What is the recommended treatment for pneumonia?

Treatment for Pneumonia

For outpatient pneumonia without comorbidities, amoxicillin 1 g three times daily for 5-7 days is the preferred first-line therapy, while hospitalized non-ICU patients should receive ceftriaxone 1-2 g IV daily plus azithromycin 500 mg daily, and ICU patients require mandatory combination therapy with a β-lactam plus either azithromycin or a respiratory fluoroquinolone. 1

Outpatient Treatment Algorithm

Previously Healthy Adults Without Comorbidities

• Amoxicillin 1 g orally three times daily for 5-7 days is the preferred first-line agent, providing excellent coverage against Streptococcus pneumoniae including drug-resistant strains 1
• Doxycycline 100 mg orally twice daily serves as an acceptable alternative for patients who cannot tolerate amoxicillin 1
• Macrolides (azithromycin 500 mg day 1, then 250 mg daily for days 2-5; or clarithromycin 500 mg twice daily) should ONLY be used when local pneumococcal macrolide resistance is documented <25% 1, 2

Adults With Comorbidities (COPD, Diabetes, Heart/Liver/Renal Disease)

• Combination therapy is required: β-lactam (amoxicillin-clavulanate 875/125 mg twice daily, cefpodoxime, or cefuroxime) PLUS macrolide (azithromycin or clarithromycin) OR doxycycline 1
• Alternative: Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg daily, moxifloxacin 400 mg daily, or gemifloxacin 320 mg daily) 1, 3

Hospitalized Non-ICU Patients

Two equally effective regimens exist with strong evidence 1:

Preferred Regimen

• Ceftriaxone 1-2 g IV daily PLUS azithromycin 500 mg IV or oral daily 1, 2
• Alternative β-lactams: cefotaxime 1-2 g IV every 8 hours OR ampicillin-sulbactam 3 g IV every 6 hours, always combined with azithromycin 4

Alternative Regimen

• Respiratory fluoroquinolone monotherapy: levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily 1, 3
• This option is preferred for penicillin-allergic patients 1

For Penicillin-Allergic Patients

• Respiratory fluoroquinolone is the preferred alternative 1
• If fluoroquinolone contraindication exists: aztreonam 2 g IV every 8 hours PLUS azithromycin 500 mg IV daily 1

Severe CAP Requiring ICU Admission

Combination therapy is MANDATORY for all ICU patients—monotherapy is inadequate and associated with higher mortality 1:

Standard ICU Regimen

• Ceftriaxone 2 g IV daily (or cefotaxime 1-2 g IV every 8 hours or ampicillin-sulbactam 3 g IV every 6 hours) PLUS azithromycin 500 mg IV daily 1, 2
• Alternative: β-lactam PLUS respiratory fluoroquinolone (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) 1, 3

Risk Factors for Pseudomonas aeruginosa

Add antipseudomonal coverage ONLY when these specific risk factors are present 1:

• Structural lung disease (bronchiectasis, cystic fibrosis)
• Recent hospitalization with IV antibiotics within 90 days
• Prior respiratory isolation of P. aeruginosa

Antipseudomonal regimen: Antipseudomonal β-lactam (piperacillin-tazobactam 4.5 g IV every 6 hours, cefepime 2 g IV every 8 hours, imipenem, or meropenem) PLUS ciprofloxacin 400 mg IV every 8 hours OR levofloxacin 750 mg IV daily PLUS aminoglycoside (gentamicin or tobramycin 5-7 mg/kg IV daily) PLUS azithromycin 4, 1

Risk Factors for MRSA

Add MRSA coverage ONLY when these specific risk factors are present 1:

• Prior MRSA infection or colonization
• Recent hospitalization with IV antibiotics
• Post-influenza pneumonia
• Cavitary infiltrates on imaging

MRSA regimen: Add vancomycin 15 mg/kg IV every 8-12 hours (target trough 15-20 mg/mL) OR linezolid 600 mg IV every 12 hours to the base regimen 1

Duration of Therapy

• Minimum of 5 days AND until afebrile for 48-72 hours with no more than one sign of clinical instability 1
• Typical duration for uncomplicated CAP: 5-7 days 1
• Extended duration (14-21 days) required for: Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli 1

Clinical Stability Criteria Before Discontinuation

• Temperature ≤37.8°C
• Heart rate ≤100 beats/min
• Respiratory rate ≤24 breaths/min
• Systolic blood pressure ≥90 mmHg
• Oxygen saturation ≥90% on room air
• Ability to maintain oral intake
• Normal mental status 1

Transition to Oral Therapy

Switch from IV to oral antibiotics when 1:

• Hemodynamically stable
• Clinically improving
• Able to ingest medications
• Normal gastrointestinal function
• Typically achievable by day 2-3 of hospitalization 1

Oral Step-Down Options

• Amoxicillin 1 g orally three times daily (preferred oral β-lactam) 1
• Amoxicillin-clavulanate 875/125 mg orally twice daily 1
• Continue azithromycin 500 mg orally daily if already started 1, 2
• Levofloxacin 750 mg orally once daily (for penicillin-allergic patients) 1, 3
• Doxycycline 100 mg orally twice daily alone is sufficient once clinical stability is achieved 1

Special Populations

Aspiration Pneumonia

Hospital ward, admitted from home 4:

• Oral or IV β-lactam/β-lactamase inhibitor (amoxicillin-clavulanate or ampicillin-sulbactam)
• OR clindamycin
• OR IV cephalosporin plus oral metronidazole
• OR moxifloxacin

ICU or admitted from nursing home 4:

• Clindamycin plus cephalosporin

Pregnant Women

• Combination of β-lactam (amoxicillin or ceftriaxone) plus macrolide (azithromycin preferred over clarithromycin) 5
• Azithromycin is the preferred macrolide in pregnancy because it did not produce birth defects in animal studies, whereas clarithromycin showed increased risk 5
• Avoid fluoroquinolones during pregnancy unless benefits outweigh risks 5
• Avoid doxycycline during pregnancy due to hepatotoxicity and fetal teeth/bone staining 5
• Treatment duration: 7-10 days for non-severe cases, 10-14 days for severe cases 5
• Monitor for preterm labor after 20 weeks gestation, as pneumonia increases risk of preterm delivery 5

Elderly or Debilitated Patients

• Lower threshold for hospitalization using PSI score 1
• Combination therapy or fluoroquinolone monotherapy even in outpatient setting 1
• Elderly patients may be more susceptible to QT prolongation with azithromycin 2

Patients with COPD or Asthma

• Require combination therapy even in outpatient setting due to increased risk of Pseudomonas aeruginosa and resistant pathogens 4
• Consider viral etiologies (influenza, RSV) more prominently in asthma patients during respiratory virus season 4

Critical Timing Considerations

• Administer the first antibiotic dose IMMEDIATELY upon diagnosis, ideally while still in the emergency department 1
• Delayed administration beyond 8 hours increases 30-day mortality by 20-30% in hospitalized patients 1

Diagnostic Testing for Hospitalized Patients

Obtain BEFORE initiating antibiotics 1:

• Blood cultures (two sets)
• Sputum Gram stain and culture
• Urinary antigen testing for Legionella pneumophila serogroup 1 (in severe CAP or ICU patients)

Management of Treatment Failure

Non-Responding Pneumonia (First 72 Hours)

Usually due to antimicrobial resistance, unusually virulent organism, host defense defect, or wrong diagnosis 4:

• Obtain repeat chest radiograph, CRP, white cell count, and additional microbiological specimens 1
• Consider chest CT to evaluate for complications (pleural effusion, lung abscess, central airway obstruction) 1
• Full reinvestigation followed by second empirical antimicrobial regimen in unstable patients 4

Treatment Failure After 72 Hours

Usually due to complications 4:

• For non-severe pneumonia initially on amoxicillin monotherapy: add or substitute macrolide 1
• For non-severe pneumonia on combination therapy: switch to respiratory fluoroquinolone 1
• For severe pneumonia not responding to combination therapy: consider adding rifampicin 1

Follow-Up and Monitoring

• Clinical review at 48 hours or sooner if clinically indicated for outpatients 1
• Scheduled clinical review at 6 weeks for all hospitalized patients 1
• Chest radiograph at 6 weeks ONLY for patients with persistent symptoms, physical signs, or high risk for underlying malignancy (smokers, age >50 years) 1
• Chest radiograph NOT required before hospital discharge in patients with satisfactory clinical recovery 1

Prevention Strategies

• Pneumococcal vaccination: 20-valent pneumococcal conjugate vaccine alone OR 15-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal polysaccharide vaccine one year later for all patients ≥65 years and those with high-risk conditions 1
• Annual influenza vaccination for all patients, especially those with medical illnesses and healthcare workers 1
• Smoking cessation as a goal for all patients hospitalized with CAP who smoke 1

Critical Pitfalls to Avoid

• NEVER use macrolide monotherapy in hospitalized patients—provides inadequate coverage for typical bacterial pathogens like S. pneumoniae 1
• NEVER use macrolide monotherapy in areas where pneumococcal macrolide resistance exceeds 25%—leads to treatment failure 1, 2
• NEVER delay antibiotic administration beyond 8 hours—increases mortality 1
• NEVER automatically escalate to broad-spectrum antibiotics based solely on immunosuppression without documented risk factors for Pseudomonas or MRSA 1
• NEVER extend therapy beyond 7-8 days in responding patients without specific indications—increases antimicrobial resistance risk without improving outcomes 1
• NEVER use oral cephalosporins (cefuroxime, cefpodoxime) as first-line oral agents—inferior in vitro activity compared to high-dose amoxicillin 1
• NEVER use standard-dose amoxicillin (500 mg three times daily)—insufficient pneumococcal coverage against resistant strains; use high-dose regimen (1 g three times daily) 1
• Avoid indiscriminate fluoroquinolone use in uncomplicated outpatient CAP due to FDA warnings about serious adverse events (tendon rupture, peripheral neuropathy, CNS effects) and resistance concerns 1, 3
• Consider QT prolongation risk with azithromycin in patients with known QT prolongation, torsades de pointes history, congenital long QT syndrome, bradyarrhythmias, uncompensated heart failure, or concurrent QT-prolonging drugs 2

Additional Supportive Therapies

• Early mobilization for all patients 4
• Low molecular weight heparin in patients with acute respiratory failure 4
• Non-invasive ventilation can be considered, particularly in patients with COPD and ARDS 4
• Oxygen therapy targeting PaO₂ >8 kPa (60 mmHg) and SaO₂ >92% 1
• Steroids are NOT recommended in the treatment of pneumonia 4