Outpatient management

1. For previously healthy patients with no risk factors for MRSA or Pseudomonas:
   • Amoxicillin, 1 g orally three times daily, or
   • Doxycycline, 100 mg orally twice a day, or
   • In regions with a low rate (< 25%) of infection with high level (MIC ≥ 16 mcg/mL) macrolide-resistant Streptococcus pneumoniae, then a macrolide (clarithromycin, 500 mg orally twice a day; or azithromycin, 500 mg orally as a first dose and then 250 mg orally daily for 4 days, or 500 mg orally daily for 3 days).
2. For patients with comorbid medical conditions such as chronic heart, lung, liver, or kidney disease; diabetes mellitus; alcohol use disorder; malignancy; asplenia; immunosuppressant conditions or use of immunosuppressive drugs; or use of antibiotics within the previous 3 months (in which case an agent from a different antibiotic class should be selected):
   • A macrolide or doxycycline (as above) plus an oral beta-lactam (amoxicillin/clavulanate 500 mg/125 mg three times daily, amoxicillin/clavulanate 875 mg/125 mg twice daily, amoxicillin/clavulanate 2 g/125 mg twice daily; cefpodoxime, 200 mg twice daily; cefuroxime, 500 mg twice daily).
   • Monotherapy with an oral fluoroquinolone (moxifloxacin, 400 mg daily; gemifloxacin, 320 mg daily; levofloxacin, 750 mg daily).

Inpatient management of nonsevere pneumonia (typically not requiring intensive care)

1. A respiratory fluoroquinolone. Oral and intravenous doses equivalent: moxifloxacin, 400 mg daily or levofloxacin, 500-750 mg daily or
2. A macrolide (see above for oral therapy) plus a beta-lactam (see above for oral beta-lactam therapy). For intravenous therapy: ampicillin/sulbactam, 1.5-3 g every 6 hours; cefotaxime, 1-2 g every 8 hours; ceftriaxone, 1-2 g every 12-24 hours; ceftaroline, 600 mg every 12 hours.
3. For patients with prior respiratory isolation of MRSA, strongly consider adding coverage for MRSA and obtain cultures or nasal PCR to confirm infection or to allow de-escalation of therapy: vancomycin, typically starting at 15 mg/kg intravenously every 12 hours with interval dosing based on kidney function to achieve serum trough concentration 15-20 mcg/mL or linezolid, 600 mg orally or intravenously every 12 hours.
4. For patients with prior respiratory isolation of Pseudomonas aeruginosa, strongly consider adding coverage for P aeruginosa and obtain cultures to confirm infection or to allow de-escalation of therapy. Intravenous therapy only: piperacillin-tazobactam, 3.375-4.5 g every 6 hours; cefepime, 1-2 g every 8 hours; imipenem, 0.5-1 g every 6 hours; meropenem, 1 g every 8 hours; or aztreonam 2 g every 8 hours.

Inpatient management of severe pneumonia (typically requiring intensive care). All agents administered intravenously, except as noted.

1. Azithromycin (500 mg orally as a first dose and then 250 mg orally daily for 4 days, or 500 mg orally daily for 3 days) or a respiratory fluoroquinolone (as above) plus an intravenous anti-pneumococcal beta-lactam (as above).
2. For patients allergic to beta-lactam antibiotics, a fluoroquinolone plus aztreonam (2 g every 8 hours).
3. For patients at risk for P aeruginosa, add coverage for P aeruginosa and obtain cultures to confirm infection or to allow de-escalation of therapy: piperacillin-tazobactam, 3.375-4.5 g every 6 hours; cefepime, 1-2 g every 8 hours; imipenem, 0.5-1 g every 6 hours; meropenem, 1 g every 8 hours; or aztreonam 2 g every 8 hours.
4. For patients at risk for Pseudomonas infection AND who are critically ill, at increased risk for drug resistance, or if local incidence of monotherapy-resistant Pseudomonas is >10%, consider adding either an anti-pseudomonal fluoroquinolone (ciprofloxacin 400 mg every 8-12 hours or levofloxacin 750 mg daily) or an aminoglycoside (gentamicin, tobramycin, amikacin, all weight-based dosing administered daily adjusted to appropriate trough levels).
5. For patients at risk for MRSA infection, add coverage for MRSA and obtain cultures and/or nasal PCR to confirm infection or to allow de-escalation of therapy: vancomycin, typically starting at 15 mg/kg intravenously every 12 hours with interval dosing based on kidney function to achieve serum trough concentration 15-20 mcg/mL or linezolid, 600 mg every 12 hours.