What medication should be avoided in pediatric patients when choosing between amoxicillin, levofloxacin, and Keflex (cefalexin)?

Levofloxacin Should Be Avoided in Pediatric Patients

Levofloxacin is the medication that should be avoided in routine pediatric prescribing among the three options listed, as fluoroquinolones cause arthropathy and musculoskeletal adverse events in children and are reserved only for specific life-threatening infections like inhalational anthrax and plague. 1

Why Levofloxacin Should Be Avoided

Musculoskeletal Toxicity in Children

• Fluoroquinolones including levofloxacin cause arthropathy and osteochondrosis in juvenile animals and significantly increase musculoskeletal disorders in pediatric patients. 1
• In clinical trials, children treated with levofloxacin had a significantly higher incidence of musculoskeletal disorders (arthralgia, arthritis, tendinopathy, gait abnormality) compared to non-fluoroquinolone-treated children during 60-day and 1-year follow-up. 1
• Most musculoskeletal disorders involved multiple weight-bearing joints, with arthralgia being the most common complaint. 1

Tendon Rupture Risk

• Levofloxacin carries a black box warning for tendon rupture, with pediatric patients at risk for tendinitis and tendon rupture that can occur during or months after therapy. 1
• The Achilles tendon is most commonly affected, but shoulder, hand, and other tendon sites can be involved. 1

Extremely Limited Indications in Pediatrics

• Levofloxacin is FDA-approved in children ≥6 months only for inhalational anthrax (post-exposure) and plague—not for routine infections. 1
• Guidelines restrict levofloxacin use to hospitalized children who have reached growth maturity or who cannot tolerate macrolides for atypical pneumonia. 2
• For community-acquired pneumonia, levofloxacin is listed only as an alternative for children with β-lactam allergy or in specific resistant organism scenarios. 2, 3

Safe First-Line Options: Amoxicillin and Cephalexin (Keflex)

Amoxicillin as First-Line Therapy

• Amoxicillin is the first-choice antibiotic for most pediatric bacterial infections, including community-acquired pneumonia, with a recommended dose of 90 mg/kg/day divided into 2 doses (maximum 4 g/day). 2, 3
• High-dose amoxicillin (90 mg/kg/day) is specifically designed to overcome penicillin-resistant Streptococcus pneumoniae, the most common bacterial cause of pediatric pneumonia. 3
• Amoxicillin is recommended for previously healthy, fully immunized children with moderate-risk community-acquired pneumonia for 5-7 days. 3

Cephalexin (Keflex) as Alternative

• Cephalosporins like cephalexin are appropriate alternatives for children with non-Type 1 penicillin allergies. 3
• Other oral cephalosporins (cefdinir, cefixime, cefpodoxime, ceftibuten) serve as alternatives when amoxicillin-clavulanate cannot be used, particularly for β-lactamase-producing Haemophilus influenzae. 4

Clinical Context: Antibiotic Adverse Events in Pediatrics

Higher Risk in Young Children

• Children, particularly those <2 years old, have a higher risk of antibiotic-related adverse events and receive antibiotics more frequently than older children. 5, 6
• Amoxicillin leads to the most emergency department visits for antibiotic adverse drug events in children ≤2 years (primarily allergic reactions), but this reflects its widespread appropriate use rather than inherent danger. 7
• When accounting for prescription volume, amoxicillin has 29.9 ED visits per 10,000 dispensed prescriptions in children ≤2 years—an acceptable safety profile for a first-line agent. 7

Antibiotic Stewardship Imperative

• At least one-third of pediatric antibiotic prescriptions are unnecessary, and only 31.4% of pediatric outpatient antibiotics are optimal for both choice and duration. 7, 8
• Reducing inappropriate fluoroquinolone use in children is a key antibiotic stewardship target to prevent both short-term musculoskeletal harm and long-term antibiotic resistance. 5, 9

Common Pitfall to Avoid

• Do not prescribe levofloxacin for routine pediatric infections (otitis media, pharyngitis, sinusitis, uncomplicated pneumonia, skin infections) when amoxicillin or cephalexin are appropriate and safe alternatives. 2, 3, 1
• Reserve fluoroquinolones exclusively for life-threatening infections where no alternative exists or for hospitalized children with documented resistant organisms and contraindications to β-lactams and macrolides. 2, 1