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Penetration of Gentamicin Into the Alveolar Lining Fluid of Critically Ill Patients With Ventilator-Associated Pneumonia^*

^* From the Laboratory of Biopharmaceutics and Pharmacokinetics (Drs. Panidis and Markantonis), School of Pharmacy, University of Athens, Panepistimiopolis; and University ICU at "KAT" General Hospital (Drs. Boutzouka, Karatzas, and Baltopoulos), School of Nursing, University of Athens, Athens, Greece.

Correspondence to: Sophia L. Markantonis, PhD, Assistant Professor of Clinical Pharmacy, Laboratory of Biopharmaceutics and Pharmacokinetics, School of Pharmacy, University of Athens, GR157.71, Panepistimiopolis, Athens, Greece; e-mail: kyroudi{at}pharm.uoa.gr

Study objectives: To estimate the penetration of gentamicin into lung tissue by measuring its concentrations in alveolar lining fluid (ALF) and blood in critically ill patients with ventilator-associated pneumonia (VAP).

Patients and interventions: The study population consisted of 24 patients who were admitted to an ICU for respiratory failure and developed VAP. Patients were scheduled to undergo bronchoscopy with BAL after IV administration of a once-daily, 240-mg schedule of gentamicin for the treatment of VAP. Patients were assigned at random to one of four groups of six patients each according to the scheduled time for bronchoscopy (1, 2, 4, or 6 h, respectively). A serum sample was obtained at 0.5 h (n = 24), and both serum and ALF samples (n = 6) were collected at each of the above specified times for measurement of antibiotic concentrations.

Measurements and results: Mean ± SEM gentamicin concentrations in the ALF were 2.95 ± 0.37, 4.24 ± 0.42, 3.10 ± 0.39, and 2.65 ± 0.35 µg/mL at 1, 2, 4, and 6 h, respectively, after the start of antibiotic infusion. Maximum gentamicin concentrations in serum (13.39 ± 0.91 µg/mL, n = 24) and ALF (4.24 ± 0.42 µg/mL, n = 6) were achieved at 0.5 h and 2 h, respectively, giving a penetration ratio of 0.32. The mean ratios of ALF/serum concentrations between 1 h and 6 h ranged from 0.30 to 1.14. After completion of the distribution phase, a significant positive correlation (p = 0.02) was found between gentamicin concentrations in the serum and ALF.

Conclusions: Once-daily IV administration of 240-mg gentamicin achieved average peak antibiotic concentrations of 4.24 µg/mL in the ALF 2 h after administration, and an ALF/serum penetration ratio of 32%. Higher gentamicin doses to produce higher peak blood levels than those found with the study dose are necessary to obtain active alveolar concentrations against less sensitive microorganisms in the treatment of VAP in ICU patients.

Key Words: alveolar lining fluid • BAL • gentamicin • penetration • ventilator-associated pneumonia

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