Antibiotic resistance mechanisms back to front: from clinic to bench

Antimicrobial resistance remains a global issue, exacerbated by the “dry pipeline” of new drug classes, which have drastically decreased in recent decades compared to the past. Increasing scientific evidence indicates that WHO projections on the number of deaths caused by this phenomenon are underestimated as there are already pathogenic microorganisms today that are not susceptible to any known therapeutic treatment. This thesis evaluates the evolution of the local ecology of Multi-drug Resistant (MDR) and Pan-drug Resistant (XDR) germs in Campania, a region with a high incidence of these pathogens. The work focused on combating these germs through targeted therapeutic regimens and timely diagnostics, minimizing the misuse of antibiotics, as well as researching new synthetic antimicrobials for future clinical applications, such as natural peptides and nanoparticles extracted from plant organisms. In a recent study published in June of this year, 1951 vaginal swabs were analyzed over the period 2018-2022. The susceptibility and resistance patterns of the isolates were evaluated. Significant epidemiological variations were observed, including increased resistance rates to fluoroquinolones and penicillin, as well as decreased susceptibility to ampicillin. The most frequently isolated microorganisms causing vaginitis and vaginosis were also evaluated. In another ongoing epidemiological study, divided into three phases: pre-pandemic (2018-2019), pandemic (2020-2021), and post-pandemic from Sars-Cov2 (2022-2023), at our University Hospital in the Virology and Microbiology Unit, the results of 10,742 blood cultures, 10,503 urine tests, along with another 4,693 samples including pus, drains, and swabs from patients were evaluated. Among these, focusing on A. baumannii, a notoriously multi-resistant pathogen, it was found that the vast majority of these strains, 89.5% out of a total of 191 isolates, were MDR. Crucial in this regard was the introduction of an Antimicrobial Diagnostic Stewardship program in our hospital in 2018, from which we observed a global decrease in antimicrobial resistance, particularly in 2020 and 2022. However, despite these efforts, a significant portion of the isolates remains resistant to carbapenems. In this context, we have thus produced research on nanoparticles (NPs) to be used as a possible therapeutic alternative against MDR and XDR germs. The antimicrobial potential of NPs was tested, among others, on commonly resistant strains from the American Type Culture Collection (ATCC, Manassas, VA, USA) and clinical MDR strains isolated at the Virology and Microbiology Unit of the “Luigi Vanvitelli” University Hospital using the Kirby-Bauer method, which showed inhibition zones with variable but overall promising diameters. Additionally, a study was conducted evaluating the antibiotic characteristics of Hylin-a1, a peptide derived from the amphibians skin secretion, which, through a series of molecular and cellular studies conducted in vitro, showed remarkable antibacterial activity with low toxicity towards eukaryotic cells at active concentrations, suggesting it could be a good candidate for the development of new antimicrobial agents.