Nocardia infections in Italy: from a local to a national view.

In this paper, we have described cases of nocardiosis that occurred in our hospital and examined the literature on other nocardiosis cases recorded in Italy. We have collected the clinical details of our recent cases and described them in full. Regarding the older cases in our hospital and the Italian cases present in the literature, we noted the clinical data, the Nocardia species involved, and the antimicrobial susceptibility reported. The survey was carried out on PubMed. The first of our cases is an elderly woman with compromised health who had a lung and bloodstream infection. A second case is a middle-aged man who developed an infection in the thigh. A third patient is a middle-aged man on immunosuppressive therapy who developed a cerebral abscess. Our review shows that patients are usually immunocompromised, with an average age of 60 years, and more frequently males. The most affected organs are the lungs and the brain, and the most reported species is Nocardia farcinica. Antimicrobial susceptibility tests show good efficacy of linezolid, cotrimoxazole and amikacin. We conclude that, if a Nocardia infection is suspected, the most likely species to be considered in Italy is N. farcinica. In addition, if empirical therapy is needed, we suggest relying on linezolid, cotrimoxazole or amikacin.

A novel phenolic derivative inhibits AHL-dependent quorum sensing signaling in Pseudomonas aeruginosa.

Increasing antibiotic resistance and the decline in the pharmaceutical industry's investments have amplified the need for novel treatments for multidrug-resistant bacteria. Quorum sensing (QS) inhibitors reduce pathogens' virulence without selective pressure on bacteria and provide an alternative to conventional antibiotic-based therapies. P. aeruginosa uses complex QS signaling to control virulence and biofilm formation. We aimed to identify inhibitors of P. aeruginosa QS acting on acyl-homoserine lactones (AHL)-mediated circuits. Bioluminescence and qRT-PCR assays were employed to screen a library of 81 small phenolic derivatives to reduce AHL-dependent signaling. We identified GM-50 as the most active compound inhibiting the expression of AHL-regulated genes but devoid of cytotoxic activity in human epithelial cells and biocidal effects on bacteria. GM-50 reduces virulence factors such as rhamnolipids, pyocyanin, elastase secretion, and swarming motility in P. aeruginosa PAO1 laboratory strain. By molecular docking, we provide evidence that GM-50 highly interacts with RhlR. GM-50 significantly improved aztreonam-mediated biofilm disruption. Moreover, GM-50 prevents adhesion of PAO1 and inflammatory damage in the human A549 cell line and protects Galleria mellonella from PAO1-mediated killing. GM-50 significantly reduces virulence factors in 20 P. aeruginosa clinical isolates from patients with respiratory tract infections. In conclusion, GM-50 inhibits AHL-signaling, reduces virulence factors, enhances the anti-biofilm activity of aztreonam, and protects G. mellonella larvae from damage induced by P. aeruginosa. Since GM-50 is active on clinical strains, it represents a starting point for identifying and developing new phenolic derivatives acting as QS-inhibitors in P. aeruginosa infections.