This study aims to provide high-level evidence for appropriate empirical antibiotic use tailored to the clinical reality in Korea by conducting a randomized controlled trial comparing monotherapy with piperacillin/tazobactam and combination therapy with piperacillin/tazobactam plus a fluoroquinolone in patients with severe community-acquired pneumonia.

• Inclusion Criteria:

  • Adult patients aged 19 years or older who visited the emergency department and were hospitalized.

  • Findings consistent with pneumonia diagnosis, meeting all of the following criteria:

  • Radiologic evidence of pulmonary infiltration on chest X-ray or chest CT.

  • At least two or more of the following clinical signs:

    i) Body temperature ≥38°C or <36°C ii) White blood cell count ≥11,000/µL or <4,000/µL iii) Presence of purulent sputum or bronchial secretions

  • Within 24 hours of admission, the patient meets one major criterion or three minor criteria according to ATS/IDSA classification:

    • Major criteria:

      i) Invasive mechanical ventilation ii) Use of vasopressors (vasopressor-dependent septic shock)

    • Minor criteria:

      i) Respiratory rate ≥30 breaths/min ii) PaO2/FiO2 ≤ 250 iii) Multilobar infiltrates iv) Confusion or disorientation v) BUN ≥20 mg/dL vi) WBC <4,000/mm³ vii) Platelet count <100,000/mm³ viii) Hypothermia (temperature <36°C) ix) Hypotension requiring aggressive fluid resuscitation

• Exclusion Criteria:

  • Transferred from another hospital after >48 hours of hospitalization
  • Died within 72 hours of hospital admission
  • Transferred to another hospital within 14 days of admission
  • Pneumonia occurring after >48 hours of mechanical ventilation, including home ventilators
  • Detection of influenza or SARS-CoV-2 virus within 7 days of hospitalization
  • Identified non-pneumonia infection requiring antibiotics within 72 hours of admission
  • Detection of piperacillin/tazobactam-resistant Enterobacterales, Pseudomonas spp., or Acinetobacter spp. in respiratory or blood cultures within the past 90 days
  • Antibiotic-related adverse events observed within 72 hours of assigned treatment, requiring discontinuation or change of antibiotics

Individual participant data (IPD) will not be shared due to concerns regarding patient confidentiality and data protection, as well as the lack of a data-sharing infrastructure or formal data request mechanism at this time.