METHODS: We used the AMR-Intervene framework to extract descriptions of the social and ecological systems of interventions to determine factors contributing to their success.
RESULTS: We identified 52 scientific publications referring to 42 unique E. coli AMR interventions. We mainly identified interventions implemented in high-income countries (36/42), at the national level (16/42), targeting primarily one sector of society (37/42) that was mainly the human sector (25/42). Interventions were primarily funded by governments (38/42). Most intervention targeted a low leverage point in the AMR system, (36/42), and aimed to change the epidemiology of AMR (14/42). Among all included publications, 55% (29/52) described at least one success factor or obstacle (29/52) and 19% (10/52) identified at least one success factor and one obstacle. Most reported success factors related to communication between the actors and stakeholders and the role of media, and stressed the importance of collaboration between disciplines and external partners. Described obstacles covered data quality, access to data and statistical analyses, and the validity of the results.
CONCLUSIONS: Overall, we identified a lack of diversity regarding interventions. In addition, most published E. coli interventions were poorly described with limited evidence of the factors that contributed to the intervention success or failure. Design and reporting guidelines would help to improve reporting quality and provide a valuable tool for improving the science of AMR interventions.
OBJECTIVE: The objective of this study was to identify whether the epithelial lining fluid components inhibit amikacin-mediated bacterial killing.
METHODS: Two amikacin-susceptible (minimum inhibitory concentrations of 2 and 8 mg/L) Pseudomonas aeruginosa isolates were exposed in vitro to amikacin concentrations up to 976 mg/L in the presence of an acidic pH, mucin and/or surfactant as a means of simulating the epithelial lining fluid, the site of bacterial infection in pneumonia. Pharmacodynamic modelling was used to describe associations between amikacin concentrations, bacterial killing and emergence of resistance.
RESULTS: In the presence of broth alone, there was rapid and extensive (> 6 - log10) bacterial killing, with emergence of resistance identified in amikacin concentrations < 976 mg/L. In contrast, the rate and extent of bacterial killing was reduced (≤ 5 - log10) when exposed to an acidic pH and mucin. Surfactant did not appreciably impact the bacterial killing or resistance emergence when compared with broth alone for either isolate. The combination of mucin and an acidic pH further reduced the rate of bacterial killing, with the maximal bacterial killing occurring 24 h following initial exposure compared with approximately 4-8 h for either mucin or an acidic pH alone.
CONCLUSIONS: Our findings indicate that simulating the epithelial lining fluid antagonises amikacin-mediated killing of P. aeruginosa, even at the high concentrations achieved following nebulised administration.