Appropriateness of Antibiotic Combination Therapy for Severe Community-acquired Pneumonia in South Korea

Official title

Verification of Anti-pseudomonal Antibiotic Combination Therapy in Severe Community-acquired Pneumonia in South Korea: A Randomized-controlled Study

Overview

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.

Interventions

• Drug Piperacillin/Tazobactam
  Piperacillin/tazobactam: 4.5g IV q6h (over 3h)
• Drug Piperacillin/tazobactam + Levofloxacin
  Piperacillin/tazobactam: 4.5g IV q6h (over 3h) \+ Levofloxacin 750mg IV q24h (over 30min)

Primary outcome measures

• All-cause 28-day mortality [Time frame: 28 days]

Secondary outcome measures (6)

• Need for mechanical ventilation [Time frame: Up to hospital discharge or 28 days, whichever comes first]
• ICU admission rate [Time frame: Up to hospital discharge or 28 days, whichever comes first]
• Length of hospital stay [Time frame: Up to hospital discharge or 28 days, whichever comes first]
• Time to fever resolution [Time frame: Up to 7 days after treatment initiation]
• Antibiotic-related adverse events [Time frame: From first dose to 28 days post-treatment]
• 14-day hospital readmission rate [Time frame: 14 days after end of antibiotic treatment]

Eligibility criteria

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

South Korea · 1 center

• Hanyang University Seoul Hospital — Seoul

Identifiers

NCT: NCT06977347 · HYUH 2025-02-033-002

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗