Antimicrobial Drug Penetration Is Enhanced by Lung Tissue Inflammation and Injury.

Rationale: Pneumonia is a frequent and feared complication in intubated critically ill patients. Tissue concentrations of antimicrobial drugs need to be sufficiently high to treat the infection and also prevent development of bacterial resistance. It is uncertain whether pulmonary inflammation and injury affect antimicrobial drug penetration into lung tissue.Objectives: To determine and compare tissue and BAL fluid concentrations of ceftaroline fosamil and linezolid in a model of unilateral acute lung injury in pigs and to evaluate whether dose adjustment is necessary to reach sufficient antimicrobial concentrations in injured lung tissue.Methods: After induction of unilateral acute lung injury, ceftaroline fosamil and linezolid were administered intravenously. Drug concentrations were measured in lung tissue through microdialysis and in blood and BAL fluid samples during the following 8 hours. The primary endpoint was the tissue concentration area under the concentration curve in the first 8 hours (AUC0-8 h) of the two antimicrobial drugs.Measurements and Main Results: In 10 pigs, antimicrobial drug concentrations were higher in inflamed and injured lung tissue compared with those in uninflamed and uninjured lung tissue (median ceftaroline fosamil AUC0-8 h [and interquartile range] = 26.7 mg ⋅ h ⋅ L-1 [19.7-39.0] vs. 16.0 mg ⋅ h ⋅ L-1 [13.6-19.9], P = 0.02; median linezolid AUC0-8 h 76.0 mg ⋅ h ⋅ L-1 [68.1-96.0] vs. 54.6 mg ⋅ h ⋅ L-1 [42.7-60.9], P = 0.01), resulting in a longer time above the minimal inhibitory concentration and in higher peak concentrations and dialysate/plasma ratios. Penetration into BAL fluid was excellent for both antimicrobials, but without left-to-right differences (ceftaroline fosamil, P = 0.78; linezolid, P = 1.00).Conclusions: Tissue penetration of two commonly used antimicrobial drugs for pneumonia is enhanced by early lung tissue inflammation and injury, resulting in longer times above the minimal inhibitory concentration. Thus, lung tissue inflammation ameliorates antimicrobial drug penetration during the acute phase.

Urinary Collectrin as Promising Biomarker for Acute Kidney Injury in Patients Undergoing Cardiac Surgery.

BACKGROUND: Early detection of acute kidney injury (AKI) is crucial for timely intervention and improved patient outcomes after cardiac surgery. This study aimed to evaluate the potential of urinary collectrin as a novel biomarker for AKI in this patient population. METHODS: In this prospective, observational cohort study, 63 patients undergoing elective cardiac surgery with cardiopulmonary bypass (CPB) were studied at the Medical University of Vienna between 2016 and 2018. We collected urine samples prospectively at four perioperative time points, and urinary collectrin was measured using an enzyme-linked immunosorbent assay. Patients were divided into two groups, AKI and non-AKI, defined by Kidney Disease: Improving Global Outcomes Guidelines, and differences between groups were analyzed. RESULTS: Postoperative AKI was found in 19 (30%) patients. Urine sample analysis revealed an inverse correlation between urinary collectrin and creatinine and AKI stages, as well as significant changes in collectrin levels during the perioperative course. Baseline collectrin levels were 5050 ± 3294 pg/mL, decreased after the start of CPB, reached their nadir at the end of surgery, and began to recover slightly on postoperative day (POD) 1. The most effective timepoint for distinguishing between AKI and non-AKI patients based on collectrin levels was POD 1, with collectrin levels of 2190 ± 3728 pg/mL in AKI patients and 3768 ± 3435 pg/mL in non-AKI patients (p = 0.01). CONCLUSIONS: Urinary collectrin shows promise as a novel biomarker for the early detection of AKI in patients undergoing cardiac surgery on CPB. Its dynamic changes throughout the perioperative period, especially on POD 1, provide valuable insights for timely diagnosis and intervention. Further research and validation studies are needed to confirm its clinical usefulness and potential impact on patient outcomes.