What first‑line antibiotic, dose, frequency, and duration does TG 18 recommend for uncomplicated community‑acquired pneumonia in an adult, and how should it be modified for a penicillin‑allergic patient or for renal impairment?

TG 18 Guidelines for Community-Acquired Pneumonia

First-Line Antibiotic Regimen for Uncomplicated CAP in Adults

For hospitalized adults with uncomplicated community-acquired pneumonia, TG 18 (the 2018 Tokyo Guidelines) does not provide specific recommendations, as these guidelines focus on acute cholangitis and cholecystitis, not pneumonia. However, based on the most authoritative current evidence for CAP management:

Standard Hospitalized Non-ICU Patients

• Ceftriaxone 1–2 g IV once daily plus azithromycin 500 mg daily is the preferred first-line regimen, providing comprehensive coverage of typical bacterial pathogens (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis) and atypical organisms (Mycoplasma, Chlamydophila, Legionella). 1
• Alternative β-lactams include cefotaxime 1–2 g IV every 8 hours or ampicillin-sulbactam 3 g IV every 6 hours, always combined with azithromycin. 1
• Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) is equally effective but should be reserved for penicillin-allergic patients due to FDA safety warnings. 1

Previously Healthy Outpatients

• Amoxicillin 1 g orally three times daily for 5–7 days retains activity against 90–95% of S. pneumoniae isolates, including many penicillin-resistant strains. 1
• Doxycycline 100 mg orally twice daily is an acceptable alternative. 1
• Macrolides should only be used when local pneumococcal macrolide resistance is documented < 25%; in most U.S. regions resistance is 20–30%, making macrolide monotherapy unsafe. 1

Outpatients with Comorbidities

• Amoxicillin-clavulanate 875/125 mg orally twice daily plus azithromycin (500 mg day 1, then 250 mg daily) provides comprehensive coverage for patients with COPD, diabetes, chronic organ disease, or recent antibiotic use. 1

Modifications for Penicillin Allergy

Non-ICU Hospitalized Patients

• Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) is the preferred alternative for penicillin-allergic patients. 1
• Both agents require no renal dose adjustment and provide coverage of typical and atypical pathogens. 1

ICU Patients with Penicillin Allergy

• Aztreonam 2 g IV every 8 hours plus levofloxacin 750 mg IV daily provides dual coverage against pneumococcal and gram-negative pathogens when β-lactams are contraindicated. 1
• For severe penicillin allergy with ICU-level severity, aztreonam plus a respiratory fluoroquinolone ensures adequate pathogen coverage. 1

Outpatients with Penicillin Allergy

• Levofloxacin 750 mg orally once daily or moxifloxacin 400 mg orally once daily for 5–7 days is appropriate for outpatients who cannot tolerate β-lactams. 1
• Doxycycline 100 mg orally twice daily is an alternative that avoids fluoroquinolone use. 1

Renal Dose Adjustments

Ceftriaxone

• No dose adjustment required for any degree of renal impairment, as ceftriaxone undergoes dual hepatic-renal elimination. 1
• Standard dosing of 1–2 g IV once daily applies even in patients with creatinine clearance < 30 mL/min. 1

Azithromycin

• No dose adjustment required for renal impairment, as azithromycin is eliminated primarily via biliary excretion. 1
• Standard dosing of 500 mg daily (IV or oral) applies across all renal function levels. 1

Levofloxacin

• Dose adjustment required for moderate-to-severe renal impairment:
  • CrCl 50–80 mL/min: no adjustment needed (750 mg daily)
  • CrCl 20–49 mL/min: 750 mg loading dose, then 500 mg every 48 hours
  • CrCl 10–19 mL/min: 750 mg loading dose, then 500 mg every 48 hours
  • Hemodialysis: 750 mg loading dose, then 500 mg every 48 hours 1

Moxifloxacin

• No dose adjustment required for renal impairment; standard dosing of 400 mg IV or orally once daily applies. 1

Amoxicillin and Amoxicillin-Clavulanate

• Dose adjustment required for severe renal impairment:
  • CrCl > 30 mL/min: no adjustment (standard dosing)
  • CrCl 10–30 mL/min: reduce frequency to every 12 hours
  • CrCl < 10 mL/min: reduce frequency to every 24 hours 1

Duration of Therapy

• Minimum treatment duration is 5 days, continuing until the patient is afebrile for 48–72 hours with no more than one sign of clinical instability. 1
• Typical duration for uncomplicated CAP is 5–7 days. 1
• Extended courses of 14–21 days are required only for infections caused by Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli. 1

Transition to Oral Therapy

• Switch from IV to oral antibiotics when the patient is 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, and able to take oral medication—typically by hospital day 2–3. 1
• Oral step-down options include amoxicillin 1 g three times daily plus azithromycin 500 mg daily. 1

Critical Timing and Pitfalls

• Administer the first antibiotic dose immediately in the emergency department; delays beyond 8 hours increase 30-day mortality by 20–30%. 1
• Obtain blood cultures and sputum Gram stain/culture before initiating antibiotics in all hospitalized patients to enable pathogen-directed therapy. 1
• Never use macrolide monotherapy in hospitalized patients, as it fails to cover typical pathogens such as S. pneumoniae and leads to treatment failure. 1
• 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