Healthcare Associated Infections: An Interoperable Infrastructure for Multidrug Resistant Organism Surveillance

Gazzarata, Roberta; Monteverde, Maria Eugenia; Ruggiero, Carmelina; Maggi, Norbert; Palmieri, Dalia; Parruti, Giustino

doi:10.3390/ijerph17020465

Cited by 8 publications

(6 citation statements)

References 47 publications

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“…Today, MDR pathogens of both Gram-positive and Gram-negative species cause infections against which traditional antibiotics are no longer effective and cause an increasing number of deaths in hospitals, long-term care facilities, and community settings. The surveillance of antibiotic resistance is a global public health concern [2][3][4][5][6][7][8], and the search for new antibacterial substances, which act by mechanisms other than those of existing Pharmaceutics 2021, 13,1976 2 of 21 antibiotics, and with a low tendency to develop resistance, is at present one of the greatest challenges for researchers [9].…”

Section: Introductionmentioning

confidence: 99%

Efficacy of Ursolic Acid-Enriched Water-Soluble and Not Cytotoxic Nanoparticles against Enterococci

et al. 2021

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Ursolic acid (UA), a pentacyclic triterpenoid acid found in many medicinal plants and aromas, is known for its antibacterial effects against multi-drug-resistant (MDR) Gram-positive bacteria, which seriously threaten human health. Unfortunately, UA water-insolubility, low bioavailability, and systemic toxicity limit the possibilities of its application in vivo. Consequently, the beneficial activities of UA observed in vitro lose their potential clinical relevance unless water-soluble, not cytotoxic UA formulations are developed. With a nano-technologic approach, we have recently prepared water-soluble UA-loaded dendrimer nanoparticles (UA-G4K NPs) non-cytotoxic on HeLa cells, with promising physicochemical properties for their clinical applications. In this work, with the aim of developing a new antibacterial agent based on UA, UA-G4K has been tested on different strains of the Enterococcus genus, including marine isolates, toward which UA-G4K has shown minimum inhibitory concentrations (MICs) very low (0.5–4.3 µM), regardless of their resistance to antibiotics. Time-kill experiments, in addition to confirming the previously reported bactericidal activity of UA against E. faecium, also established it for UA-G4K. Furthermore, cytotoxicity experiments on human keratinocytes revealed that nanomanipulation of UA significantly reduced the cytotoxicity of UA, providing UA-G4K NPs with very high LD50 (96.4 µM) and selectivity indices, which were in the range 22.4–192.8, depending on the enterococcal strain tested. Due to its physicochemical and biological properties, UA-G4K could be seriously evaluated as a novel oral-administrable therapeutic option for tackling difficult-to-treat enterococcal infections.

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Section: Introductionmentioning

confidence: 99%

Efficacy of Ursolic Acid-Enriched Water-Soluble and Not Cytotoxic Nanoparticles against Enterococci

et al. 2021

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“…In this regard, the possible dissemination and appropriate use of innovative tests able to provide information on either the precise mechanisms of resistance or other phenotypic/genotypic features of MDR-GNB may further and considerably improve the ability of ML algorithms to help clinicians predicting MDR-GNB risks in routine care [32,33]. Very importantly, this should occur against a background of wide adherence to the FAIR principles (findable, accessible, interoperable, and reusable) connected to the availability of standardized systems [34][35][36][37][38].…”

Section: Discussionmentioning

confidence: 99%

Machine Learning and Multidrug-Resistant Gram-Negative Bacteria: An Interesting Combination for Current and Future Research

2020

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The dissemination of multidrug-resistant Gram-negative bacteria (MDR-GNB) is associated with increased morbidity and mortality in several countries. Machine learning (ML) is a branch of artificial intelligence that consists of conferring on computers the ability to learn from data. In this narrative review, we discuss three existing examples of the application of ML algorithms for assessing three different types of risk: (i) the risk of developing a MDR-GNB infection, (ii) the risk of MDR-GNB etiology in patients with an already clinically evident infection, and (iii) the risk of anticipating the emergence of MDR in GNB through the misuse of antibiotics. In the next few years, we expect to witness an increasingly large number of research studies perfecting the application of ML techniques in the field of MDR-GNB infections. Very importantly, this cannot be separated from the availability of a continuously refined and updated ethical framework allowing an appropriate use of the large datasets of medical data needed to build efficient ML-based support systems that could be shared through appropriate standard infrastructures.

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“…They are responsible for infections against which traditional antibiotics are no longer effective, thus causing an increasing number of deaths in hospitals, long-term care facilities, and community settings. The scrutiny of antibiotic resistance is a global health concern [ 7 , 8 , 9 , 10 , 11 , 12 ], and the search for new antibacterial agents, acting by means of mechanisms different from those of available antibiotics, and having a lower propensity to develop resistance, represents one of the greatest challenges for researchers [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Pyrazole-Based Water-Soluble Dendrimer Nanoparticles as a Potential New Agent against Staphylococci

et al. 2021

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Although the antimicrobial potency of the pyrazole nucleus is widely reported, the antimicrobial effects of the 2-(4-bromo-3,5-diphenyl-pyrazol-1-yl)-ethanol (BBB4), found to be active against several other conditions, have never been investigated. Considering the worldwide need for new antimicrobial agents, we thought it noteworthy to assess the minimum inhibitory concentration (MICs) of BBB4 but, due to its scarce water-solubility, unequivocal determinations were tricky. To obtain more reliable MICs and to obtain a substance also potentially applicable in vivo, we recently prepared water-soluble, BBB4-loaded dendrimer nanoparticles (BBB4-G4K NPs), which proved to have physicochemical properties suitable for clinical application. Here, with the aim of developing a new antibacterial agent based on BBB4, the BBB4-G4K NPs were tested on several strains of different species of the Staphylococcus genus. Very low MICs (1.5–3.0 µM), 15.5–124.3-fold lower than those of the free BBB4, were observed against several isolates of S. aureus and S. epidermidis, the most pathogenic species of this genus, regardless of their resistance patterns to antibiotics. Aiming at hypothesizing a clinical use of BBB4-G4K NPs for staphylococcal skin infections, cytotoxicity experiments on human keratinocytes were performed; it was found that the nano-manipulated BBB4 released from BBB4-G4K NPs (LD50 138.6 µM) was 2.5-fold less cytotoxic than the untreated BBB4 (55.9 µM). Due to its physicochemical and biological properties, BBB4-G4K NPs could be considered as a promising novel therapeutic option against the very frequent staphylococcal skin infections.

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Healthcare Associated Infections: An Interoperable Infrastructure for Multidrug Resistant Organism Surveillance

Cited by 8 publications

References 47 publications

Efficacy of Ursolic Acid-Enriched Water-Soluble and Not Cytotoxic Nanoparticles against Enterococci

Efficacy of Ursolic Acid-Enriched Water-Soluble and Not Cytotoxic Nanoparticles against Enterococci

Machine Learning and Multidrug-Resistant Gram-Negative Bacteria: An Interesting Combination for Current and Future Research

Pyrazole-Based Water-Soluble Dendrimer Nanoparticles as a Potential New Agent against Staphylococci

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