Treatment of Atypical Pneumonia

Introduction to Atypical Pneumonia

Atypical pneumonia is commonly caused by Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella pneumophila, and respiratory viruses 1
The most common pathogens in outpatient community-acquired pneumonia are Streptococcus pneumoniae, Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Haemophilus influenzae 2

The American Thoracic Society recommends combination therapy with a β-lactam (such as oral cefpodoxime, cefuroxime, high-dose amoxicillin, or amoxicillin/clavulanate) plus a macrolide (such as azithromycin) or doxycycline for the treatment of atypical pneumonia 1
The Infectious Diseases Society of America recommends respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin 750 mg) as a treatment option for community-acquired pneumonia 2
The Infectious Diseases Society of America recommends combination therapy with a β-lactam plus a macrolide as a treatment option for community-acquired pneumonia, with high-dose amoxicillin (1 g three times daily) or amoxicillin-clavulanate (875/125 mg twice daily or 2 g twice daily) as the preferred β-lactam 2
Azithromycin 500 mg on day 1, followed by 250 mg daily for days 2-5 is recommended as the first-line treatment for atypical pneumonia in adults without comorbidities, with a strength of evidence of moderate to high 3
Doxycycline 100 mg twice daily for 7-14 days is a treatment option for adults with atypical pneumonia, with some experts suggesting a loading dose of 200 mg for the first dose 3

Macrolides should only be used as monotherapy in areas where pneumococcal resistance to macrolides is <25%, with a strength of evidence of moderate to high 3
Be cautious when using macrolides or fluoroquinolones in patients taking other medications that prolong the QT interval, with a strength of evidence of high 3
Monotherapy with a macrolide is not recommended in areas with high rates (>25%) of macrolide-resistant S. pneumoniae 2
Fluoroquinolone use should be restricted in patients without comorbidities to prevent development of resistance 2
An alternative antibiotic from a different class should be selected if the patient has used antibiotics within the previous 3 months 2

No dosage adjustment is needed for patients with GFR 10-80 mL/min, but use caution in severe renal impairment (GFR <10 mL/min) as AUC increases by 35%, as noted by the National Kidney Foundation 4
For children ≥6 months, azithromycin should be dosed at 10 mg/kg on day 1, followed by 5 mg/kg daily for days 2-5, as recommended by the Infectious Diseases Society of America 4, 5
Weight-based dosing examples are available, such as 2.5 mL (½ tsp) of 100 mg/5 mL suspension on day 1, then 1.25 mL (¼ tsp) on days 2-5 for a 5 kg child 5
Clarithromycin 15 mg/kg/day in 2 doses for 7-14 days is an alternative option for the treatment of atypical pneumonia in children, with a strength of evidence of moderate 4

Patients should be afebrile for 48-72 hours and have no more than one pneumonia-associated sign of clinical instability before discontinuing therapy, according to the Infectious Diseases Society of America (IDSA) (strong recommendation, moderate quality evidence) 6
Clinical improvement typically includes reduction in fever, improvement in respiratory symptoms, and stabilization of vital signs, based on moderate-strength evidence 2
For Legionella infections, extend treatment to 14 days, with a strength of evidence of high 3, 7
Undertreatment of Legionella with shorter courses can lead to treatment failure, as warned by the European Respiratory Society 8

For non-severe inpatient pneumonia, the American Thoracic Society recommends β-lactam (including amoxicillin/clavulanate) plus a macrolide or respiratory fluoroquinolone 3
For severe inpatient pneumonia, the American Thoracic Society recommends β-lactam plus a macrolide or β-lactam plus a fluoroquinolone 3
The preferred regimen for severe pneumonia is β-lactam (ceftriaxone, cefotaxime, ampicillin-sulbactam) plus a macrolide, as recommended by the Infectious Diseases Society of America (IDSA) (strong recommendation, moderate quality evidence) 9, 3
Combination therapy with a beta-lactam (amoxicillin/clavulanate, cefpodoxime, or cefuroxime) and a macrolide (azithromycin) is recommended for patients with comorbidities, such as chronic heart, lung, liver, or renal disease; diabetes mellitus; alcoholism; malignancy; or asplenia 3
Patients with chronic heart, lung, liver, or renal disease; diabetes; alcoholism; malignancy; or asplenia may benefit from combination therapy with a beta-lactam plus a macrolide, as recommended by the American College of Chest Physicians and European Respiratory Society 8