scholarly journals Lung Pharmacokinetics of Tobramycin by Intravenous and Nebulized Dosing in a Mechanically Ventilated Healthy Ovine Model

2019 ◽  
Vol 131 (2) ◽  
pp. 344-355 ◽  
Author(s):  
Jayesh A. Dhanani ◽  
Sara Diab ◽  
Jivesh Chaudhary ◽  
Jeremy Cohen ◽  
Suzanne L. Parker ◽  
...  
Keyword(s):  
Interstitial Fluid ◽  
Jugular Vein ◽  
Interstitial Space ◽  
Interquartile Range ◽  
Pharmacokinetic Studies ◽  
Ventilator Associated Pneumonia ◽  
Epithelial Lining ◽  
Ovine Model ◽  
Epithelial Lining Fluid ◽  
Mechanically Ventilated

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Nebulized antibiotics may be used to treat ventilator-associated pneumonia. In previous pharmacokinetic studies, lung interstitial space fluid concentrations have never been reported. The aim of the study was to compare intravenous and nebulized tobramycin concentrations in the lung interstitial space fluid, epithelial lining fluid, and plasma in mechanically ventilated sheep with healthy lungs. Methods Ten anesthetized and mechanically ventilated healthy ewes underwent surgical insertion of microdialysis catheters in upper and lower lobes of both lungs and the jugular vein. Five ewes were given intravenous tobramycin 400 mg, and five were given nebulized tobramycin 400 mg. Microdialysis samples were collected every 20 min for 8 h. Bronchoalveolar lavage was performed at 1 and 6 h. Results The peak lung interstitial space fluid concentrations were lower with intravenous tobramycin 20.2 mg/l (interquartile range, 12 mg/l, 26.2 mg/l) versus the nebulized route 48.3 mg/l (interquartile range, 8.7 mg/l, 513 mg/l), P = 0.002. For nebulized tobramycin, the median epithelial lining fluid concentrations were higher than the interstitial space fluid concentrations at 1 h (1,637; interquartile range, 650, 1,781, vs. 16 mg/l, interquartile range, 7, 86, P < 0.001) and 6 h (48, interquartile range, 17, 93, vs. 4 mg/l, interquartile range, 2, 9, P < 0.001). For intravenous tobramycin, the median epithelial lining fluid concentrations were lower than the interstitial space fluid concentrations at 1 h (0.19, interquartile range, 0.11, 0.31, vs. 18.5 mg/l, interquartile range, 9.8, 23.4, P < 0.001) and 6 h (0.34, interquartile range, 0.2, 0.48, vs. 3.2 mg/l, interquartile range, 0.9, 4.4, P < 0.001). Conclusions Compared with intravenous tobramycin, nebulized tobramycin achieved higher lung interstitial fluid and epithelial lining fluid concentrations without increasing systemic concentrations.

scholarly journals Penetration of Meropenem into Epithelial Lining Fluid of Patients with Ventilator-Associated Pneumonia

2011 ◽  
Vol 55 (4) ◽  
pp. 1606-1610 ◽  
Author(s):  
T. P. Lodise ◽  
F. Sorgel ◽  
D. Melnick ◽  
B. Mason ◽  
M. Kinzig ◽  
...  
Keyword(s):  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Compartment Model ◽  
Ventilator Associated Pneumonia ◽  
Epithelial Lining ◽  
Time Data ◽  
Time Curve ◽  
Epithelial Lining Fluid ◽  
Time Profiles ◽  
Concentration Time

ABSTRACTAntibiotic penetration to the infection site is critical for obtaining a good clinical outcome in patients with ventilator-associated pneumonia (VAP). Surprisingly few studies have quantified the penetration of β-lactam agents into the lung, as measured by the ratio of area under the concentration-time curve (AUC) in epithelial lining fluid (ELF) to AUC in plasma (AUCELF/AUCplasmaratio). These have typically involved noninfected patients. This study examines the penetration and pharmacodynamics of meropenem in the ELF among patients with VAP. Meropenem plasma and ELF concentration-time data were obtained from patients in a multicenter clinical trial. Concentration-time profiles in plasma and ELF were simultaneously modeled using a three-compartment model with zero-order infusion and first-order elimination and transfer (big nonparametric adaptive grid [BigNPAG]). A Monte Carlo simulation was performed to estimate the range of ELF/plasma penetration ratios one would expect to observe in patients with VAP, as measured by the AUCELF/AUCplasmaratio. The range of AUCELF/AUCplasmapenetration ratios predicted by the Monte Carlo simulation was large. The 10th percentile of lung penetration was 3.7%, while the 90th percentile of penetration was 178%. The variability of ELF penetration is such that if relatively high ELF exposure targets are required to attain multilog kill or resistance suppression for bacteria likePseudomonas aeruginosa, then even receiving the largest licensed dose of meropenem with an optimal prolonged infusion may not result in target attainment for a substantial fraction of the population.

scholarly journals Lung Concentrations of Ceftazidime Administered by Continuous versus Intermittent Infusion in Patients with Ventilator-Associated Pneumonia

2015 ◽  
Vol 59 (4) ◽  
pp. 1905-1909 ◽  
Author(s):  
Joël Cousson ◽  
Thierry Floch ◽  
Thomas Guillard ◽  
Véronique Vernet ◽  
Pascal Raclot ◽  
...  
Keyword(s):  
Continuous Infusion ◽  
Controlled Trial ◽  
Intermittent Infusion ◽  
Ventilator Associated Pneumonia ◽  
Epithelial Lining ◽  
Beta Lactam ◽  
Continuous Administration ◽  
Epithelial Lining Fluid ◽  
Group A ◽  
Group B

ABSTRACTCeftazidime is a beta-lactam compound that exerts a time-dependent bactericidal effect. Numerous arguments are in favor of continuous administration of ceftazidime, both for reasons of clinical efficacy and to preserve bacteriological mutation. We report a prospective, single-center, parallel-group, randomized, controlled trial comparing two modes of administration of ceftazidime, namely, continuous administration (loading dose of 20 mg/kg of body weight followed by 60 mg/kg/day) versus intermittent administration (20 mg/kg over 30 min every 8 h) in 34 patients with ventilator-associated pneumonia due to Gram-negative bacilli. The study was performed over 48 h with 13 and 18 assessments of serum ceftazidime in the continuous-infusion group (group A) and the intermittent-fusion group (group B), respectively. Bronchoalveolar lavage (BAL) was performed at steady state in both groups at 44 h to determine ceftazidime levels in the epithelial lining fluid. We chose a predefined threshold of 20 mg/liter for serum concentrations of ceftazidime because of ecological conditions in our center. The median time above 20 mg/liter (T>20 mg) was 100% in group A versus 46% in group B. In group A, 14/17 patients had 100%T>20 mg, versus only 1/17 patients in group B. In the epithelial lining fluid, the median concentration of ceftazidime was 12 mg/liter in group A versus 6 mg/liter in group B. A threshold of 8 mg/liter in the epithelial lining fluid was achieved twice as often in group A as in group B. This study of ceftazidime concentrations in the epithelial lining fluid indicates that continuous infusion presents advantages in terms of pharmacodynamics and predictable efficacy in patients presenting ventilator-associated pneumonia.

Steady-state trough serum and epithelial lining fluid concentrations of teicoplanin 12 mg/kg per day in patients with ventilator-associated pneumonia

2006 ◽  
Vol 32 (5) ◽  
pp. 775-779 ◽  
Author(s):  
Olivier Mimoz ◽  
Delphine Rolland ◽  
Michèle Adoun ◽  
Sandrine Marchand ◽  
Dominique Breilh ◽  
...  
Keyword(s):  
Steady State ◽  
Ventilator Associated Pneumonia ◽  
Epithelial Lining ◽  
Epithelial Lining Fluid ◽  
Trough Serum

Evaluation of Epithelial Lining Fluid Concentration of Amikacin in Critically Ill Patients With Ventilator-Associated Pneumonia

2018 ◽  
Vol 35 (4) ◽  
pp. 400-404 ◽  
Author(s):  
Farhad Najmeddin ◽  
Bita Shahrami ◽  
Sayna Azadbakht ◽  
Mehrnoush Dianatkhah ◽  
Mohammad Reza Rouini ◽  
...  
Keyword(s):  
Critically Ill ◽  
Lung Tissue ◽  
Critically Ill Patients ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Adult Patients ◽  
Ventilator Associated Pneumonia ◽  
Epithelial Lining ◽  
Epithelial Lining Fluid ◽  
The Mean

Introduction: Classically, aminoglycosides are known to have low penetration into the lung tissue. So far, no study has been conducted on human adult patients to evaluate amikacin concentration in epithelial lining fluid (ELF) of the alveoli. Therefore, convincing data are not available from the perspective of pharmacokinetics to support the fact that a dosage of 20 mg/kg of amikacin is sufficient to treat patients with ventilator-associated pneumonia (VAP). Method: This was a pilot study of amikacin concentration measurement in the alveolar site of action in critically ill adult patients with VAP who required aminoglycoside therapy. A dose of 20 mg/kg of amikacin was administered over a 30-minute infusion. The serum concentrations of amikacin were evaluated in the first, second, fourth, and sixth hours. However, the ELF concentration of amikacin was evaluated in the second hour with the help of bronchoalveolar lavage sampling technique. Results: A total number of 8 patients was included in the study. The mean (SD) administered dose was 20 (0.9) mg/kg. The mean (SD) peak plasma concentration of amikacin was 59.6 (23) mg/L, with the volume of distribution of 0.36 (0.13)L/kg. The amikacin concentration in ELF was successfully measured in 7 patients (6.3) mg/L. The lung tissue penetration of the drug was described as alveolar percentage, proportional to both the first- and second-hour plasma concentrations, with a mean (SD) of 10.1% (8.4%) and 18% (16.7%), respectively. Conclusion: To our knowledge, the current study is the first that investigates whether standard doses of amikacin may lead to sufficient alveolar concentration of the drug. The results show that administration of amikacin in doses of 20 mg/kg in critically ill patients with VAP may not provide sufficient concentrations in ELF.

scholarly journals Prognostic biomarkers in predicting mortality in respiratory patients with ventilator-associated pneumonia

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Nermeen A. Abdelaleem ◽  
Hoda A. Makhlouf ◽  
Eman M. Nagiub ◽  
Hassan A. Bayoumi
Keyword(s):  
Sofa Score ◽  
Diagnostic Performance ◽  
Mortality Prediction ◽  
Ventilator Associated Pneumonia ◽  
Distribution Width ◽  
Mechanically Ventilated ◽  
Neutrophil Lymphocyte Ratio ◽  
Prognostic Accuracy ◽  
Severity Scores ◽  
Critical Patients

Abstract Background Ventilator-associated pneumonia (VAP) is the most common nosocomial infection. Red cell distribution width (RDW) and neutrophil-lymphocyte ratio (NLR) are prognostic factors to mortality in different diseases. The aim of this study is to evaluate prognostic efficiency RDW, NLR, and the Sequential Organ Failure Assessment (SOFA) score for mortality prediction in respiratory patients with VAP. Results One hundred thirty-six patients mechanically ventilated and developed VAP were included. Clinical characteristics and SOFA score on the day of admission and at diagnosis of VAP, RDW, and NLR were assessed and correlated to mortality. The average age of patients was 58.80 ± 10.53. These variables had a good diagnostic performance for mortality prediction AUC 0.811 for SOFA at diagnosis of VAP, 0.777 for RDW, 0.728 for NLR, and 0.840 for combined of NLR and RDW. The combination of the three parameters demonstrated excellent diagnostic performance (AUC 0.889). A positive correlation was found between SOFA at diagnosis of VAP and RDW (r = 0.446, P < 0.000) and with NLR (r = 0.220, P < 0.010). Conclusions NLR and RDW are non-specific inflammatory markers that could be calculated quickly and easily via routine hemogram examination. These markers have comparable prognostic accuracy to severity scores. Consequently, RDW and NLR are simple, yet promising markers for ICU physicians in monitoring the clinical course, assessment of organ dysfunction, and predicting mortality in mechanically ventilated patients. Therefore, this study recommends the use of blood biomarkers with the one of the simplest ICU score (SOFA score) in the rapid diagnosis of critical patients as a daily works in ICU.

scholarly journals Gastroesophageal reflux in mechanically ventilated pediatric patients and its relation to ventilator-associated pneumonia

Critical Care ◽  
2009 ◽  
Vol 13 (5) ◽  
pp. R164 ◽  
Author(s):  
Tarek A Abdel-Gawad ◽  
Mostafa A El-Hodhod ◽  
Hanan M Ibrahim ◽  
Yousef W Michael
Keyword(s):  
Gastroesophageal Reflux ◽  
Pediatric Patients ◽  
Ventilator Associated Pneumonia ◽  
Mechanically Ventilated
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