TY - JOUR
TI - Intrapulmonary pharmacokinetics of high doses of tigecycline in patients
with ventilator-associated pneumonia
AU - Dimopoulos, G.
AU - Almyroudi, M. P.
AU - Kapralos, I
AU - Apostolopoulou,
AU - O.
AU - Flevari, A.
AU - Nicolau, D. P.
AU - Dokoumetzidis, A.
JO - International Journal of Antimicrobial Agents
PY - 2022
VL - 59
TODO - 1
SP - null
PB - Elsevier
SN - 0924-8579
TODO - 10.1016/j.ijantimicag.2021.106487
TODO - Ventilator-associated pneumonia; VAP; Tigecycline; Intrapulmonary
pharmacokinetics
TODO - Tigecycline is commonly used for infections by multidrug-resistant
bacteria. However, it is not approved for ventilator-associated
pneumonia (VAP) as increased mortality has been reported in VAP patients
treated with conventional doses. The purpose of this study was to
prospectively evaluate the intrapulmonary pharmacokinetics of off-label
high-dose tigecycline in patients with VAP. Nine mechanically ventilated
patients received tigecycline intravenously (loading dose 200 mg
followed by 100 mg every 12 h). After = 5 doses, two bronchoscopies were
performed in each patient on consecutive days and eight blood samples
were collected. Tigecycline concentrations in plasma and bronchoalveolar
lavage fluid were determined by liquid chromatography. The urea dilution
method was used to calculate epithelial lining fluid (ELF)
concentrations. A two-compartmental pharmacokinetic (PK) model with
linear elimination was used to estimate PK parameters. Mean patient age
was 69 +/- 11.86 years and mean APACHE II score was 21. The estimated
population mean PK parameters (relative standard error) were: clearance,
11.64 L/h (54%); volume of distribution in central compartment, 79.01 L
(37%); volume of distribution in peripheral compartment, 92.95 L
(17%); intercompartmental clearance, 62.81 L/h (34%); and ELF
penetration ratio, 2.41 (40%). C-max, C-min, plasma AUC(0-12), plasma
fAUC(0-12) and ELF AUC(0-12) were 1.99 +/- 1.82 mu g/mL, 0.81 +/- 1.27
mu g/mL, 12.89 +/- 17.25 mu g.h/mL, 3.24 +/- 3.09 mu g.h/mL and 7.13 +/-
2.61 mu g.h/mL, respectively. The increased plasma and ELF AUC(0-12)
achieved with a 200 mg daily tigecycline dose, combined with high ELF
penetration, support the effectiveness of off-label high-dose
tigecycline in VAP. (c) 2021 Elsevier Ltd and International Society of
Antimicrobial Chemotherapy. All rights reserved.
ER -