2021
DOI: 10.1007/s40268-021-00344-5
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Impact of the Epithelial Lining Fluid Milieu on Amikacin Pharmacodynamics Against Pseudomonas aeruginosa

Abstract: Background Even though nebulised administration of amikacin can achieve high epithelial lining fluid concentrations, this has not translated into improved patient outcomes in clinical trials. One possible reason is that the cellular and chemical composition of the epithelial lining fluid may inhibit amikacin-mediated bacterial killing. Objective The objective of this study was to identify whether the epithelial lining fluid components inhibit amikacin-mediated bacterial killing. Methods Two amikacin-susceptibl… Show more

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“…In vivo studies demonstrate that bacterial killing is dependent on the area under the concentration time curve (AUC) to MIC (AUC/MIC) ratio, whilst clinical studies report favourable clinical outcomes in patients with a maximum concentration (C max ) to MIC ratio >8 (Table 1). An acidic (pH < 7) milieu, such as occurs in infected CSF, is known to inhibit aminoglycoside killing of bacteria [42]. Despite this, in vitro and in vivo studies of aminoglycoside mediated bacterial killing in CSF show mixed results [43].…”
Section: Aminoglycosidesmentioning
confidence: 99%
“…In vivo studies demonstrate that bacterial killing is dependent on the area under the concentration time curve (AUC) to MIC (AUC/MIC) ratio, whilst clinical studies report favourable clinical outcomes in patients with a maximum concentration (C max ) to MIC ratio >8 (Table 1). An acidic (pH < 7) milieu, such as occurs in infected CSF, is known to inhibit aminoglycoside killing of bacteria [42]. Despite this, in vitro and in vivo studies of aminoglycoside mediated bacterial killing in CSF show mixed results [43].…”
Section: Aminoglycosidesmentioning
confidence: 99%