Lung Ultrasound and Microbubbles Enhance Aminoglycoside Efficacy and Delivery to the Lung in Escherichia coli–induced Pneumonia and Acute Respiratory Distress Syndrome

Sonobactericide: An Emerging Treatment Strategy for Bacterial Infections

“…For example, in vitro studies reported by Dong et al (2013) utilized Sonovue and reduced colonyforming units of S. epidermidis eightfold relative to treatment with vancomycin and ultrasound (1-MHz frequency, 0.5-W/cm 2 intensity, 50% duty cycle, 5 min). In in vivo studies, findings of enhanced bacterial killing when sonobactericide included an antimicrobial were also reported; for example, Sugiyama et al (2018) observed an almost 1-log reduction in colony-forming units compared with all controls. Sonobactericide could produce equivalent therapeutic effects at a lower antibiotic dose, which may reduce complications associated with systemic toxicity, especially renal and liver complications.…”

“…All sonobactericide studies used an appropriate antibiotic targeting a specific microbe, according to therapeutic guidelines (Mandell et al 2000;Mermel et al 2009;Osmon et al 2012;Baddour et al 2015;Habib et al 2015;Lanjouw et al 2016), excluding 2 studies that could not be linked to guidelines because of nondisclosure of microbe information beyond species (Lin et al 2015) and no disease aim (Zhu et al 2013). Two examples of correct antibiotic and microbe pairings are found in Sugiyama et al (2018), who aimed to treat severe GramÀ bacterial pneumonia and used an E. coli strain for which the Canadian guideline recommends gentamicin (Mandell et al 2000), and Lattwein et al (2018), who aimed to treat infective endocarditis and used a methicillin-susceptible S. aureus isolate for which both the European (Habib et al 2015) and American (Baddour et al 2015) guidelines recommend oxacillin. Additionally, of the studies using an antibiotic, 2 of 9 focusing on Gram+ bacteria used strains already resistant to first-line antibiotics.…”

“…Another study focused on harnessing sonobactericide in a model of severe bacterial pneumonia with the goal of enhancing antibiotic delivery to infected lung tissue in mice (Sugiyama et al 2018). E. coli were administered intratracheally, and 6 h later gentamicin was injected intraperitoneally.…”

“…Besides using fluorophore internalization, one group used a fluorescence polarization immunoassay to determine the amount of vancomycin eluted from bone cement after in vitro treatments (Lin et al 2015). An enzyme-linked immunosorbent assay was also used after treatments to determine levels of gentamicin (Sugiyama et al 2018) and inflammatory cytokines (Yi et al 2016) in tissue. Both immunoassays are highly specific, even in samples with protein content such as serum (Yu et al 2010;Odekerken et al 2015), and are commercially available for various antibiotics on the market.…”

Enhanced Amikacin Diffusion With Ultrasound and Microbubbles in a Mechanically Ventilated Condensed Lung Rabbit Model

“…Few studies investigated the therapeutic benefit of antibiotic treatments combined with USMB for improving antibiotic activity against bacterial infections (He et al, 2011;Shih et al, 2013;Lin et al, 2015;Shang et al, 2015;Dong et al, 2018;Sugiyama et al, 2018). Thus, USMB enhanced the antibacterial effect of free vancomycin against Staphylococcus epidermidis in-vivo biofilms compared to antibiotic treatment alone (He et al, 2011;Dong et al, 2018).…”