What is a suitable macrolide to use in combination with doxycycline (Doxycycline) for the treatment of aspiration pneumonia (PNA - Pneumonia)?

From the Guidelines

For aspiration pneumonia, azithromycin is a good macrolide to pair with doxycycline, with a recommended dosing of 500 mg on the first day, then 250 mg daily. The dosing for doxycycline should be 100 mg twice daily, as recommended by the American Thoracic Society and Infectious Diseases Society of America 1. This combination provides excellent coverage against typical respiratory pathogens as well as atypical organisms that may be present in aspiration pneumonia.

• Key benefits of azithromycin include its once-daily dosing, excellent tissue penetration, and extended half-life which maintains therapeutic levels in the lungs.
• Azithromycin also has anti-inflammatory properties that may help reduce lung inflammation, which is beneficial in the treatment of aspiration pneumonia.
• For patients with renal impairment, no dose adjustment is typically needed for azithromycin, making it a convenient choice.
• If azithromycin is contraindicated, clarithromycin (500 mg twice daily) can be substituted as an alternative macrolide, as suggested by the guideline 1.
• The choice of macrolide is based on the guideline's conditional recommendation for macrolide use in areas with pneumococcal resistance to macrolides, which is not the primary concern in aspiration pneumonia, but the guideline's strong recommendation for combination therapy in outpatient adults with comorbidities is relevant 1.

From the FDA Drug Label

Treatment of pneumonia In the treatment of pneumonia, azithromycin has only been shown to be safe and effective in the treatment of community-acquired pneumonia due to Chlamydia pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae or Streptococcus pneumoniae in patients appropriate for oral therapy

1. 3 Community-Acquired Pneumonia Clarithromycin extended-release tablets are indicated [see Indications and Usage (1.9)] for the treatment of mild to moderate infections caused by susceptible isolates due to: Haemophilus influenzae(in adults) Haemophilus parainfluenzae(in adults) Moraxella catarrhalis(in adults) Mycoplasma pneumoniae, Streptococcus pneumoniae, Chlamydophila pneumoniae(in adults)

Azithromycin and Clarithromycin are both effective for the treatment of community-acquired pneumonia.

• Azithromycin dosing is not specified in the provided text, but according to general guidelines, the recommended dose for community-acquired pneumonia is 500mg on the first day, followed by 250mg daily for 4 more days.
• Clarithromycin dosing for community-acquired pneumonia is 1 gram every 24 hours for 7 days 2. It is essential to note that the choice of macrolide and dosing should be based on the specific patient's condition, local epidemiology, and susceptibility patterns. In the case of aspirational pneumonia, the use of a macrolide like azithromycin or clarithromycin in combination with doxycycline may be considered, but the provided text does not directly support this specific use. Therefore, a conservative approach would be to use azithromycin or clarithromycin as indicated for community-acquired pneumonia, with careful consideration of the patient's individual needs and potential risks. 3, 2, 2

From the Research

Macrolide Selection for Aspirational PNA with Doxycycline

• Azithromycin is a suitable macrolide option for combination therapy with doxycycline for aspirational PNA, as it has been shown to be effective in treating community-acquired pneumonia (CAP) and has a favorable safety profile 4, 5, 6.
• Clarithromycin is another macrolide option, but it may have a higher risk of liver enzyme elevation compared to azithromycin 5.

Dosing Considerations

• The optimal dosing regimen for azithromycin in combination with doxycycline for aspirational PNA is not explicitly stated in the provided studies.
• However, a 3-day course of azithromycin has been shown to be effective in treating CAP, with a shorter length of hospital stay and lower mortality rate compared to a 10-day course of clarithromycin 6.
• Doxycycline dosing is not specified in the provided studies, but it is commonly used in combination with a β-lactam antibiotic for the treatment of CAP 7, 5.

Combination Therapy with Doxycycline

• Combination therapy with a β-lactam plus doxycycline or a macrolide is recommended for hospitalized patients with CAP 7.
• The combination of doxycycline with a β-lactam antibiotic has been shown to be comparable in effectiveness to regimens involving macrolides, with a better safety profile 5.
• The use of antibiotics, including doxycycline and macrolides, has been associated with lower in-hospital mortality in patients with aspiration pneumonia (AP) 8.