Intravenous polymyxin B and colistin for carbapenem-resistant gram-negative infections

A Retrospective, Observational, Post-Marketing Study to Assess the Efficacy and Safety of Intravenous Infusions Polymyxin B and Colistin Methanesulfonate in Patients With Carbapenem-Resistant Gram-Negative Bacterial Infection

This study looks to see how well intravenous polymyxin B and colistin work and how safe they are in adults with carbapenem-resistant gram-negative bloodstream or lung infections.

Quick facts

• Study type: Observational
• Enrollment: 480 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: TTY Biopharm (industry)
• Locations: 1 site (Taipei)
• Trial ID: NCT06966284 on ClinicalTrials.gov

What this trial studies

This is a retrospective, observational post-marketing review of adult patients treated with intravenous polymyxin B or colistin methanesulfonate for carbapenem-resistant gram-negative bacterial infections at Tri-Service General Hospital in Taipei. Investigators will extract clinical and microbiological response, mortality, and safety outcomes, with particular attention to renal adverse events. Planned subgroup analyses will compare outcomes by site of infection (bacteremia versus hospital- or ventilator-associated pneumonia), causative pathogen, and baseline renal function. No experimental interventions are administered; the study analyzes existing medical records of treated patients.

Who should consider this trial

Good fit: Adults (age ≥18) who had bacteremia or hospital-acquired/ventilator-associated pneumonia or other serious non-UTI infections caused by carbapenem-resistant gram-negative bacteria and who received intravenous polymyxin B or colistin are ideal candidates.

Not a fit: Patients with urinary tract infections (excluded from this protocol), children under 18, or infections not caused by carbapenem-resistant gram-negative organisms are unlikely to be represented or benefit from this study's findings.

Why it matters

Potential benefit: If successful, the results could provide real-world evidence on effectiveness and safety to help clinicians choose and dose polymyxin B or colistin for carbapenem-resistant gram-negative infections.

How similar studies have performed: Previous observational and cohort studies of polymyxins for carbapenem-resistant gram-negative infections exist and report mixed effectiveness with a consistent risk of nephrotoxicity, so this work adds additional real-world outcome data rather than introducing a novel therapy.

Eligibility criteria

Inclusion Criteria:

1. Patient ≥ 18 years of age.
2. Patient diagnosed with bacterial pneumonia and/or bacteremia, or other physician judged serious infection (except urinary tract infection, UTI) caused by Carbapenem-Resistant Gram-Negative Bacteria (CR-GNB).

   CR-GNB: Resistant to at least one of the carbapenem antibiotics or produce a carbapenemase (an enzyme that can make them resistant to carbapenem antibiotics).

   Diagnosis Criteria of HABP/VABP:

   • Met the clinical diagnosis criteria for HABP/VABP. HABP: Acute bacterial pneumonia in a subject hospitalized for more than 48 hours or developing within 7 days after discharge from a hospital. Subject could have experienced acute respiratory failure and required mechanical ventilation for HABP.

   VABP: Acute bacterial pneumonia in a subject receiving mechanical ventilation via an endotracheal (or nasotracheal) tube for a minimum of 48 hours.
   * ≥ 1 of the following clinical features: new onset or worsening of pulmonary symptoms or signs, hypoxemia, need for acute changes in the ventilator support system to enhance oxygenation, new onset of or increase in suctioned respiratory secretions.
   * ≥ 1 of the following signs: documented fever, hypothermia, WBC ≥ 10,000 cells/mm3, WBC ≤ 4500 cells/mm3, \>15% immature neutrophils(bands)
   * CXR or lung CT: presence of new or progressive infiltrates suggestive of bacterial pneumonia.

   Diagnosis Criteria of BSI/Bacteremia: the BSI/sepsis category included bacteremia or sepsis caused by infections other than HABP/VABP, or UTI:
   * Documented BSI caused by a carbapenem-resistant Gram-negative pathogen; or
   * Systemic response to infection, meeting the clinical criteria of SIRS and an identified infection source (eg, severe skin infection, intra-abdominal infection) caused by a carbapenem-resistant Gram-negative pathogen.
3. Patient received intravenous polymyxin B or CMS treatment for ≥72 h.
4. Administration of polymyxin B or CMS within 7 days from the infection onset day.

Infection onset day: The date of specimen collection for index pathogen.

Exclusion Criteria:

1. Patient with bacteremia caused by urinary tract infection.
2. CR-GNB known to be resistant to polymyxin B or CMS.
3. Patient has infectious disease (s) caused by the following gram-negative bacteria which are known to have no response to polymyxin B and/or colistin treatment: Proteus spp., Providencia spp., Morganella spp., Serratia marcescens, Burkholderia spp., and Neisseria spp.
4. Intravenous administration of polymyxin B or colistin more than 28 days.
5. Both the treatment efficacy and safety could not be evaluated.

Where this trial is running

Taipei

• Tri-Service General Hospital — Taipei, Taiwan (RECRUITING)

Study contacts

• Study coordinator: Angel Chen

Conditions: Bacteremia Caused by Gram-Negative Bacteria, Bacterial Pneumonia, polymyxin B sulfate