Targeting bacteria causing otitis media using nanosystems containing nonspherical gold nanoparticles and ceragenins.

Aim: To evaluate the antibacterial and antibiofilm activity of ceragenin-conjugated nonspherical gold nanoparticles against the most common agents of otitis media. Methods: Minimal inhibitory and bactericidal concentrations and colony-counting assays, as well as colorimetric and fluorimetric methods, were used to estimate the antibacterial activity of compounds in phosphate-buffered saline and human cerumen. The nanosystems' biocompatibility and ability to decrease IL-8 release was tested using keratinocyte cells. Results: The tested compounds demonstrated strong antimicrobial activity against planktonic and biofilm cultures at nontoxic doses due to the induction of oxidative stress followed by the damage of bacterial membranes. Conclusion: This study indicates that ceragenin-conjugated nonspherical gold nanoparticles have potential as new treatment methods for eradicating biofilm-forming pathogens associated with otitis media.

Lay abstract Middle-ear infections can be painful and cause hearing difficulties. If untreated, they can lead to hearing loss. These infections are usually treated with antibiotic drugs. However, the microbes causing the infection can gain drug resistance. This article reports research into a new way of delivering antibiotics to kill the microbes and the communities they form (biofilms). The authors developed tiny gold particles loaded with the antimicrobial drug ceragenin and tested the drug-loaded particles on three common middle-ear infection-causing bacteria. Compared with ceragenin alone, the ceragenin-loaded particles were better at killing the bacteria and their biofilm communities.

Comparative in vitro antimicrobial activities of CSA-142 and CSA-192, second-generation ceragenins, with CSA-13 against various microorganisms.

Ceragenins, a novel family of antibiotics, are cationic derivatives of cholic acid and display broad-spectrum antimicrobial activities. Multiple ceragenins have been synthesized and studied, and most published data are with ceragenin CSA-13. This study aimed to investigate the in vitro antimicrobial properties of second-generation ceragenins, CSA-142 and CSA-192, and compare them to CSA-13. The antimicrobial activities of CSA-13, CSA-142 and CSA-192 were studied against 20 strains of Escherichia coli, Acinetobacter baumannii, Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans. Time-kill curve methods were performed to determine the bactericidal and fungicidal activities of the ceragenins against three strains of each microorganism. Overall, CSA-13 showed the lowest MIC values, but also CSA-142 and CSA-192 had good activities against tested microorganisms. The killing curves showed that ceragenins generally had bactericidal and fungicidal effects. The bactericidal and fungicidal behaviours of CSA-142 and CSA-192 may make them good alternative agents to CSA-13.