English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background  Amikacin inhale (BAY41-6551), a unique drug—device combination of a specially formulated drug solution and a pulmonary drug delivery system device (AMK-I) is currently under phase III study as an adjunctive therapy to IV antibiotics for the treatment of Gram-negative pneumonia in mechanically ventilated patients. While the epidemiology of nosocomial pneumonia is predominated by Gram-negative pathogens such as  Pseudomonas aeruginosa  and the Enterobacteriaceae,  Staphylococcus aureus  is increasingly recognized as a pathogen of concern for these pulmonary based infections. Since the aminoglycosides are historically quite active against  S. aureus  the use of adjunctive AMK-I may enhance bacterial eradication. Herein, we aimed to characterize the in vitro pharmacodynamic (PD) profile of human-simulated ELF exposures of AMK-I against both methicillin-sensitive (MSSA) and -resistant (MRSA)  S. aureus .    Methods  An in vitro model was used to simulate the resultant ELF pharmacokinetic profile of amikacin after the administration of AMK-I 400 mg q12h. The antibacterial activity of this regimen was tested against 7  S. aureus  isolates that display MIC profiles encountered clinically (4 MRSA; MIC range 4–64, 3 MSSA; MIC range 8–16 mg/L). Experiments were conducted over 24 h and samples were taken throughout this period to assess the bacterial density in both control and treatments.    Results  The mean ± SD inoculum 0 h bacterial density was 6.4 ± 0.09 which increased to 8.6 ± 0.19 log 10  CFU/mL in the control models by the end of 24 h experiments. Simulated ELF concentrations of AMK-I resulted in a rapid, 5 log 10  declined in CFU over the initial 12 h for all MRSA and MSSA isolates. After 12 h, all bacterial counts remained below the limit of detection (LOD, 1.7 log 10  CFU/mL) and no regrowth was evident at the end of the study.    Conclusion  AMK-I produced an ELF exposure profile that was rapidly bactericidal against  S. aureus  displaying typical MICs to amikacin irrespective of their phenotypic profile to methicillin. While the Gram-negative organisms are the target pathogens for AMK-I in the ongoing clinical trials, these data suggest that this adjunctive regimen may also have the potential to eradicate both MSSA and MRSA from lower airway which needs to be further evaluated in randomized-controlled clinical trials.

annals of clinical microbiology and antimicrobials

Anti-staphylococcal activity resulting from epithelial lining fluid (ELF) concentrations of amikacin inhale administered via the pulmonary drug delivery system