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 microg/mL at 1, 2, 4, and 6 h, respectively, after the start of antibiotic infusion. Maximum gentamicin concentrations in serum (13.39 +/- 0.91 mug/mL, n = 24) and ALF (4.24 +/- 0.42 microg/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 microg/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.
RCT Entities:
STUDY OBJECTIVES: To estimate the penetration of gentamicin into lung tissue by measuring its concentrations in alveolar lining fluid (ALF) and blood in critically illpatients 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 microg/mL at 1, 2, 4, and 6 h, respectively, after the start of antibiotic infusion. Maximum gentamicin concentrations in serum (13.39 +/- 0.91 mug/mL, n = 24) and ALF (4.24 +/- 0.42 microg/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 microg/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.
Authors: T Tängdén; V Ramos Martín; T W Felton; E I Nielsen; S Marchand; R J Brüggemann; J B Bulitta; M Bassetti; U Theuretzbacher; B T Tsuji; D W Wareham; L E Friberg; J J De Waele; V H Tam; Jason A Roberts Journal: Intensive Care Med Date: 2017-04-13 Impact factor: 17.440
Authors: Cornelius J Clancy; Binghua Hao; Ryan K Shields; Liang Chen; David S Perlin; Barry N Kreiswirth; M Hong Nguyen Journal: Antimicrob Agents Chemother Date: 2014-02-24 Impact factor: 5.191
Authors: Zoe E Athanassa; Sophia L Markantonis; Marina-Zoe F Fousteri; Pavlos M Myrianthefs; Eleni G Boutzouka; Athanassios Tsakris; George J Baltopoulos Journal: Intensive Care Med Date: 2012-07-19 Impact factor: 17.440
Authors: Aaron J Heffernan; Fekade B Sime; Derek S Sarovich; Michael Neely; Yarmarly Guerra-Valero; Saiyuri Naicker; Kyra Cottrell; Patrick Harris; Katherine T Andrews; David Ellwood; Steven C Wallis; Jeffrey Lipman; Keith Grimwood; Jason A Roberts Journal: Antimicrob Agents Chemother Date: 2020-08-20 Impact factor: 5.191
Authors: Timothy D Starner; Joshua D Shrout; Matthew R Parsek; Peter C Appelbaum; GunHee Kim Journal: Antimicrob Agents Chemother Date: 2007-10-22 Impact factor: 5.191
Authors: Charles-Edouard Luyt; Marc Clavel; Kalpalatha Guntupalli; Jay Johannigman; John I Kennedy; Christopher Wood; Kevin Corkery; Dennis Gribben; Jean Chastre Journal: Crit Care Date: 2009-12-10 Impact factor: 9.097