IDSA Guidelines for Community-Acquired Pneumonia Antibiotic Therapy
Outpatient Treatment
Previously Healthy Adults Without Comorbidities
Amoxicillin 1 g orally three times daily for 5–7 days is the preferred first-line therapy, providing superior pneumococcal coverage against 90–95% of Streptococcus pneumoniae isolates, including many penicillin-resistant strains 1.
- Doxycycline 100 mg orally twice daily serves as an acceptable alternative when amoxicillin is contraindicated 1.
- Macrolide monotherapy (azithromycin or clarithromycin) should only be used when local pneumococcal macrolide resistance is documented to be <25%; in most U.S. regions resistance is 20–30%, making macrolides unsafe as first-line agents 1, 2.
Adults With Comorbidities or Recent Antibiotic Use
Combination therapy is required for patients with chronic heart, lung, liver, or renal disease, diabetes, alcoholism, malignancy, asplenia, immunosuppression, or antibiotic use within 90 days 1, 3.
- Option 1 – Combination regimen: β-lactam (amoxicillin-clavulanate 875/125 mg twice daily, cefpodoxime, or cefuroxime) plus macrolide (azithromycin or clarithromycin) or doxycycline 100 mg twice daily 1.
- Option 2 – Respiratory fluoroquinolone monotherapy: levofloxacin 750 mg daily or moxifloxacin 400 mg daily for 5–7 days, reserved for β-lactam allergy or contraindications to macrolides 1, 2.
Inpatient Non-ICU Treatment
Two equally effective regimens exist with strong recommendations and high-quality evidence 1:
Preferred Regimen
Ceftriaxone 1–2 g IV once daily plus azithromycin 500 mg IV or orally daily, providing comprehensive coverage for typical pathogens (S. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis) and atypical organisms (Mycoplasma, Chlamydophila, Legionella) 1, 4, 3.
- Alternative β-lactams include cefotaxime 1–2 g IV every 8 hours or ampicillin-sulbactam 3 g IV every 6 hours, always combined with a macrolide 1.
Alternative Regimen
Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) is equally effective and associated with fewer clinical failures compared to β-lactam/macrolide combinations 1.
Critical Timing
Administer the first antibiotic dose in the emergency department immediately upon diagnosis; delays beyond 8 hours increase 30-day mortality by 20–30% 1, 2.
ICU Treatment (Severe CAP)
Combination therapy is mandatory for all ICU patients; β-lactam monotherapy is associated with higher mortality in critically ill patients with bacteremic pneumococcal pneumonia 1, 2.
Standard ICU Regimen
Ceftriaxone 2 g IV once 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, 3.
- Alternative: β-lactam plus respiratory fluoroquinolone (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) 1, 2.
Penicillin-Allergic ICU Patients
Aztreonam 2 g IV every 8 hours plus respiratory fluoroquinolone (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) 1.
Special Pathogen Coverage (Risk Factor–Based)
Pseudomonas aeruginosa Coverage
Add antipseudomonal therapy only when specific risk factors are present: structural lung disease (bronchiectasis, cystic fibrosis), recent hospitalization with IV antibiotics within 90 days, prior respiratory isolation of P. aeruginosa, or chronic broad-spectrum antibiotic exposure ≥7 days in the past month 1, 5.
- Regimen: Antipseudomonal β-lactam (piperacillin-tazobactam 4.5 g IV every 6 hours or cefepime 2 g IV every 8 hours or carbapenem) 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) for dual coverage 1, 2.
MRSA Coverage
Add MRSA therapy only when risk factors are present: prior MRSA infection/colonization, recent hospitalization with IV antibiotics, post-influenza pneumonia, or cavitary infiltrates on imaging 1, 2, 5.
- Regimen: Vancomycin 15 mg/kg IV every 8–12 hours (target trough 15–20 µg/mL) or linezolid 600 mg IV every 12 hours, added to the base CAP regimen 1, 2.
Duration of Therapy
Treat for a minimum of 5 days and continue until the patient is afebrile for 48–72 hours with no more than one sign of clinical instability 1, 4, 3.
- Typical duration for uncomplicated CAP: 5–7 days 1, 2.
- Extended duration (14–21 days) is required only for Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli 1, 4, 3.
Transition to Oral Therapy
Switch from IV to oral antibiotics when the patient meets all clinical stability criteria: hemodynamically stable (systolic BP ≥90 mmHg, heart rate ≤100 bpm), clinically improving, afebrile for 48–72 hours, respiratory rate ≤24 breaths/min, oxygen saturation ≥90% on room air, able to take oral medications, and normal GI function—typically by hospital day 2–3 1, 3.
- Oral step-down options include amoxicillin 1 g three times daily plus azithromycin 500 mg daily 1.
Diagnostic Testing
Obtain blood cultures and sputum Gram stain/culture before initiating antibiotics in all hospitalized patients to enable pathogen-directed therapy and safe de-escalation 1, 4, 3, 6.
- Urinary antigen testing for Legionella pneumophila serogroup 1 should be considered in severe CAP or ICU patients 1.
Critical Pitfalls to Avoid
- Never use macrolide monotherapy in hospitalized patients; it fails to cover typical pathogens such as S. pneumoniae and leads to treatment failure 1, 3.
- Avoid macrolide monotherapy in outpatients when local pneumococcal macrolide resistance exceeds 25%; this increases risk of breakthrough bacteremia 1, 2.
- Do not add broad-spectrum antipseudomonal or MRSA agents routinely; restrict to patients with documented risk factors to prevent resistance without clinical benefit 1, 5.
- Do not delay antibiotic administration beyond 8 hours; this increases 30-day mortality by 20–30% in hospitalized patients 1, 2.
- Avoid indiscriminate fluoroquinolone use in uncomplicated outpatient CAP due to FDA warnings about serious adverse events (tendon rupture, peripheral neuropathy, aortic dissection) and rising resistance 1.
Follow-Up and Prevention
- Clinical review at 48 hours (or sooner if symptoms worsen) for outpatients to assess response, oral intake, and adherence 1.
- Routine follow-up at 6 weeks for all patients; chest radiograph only for those with persistent symptoms, abnormal physical findings, or high risk for underlying malignancy (smokers >50 years) 1.
- Pneumococcal polysaccharide vaccine for all adults ≥65 years and those with high-risk conditions 1, 2.
- Annual influenza vaccination for all patients 1, 2.
- Smoking cessation counseling for all current smokers 1.