Reliability of mini-bronchoalveolar lavage for the measurement of epithelial lining fluid concentrations of tobramycin in critically ill patients

Boselli, Emmanuel; Breilh, Dominique; Djabarouti, Sarah; Guillaume, C.; Rimmelé, Thomas; Gordien, Jean-Baptiste; Xuereb, Fabien; Saux, Marie-Claude; Allaouchiche, Bernard

doi:10.1007/s00134-007-0688-x

Cited by 71 publications

(55 citation statements)

References 20 publications

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“…1). To compare our data with already published evidence, we performed a systematic literature search on aminoglycoside (amikacin [8,12,17,20,23], tobramycin [5,7,9,17,19,20], gentamicin [21,22], and netilmicin [26]) quantification in BAL fluid after parenteral (i.v. or i.m.)…”

Section: Discussionmentioning

confidence: 98%

Quantification of Amikacin in Bronchial Epithelial Lining Fluid in Neonates

Tayman

El-Attug

Adams

et al. 2011

Antimicrob Agents Chemother

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Aminoglycosides like amikacin are frequently administered in the treatment of suspected or proven Gram-negative infections in neonates, often in combination with penicillins. Due to a concentration-dependent killing combined with a postantibiotic effect, the bactericidal efficacy of amikacin relates to its peak serum concentration. Consequently, therapeutic peak levels at the infection site will define the effectiveness of antibiotic therapy. Renal side effects and ototoxicity relate to the trough serum amikacin concentration, based on the saturation of renal and cochlear cell-binding sites. The pharmacokinetics (PK) of amikacin displays extensive interindividual variability, which makes it difficult to achieve an effective and safe administration in the individual neonate (1).Based on maturational differences in body composition and renal immaturity in early life, differences in both distribution volume (V d , in liters/kg) and clearance (CL t , in ml/kg/min) of this hydrophilic drug have been observed. Because of the higher water content in preterm infants, and thus a higher distribution volume for hydrophilic drugs, a relatively higher amikacin dose is necessary in this population (3,25).Since pulmonary infections can be a major cause of neonatal morbidity and mortality, antibiotic levels in bronchial secretions and bronchial and alveolar epithelial lining fluid (ELF) are of specific interest. Measuring antibiotic concentrations in the lung is not easy and is usually represented by ELF concentrations. Keeping the anatomy of the blood-bronchial barrier in mind, one can imagine that to reach ELF, the antibiotic must pass through the epithelial lining cells linked by tight junctions (14). Consequently, biochemical characteristics like the degree of protein binding and the lipophilicity and diffusibility of the antibiotic will influence antibiotic concentrations in interstitial fluid and in ELF. In adults, we are aware of studies to assess the blood-alveolar barrier after parenteral administration of amikacin. Dull et al. showed that, after intramuscular (i.m.) administration, the highest amikacin serum concentration correlated significantly with the highest bronchial secretion concentration of that individual and that elimination of amikacin from serum and bronchial secretions occurred at approximately the same rate, with a peak concentration that is blunted in the alveolar compared to the blood compartment (12). Since data in neonates are lacking, the aim of this study is to describe amikacin concentration in the bronchial ELF of newborns.

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Section: Discussionmentioning

confidence: 98%

Quantification of Amikacin in Bronchial Epithelial Lining Fluid in Neonates

Tayman

El-Attug

Adams

et al. 2011

Antimicrob Agents Chemother

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“…limitations (10). A more recent and promising technique for measuring ELF concentrations is bronchoscopic microsampling (BMS), which allows for repeated measurement of concentrations over time (11).…”

Section: Introductionmentioning

confidence: 99%

Structure-Based Prediction of Anti-infective Drug Concentrations in the Human Lung Epithelial Lining Fluid

et al. 2015

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Purpose Obtaining pharmacologically relevant exposure levels of antibiotics in the epithelial lining fluid (ELF) is of critical importance to ensure optimal treatment of lung infections. Our objectives were to develop a model for the prediction of the ELF-plasma concentration ratio (EPR) of antibiotics based on their chemical structure descriptors (CSDs). Methods EPR data was obtained by aggregating ELF and plasma concentrations from historical clinical studies investigating antibiotics and associated agents. An elastic net regularized regression model was used to predict EPRs based on a large number of CSDs. The model was tuned using leave-one-drug-out cross validation, and the predictions were further evaluated using a test dataset. Results EPR data of 56 unique compounds was included. A high degree of variability in EPRs both between-and within drugs was apparent. No trends related to study design or pharmacokinetic factors could be identified. The model predicted 80% of the within-drug variability (R 2 WDV ) and 78.6% of drugs were within 3-fold difference from the observations. Key CSDs were related to molecular size and lipophilicity. When predicting EPRs for a test dataset the R 2 WDV was 75%. Conclusions This model is of relevance to inform dose selection and optimization during antibiotic drug development of agents targeting lung infections.

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“…It is now recognized that drug concentrations in whole tissue homogenates are difficult to interpret and therefore not informative (19). In humans, the most popular experimental approach for characterizing antibiotic distribution in lungs relies on bronchoalveolar lavages (BAL) (3,4,5), and micro-BAL was recently proposed (2). Microdialysis is an appealing technique that has increasingly been used in recent years to investigate antibiotic distribution in the extracellular fluids (ECFs) of various tissues, including lungs, in both rats and humans (6,9,13,16,18,23).…”

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confidence: 99%

Lung Microdialysis Study of Levofloxacin in Rats following Intravenous Infusion at Steady State

Marchand

Frasca

Dahyot‐Fizelier

et al. 2008

Antimicrob Agents Chemother

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Lung microdialysis has been used with rats to investigate antibiotic distribution after single-dose administration. However, conducting such experiments after intravenous infusion at steady state would constitute a more convenient alternative, which was evaluated here, using levofloxacin (LVX) as a test compound. Microdialysis probes were inserted in blood and muscle, used as a comparator, between 9:00 a.m. and 11:00 a.m. Intravenous LVX infusion was started 6 h later and maintained until the end of the experiment at a rate of 1.0 mg ⅐ h ؊1 . Lung microdialysis probes were inserted on the morning of the next day. Rats were kept anesthetized during dialysate collection. In vivo probe recoveries were estimated by retrodialysis using a calibrator method, with ciprofloxacin (CIP) as the calibrator. LVX and CIP were analyzed in dialysates by high-performance liquid chromatography. The steady-state tissue-to-blood unbound-drug concentration ratios were 1.00 ؎ 0.15 in muscle tissues and 1.06 ؎ 0.40 in lungs, suggesting passive distribution of LVX in tissue. Although providing no information on rate of distribution, microdialysis investigations following drug infusion at steady state appear to be an interesting approach for characterization of antibiotic distribution in rat lungs.

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Reliability of mini-bronchoalveolar lavage for the measurement of epithelial lining fluid concentrations of tobramycin in critically ill patients

Cited by 71 publications

References 20 publications

Quantification of Amikacin in Bronchial Epithelial Lining Fluid in Neonates

Quantification of Amikacin in Bronchial Epithelial Lining Fluid in Neonates

Structure-Based Prediction of Anti-infective Drug Concentrations in the Human Lung Epithelial Lining Fluid

Lung Microdialysis Study of Levofloxacin in Rats following Intravenous Infusion at Steady State

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