Antimicrobial Therapeutic Drug Monitoring During Lung Transplant Perioperative Phase

NCT06583642 | Not Yet Recruiting

• 1 other identifier: ATB_LuTx
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Post-LUTX pneumonia represents a leading cause of death along the first month after LUTX. Donor-derived transmission of pathogenic species occurs up to 25% of recipients receiving a graft with a positive BAL culture, despite in-vitro adequate antimicrobial prophylaxis. Hypothesis: LUTX recipients are either exposed to suboptimal antimicrobial doses or antimicrobial penetration into the lug parenchyma is altered either due to surgery (absence of bronchial anastomoses) or to the hyperinflammatory state. Methods: LUTX recipients admitted to the intensive care unit at the Fondazione IRCCS Ca' Granda Policlinico Hospital. According to the institutional perioperative prophylaxis protocol and the donor/recipient ecology the most frequent antimicrobial molecules administered will be: cefepime, vancomycin, and meropenem. Antimicrobial pharmacokinetics will be investigated at three timepoints. Plasma levels of the ongoing antimicrobial molecule will be assessed at ICU admission, on postoperative day 1 and on postoperative day 3. Bronchoalveolar lavage (BAL) samples for the measurement of BAL antimicrobial levels will be collected during the BAL performed for clinical indication on postoperative day 1 and on postoperative day 3. Absolute plasma and BAL antimicrobial levels will be assessed. The ratio of BAL to plasma dosage of antimicrobial will be assessed to evaluate antimicrobial penetration within the target tissue. Correlation between both plasma and BAL antimicrobial dosage and recipients' postoperative fluid balance, body weight, vasopressor requirement, renal function will be performed.

Conditions

Lung Transplant Infection; Pneumonia, Bacterial; Antibiotic Resistant Strain

Outcome Measures

Primary Outcomes (3)

• Plasma Antimicrobial Concentration

  Dosage of plasma levels of Cefepime or Meropenem or Vancomycin

  ICU admission after LuTX; 12 hours after LuTX; 72 hours after LuTX

• Bronchoalveolar Antimicrobial Concentration

  Dosage of bronchoalveolar levels of Cefepime or Meropenem or Vancomycin

  ICU admission after LuTX; 12 hours after LuTX; 72 hours after LuTX

• Antimicrobial lung tissue penetration

  Ratio of bronchoalveolar to plasma concentration of Cefepime or Meropenem or Vancomycin

  ICU admission after LuTX; 12 hours after LuTX; 72 hours after LuTX

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The study population will comprise adult patients undergone primary double lung transplant without pre-operative lung colonization, and undergoing perioperative antibiotic therapy with cefepime, or meropenem.

You may qualify if:

• Recipient of LUTX
• Age \> 18 years
• Signed informed consent

You may not qualify if:

• Age \< 18 years old
• Already undergone LUTX
• Documented respiratory colonization in the 12 months preceding LUTX
• Undergoing any antimicrobial therapy preceding LUTX
• Documented post-LUTX endobronchial plasma leak requiring high levels of PEEP \> 15 cmH2O.

Sponsors & Collaborators

• Policlinico Hospital: lead

Study Sites (1)

Fondazione IRCCS Ca'Granda - Ospedale Maggiore Policlinico

Milan, Milan, 20122, Italy

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples will be collected: at ICU admission, the first morning after LuTx and at 72h after LUTX. Each blood sample (4 mL) will be centrifuged, and plasma samples stored at -20°C until analysis; Bronchoalveolar lavage samples will be collected exclusively first morning after LuTx and at 72h after LUTX. Each BAL sample (4 mL) will be centrifuged, and supernatant samples stored at -20°C until analysis.

MeSH Terms

Conditions

Pneumonia, Bacterial

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Vittorio Scaravilli, MD

CONTACT

+39 02 5503 3275; vittorio.scaravilli@gmail.com

Jacopo Fumagalli, MD

CONTACT

+39 02 5503 3275; jacopo.fumagalli@live.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: September 1, 2024
• First Posted: September 4, 2024
• Study Start: July 1, 2025
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: May 22, 2025

Record last verified: 2025-05

Locations

IT (1)