Recommended Antibiotic Regimens for Inpatient Treatment of Community-Acquired Pneumonia (CAP)
For inpatient treatment of community-acquired pneumonia (CAP), the recommended first-line regimens are either a β-lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam) plus a macrolide, or a respiratory fluoroquinolone alone. 1
Standard Treatment Regimens by Severity
Non-ICU Hospitalized Patients
Two equally effective options:
β-lactam plus macrolide combination:
Respiratory fluoroquinolone monotherapy:
ICU Hospitalized Patients
For severe CAP requiring ICU admission:
β-lactam plus either azithromycin or respiratory fluoroquinolone 1
- β-lactam options: cefotaxime, ceftriaxone, or ampicillin-sulbactam
- Plus: azithromycin or a respiratory fluoroquinolone (levofloxacin or moxifloxacin)
For penicillin-allergic patients: respiratory fluoroquinolone plus aztreonam 1
Special Considerations
Pseudomonas aeruginosa Risk Factors
If risk factors for P. aeruginosa are present (recent hospitalization, frequent/recent antibiotic use, severe lung disease, prior P. aeruginosa isolation):
- Antipseudomonal β-lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) plus either:
MRSA Risk Factors
If risk factors for methicillin-resistant Staphylococcus aureus (MRSA) are present:
- Add vancomycin or linezolid to standard regimen 1
- Obtain cultures and nasal PCR to allow de-escalation if negative 1
Evidence Supporting Recommendations
The combination of a β-lactam plus macrolide has shown excellent efficacy in multiple studies. A 2004 study demonstrated that ceftriaxone plus azithromycin achieved 91.5% favorable clinical outcomes in hospitalized patients with moderate to severe CAP 4. This combination was particularly effective against Streptococcus pneumoniae, with 100% eradication rates compared to 44% with levofloxacin 4.
A 2007 study confirmed that intravenous ceftriaxone plus intravenous azithromycin, followed by oral azithromycin, achieved clinical success rates of 84.3% in hospitalized CAP patients, including those with high severity scores 5.
A recent 2023 study suggests that ampicillin (with macrolide) may be comparable to ceftriaxone (with macrolide) for hospitalized CAP patients, with potentially lower rates of Clostridioides difficile infection 6. This supports considering narrower-spectrum options when appropriate.
Duration of Therapy
- Standard duration: 7-10 days for most patients 3
- Extended duration (14 days): For atypical pathogens like Legionella 3
- Extended duration (14-21 days): For Pseudomonas infections, slow clinical response, severe immunosuppression, or complicated pneumonia 3
Common Pitfalls to Avoid
- Inadequate initial coverage: Ensure coverage for both typical and atypical pathogens
- Delayed switch from IV to oral therapy: Transition to oral antibiotics when clinically stable (afebrile for 48-72 hours, normal vital signs, able to take oral medications)
- Inappropriate duration: Avoid unnecessarily prolonged courses
- Failure to recognize treatment failure: Consider treatment failure if no improvement after 72 hours
- Overuse of broad-spectrum antibiotics: De-escalate therapy based on culture results when available
Monitoring Response
- Monitor clinical response using body temperature, respiratory parameters, and hemodynamic stability
- Consider treatment failure if no improvement is seen after 72 hours
- Differentiate between non-responding pneumonia and slowly resolving pneumonia
The evidence strongly supports that combination therapy with a β-lactam and a macrolide or monotherapy with a respiratory fluoroquinolone are equally effective first-line options for hospitalized patients with CAP, with the choice depending on patient factors, local resistance patterns, and risk factors for specific pathogens.