What is the recommended first‑line treatment and dosing for Mycoplasma pneumoniae infection in children, and what are the alternative regimens for macrolide‑resistant disease or contraindications?

Treatment of Mycoplasma Pneumonia in Children

First-Line Treatment: Age-Stratified Approach

For children ≥5 years old, azithromycin is the first-line treatment at 10 mg/kg (max 500 mg) on day 1, followed by 5 mg/kg (max 250 mg) once daily on days 2-5. 1

Children Under 5 Years Old

• Start with amoxicillin 90 mg/kg/day divided in 2 doses as first-line therapy, because Streptococcus pneumoniae remains the most common bacterial pathogen in this age group and Mycoplasma pneumoniae is less prevalent. 2, 3
• If fever persists or clinical deterioration occurs at 48-72 hours after starting amoxicillin, switch to azithromycin (10 mg/kg day 1, then 5 mg/kg days 2-5), as this suggests atypical bacterial infection. 2

Children 5 Years and Older

• Azithromycin is the preferred macrolide because atypical pathogens (Mycoplasma pneumoniae and Chlamydophila pneumoniae) predominate as causative organisms in school-aged children. 1
• Alternative macrolides include clarithromycin 15 mg/kg/day divided in 2 doses or erythromycin 40 mg/kg/day divided in 4 doses, though erythromycin carries higher risk of gastrointestinal side effects. 1

Treatment Duration

Mycoplasma pneumonia requires at least 14 days of macrolide therapy, which is substantially longer than the typical 5-10 day course used for pneumococcal pneumonia. 1

Route of Administration

• Oral antibiotics are safe and effective for children with mild to moderate pneumonia, allowing outpatient management. 1
• Intravenous antibiotics are indicated when the child cannot absorb oral medications, has severe illness requiring hospitalization, or has oxygen saturation <92% on room air. 2

Macrolide-Resistant Mycoplasma Pneumoniae

When to Suspect Resistance

• Consider macrolide resistance if fever persists or chest x-ray shows deterioration 48-72 hours after starting macrolide treatment. 4, 5
• Macrolide resistance prevalence in Taiwan is 12-23%, substantially lower than China, Japan, and Korea (up to 90-100%), but higher than Europe and North America (0-15%). 4, 6

Second-Line Treatment Options

For children >7-8 years old with suspected macrolide-resistant disease:

• Doxycycline 2-4 mg/kg/day divided in 2 doses is the preferred alternative. 1
• Recent evidence demonstrates that short-course doxycycline does not cause enamel staining in children under 8 years old, addressing a major historical concern. 4

For children ≥5 years old when tetracyclines are contraindicated:

• Levofloxacin can be used:
  • Ages 5-16 years: 8-10 mg/kg once daily (maximum 750 mg/day)
  • Ages 6 months-5 years: 16-20 mg/kg/day divided twice daily 1

Important Clinical Caveat

Clinicians must weigh potential adverse effects against clinical benefits before starting tetracyclines or fluoroquinolones in children, as these agents have age-related safety concerns. 4, 5

Clinical Assessment Timeline

• Reassess at 48-72 hours after starting treatment; fever is the principal assessment criterion. 1
• Apyrexia may take 2-4 days with Mycoplasma pneumonia, compared to <24 hours with pneumococcal pneumonia—this does not indicate treatment failure. 1, 2
• Persistent cough does not indicate treatment failure and may continue even after fever resolves. 1

Combination Therapy for Hospitalized Children

For hospitalized patients where both typical and atypical pathogens are possible, combine a macrolide with a β-lactam antibiotic:

β-Lactam	Dose (IV)	Frequency
Ampicillin	150-200 mg/kg/day	Every 6 hours
Ceftriaxone	50-100 mg/kg/day	Every 12-24 hours
Cefotaxime	150 mg/kg/day	Every 8 hours

1

Refractory Mycoplasma Pneumonia

For severe cases with clinical deterioration despite appropriate antibiotics, consider immunomodulatory therapy:

• Corticosteroids (intravenous methylprednisolone) and intravenous immunoglobulin (IVIG) have shown promising results when combined with appropriate antimicrobials, particularly in refractory cases reflecting excessive immune response. 7
• This approach is reserved for children with radiological deterioration and persistent fever despite macrolide therapy, suggesting hyperinflammatory response rather than treatment failure. 7

Supportive Care

• Maintain oxygen saturation >92% with supplemental oxygen if hypoxic. 1
• Antipyretics and analgesics help keep the child comfortable and assist with coughing. 1
• Chest physiotherapy is not beneficial and should not be performed. 1

Critical Pitfalls to Avoid

• Do not assume treatment failure before 48-72 hours, as Mycoplasma pneumonia requires longer for clinical improvement than pneumococcal pneumonia. 1
• Do not use macrolides as monotherapy in toddlers unless Mycoplasma is strongly suspected, as this provides inadequate coverage for S. pneumoniae. 2
• Do not routinely combine β-lactam with macrolide in outpatient settings; reserve combination therapy for hospitalized children with uncertain diagnosis. 1