoms.
Conclusion: It appears that levofloxacin works as well as standard-of-care antibiotics (typically amoxicillin/clavulanic acid [Augmentin] or a macrolide) for treating CAP in children. The authors conclude that, in this study, the safety profile of levofloxacin in children (2 percent rate of treatment-limiting adverse events) is similar to that of nonfluoroquinolone antibiotics.