What are the guidelines for using fluoroquinolones (e.g. ciprofloxacin, levofloxacin) in pediatric patients?

Guidelines for Fluoroquinolone Use in Pediatric Patients

Fluoroquinolones should be restricted in pediatric patients to situations where there is no safe and effective alternative to treat an infection caused by multidrug-resistant bacteria or when oral therapy is needed but no other effective oral agent is available. 1

Approved Indications for Pediatric Use

• FDA-approved indications for fluoroquinolones in patients under 18 years are limited to:
  • Complicated urinary tract infections and pyelonephritis 1
  • Post-exposure treatment for inhalation anthrax 1, 2
  • Treatment of plague (including pneumonic and septicemic plague) for children 6 months and older 2

Safety Concerns in Pediatric Patients

Musculoskeletal Concerns

• Fluoroquinolones cause arthropathy in juvenile animals, which was the original basis for restricting their use in children 1, 3
• Clinical studies show higher rates of musculoskeletal adverse events in children receiving fluoroquinolones compared to control groups:
  • 9.3% of pediatric patients receiving ciprofloxacin experienced musculoskeletal adverse events compared to 6.0% in control patients 4
  • Levofloxacin-treated children showed higher incidence of musculoskeletal disorders at 2 months (2.1% vs 0.9%) and 12 months (3.4% vs 1.8%) compared to children treated with non-fluoroquinolone antibiotics 5
• Most reported musculoskeletal events in children are of moderate intensity and transient in nature 4, 5

Other Adverse Effects

• Additional adverse events associated with fluoroquinolones include:
  • Central nervous system disorders 2, 6
  • Photosensitivity 2
  • Disorders of glucose homeostasis 2
  • QT interval prolongation with risk of torsade de pointes 2
  • Hepatic dysfunction 1
  • Rashes 1
  • Peripheral neuropathy 2
  • Clostridium difficile-associated diarrhea 2

Appropriate Use Guidelines

When to Consider Fluoroquinolones in Children

Fluoroquinolones should be considered only in the following circumstances:

• Infections caused by multidrug-resistant pathogens with no alternative effective therapy 1, 3
• Situations where parenteral therapy is not feasible and no other effective oral agent is available 1
• Specific clinical scenarios that may warrant fluoroquinolone use:
  • Complicated urinary tract infections caused by P. aeruginosa or other multidrug-resistant gram-negative bacteria 4
  • Chronic suppurative otitis media 3
  • Chronic/acute osteomyelitis 3
  • Pulmonary exacerbations in cystic fibrosis patients 3
  • Mycobacterial infections 3
  • Multidrug-resistant gastrointestinal infections 3

Contraindications and Precautions

• Absolute contraindications:

  • History of hypersensitivity to fluoroquinolones 3
  • Tendon disorders related to previous quinolone use 3, 6
  • Congenital or documented QT prolongation 3
  • Concurrent use with other QT-prolonging medications 3

• Relative contraindications:

  • Seizure disorders or CNS conditions that may lower seizure threshold 2, 6
  • Myasthenia gravis due to risk of exacerbation 3
  • G6PD deficiency due to risk of hemolytic reactions 3
  • Uncorrected hypokalemia or hypomagnesemia 3

Monitoring Recommendations

• When fluoroquinolones must be used in children:
  • Monitor for signs of musculoskeletal adverse events (arthralgia, arthritis, tendinopathy, gait abnormality) 5
  • Consider ECG monitoring in patients with cardiac risk factors or those taking other QT-prolonging medications 3
  • Monitor blood glucose in patients with diabetes 3, 2
  • Adjust dosage in patients with renal impairment 3

Antimicrobial Stewardship Considerations

• Inappropriate use of fluoroquinolones contributes to increasing bacterial resistance 1, 7
• Studies have shown rapid development of resistance:
  • In cystic fibrosis patients, susceptible P. aeruginosa isolates decreased from 100% to 45% after just 14 days of treatment 1
  • Resistance has been reported among Campylobacter jejuni, Shigella species, Salmonella species, and shiga toxin-producing E. coli 1

Common Pitfalls to Avoid

• Using fluoroquinolones as first-line therapy for uncomplicated infections when other safer alternatives exist 4, 7
• Failure to adjust dosage in patients with renal impairment 3
• Overlooking drug interactions, particularly with divalent cations (e.g., antacids containing magnesium or aluminum) which can decrease fluoroquinolone absorption 3
• Ignoring QT prolongation risk, especially when combining with other QT-prolonging medications 3, 2

Despite concerns about musculoskeletal adverse effects, most reported events are reversible and resolve without long-term sequelae 5, 8. However, the risk of promoting antimicrobial resistance through inappropriate use represents a greater long-term public health concern 7.