What are the uses of different antibiotics in the treatment of pneumonia?

Antibiotic Selection in Pneumonia

The choice of antibiotics for pneumonia depends fundamentally on three factors: the setting of acquisition (community vs. hospital), disease severity, and specific risk factors for multidrug-resistant organisms (MDROs) or atypical pathogens.

Community-Acquired Pneumonia (CAP)

Outpatient Treatment - Low Severity

For previously healthy patients without recent antibiotic exposure, monotherapy with either a β-lactam (amoxicillin 500 mg-1g PO q8h) or a macrolide/tetracycline for suspected atypical pathogens is appropriate 1.

• Preferred β-lactam options: Amoxicillin, amoxicillin/clavulanate, or ampicillin/sulbactam for 5-7 days 1
• For atypical pathogens (Mycoplasma, Chlamydophila): Azithromycin 500 mg PO daily for 3-5 days, clarithromycin 500 mg PO q12h, or doxycycline 100 mg PO q12h 1

For patients with comorbidities or recent antibiotic use (within 3 months), combination therapy is essential: a β-lactam PLUS a macrolide, or alternatively a respiratory fluoroquinolone (moxifloxacin 400 mg PO daily or levofloxacin 500-750 mg PO daily) as monotherapy 1.

Hospitalized Patients - Moderate Severity (Non-ICU)

Combination therapy is the standard approach for hospitalized CAP patients to cover both typical and atypical pathogens 1.

• Preferred regimen: β-lactam (amoxicillin/clavulanate 1.2g IV q8h, ampicillin/sulbactam 1.5-3g IV q6h, ceftriaxone 2g IV daily, or cefotaxime 1-2g IV q8h) PLUS a macrolide (azithromycin 500 mg or clarithromycin 500 mg q12h) 1
• Alternative monotherapy: Respiratory fluoroquinolone (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) 1
• Duration: 5-7 days for most cases; treatment should generally not exceed 8 days in responding patients 1

Severe CAP Requiring ICU Admission

All severe CAP patients require immediate parenteral combination therapy with broad-spectrum coverage 1.

Without Pseudomonas risk factors:

• Preferred: Non-antipseudomonal cephalosporin III (ceftriaxone or cefotaxime) PLUS macrolide 1
• Alternative: Moxifloxacin or levofloxacin ± non-antipseudomonal cephalosporin III 1

With Pseudomonas risk factors (recent hospitalization, frequent antibiotic use >4 courses/year, severe COPD with FEV1 <30%, oral steroid use >10mg prednisolone daily):

• Antipseudomonal β-lactam (piperacillin-tazobactam, cefepime, ceftazidime, or carbapenem) PLUS ciprofloxacin OR PLUS macrolide + aminoglycoside (gentamicin, tobramycin, or amikacin) 1
• Duration: 7 days minimum; extend to 14-21 days for Legionella, Staphylococcus aureus, or gram-negative enteric bacilli 1

Hospital-Acquired Pneumonia (HAP)

Low Mortality Risk, No MRSA Risk Factors

Monotherapy with an antipseudomonal agent is sufficient 1:

• Piperacillin-tazobactam 4.5g IV q6h, cefepime 2g IV q8h, levofloxacin 750 mg IV daily, imipenem 500 mg IV q6h, or meropenem 1g IV q8h 1

MRSA Risk Factors Present (IV antibiotics in prior 90 days, MRSA prevalence >20% or unknown)

Add MRSA coverage to the antipseudomonal regimen 1:

• Preferred MRSA agents: Vancomycin 15 mg/kg IV q8-12h (target trough 15-20 mg/mL) OR linezolid 600 mg IV q12h 1
• Base regimen: Same antipseudomonal options as above 1

High Mortality Risk or Recent IV Antibiotics

Dual antipseudomonal coverage PLUS MRSA coverage is required 1:

• Two agents from different classes (avoid two β-lactams): antipseudomonal β-lactam PLUS fluoroquinolone (ciprofloxacin 400 mg IV q8h or levofloxacin 750 mg IV daily) OR aminoglycoside (amikacin 15-20 mg/kg IV daily, gentamicin 5-7 mg/kg IV daily, or tobramycin 5-7 mg/kg IV daily) 1
• PLUS: Vancomycin or linezolid for MRSA coverage 1

Pathogen-Specific Therapy

Streptococcus pneumoniae

• Penicillin MIC <2: Penicillin G 2-3 MU IV q4h, amoxicillin 1g PO q8h, or ceftriaxone 1-2g IV q12h 1
• Penicillin MIC ≥2: Base on susceptibility testing; options include high-dose amoxicillin (3g/day), ceftriaxone, cefotaxime, or respiratory fluoroquinolones 1

Methicillin-Susceptible S. aureus (MSSA)

• Preferred: Oxacillin 2g IV q4-6h or cefazolin 2g IV q8h 1
• Alternatives: Amoxicillin/clavulanate, levofloxacin, or vancomycin 1

Methicillin-Resistant S. aureus (MRSA)

• Preferred: Vancomycin 15-20 mg/kg IV q8-12h ± rifampicin OR linezolid 600 mg PO/IV q12h 1

Atypical Pathogens

Mycoplasma pneumoniae:

• Preferred: Doxycycline 100 mg IV/PO q12h for 7-14 days 1
• Alternatives: Azithromycin, levofloxacin 750 mg daily, or moxifloxacin 400 mg daily 1

Legionella species:

• Preferred: Levofloxacin 750 mg IV/PO daily or moxifloxacin 400 mg IV/PO daily 1
• Alternative: Azithromycin 1000 mg IV day 1, then 500 mg IV/PO daily ± rifampicin 1

Chlamydophila pneumoniae:

• Preferred: Azithromycin 500 mg PO day 1, then 250 mg daily for 4 days 1
• Alternatives: Doxycycline, levofloxacin, or moxifloxacin 1

Critical Management Principles

Timing of Antibiotic Administration

Antibiotics must be initiated immediately after pneumonia diagnosis, particularly in patients with septic shock 1. In severe CAP, parenteral antibiotics should be administered without delay 1.

IV to Oral Conversion

Switch to oral therapy when clinical stability is achieved: temperature ≤37.8°C, heart rate ≤100 bpm, respiratory rate ≤24 breaths/min, systolic BP ≥90 mmHg, oxygen saturation ≥90%, and ability to maintain oral intake 1. This transition is safe even in severe pneumonia once stability is reached 1.

Common Pitfalls

• Avoid fluoroquinolone monotherapy in patients at risk for QT prolongation (known QT prolongation, torsades de pointes history, congenital long QT syndrome, bradyarrhythmias, uncompensated heart failure, or concurrent Class IA/III antiarrhythmics) 2
• Do not use azithromycin in patients with severe penicillin allergy requiring aztreonam, as MSSA coverage must be maintained 1
• Recognize that piperacillin-tazobactam is a risk factor for renal failure in critically ill patients (odds ratio 1.7) and may delay renal recovery 3
• For Pseudomonas pneumonia, consider dual antipseudomonal therapy initially to reduce treatment failure, then de-escalate to monotherapy once susceptibilities are available 1