Antimicrobial Therapeutic Drug Monitoring During Lung Transplant Perioperative Phase

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.