What are the recommended antibiotic regimens for treating community-acquired and hospital-acquired pneumonia?

Pneumonia Antibiotic Guidelines

Community-Acquired Pneumonia (CAP) - Outpatient Treatment

For previously healthy adults without comorbidities, amoxicillin 1 gram three times daily is the first-line antibiotic of choice, with doxycycline 100 mg twice daily as the preferred alternative. 1

• Amoxicillin targets Streptococcus pneumoniae (the most common pathogen, accounting for 48% of identified cases) with 90-95% activity against pneumococcal strains at high doses 1
• Doxycycline 100 mg twice daily provides broad-spectrum coverage including atypical organisms and demonstrates comparable efficacy to fluoroquinolones at significantly lower cost 1
• Macrolide monotherapy (azithromycin or clarithromycin) should only be used if local pneumococcal macrolide resistance is documented to be <25%, due to risk of breakthrough bacteremia with resistant strains 1

For Patients with Comorbidities (Outpatient)

• Combination therapy with amoxicillin-clavulanate plus a macrolide (azithromycin or clarithromycin) is recommended 1
• Alternatively, respiratory fluoroquinolone monotherapy (levofloxacin 750 mg daily or moxifloxacin 400 mg daily) can be used 1

Special Considerations for Outpatients

• Patients with recent antibiotic exposure (within 90 days) must receive treatment from a different antibiotic class to reduce resistance risk 1
• For suspected aspiration pneumonia, use amoxicillin-clavulanate or clindamycin 1

CAP - Inpatient Treatment (Non-ICU)

For hospitalized patients with non-severe CAP, use combination therapy with a β-lactam (ceftriaxone 1 gram daily, cefotaxime 1 gram every 8 hours, or ampicillin-sulbactam) plus a macrolide, OR monotherapy with a respiratory fluoroquinolone. 1

• Combination β-lactam/macrolide therapy achieves 91.5% favorable clinical outcomes versus 89.3% with fluoroquinolone monotherapy 2
• Ceftriaxone plus azithromycin demonstrates superior eradication rates for S. pneumoniae (100% vs 44% with levofloxacin alone) 2
• Second-generation cephalosporins (cefuroxime 750-1500 mg every 8 hours IV) are acceptable alternatives 3

Inpatient Dosing Specifics

• Azithromycin IV: 500 mg daily for at least 2 days, then switch to oral 500 mg daily to complete 7-10 days total 4
• Ceftriaxone: 1 gram every 24 hours IV 3
• Levofloxacin: 750 mg daily (oral or IV) 1

Severe CAP (ICU Patients)

For severe CAP requiring ICU admission, use a β-lactam (ceftriaxone, cefotaxime, or ceftaroline) plus either a macrolide OR a respiratory fluoroquinolone. 1

When Pseudomonas is Suspected

• Use an antipseudomonal β-lactam (piperacillin-tazobactam 4.5 grams every 6 hours) plus either ciprofloxacin OR an aminoglycoside plus a macrolide 1, 5
• For nosocomial pneumonia caused by P. aeruginosa, piperacillin-tazobactam must be combined with an aminoglycoside 5

ICU-Specific Considerations

• Assess clinical response at day 2-3 (fever resolution, lack of progression of pulmonary infiltrates) 3
• For pulmonary abscess, cavitated pneumonia, or suspected aspiration: use amoxicillin-clavulanate 2 grams every 6 hours IV 3

Hospital-Acquired/Nosocomial Pneumonia

Initial treatment should be piperacillin-tazobactam 4.5 grams every 6 hours IV plus an aminoglycoside, administered over 30 minutes. 5

• Treatment duration: 7-14 days 5
• Continue aminoglycoside therapy in patients from whom P. aeruginosa is isolated 5
• Piperacillin-tazobactam covers β-lactamase producing S. aureus, Acinetobacter baumannii, H. influenzae, K. pneumoniae, and P. aeruginosa 5

Treatment Duration

Standard treatment duration is 5-7 days for most antibiotics in responding patients. 1

• Extend to 14-21 days ONLY for: Legionella pneumophila, Staphylococcus aureus, or gram-negative enteric bacilli 1
• Treatment should not exceed 8 days in responding patients with uncomplicated pneumonia 1
• Clinical stability criteria for stopping therapy: resolution of vital sign abnormalities, ability to eat, and normal mentation 1

Short-Course Evidence

• Meta-analysis of 2,796 patients demonstrates no difference in clinical failure between ≤7 days versus >7 days of treatment (RR 0.89,95% CI 0.78-1.02) 6
• No differences in mortality (RR 0.81,95% CI 0.46-1.43) or bacteriologic eradication (RR 1.11,95% CI 0.76-1.62) with shorter courses 6

Critical Pitfalls to Avoid

• Never use macrolide monotherapy in areas with >25% pneumococcal macrolide resistance or in patients with comorbidities, as breakthrough bacteremia is significantly more common 1
• Fluoroquinolones should be used cautiously due to risks of tendinopathy, peripheral neuropathy, and CNS effects 1
• Do not use piperacillin-tazobactam as a bolus or IM injection—must be infused over 30 minutes 5
• For patients not improving by day 2-3, reassess for alternative diagnoses or complications rather than automatically extending antibiotic duration 1

Renal Dosing Adjustments

Piperacillin-Tazobactam 5

• CrCl 20-40 mL/min: 2.25 grams every 6 hours (3.375 grams every 6 hours for nosocomial pneumonia)
• CrCl <20 mL/min: 2.25 grams every 8 hours (every 6 hours for nosocomial pneumonia)
• Hemodialysis: 2.25 grams every 8 hours plus 0.75 grams after each dialysis session

Azithromycin 4

• No adjustment needed for GFR >10 mL/min
• Exercise caution with GFR <10 mL/min (35% increase in AUC) 4