What is the recommended treatment for community-acquired pneumonia (CAP)?

Treatment of Community-Acquired Pneumonia

For hospitalized adults with community-acquired pneumonia without risk factors for resistant bacteria, use combination therapy with a β-lactam (ceftriaxone or cefotaxime) plus a macrolide (azithromycin or clarithromycin) for a minimum of 3 days. 1, 2, 3

Initial Site-of-Care Decision

The treatment setting should be determined using a three-step process 1:

• Step 1: Assess preexisting conditions that compromise safety of home care 1
• Step 2: Calculate the Pneumonia PORT Severity Index (PSI) with recommendation for home care for risk classes I, II, and III 1
• Step 3: Apply clinical judgment to finalize the decision 1

Outpatient Treatment Regimens

Previously Healthy Patients (No Recent Antibiotics)

• First-line: A macrolide (azithromycin or clarithromycin) or doxycycline 1, 2
• Amoxicillin at higher doses is an alternative 2

Previously Healthy Patients (Recent Antibiotic Use)

• Preferred: A respiratory fluoroquinolone (levofloxacin or moxifloxacin) alone 1, 2
• Alternative: An advanced macrolide plus high-dose amoxicillin or amoxicillin-clavulanate 1

Patients with Comorbidities

Comorbidities include COPD, diabetes, renal failure, congestive heart failure, or malignancy 1:

• No recent antibiotics: An advanced macrolide or a respiratory fluoroquinolone 1, 2
• Recent antibiotics: A respiratory fluoroquinolone alone or an advanced macrolide plus a β-lactam 1

Inpatient Treatment Regimens (Non-ICU)

Standard Medical Ward Patients

• Preferred regimen: A β-lactam (ceftriaxone, cefotaxime, ampicillin-sulbactam, or cefuroxime) plus a macrolide (azithromycin or clarithromycin) 1, 2
• Alternative: A respiratory fluoroquinolone (levofloxacin or moxifloxacin) alone 1
• Most patients can be adequately treated with oral antibiotics 1

Key evidence: The addition of a macrolide to a β-lactam is associated with decreased mortality and reduced length of stay compared to β-lactam monotherapy 4. This combination provides coverage for both typical bacteria (S. pneumoniae, H. influenzae) and atypical pathogens (Legionella, Mycoplasma, Chlamydophila) 1, 3.

Patients with Recent Antibiotic Therapy

• Select regimen based on the nature of recent antibiotic exposure 1
• If recent β-lactam use: Consider respiratory fluoroquinolone 1
• If recent fluoroquinolone use: Consider β-lactam plus macrolide 1

Inpatient Treatment Regimens (ICU/Severe CAP)

Without Pseudomonas Risk Factors

• Preferred: A β-lactam (ceftriaxone, cefotaxime, or ampicillin-sulbactam) plus either an advanced macrolide or a respiratory fluoroquinolone 1, 2
• For β-lactam allergy: A respiratory fluoroquinolone with or without clindamycin 1

With Pseudomonas Risk Factors

Risk factors include structural lung disease, recent hospitalization, or prior isolation of P. aeruginosa 1:

• Option 1: An antipseudomonal β-lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) plus ciprofloxacin or levofloxacin 750 mg 1
• Option 2: An antipseudomonal β-lactam plus an aminoglycoside (gentamicin, tobramycin, or amikacin) plus either a respiratory fluoroquinolone or azithromycin 1
• For β-lactam allergy: Aztreonam plus levofloxacin or aztreonam plus moxifloxacin/gatifloxacin with or without an aminoglycoside 1

With MRSA Risk Factors

• Add vancomycin or linezolid to the base regimen when MRSA is suspected or confirmed 1, 5

Special Clinical Situations

Suspected Aspiration with Infection

• Amoxicillin-clavulanate or clindamycin 1

Influenza with Bacterial Superinfection

• A β-lactam or respiratory fluoroquinolone 1
• Add oseltamivir for influenza treatment 1, 5

Nursing Home Patients

• Treated in nursing home: A respiratory fluoroquinolone alone or amoxicillin-clavulanate plus an advanced macrolide 1
• Hospitalized: Same regimens as for medical ward or ICU patients 1

Timing of Antibiotic Administration

The first antibiotic dose must be administered in the emergency department for hospitalized patients to reduce mortality 1, 5. Antibiotic treatment should be initiated immediately after diagnosis 1.

Switching from IV to Oral Therapy

Patients should be switched from intravenous to oral therapy when they meet all of the following criteria 1, 2, 5:

• Hemodynamically stable 1
• Clinically improving 1
• Able to ingest medications 1
• Normally functioning gastrointestinal tract 1

Patients should be discharged as soon as clinically stable with no other active medical problems and a safe environment for continued care 1. Inpatient observation while receiving oral therapy is not necessary 1.

Duration of Therapy

• Minimum duration: 5 days 1, 2
• Additional criteria before discontinuation: Patient must be afebrile for 48-72 hours and have no more than 1 CAP-associated sign of clinical instability 1, 2
• General recommendation: Treatment should not exceed 8 days in a responding patient 1
• Extended duration: 10-14 days for Legionella, Staphylococcus aureus, or Gram-negative enteric bacilli pneumonia 1

Pathogen-Directed Therapy

Once the etiology of CAP has been identified using reliable microbiological methods, antimicrobial therapy should be directed at that specific pathogen 1, 2. Changing to the most cost-effective, least toxic, and most narrow-spectrum agent is encouraged when culture results become available 1.

Common Pitfalls and Caveats

Diagnostic Testing

• All patients with CAP should be tested for COVID-19 and influenza when these viruses are common in the community 3
• Blood and sputum cultures should be obtained when expanded therapy for multidrug-resistant pathogens is initiated 1
• If cultures are negative and the patient is improving, expanded therapy should be narrowed within 48 hours 1

Resistance Considerations

• Only 38% of hospitalized CAP patients have a pathogen identified 3
• Up to 40% of identified pathogens are viruses 3
• S. pneumoniae accounts for approximately 15% of cases with identified etiology 3
• Multidrug-resistant S. pneumoniae (MDRSP) is defined as resistance to ≥2 of the following: penicillin (MIC ≥2 mcg/mL), second-generation cephalosporins, macrolides, tetracyclines, and trimethoprim/sulfamethoxazole 6

Failure to Respond

For patients who fail to improve within 3-5 days, consider 1:

• Incorrect diagnosis 1
• Host failure or immunosuppression 1
• Inappropriate antibiotic, dose, or route 1
• Unusual or unanticipated pathogen 1
• Adverse drug reaction 1
• Complications such as pulmonary superinfection or empyema 1

A careful review by an experienced clinician of the clinical history, examination, prescription chart, and all available investigation results should be performed 1.

Follow-Up Care

• Clinical review should be arranged at approximately 6 weeks with either the general practitioner or in a hospital clinic 1, 2
• A chest radiograph should be obtained at that time for patients with persistent symptoms, physical signs, or higher risk of underlying malignancy (especially smokers and those over 50 years) 1, 2