Abstract
The poor diffusion of intravenous antibiotics in lung tissue makes nosocomial pneumonia challenging to treat, notably in critical patients under mechanical ventilation. The combination of ultrasound and microbubbles (USMB) is an emerging method for non-invasive and targeted enhancement of uptake of various drugs in several organs. This study aims to evaluate if USMB may increase amikacin concentration in condensed lung tissues in a mechanically ventilated rabbit model. When applied 60 or 160 min after the beginning of an intravenous amikacin infusion, USMB increased amikacin concentration in the condensed lung tissue by 1.33 (p = 0.025) or 1.56-fold (p = 0.028) respectively. When applied 70 min after the beginning of an intravenous amikacin infusion, USMB increased amikacin concentration in the muscle tissue by 2.52 (p = 0.025). In conclusion, this study demonstrates that USMB is a promising method for the targeted delivery of amikacin in mechanically ventilated condensed lung, thus opening new therapeutic fields against lung infections.
Highlights
Hospital-acquired and ventilator associated pneumonia (VAP) are among the most common infections in intensive care units (ICU) (Leone et al, 2018)
The development of innovative targeted delivery methods is required to increase the local concentration of antibiotics in infected lung tissues, while minimizing general side effects related to the systemic antibiotherapy
The blood amikacin concentrations were measured over time by fluorescence polarization immunoassay after iv infusion of 15 mg/kg amikacin in mechanically ventilated anesthetized rabbits
Summary
Hospital-acquired and ventilator associated pneumonia (VAP) are among the most common infections in intensive care units (ICU) (Leone et al, 2018). They increase morbidity, and ICU and hospital length of stay (Rello et al, 2002; Koulenti et al, 2017). The risk of systemic toxicity limits the use of high dose of iv antibiotics To overcome these limitations, the development of innovative targeted delivery methods is required to increase the local concentration of antibiotics in infected lung tissues, while minimizing general side effects related to the systemic antibiotherapy
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