Empiric Treatment for Community-Acquired Pneumonia in Singapore
For hospitalized non-ICU patients in Singapore, initiate ceftriaxone 1–2 g IV daily plus azithromycin 500 mg daily immediately; for ICU patients, escalate to ceftriaxone 2 g IV daily plus azithromycin 500 mg IV daily, and add coverage for melioidosis (Pseudomonas pseudomallei) with ceftazidime or meropenem in endemic regions. 1, 2, 3
Outpatient Management
Previously Healthy Adults (No Comorbidities)
First-line: Amoxicillin 1 g orally three times daily for 5–7 days provides superior pneumococcal coverage (90–95% of Streptococcus pneumoniae isolates, including penicillin-resistant strains) compared with oral cephalosporins. 1
Alternative: Doxycycline 100 mg orally twice daily for 5–7 days covers both typical and atypical pathogens when amoxicillin is contraindicated. 1
Macrolide restriction: Azithromycin (500 mg day 1, then 250 mg daily) or clarithromycin (500 mg twice daily) should be used only when local pneumococcal macrolide resistance is documented <25%; in most regions resistance is 20–30%, making macrolide monotherapy unsafe. 1, 4
Adults with Comorbidities or Recent Antibiotic Use
Combination therapy: Amoxicillin-clavulanate 875/125 mg orally twice daily plus azithromycin (500 mg day 1, then 250 mg daily) or doxycycline 100 mg twice daily for 5–7 days achieves 91.5% favorable outcomes by covering typical bacteria and atypical pathogens. 1
Fluoroquinolone alternative: Levofloxacin 750 mg orally daily or moxifloxacin 400 mg orally daily for 5–7 days is reserved for β-lactam allergy or when combination therapy is contraindicated, given FDA warnings about serious adverse events (tendon rupture, peripheral neuropathy, aortic dissection). 1, 4
Inpatient Non-ICU Management
Standard Empiric Regimen
Preferred: Ceftriaxone 1–2 g IV once daily plus azithromycin 500 mg IV or orally daily provides coverage for typical pathogens (S. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis) and atypical organisms (Mycoplasma, Chlamydophila, Legionella). Strong recommendation, Level I evidence. 1, 5
Alternative β-lactams: Cefotaxime 1–2 g IV every 8 hours or ampicillin-sulbactam 3 g IV every 6 hours, each combined with azithromycin. 1
Fluoroquinolone monotherapy: Levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily is equally effective and preferred for penicillin-allergic patients. 1, 5
Singapore-Specific Considerations
Gram-negative predominance: Singapore data show gram-negative organisms (especially Klebsiella pneumoniae) account for 47% of severe CAP cases, supporting ceftriaxone as the preferred β-lactam over ampicillin-sulbactam. 2, 3
Melioidosis risk: Pseudomonas pseudomallei causes 7% of severe CAP in Singapore with 100% mortality when untreated; empiric coverage with ceftazidime 2 g IV every 8 hours or meropenem 1 g IV every 8 hours should be added for patients with diabetes, chronic kidney disease, or soil/water exposure. 2, 3
ICU Management (Severe CAP)
Mandatory Combination Therapy
Standard regimen: Ceftriaxone 2 g IV once daily plus azithromycin 500 mg IV daily or levofloxacin 750 mg IV daily. β-lactam monotherapy is linked to higher mortality in critically ill patients. Strong recommendation. 1, 5
Melioidosis coverage: Add ceftazidime 2 g IV every 8 hours or meropenem 1 g IV every 8 hours to the base regimen in endemic areas or when risk factors are present. 2, 3
Special Pathogen Coverage (Risk-Based)
Pseudomonas aeruginosa
Risk factors: Structural lung disease (bronchiectasis, cystic fibrosis), recent hospitalization with IV antibiotics (≤90 days), prior Pseudomonas isolation, chronic broad-spectrum antibiotic exposure (≥7 days in past month). 1
Regimen: Piperacillin-tazobactam 4.5 g IV every 6 hours or cefepime 2 g IV every 8 hours plus ciprofloxacin 400 mg IV every 8 hours or levofloxacin 750 mg IV daily plus gentamicin 5–7 mg/kg IV daily for dual antipseudomonal coverage. 1, 6
Methicillin-Resistant Staphylococcus aureus (MRSA)
Risk factors: Prior MRSA infection/colonization, recent hospitalization with IV antibiotics, post-influenza pneumonia, cavitary infiltrates on imaging. 1, 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 regimen. 1, 5
Special Populations
β-Lactam Allergy
Outpatient: Levofloxacin 750 mg orally daily or moxifloxacin 400 mg orally daily for 5–7 days. 7
Inpatient non-ICU: Levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily. For severe fluoroquinolone contraindications, aztreonam 2 g IV every 8 hours plus azithromycin 500 mg IV daily. 7
ICU: Aztreonam 2 g IV every 8 hours plus levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily. 7
Immunocompromised Patients
Outpatient: Levofloxacin 750 mg orally daily or moxifloxacin 400 mg orally daily; macrolide monotherapy is contraindicated. 1
Hospitalization threshold: Low threshold for admission when respiratory rate >24/min, SpO₂ <92%, inability to maintain oral intake, altered mental status, or unstable comorbidities. 1
Renal Impairment
Ceftriaxone: No dose adjustment required (dual hepatic-renal elimination). 1
Azithromycin: No dose adjustment required (biliary excretion). 1
Levofloxacin: Reduce to 750 mg loading dose, then 500 mg every 48 hours if CrCl 20–49 mL/min. 1
Pregnancy
Preferred: Ceftriaxone 1–2 g IV daily plus azithromycin 500 mg daily (both FDA Pregnancy Category B). 1
Avoid: Fluoroquinolones (FDA Pregnancy Category C; risk of cartilage damage), doxycycline (FDA Pregnancy Category D; risk of tooth discoloration). 1
Duration of Therapy
Minimum: 5 days, continuing until afebrile for 48–72 hours with no more than one sign of clinical instability (temperature ≤37.8°C, HR ≤100 bpm, RR ≤24/min, SBP ≥90 mmHg, SpO₂ ≥90% on room air, able to maintain oral intake, normal mental status). 1
Uncomplicated CAP: 5–7 days total. 1
Extended courses (14–21 days): Required only for Legionella pneumophila, Staphylococcus aureus, or gram-negative enteric bacilli. 1, 6
Transition to Oral Therapy
Criteria: Hemodynamically stable (SBP ≥90 mmHg, HR ≤100 bpm), clinically improving, afebrile 48–72 hours, RR ≤24/min, SpO₂ ≥90% on room air, able to take oral medication, normal GI function—typically by hospital day 2–3. 1
Oral step-down: Amoxicillin 1 g three times daily plus azithromycin 500 mg daily (or azithromycin alone after 2–3 days IV therapy). 1
Critical Pitfalls to Avoid
Never delay antibiotics: Administer the first dose in the emergency department immediately; delays >8 hours increase 30-day mortality by 20–30%. 1, 6
Avoid macrolide monotherapy: In hospitalized patients or areas where pneumococcal macrolide resistance exceeds 25%, macrolide monotherapy fails to cover typical pathogens and leads to treatment failure. 1, 4
Do not omit melioidosis coverage: In Singapore, P. pseudomallei causes 7% of severe CAP with 100% mortality when untreated; add ceftazidime or meropenem for at-risk patients. 2, 3
Restrict broad-spectrum agents: Add antipseudomonal or MRSA coverage only when documented risk factors are present to avoid unnecessary resistance and adverse effects. 1, 6
Obtain cultures before antibiotics: Blood and sputum cultures must be collected before the first dose in all hospitalized patients to enable pathogen-directed therapy. 1