195 results on '"Oscar Cirioni"'
Search Results
2. In Vitro Activity of Novel Lipopeptides against Triazole-Resistant Aspergillus fumigatus
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Simona Fioriti, Oscar Cirioni, Oriana Simonetti, Lucia Franca, Bianca Candelaresi, Francesco Pallotta, Damian Neubauer, Elzbieta Kamysz, Wojciech Kamysz, Benedetta Canovari, Lucia Brescini, Gianluca Morroni, and Francesco Barchiesi
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Microbiology (medical) ,Aspergillus fumigatus ,azole resistance ,antimicrobial peptides ,lipopeptides ,Plant Science ,Ecology, Evolution, Behavior and Systematics - Abstract
Aspergillosis, which is mainly sustained by Aspergillus fumigatus, includes a broad spectrum of diseases. They are usually severe in patients with co-morbidities. The first-line therapy includes triazoles, for which an increasing incidence of drug resistance has been lately described. As a consequence of this, the need for new and alternative antifungal molecules is absolutely necessary. As peptides represent promising antimicrobial molecules, two lipopeptides (C14-NleRR-NH2, C14-WRR-NH2) were tested to assess the antifungal activity against azole-resistant A. fumigatus. Antifungal activity was evaluated by determination of minimum inhibitory concentrations (MICs), time–kill curves, XTT assay, optical microscopy, and checkerboard combination with isavuconazole. Both lipopeptides showed antifungal activity, with MICs ranging from 8 mg/L to 16 mg/L, and a dose-dependent effect was confirmed by both time–kill curves and XTT assays. Microscopy showed that hyphae growth was hampered at concentrations equal to or higher than MICs. The rising antifungal resistance highlights the usefulness of novel compounds to treat severe fungal infections. Although further studies assessing the activity of lipopeptides are necessary, these molecules could be effective antifungal alternatives that overcome the current resistances.
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- 2022
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3. In Vitro Activity of Novel Lipopeptides against Triazole-Resistant
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Simona, Fioriti, Oscar, Cirioni, Oriana, Simonetti, Lucia, Franca, Bianca, Candelaresi, Francesco, Pallotta, Damian, Neubauer, Elzbieta, Kamysz, Wojciech, Kamysz, Benedetta, Canovari, Lucia, Brescini, Gianluca, Morroni, and Francesco, Barchiesi
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Aspergillosis, which is mainly sustained by
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- 2022
4. Clinical and microbiological features of ceftolozane/tazobactam-resistant Pseudomonas aeruginosa isolates in a university hospital in central Italy
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Gianluca Morroni, Lucia Brescini, Alberto Antonelli, Vincenzo Di Pilato, Sefora Castelletti, Andrea Brenciani, Gloria D'Achille, Marina Mingoia, Eleonora Giovanetti, Simona Fioriti, Annamaria Masucci, Tommaso Giani, Andrea Giacometti, Gian Maria Rossolini, and Oscar Cirioni
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Microbiology (medical) ,Tazobactam ,Drug Resistance, Multiple, Bacterial ,Immunology ,Pseudomonas aeruginosa ,Immunology and Allergy ,Humans ,Pseudomonas Infections ,Microbiology ,Hospitals ,Anti-Bacterial Agents ,Cephalosporins - Abstract
Ceftolozane/tazobactam (C/T) is a novel cephalosporin and β-lactamase inhibitor combination with great activity against Pseudomonas aeruginosa. To assess P. aeruginosa susceptibility to C/T, a surveillance study was conducted from October 2018 to March 2019 at the University Hospital 'Ospedali Riuniti' in Ancona, Italy.Minimum inhibitory concentrations (MICs) to C/T were determined by Etest strip. Resistant isolates were characterized by phenotypic (broth microdilution antimicrobial susceptibility testing and modified Carbapenem Inactivation Method [mCIM]) and genotypic (Polymerase Chain Reaction [PCR], Pulsed Field Gel Electrophoresis [PFGE], and whole-genome sequencing [WGS]) methods. Clinical variables of patients infected by C/T-resistant P. aeruginosa were collected from medical records.Fifteen of 317 P. aeruginosa collected showed resistance to C/T (4.7%). Ten strains demonstrated carbapenemase activity by mCIM method, and PCR confirmed that eight strains harbored a blaVIM gene while the other two were positive for blaIMP. Additionally, three isolates carried acquired extended spectrum β-lactamase genes (two isolates carried blaPER and one carried blaGES). Eight strains were strictly related by PFGE and WGS analysis confirmed that they belonged to sequence type (ST)111. The other STs found were ST175 (two isolates), ST235 (two isolates), ST70 (one isolate), ST621 (one isolate), and the new ST3354 (one isolate). Most patients had received previous antibiotic therapies, carried invasive devices, and experienced prolonged hospitalization.This study demonstrated the presence of C/T-resistant P. aeruginosa isolates in a regional hospital carrying a number of resistance mechanisms acquired by different high-risk clones.
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- 2022
5. Synergistic effect of antimicrobial peptide LL-37 and colistin combination against multidrug-resistant Escherichia coli isolates
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Lucia Brescini, Oriana Simonetti, Marina Mingoia, Laura Di Sante, Gianluca Morroni, Patrizia Bagnarelli, Andrea Brenciani, Eleonora Giovanetti, Elżbieta Kamysz, Andrea Giacometti, Wojciech Kamysz, and Oscar Cirioni
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Microbiology (medical) ,Chemistry ,Antimicrobial peptides ,Antimicrobial pharmacodynamics ,medicine.disease_cause ,Antimicrobial ,Microbiology ,Multiple drug resistance ,Minimum inhibitory concentration ,Antibiotic resistance ,medicine ,Colistin ,Escherichia coli ,medicine.drug - Abstract
Overview: The global spread of antibiotic resistance represents a serious threat for public health. Aim: We evaluated the efficacy of the antimicrobial peptide LL-37 as antimicrobial agent against multidrug-resistant Escherichia coli. Results: LL-37 showed good activity against mcr-1 carrying, extended spectrum β-lactamase- and carbapenemase-producing E. coli (minimum inhibitory concentration, MIC, from 16 to 64 mg/l). Checkerboard assays demonstrated synergistic effect of LL-37/colistin combination against all tested strains, further confirmed by time–kill and post antibiotic effect assays. MIC and sub-MIC concentrations of LL-37 were able to reduce biofilm formation. Conclusion: Our preliminary data indicated that LL-37/colistin combination was effective against multidrug-resistant E. coli strains and suggested a new possible clinical application.
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- 2021
6. Trend of clinical vancomycin-resistant enterococci isolated in a regional Italian hospital from 2001 to 2018
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Francesca Biavasco, Eleonora Giovanetti, Stefano Menzo, Simona Fioriti, Serena Simoni, Lucia Brescini, Sonia Nina Coccitto, Andrea Brenciani, Gianluca Morroni, Elisa Ponzio, Carla Vignaroli, Oscar Cirioni, and Sara Caucci
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medicine.medical_specialty ,Enterococcus faecium ,Microbiology ,Bacterial Fungal and Virus Molecular Biology - Short Communication ,Enterococcus faecalis ,Vancomycin-Resistant Enterococci ,03 medical and health sciences ,Medical microbiology ,Epidemiology ,Media Technology ,medicine ,Humans ,Infection control ,Gram-Positive Bacterial Infections ,Retrospective Studies ,030304 developmental biology ,Cross Infection ,Infection Control ,0303 health sciences ,biology ,030306 microbiology ,Teicoplanin ,biochemical phenomena, metabolism, and nutrition ,bacterial infections and mycoses ,biology.organism_classification ,Italy ,Vancomycin ,Multilocus sequence typing ,medicine.drug - Abstract
A retrospective study of the epidemiology of vancomycin-resistant enterococci (VRE) in a regional hospital of central Italy in 2001–2018 demonstrated an increased VRE prevalence since 2016. A total of 113 VRE isolates, 89 E. faecium (VREfm) and 24 E. faecalis (VREfs), were collected in the study period. All strains showed high-level resistance to vancomycin; 107 also showed teicoplanin resistance. Altogether, 84 VREfm and 20 VREfs carried vanA, whereas 5 VREfm and 1 VREfs carried vanB. MLST analysis documented that 89 VREfm isolates mainly belonged to ST78, ST80, and ST117. Most strains were isolated from 2001 to 2007, ST78 being the predominant clone. VREfm re-emerged in 2016 with a prevalence of the ST80 lineage. Most VREfs were isolated from 2001 to 2006; although they belonged to 7 different STs, there was a prevalence of ST88 and ST6. Notably, ST88 was sporadically recovered throughout the study period. The increasing rate of VREfm isolation from 2016 to 2018 may be related to the influx of new successful clones and to the renewed and widespread use of vancomycin. Improved infection control measures in hospital wards should be adopted to limit the spread of new epidemic VRE strains.
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- 2020
7. Synergistic combinations of antimicrobial peptides against biofilms of methicillin-resistant Staphylococcus aureus (MRSA) on polystyrene and medical devices
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Gianluca Morroni, Eleonora Ciandrini, Raffaella Campana, Lucia Brescini, Wojciech Kamysz, Elżbieta Kamysz, Oscar Cirioni, and Wally Baffone
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Methicillin-Resistant Staphylococcus aureus ,Pore Forming Cytotoxic Proteins ,0301 basic medicine ,Microbiology (medical) ,Staphylococcus aureus ,Medical device ,030106 microbiology ,Immunology ,Antimicrobial peptides ,MRSA ,medicine.disease_cause ,Microbiology ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Central Venous Catheters ,Immunology and Allergy ,030212 general & internal medicine ,biology ,Chemistry ,Biofilm ,Synergistic activity ,biochemical phenomena, metabolism, and nutrition ,biology.organism_classification ,Antimicrobial ,Methicillin-resistant Staphylococcus aureus ,QR1-502 ,Temporin ,Anti-Bacterial Agents ,Biofilms ,Equipment Contamination ,Polystyrenes ,Antimicrobial peptide ,Bacteria - Abstract
Objectives Antimicrobial research is being focused to look for more effective therapeutics against antibiotic-resistant infections such as those caused by methicillin-resistant Staphylococcus aureus (MRSA). In this regard, antimicrobial peptides (AMPs) appear to be a promising solution. The aim of the present study was to investigate the potential activity of temporin A, citropin 1.1, CA(1–7)M(2–9)NH2 and Pal-KGK-NH2 in synergistic activity against MRSA biofilms developed on polystyrene surface (PSS) and central venous catheter (CVC). Methods The study was subdivided into distinct phases to assess the ability of AMPs to inhibit biofilm formation, to identify possible synergy between AMPs, and to eradicate preformed biofilms on PSS and CVC using AMPs alone or in combination. Results Activity of the AMPs was particularly evident in the inhibition of biofilm formation on PSS and CVC, whilst the eradication of preformed biofilms was more difficult and was reached only after 24 h of contact. The synergistic activity of AMP combinations, selected by their fractional inhibitory concentration index (FICI), led to an improvement in the performance of all of the molecules in the removal of different biofilms. Conclusion Overall, AMPs could represent the next generation of antimicrobial agents for a prophylactic or therapeutic tool to control biofilms of antibiotic-resistant bacteria and/or biofilm-associated infections on different medical devices.
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- 2020
8. Potential application of berberine in the treatment of Escherichia coli sepsis
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Paolo Lombardi, Mauro Provinciali, Oriana Simonetti, Andrea Giacometti, Fiorenza Orlando, Elisa Pierpaoli, and Oscar Cirioni
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medicine.drug_class ,medicine.medical_treatment ,Antibiotics ,Population ,Plant Science ,Pharmacology ,01 natural sciences ,Biochemistry ,Analytical Chemistry ,Sepsis ,chemistry.chemical_compound ,Berberine ,In vivo ,Intensive care ,Medicine ,education ,Cause of death ,education.field_of_study ,010405 organic chemistry ,business.industry ,Organic Chemistry ,medicine.disease ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,chemistry ,business ,Adjuvant - Abstract
Gram-negative sepsis ranks as the leading cause of death in intensive care units. Despite the development of new antibiotics, mortality from gram-negative sepsis remains high. The present study aims to investigate the in vivo effects of berberine (BBR) administration on septic death induced by intraperitoneal Escherichia coli injection. The results showed that (i) single 5 mg/kg dose of BBR increases the survival of septic mice, (ii) BBR administration improves the antimicrobial efficacy of antibiotic drug, (iii) BBR pre-treatment prevents improvements of BBR therapy without affecting the pro-survival effects of antibiotic drug. The effects of BBR administration were associated with immunological alterations represented by changes in CD4+ and CD8+ lymphocytes population and IL-6 and TNF-α production. This study highlighted the benefits of berberine administration as antibiotic adjuvant in E. coli sepsis. Furthermore, information about berberine-induced immunological perturbations and their influence on host response to infection and therapy has been shown.
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- 2020
9. New insight into old and new antimicrobial molecules targeting quorum sensing for MRSA wound infection
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Oriana Simonetti, Giulio Rizzetto, Oscar Cirioni, Elisa Molinelli, Gianluca Morroni, Andrea Giacometti, and Annamaria Offidani
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Microbiology (medical) ,Methicillin-Resistant Staphylococcus aureus ,Anti-Infective Agents ,Wound Infection ,Humans ,Quorum Sensing ,biochemical phenomena, metabolism, and nutrition ,Microbiology ,Anti-Bacterial Agents - Abstract
MRSA represents one of the largest problems in wound healing as a result of its increasing incidence and the complex therapeutic approach required to treat it. The need for new solutions to overcome antibiotic resistance led to the development of antimicrobial molecules that are effective at blocking quorum sensing. This special report provides an up-to-date review, based on the latest evidence in the literature, of old and new molecules that can positively influence the process of wound healing via their action on MRSA quorum sensing. Quorum sensing-inhibiting molecules, applied topically or injected in situ, have excellent potential to improve both MRSA eradication and quality of wound healing, especially when combined with conventional systemic MRSA therapy. Further human studies are needed to evaluate the efficacy of these molecules.
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- 2022
10. Methicillin-resistant Staphylococcus aureus as a cause of chronic wound infections: Alternative strategies for management
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Oriana Simonetti, Samuele Marasca, Matteo Candelora, Giulio Rizzetto, Giulia Radi, Elisa Molinelli, Lucia Brescini, Oscar Cirioni, and Annamaria Offidani
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Microbiology (medical) ,Microbiology - Abstract
Biofilm formation at the level of a wound plays an important role in its chronicization. The difficulty of its eradication has driven research toward the discovery and synthesis of new molecules that can act on biofilm to promote wound healing. This narrative review focuses on alternative molecules that can act and promote the eradication of methicillin-resistant Staphylococcus aureus, taking into consideration its antibiotic resistance, virulence, tendency toward the tenacious colonization of wounds by biofilms, and its increased prevalence in both community and hospital settings. A selection of promising studies were reported, analyzing the in vitro and/or in vivo efficacy of bacteriophages, metal nanoparticles, RNAIII inhibiting peptide (RIP), synthetized RIP derivatives, proteinase K and hamamelitannin.
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- 2021
11. Our Experience over 20 Years: Antimicrobial Peptides against Gram Positives, Gram Negatives, and Fungi
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Giulio Rizzetto, Daisy Gambini, Andrea Maurizi, Matteo Candelora, Elisa Molinelli, Oscar Cirioni, Lucia Brescini, Andrea Giacometti, Annamaria Offidani, and Oriana Simonetti
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Pharmaceutical Science - Abstract
Antibiotic resistance is rapidly increasing, and new anti-infective therapies are urgently needed. In this regard, antimicrobial peptides (AMPs) may represent potential candidates for the treatment of infections caused by multiresistant microorganisms. In this narrative review, we reported the experience of our research group over 20 years. We described the AMPs we evaluated against Gram-positive, Gram-negative, and fungi. In conclusion, our experience shows that AMPs can be a key option for treating multiresistant infections and overcoming resistance mechanisms. The combination of AMPs allows antibiotics and antifungals that are no longer effective to exploit the synergistic effect by restoring their efficacy. A current limitation includes poor data on human patients, the cost of some AMPs, and their safety, which is why studies on humans are needed as soon as possible.
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- 2022
12. The Effect of Dalbavancin in Moderate to Severe Hidradenitis Suppurativa
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Elisa Molinelli, Claudia Sapigni, Giovanni Marco D’Agostino, Valerio Brisigotti, Giulio Rizzetto, Ivan Bobyr, Oscar Cirioni, Andrea Giacometti, Lucia Brescini, Sara Mazzanti, Annamaria Offidani, and Oriana Simonetti
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Microbiology (medical) ,Infectious Diseases ,Pharmacology (medical) ,General Pharmacology, Toxicology and Pharmaceutics ,Biochemistry ,Microbiology - Abstract
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by painful nodules, abscesses, and fistulas, localized to the areas of the folds where apocrine glands are present: the armpits, groin, inframammary region, and genital or perineal region. The management is still challenging, and it includes mainly systemic antibiotics, immunosuppressors, and biologic agents. Antibiotics are frequently used in the management of HS for their anti-inflammatory, immunomodulatory, and antimicrobial properties, but no data have been reported regarding the use of dalbavancin in HS. The aim of our practice was to evaluate efficacy, flare, and disease-free survival after dalbavancin therapy in a selected population with HS. We report the experience of the Ancona Dermatology Clinic in treating HS flare-ups with dalbavancin and its rationale for use. Our observation shows that the use of dalbavancin is an effective and well-tolerated treatment for the management of Hurley stage II-III HS; currently, dalbavancin should be considered as a supportive therapy for selected patients.
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- 2022
13. Has COVID-19 changed the approach to HIV diagnosis?
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Gianmaria Baldin, Giovanni Guaraldi, Carlo Torti, Bianca Candelaresi, Vanni Borghi, Gaetana Sterrantino, Cristina Mussini, Filippo Lagi, Simona Di Giambenedetto, Andrea Giacomelli, Roberto Cauda, Letizia Oreni, Arturo Ciccullo, Stefano Rusconi, Andrea De Vito, Oscar Cirioni, Barbara Rossetti, and Maria Mazzitelli
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Adult ,Male ,Pediatrics ,medicine.medical_specialty ,Cross-sectional study ,Observational Study ,HIV Infections ,Disease ,Settore MED/17 - MALATTIE INFETTIVE ,CD4 Lymphocyte Count ,COVID-19 ,Cross-Sectional Studies ,Delivery of Health Care ,Female ,Humans ,Italy ,Mass Screening ,Middle Aged ,Pandemics ,Retrospective Studies ,Risk Factors ,SARS-CoV-2 ,Men who have sex with men ,lockdown ,Acquired immunodeficiency syndrome (AIDS) ,Health care ,Pandemic ,medicine ,late presentation ,Mass screening ,business.industry ,Incidence (epidemiology) ,virus diseases ,HIV ,General Medicine ,medicine.disease ,AIDS ,business ,Research Article - Abstract
The occurrence of COVID-19 pandemic had a significant negative effect on health care systems over the last year. Health care providers were forced to focus mainly on COVID-19 patients, neglecting in many cases equally important diseases, both acute and chronic. Therefore, also screening and diagnostic strategies for HIV could have been significantly impaired. This retrospective, multicenter, observational study aimed at assessing the number and characteristics of new HIV/AIDS diagnoses during COVID-19 pandemic in Italy and compared characteristics of people living with HIV at diagnosis between pre- and post-COVID-19 era (2019 vs 2020). Our results showed a significant reduction of HIV diagnoses during pandemic. By contrast, people living with HIV during pandemic were older and were diagnosed in earlier stage of disease (considering CD4+ T cell count) compared to those who were diagnosed the year before. Moreover, there was a significant decrease of new HIV diagnoses among men who have sex with men, probably for the impact of social distancing and restriction applied by the Italian Government. Late presentation incidence, if numbers in 2020 were lower than those in 2019, is still an issue. Routinely performing HIV testing in patients with suspected SARS-CoV-2 infection is identifying and linking to care underdiagnosed people living with HIV earlier. Thus, combined tests (HIV and SARS-CoV-2) should be implemented in patients with SARS-CoV-2 symptoms overlapping HIV's ones. Lastly, our results lastly showed how urgent implementation of a national policy for HIV screening is necessary.
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- 2021
14. Use of Dalbavancin in Skin, Bone and Joint Infections: A Real-Life Experience in an Italian Center
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Emanuele Cocci, Filippo Della Martera, Francesco Pallotta, Andrea Giacometti, Valentina Iencinella, Silvia Olivieri, Bianca Candelaresi, Sara Mazzanti, Rosaria G. Polo, Marcello Tavio, Sefora Castelletti, Salvatore Veccia, Lucia Brescini, Gianluca Morroni, Maria Di Pietrantonio, Paolo Mantini, and Oscar Cirioni
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Microbiology (medical) ,medicine.medical_specialty ,Lipoglycopeptide ,RM1-950 ,prosthetic joint infections ,Off-label use ,Joint infections ,Biochemistry ,Microbiology ,Article ,chemistry.chemical_compound ,Internal medicine ,medicine ,Pharmacology (medical) ,General Pharmacology, Toxicology and Pharmaceutics ,business.industry ,Osteomyelitis ,Dalbavancin ,osteomyelitis ,Retrospective cohort study ,ABSSSI ,medicine.disease ,Infectious Diseases ,Tolerability ,chemistry ,Skin structure ,Therapeutics. Pharmacology ,business ,dalbavancin - Abstract
Dalbavancin is a lipoglycopeptide approved for the treatment of acute bacterial skin and skin structure infections (ABSSSI). The aim of the study was to evaluate the efficacy and safety in all patients who received at least one administration of dalbavancin. Methods: We carried out a retrospective study of the use of dalbavancin in 55 patients at the Azienda Ospedaliera Ospedali Riuniti Umberto I (Ancona, Italy) from February 2017 to May 2020 and compared “on label” and “off label” use of dalbavancin in ABSSSI and non-ABSSSI. Results: A total of 55 patients were included in the study. The median age was 61 years, 51% had ABSSSI, 24% had prosthetic joint infections, and 14% had osteomyelitis. A total of 53% received a single 1500 mg infusion of dalbavancin, and 18% received a second dose 14 days later, 24% of patients received further doses at 14-day intervals. In 91% of cases, patients achieved clinical objectives with dalbavancin: 96% of patients with ABSSSI and 69% of those with prosthetic joint infections. Conclusions: Dalbavancin was shown to have an excellent tolerability profile and to be a highly successful therapeutic approach even in those cases treated “off-label”.
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- 2021
15. Characterization and Clonal Diffusion of Ceftaroline Non-Susceptible MRSA in Two Hospitals in Central Italy
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Simona Fioriti, Elisa Molinelli, Eleonora Giovanetti, Gianluca Morroni, Lucia Brescini, Antonella Pocognoli, Oriana Simonetti, Federica Salari, Annamaria Offidani, Oscar Cirioni, Andrea Brenciani, Andrea Giacometti, and Marina Mingoia
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Microbiology (medical) ,Penicillin binding proteins ,medicine.drug_class ,Cephalosporin ,SCCmec ,Virulence ,MRSA ,RM1-950 ,Biology ,medicine.disease_cause ,Biochemistry ,Microbiology ,Article ,Antibiotic resistance ,medicine ,Pharmacology (medical) ,General Pharmacology, Toxicology and Pharmaceutics ,Whole genome sequencing ,penicillin-binding proteins ,biochemical phenomena, metabolism, and nutrition ,Infectious Diseases ,Staphylococcus aureus ,Multilocus sequence typing ,ceftaroline ,Therapeutics. Pharmacology - Abstract
Background: Ceftaroline represents a novel fifth-generation cephalosporin to treat infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Methods: Ceftaroline susceptibility of 239 MRSA isolates was assessed by disk diffusion and a MIC test strip following both EUCAST and CLSI guidelines. Non-susceptible isolates were epidemiologically characterized by pulsed-field gel electrophoresis, spa typing, and multilocus sequence typing, and further investigated by PCR and whole genome sequencing to detect penicillin-binding protein (PBP) mutations as well as antibiotic resistance and virulence genes. Results: Fourteen isolates out of two hundred and thirty-nine (5.8%) were non-susceptible to ceftaroline (MIC >, 1 mg/L), with differences between the EUCAST and CLSI interpretations. The characterized isolates belonged to seven different pulsotypes and three different clones (ST228/CC5-t041-SCCmecI, ST22/CC22-t18014-SCCmecIV, and ST22/CC22-t022-SCCmecIV), confirming a clonal diffusion of ceftaroline non-susceptible strains. Mutations in PBPs involved PBP2a for ST228-t041-SCCmecI strains and all the other PBPs for ST22-t18014-SCCmecIV and ST22-t022-SCCmecIV clones. All isolates harbored antibiotic resistance and virulence genes with a clonal distribution. Conclusion: Our study demonstrated that ceftaroline non-susceptibile isolates belonged not only to ST228 strains (the most widespread clone in Italy) but also to ST22, confirming the increasing role of these clones in hospital infections.
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- 2021
16. MRSA and Skin Infections in Psoriatic Patients: Therapeutic Options and New Perspectives
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Giulio Rizzetto, Elisa Molinelli, Giulia Radi, Oscar Cirioni, Lucia Brescini, Andrea Giacometti, Annamaria Offidani, and Oriana Simonetti
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Microbiology (medical) ,Infectious Diseases ,Pharmacology (medical) ,General Pharmacology, Toxicology and Pharmaceutics ,Biochemistry ,Microbiology - Abstract
Psoriatic patients present various infectious risk factors, but there are few studies in the literature evaluating the actual impact of psoriasis in severe staphylococcal skin infections. Our narrative review of the literature suggests that psoriatic patients are at increased risk of both colonization and severe infection, during hospitalization, by S. aureus. The latter also appears to play a role in the pathogenesis of psoriasis through the production of exotoxins. Hospitalized psoriatic patients are also at increased risk of MRSA skin infections. For this reason, new molecules are needed that could both overcome bacterial resistance and inhibit exotoxin production. In our opinion, in the near future, topical quorum sensing inhibitors in combination with current anti-MRSA therapies will be able to overcome the increasing resistance and block exotoxin production. Supplementation with Vitamin E (VE) or derivatives could also enhance the effect of anti-MRSA antibiotics, considering that psoriatic patients with metabolic comorbidities show a low intake of VE and low serum levels, making VE supplementation an interesting new perspective.
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- 2022
17. Efficacy of Cathelicidin LL-37 in an MRSA Wound Infection Mouse Model
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Mauro Provinciali, Elisa Molinelli, Oriana Simonetti, Gaia Goteri, Elżbieta Kamysz, Guendalina Lucarini, Annamaria Offidani, Giulio Rizzetto, Fiorenza Orlando, Andrea Giacometti, Wojciech Kamysz, Oscar Cirioni, Roberto Ghiselli, and Gianluca Morroni
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Microbiology (medical) ,Pathology ,medicine.medical_specialty ,Microbiological culture ,Angiogenesis ,medicine.medical_treatment ,wound ,RM1-950 ,medicine.disease_cause ,Biochemistry ,Microbiology ,Article ,Cathelicidin ,cathelicidin ,medicine ,Pharmacology (medical) ,General Pharmacology, Toxicology and Pharmaceutics ,Teicoplanin ,business.industry ,Granulation tissue ,LL-37 ,Surgical wound ,Antimicrobial ,VEGF ,animal models ,Infectious Diseases ,medicine.anatomical_structure ,Staphylococcus aureus ,Therapeutics. Pharmacology ,business ,medicine.drug - Abstract
Background: LL-37 is the only human antimicrobial peptide that belongs to the cathelicidins. The aim of the study was to evaluate the efficacy of LL-37 in the management of MRSA-infected surgical wounds in mice. Methods: A wound on the back of adult male BALB/c mice was made and inoculated with Staphylococcus aureus. Two control groups were formed (uninfected and not treated, C0, infected and not treated, C1) and six contaminated groups were treated, respectively, with: teicoplanin, LL-37, given topically and /or systemically. Histological examination of VEGF expression and micro-vessel density, and bacterial cultures of wound tissues, were performed. Results: Histological examination of wounds in the group treated with topical and intraperitoneal LL-37 showed increased re-epithelialization, formation of the granulation tissue, collagen organization, and angiogenesis. Conclusions: Based on the mode of action, LL-37 has a potential future role in the management of infected wounds.
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- 2021
18. Vaccines for COVID-19 in patients with atopic dermatitis: three things every dermatologist should know
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Federico, Diotallevi, Oriana, Simonetti, Giulia, Radi, Elisa, Molinelli, Giulio, Rizzetto, Oscar, Cirioni, Marcello Mario, D'Errico, and Annamaria, Offidani
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Europe ,COVID-19 Vaccines ,COVID-19 ,Humans ,Clinical Competence ,Practice Patterns, Physicians' ,Dermatitis, Atopic ,Dermatologists - Abstract
Almost 13 months have passed since the World Health Organization (WHO) declared the coronavirus disease 19 (COVID-19) pandemic, caused by the SARS-CoV-2, on March 11th, 2020. During this period, we have realized that the most effective weapon we have to prevent SARS-CoV-2 infection, or to make it less aggressive, is vaccines. Currently, according to the WHO document "Draft landscape of COVID-19 candidate vaccines," there are 275 vaccines in development against the virus, although at the moment there are four preparations in distribution in the United States and in Europe. The characteristics of these vaccines are quite different from each other and may even be unfamiliar in the medical field. In particular, among dermatologists, knowledge of vaccines is of fundamental importance, especially in atopic dermatitis. Atopic patients are aware of having a predisposition to develop allergies, and so they are asking dermatologists about the safety of the vaccines currently available against the SARS-CoV-2. This article provides an up-to-date overview of this topic by reviewing current literature and sharing our personal experience.
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- 2021
19. In vitro activity of Protegrin-1, alone and in combination with clinically useful antibiotics, against Acinetobacter baumannii strains isolated from surgical wounds
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Gianluca Morroni, Oscar Cirioni, Oriana Simonetti, Damian Neubauer, Wojciech Kamysz, Monia Orciani, Lucia Brescini, Eleonora Giovanetti, Miriam Caffarini, Andrea Brenciani, Annamaria Offidani, Andrea Giacometti, and Elżbieta Kamysz
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Acinetobacter baumannii ,0301 basic medicine ,Microbiology (medical) ,Cell Survival ,medicine.drug_class ,Surgical Wound ,030106 microbiology ,Immunology ,Antibiotics ,Microbial Sensitivity Tests ,Microbiology ,03 medical and health sciences ,Minimum inhibitory concentration ,Anti-Infective Agents ,medicine ,Humans ,Immunology and Allergy ,Drug Interactions ,Minimum bactericidal concentration ,Staining and Labeling ,biology ,Epithelial Cells ,Surgical wound ,General Medicine ,biology.organism_classification ,Antimicrobial ,Multiple drug resistance ,030104 developmental biology ,Biofilms ,Colistin ,Antimicrobial Cationic Peptides ,HeLa Cells ,medicine.drug - Abstract
In the past few years the increasing incidence of hospital infections with Acinetobacter baumannii, especially in immunocompromised patients, and its proneness to develop multidrug resistance have been raising considerable concern. This study examines the antimicrobial and antibiofilm activity of protegrin 1 (PG-1), an antimicrobial peptide from porcine leukocytes, against A. baumannii strains isolated from surgical wounds. PG-1 was tested both alone and combined with the antibiotics commonly used in clinical settings. Its antimicrobial activity was evaluated by determination of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), checkerboard assays, and time-kill experiments. Its effects on biofilm inhibition/eradication were tested with crystal violet staining. The strains were grown in subinhibitory or increasing PG-1 concentrations to test the development of resistance. Mammalian cell toxicity was tested by XTT assays. PG-1 MICs and MBCs ranged from 2 to 8 µg/ml. PG-1 was most active and demonstrated a synergistic interaction with colistin, a last resort antibiotic. Interestingly, antagonism was never observed. In time-kill experiments, incubation with 2 × MIC for 30 min suppressed all viable cells. PG-1 did not select resistant strains and showed a limited effect on cell viability, but it did exert a strong activity against multidrug-resistant A. baumannii. In contrast, in our experimental conditions it had no effect on biofilm inhibition/eradication. PG-1 thus seems to be a promising antimicrobial agent against multidrug-resistant Gram-negative infections.
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- 2019
20. Antimicrobial Activity of Different Antimicrobial Peptides (AMPs) Against Clinical Methicillin-resistant Staphylococcus aureus (MRSA)
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Wojciech Kamysz, Gianluca Morroni, Wally Baffone, D. Arzeni, Eleonora Ciandrini, Oscar Cirioni, Elżbieta Kamysz, Damian Neubauer, Raffaella Campana, and Lucia Brescini
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Methicillin-Resistant Staphylococcus aureus ,Dose-Response Relationship, Drug ,Antimicrobial peptides ,Microbial Sensitivity Tests ,General Medicine ,Bacterial growth ,medicine.disease_cause ,Antimicrobial ,01 natural sciences ,Methicillin-resistant Staphylococcus aureus ,Temporin ,Anti-Bacterial Agents ,0104 chemical sciences ,Microbiology ,Structure-Activity Relationship ,010404 medicinal & biomolecular chemistry ,chemistry.chemical_compound ,Minimum inhibitory concentration ,chemistry ,Staphylococcus aureus ,Drug Discovery ,medicine ,Growth inhibition ,Antimicrobial Cationic Peptides - Abstract
Background: Antimicrobial research is being focused to look for more effective therapeutics against antibiotic-resistant infections caused by methicillin-resistant Staphylococcus aureus (MRSA). In this direction, antimicrobial peptides (AMP) appear as promising tool. Objectives: This study evaluated the antimicrobial activity of different AMPs (Citropin 1.1, Temporin A, Pexiganan, CA(1–7)M(2–9)NH2, Pal-KGK-NH2, Pal-KKKK-NH2, LL-37) against human MRSA clinical isolates. Methods: The Minimum Inhibitory Concentration (MIC) was assessed for each AMP; then, the most active ones (Citropin 1.1, Temporin A, CA(1–7)M(2–9)NH2 and Pal-KGK-NH2) were tested against selected MRSA strains by time-kill studies. Results: The lowest MIC value was observed for Pal-KGK-NH2 (1 µg/ml), followed by Temporin A (4- 16 µg/ml), CA(1–7)M(2–9)NH2 (8-16 µg/ml) and Citropin 1.1 (16-64 µg/ml), while higher MICs were evidenced for LL-37, Pexiganan and Pal-KKKK-NH2 (> 128 µg/ml). In time-kill experiments, Citropin 1.1 and CA(1-7)M(2-9)NH2 showed a relatively high percentage of growth inhibition (>30 %) for all the tested MRSA clinical isolates, with a dose-dependent activity resulting in the highest percentage of bacterial growth inhibition (89.39%) at 2MIC concentration. Conclusion: Overall, our data demonstrated the potential of some AMPs against MRSA isolates, such as Citropin 1.1 and CA(1-7)M(2-9)NH2, that represents a promising area of development for different clinical applications.
- Published
- 2019
21. Characterization of a new transferable MDR plasmid carrying thepbp5gene from a clade B commensalEnterococcus faecium
- Author
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Gianmarco Mangiaterra, Gianluca Morroni, Eleonora Giovanetti, Simona Fioriti, Carla Vignaroli, Andrea Brenciani, Barbara Citterio, Francesca Biavasco, Oscar Cirioni, and Alice Litta-Mulondo
- Subjects
0301 basic medicine ,Microbiology (medical) ,Gene Transfer, Horizontal ,Genotype ,Listeria ,Enterococcus faecium ,030106 microbiology ,Microbial Sensitivity Tests ,Real-Time Polymerase Chain Reaction ,Microbiology ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Plasmid ,Antibiotic resistance ,Amp resistance ,law ,Drug Resistance, Multiple, Bacterial ,Humans ,Penicillin-Binding Proteins ,Pharmacology (medical) ,030212 general & internal medicine ,Polymerase chain reaction ,Southern blot ,Pharmacology ,biology ,Chromosome Mapping ,High-Throughput Nucleotide Sequencing ,Methyltransferases ,biochemical phenomena, metabolism, and nutrition ,biology.organism_classification ,Healthy Volunteers ,Anti-Bacterial Agents ,Electrophoresis, Gel, Pulsed-Field ,Blotting, Southern ,Infectious Diseases ,Listeria welshimeri ,Genes, Bacterial ,Conjugation, Genetic ,Chromosomal region ,Plasmids - Abstract
OBJECTIVES To evaluate the transferability of antibiotic resistance from an MDR clade B Enterococcus faecium and to characterize the genetic elements involved. METHODS The erm(B)-positive strain E. faecium 37BA (donor) and strains E. faecium 64/3 and Listeria welshimeri 11857RF (recipients) were used in mating experiments. Donors and transconjugants were characterized using MIC assays, PFGE, Southern blotting and hybridization, quantitative RT-PCR (RT-qPCR), next-generation sequencing and PCR mapping. RESULTS One E. faecium and one L. welshimeri transconjugant were selected for in-depth investigation. Both acquired an ∼40 kb plasmid carrying erm(B). An additional plasmid of ∼200 kb, encoding the full conjugation machinery, was detected in the donor and in the E. faecium transconjugant. Next-generation sequencing revealed a new 40 396 bp plasmid that was designated pEf37BA; it contained 10 antibiotic resistance genes, tet(M), tet(L), erm(B), aadE, sat4, aphA, spw, lsa(E), lnu(B) and pbp5, resulting from the recombination of pM7M2 of E. faecium with an MDR chromosomal region of Erysipelothrix rhusiopathiae. A pbp5-carrying circular form was also detected. The PBP5 amino acid sequence differed from the C46 variant by two mutations (S39T and D644N). Its expression was documented in both transconjugants. pEf37BA persisted in the absence of selective pressure. CONCLUSIONS The MDR clade B E. faecium plasmid, deriving from the recombination of two different resistance regions, carried a pbp5 element and was transferable to different bacterial species. This finding further documents the dissemination of ampicillin resistance among community-associated E. faecium and the key role of commensal strains in the spread of antibiotic resistance.
- Published
- 2019
22. Role of Daptomycin in Cutaneous Wound Healing: A Narrative Review
- Author
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Giulio Rizzetto, Elisa Molinelli, Giulia Radi, Federico Diotallevi, Oscar Cirioni, Lucia Brescini, Andrea Giacometti, Annamaria Offidani, and Oriana Simonetti
- Subjects
Microbiology (medical) ,Infectious Diseases ,Pharmacology (medical) ,General Pharmacology, Toxicology and Pharmaceutics ,Biochemistry ,Microbiology - Abstract
Daptomycin is active against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and the on-label indications for its use include complicated skin and skin structure infections (cSSSI). We performed a narrative review of the literature with the aim to evaluate the role of daptomycin in the skin wound healing process, proposing our point of view on the possible association with other molecules that could improve the skin healing process. Daptomycin may improve wound healing in MRSA-infected burns, surgical wounds, and diabetic feet, but further studies in humans with histological examination are needed. In the future, the combination of daptomycin with other molecules with synergistic action, such as vitamin E and derivates, IB-367, RNA III-inhibiting peptide (RIP), and palladium nanoflowers, may help to improve wound healing and overcome forms of antibiotic resistance.
- Published
- 2022
23. Safety and Efficacy of Vaccines during COVID-19 Pandemic in Patients Treated with Biological Drugs in a Dermatological Setting
- Author
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Elisa Molinelli, Giulio Rizzetto, Oriana Simonetti, Giulia Radi, Oscar Cirioni, Marcello Mario D’Errico, Federico Diotallevi, and Annamaria Offidani
- Subjects
medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,Leadership and Management ,lcsh:Medicine ,Health Informatics ,Review ,Omalizumab ,Immunoglobulin E ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Health Information Management ,Randomized controlled trial ,law ,Pandemic ,medicine ,030212 general & internal medicine ,biologic therapy ,Interleukin inhibitors ,Intensive care medicine ,TNF-α inhibitors ,030203 arthritis & rheumatology ,Covid-19 vaccine ,Attenuated vaccine ,biology ,business.industry ,Health Policy ,lcsh:R ,Evidence-based medicine ,Vaccination ,dermatology ,biology.protein ,business ,medicine.drug - Abstract
The BNT162b2 and mRNA-1273 vaccines, consisting of mRNA, have recently become available. The absolute novelty of these vaccines introduces questions about their safety and efficacy, especially in patients who are treated with biological drugs in dermatology. The aim of our review was to provide a broad overview of the current use of all available vaccinations in concomitance with biological therapy and to suggest indications for the new mRNA Covid-19 vaccines. We conducted a narrative review of the literature regarding the indications and safety of the various types of vaccines currently available in dermatological patients treated with biological therapy. The safety and efficacy of administering inactivated vaccines in patients undergoing biological therapy with inhibitors of TNF-α, IL-17, IL-12/23, and IL-4/13 was confirmed. Inactivated vaccines can be administered during therapy with inhibitors of IL-23 and IgE, taking into account that the level of evidence is lower due to the lack of specific studies. Live attenuated vaccines were contraindicated in concomitance with all biological therapies considered, except omalizumab. According to this evidence, we assume that there are currently no contraindications to the administration of the new Covid-19 BNT162b2 and mRNA-1273 vaccines during biological therapy with inhibitors of TNF-α, IL-17, IL-12/23, IL-23, and IL-4/13, since these vaccines are comparable to inactivated ones. For patients with chronic urticaria or allergic asthma treated with omalizumab, we currently recommend caution in using the mRNA Covid-19 vaccines (30 min observation). The only contraindications were a previous history of hypersensitivity to the Covid-19 vaccines themself or to their excipients. In conclusion, further randomized clinical trials are needed to evaluate the efficacy of the antibody response in these patients.
- Published
- 2021
24. Synergistic effect of antimicrobial peptide LL-37 and colistin combination against multidrug-resistant
- Author
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Gianluca, Morroni, Laura Di, Sante, Oriana, Simonetti, Lucia, Brescini, Wojciech, Kamysz, Elzbieta, Kamysz, Marina, Mingoia, Andrea, Brenciani, Eleonora, Giovanetti, Patrizia, Bagnarelli, Andrea, Giacometti, and Oscar, Cirioni
- Subjects
Colistin ,Cathelicidins ,Drug Resistance, Multiple, Bacterial ,Escherichia coli Proteins ,Escherichia coli ,Humans ,Drug Synergism ,Microbial Sensitivity Tests ,Escherichia coli Infections ,Anti-Bacterial Agents ,Antimicrobial Cationic Peptides - Published
- 2021
25. Review: A Safety Profile of Dalbavancin for On- and Off-Label Utilization
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Giulio Rizzetto, Oriana Simonetti, Annamaria Offidani, Elisa Molinelli, and Oscar Cirioni
- Subjects
safety ,medicine.medical_specialty ,Lipoglycopeptide ,Review ,030204 cardiovascular system & hematology ,Skin infection ,Off-label use ,law.invention ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,Medicine ,Pharmacology (medical) ,030212 general & internal medicine ,General Pharmacology, Toxicology and Pharmaceutics ,Adverse effect ,Chemical Health and Safety ,business.industry ,Incidence (epidemiology) ,Dalbavancin ,Retrospective cohort study ,General Medicine ,ABSSSI ,medicine.disease ,adverse events ,skin infections ,chemistry ,business ,Safety Research ,dalbavancin - Abstract
Introduction Dalbavancin is a bactericidal lipoglycopeptide active against gram-positives. Its use has been approved for the treatment of acute bacterial skin and skin structure infections (ABSSSI). Methods We conducted a narrative review of the literature on the safety profile of dalbavancin. The bibliographic research was carried out on the PubMed database on 6 November 2020 by seeking combinations of the following keywords: dalbavancin, adverse effects, safety, drug interactions, and skin infections. Results Five double-blind Phase 3 randomized clinical trials, 2 open-label randomized trials, and 4 retrospective studies were identified. No statistically significant differences were found between dalbavancin and comparators in the incidence of adverse events. Retrospective studies confirm the low incidence of adverse events. Conclusion Dalbavancin is a therapeutic option that has demonstrated an excellent safety profile, also in relation to the other MRSA therapies available. Its use represents a cost-effective solution for the treatment of those patients with ABSSSI who would need hospitalization. One limitation of this study is that most of the available data are from Phase III clinical trials. Further real-life studies with a larger sample size are therefore needed to better assess the safety profile of the dalbavancin, especially to investigate the true incidence of rare adverse events.
- Published
- 2020
26. New Evidence and Insights on Dalbavancin and Wound Healing in a Mouse Model of Skin Infection
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Lucia Brescini, Mauro Provinciali, Fiorenza Orlando, Raffaella Lazzarini, Oscar Cirioni, Annamaria Offidani, Oriana Simonetti, Andrea Giacometti, Gianluca Morroni, Antonio Zizzi, and Guendalina Lucarini
- Subjects
Vascular Endothelial Growth Factor A ,Staphylococcus aureus ,medicine.drug_class ,Antibiotics ,Pharmacology ,Skin infection ,medicine.disease_cause ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Vancomycin ,Matrix Metalloproteinase 13 ,Animals ,Surgical Wound Infection ,Medicine ,Pharmacology (medical) ,Mechanisms of Action: Physiological Effects ,030304 developmental biology ,Mice, Inbred BALB C ,Wound Healing ,0303 health sciences ,integumentary system ,030306 microbiology ,business.industry ,Dalbavancin ,Granulation tissue ,medicine.disease ,Bacterial Load ,Anti-Bacterial Agents ,ErbB Receptors ,Vascular endothelial growth factor ,Disease Models, Animal ,Infectious Diseases ,medicine.anatomical_structure ,Matrix Metalloproteinase 9 ,chemistry ,Staphylococcal Skin Infections ,Teicoplanin ,business ,Wound healing ,medicine.drug - Abstract
Dalbavancin is an effective antibiotic that is widely used to treat skin infection. Our aim was to determine the effect of dalbavancin administration on wound healing compared to that of vancomycin and to elucidate if epidermal growth factor receptor (EGFR), matrix metalloproteinase 1 (MMP-1), MMP-9, and vascular endothelial growth factor (VEGF) could be involved in its therapeutic mechanism. A mouse model of methicillin-resistant Staphylococcus aureus (MRSA) skin infection was established. Mice were treated daily with vancomycin (10 mg/kg) and weekly with dalbavancin at day 1 (20 mg/kg) and day 8 (10 mg/kg). After 14 days, wounds were excised, and bacterial counts were performed. Wound healing was assessed by histological and immunohistochemical staining, followed by protein extraction and immunoblotting. Our microbiological results confirmed that both dalbavancin and vancomycin are effective in reducing the bacterial load in wounds. The dalbavancin group showed a strong effect compared with infected untreated animals and the vancomycin-treated group. The wounds treated with dalbavancin showed robust epidermal coverage with reconstitution of the regular and keratinized epidermal lining and well-organized granulation tissue with numerous blood vessels, although slightly less than that in the uninfected group. While in the vancomycin-treated group the epithelium appeared, in general, still hypertrophic, the granulation tissue appeared even less organized. We observed elevated EGFR and VEGF expression in both treated groups, although it was higher in dalbavancin-treated mice. MMP-1 and MMP-9 were decreased in uninfected tissue and in both treated tissues compared with untreated infected wounds. This study showed faster healing with dalbavancin treatment that might be associated with higher EGFR and VEGF levels.
- Published
- 2020
27. Potential application of berberine in the treatment of
- Author
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Elisa, Pierpaoli, Oscar, Cirioni, Oriana, Simonetti, Fiorenza, Orlando, Andrea, Giacometti, Paolo, Lombardi, and Mauro, Provinciali
- Subjects
Mice ,Berberine ,Sepsis ,Escherichia coli ,Animals - Abstract
Gram-negative sepsis ranks as the leading cause of death in intensive care units. Despite the development of new antibiotics, mortality from gram-negative sepsis remains high. The present study aims to investigate the
- Published
- 2020
28. Antimicrobial Resistance: A Challenge for the Future
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Lucia Brescini, Andrea Giacometti, Marcello Mario D’Errico, Emilia Prospero, Francesco Barchiesi, Stefano Menzo, Andrea Brenciani, Patrizia Bagnarelli, Oscar Cirioni, Pietro E. Varaldo, Bruna Facinelli, Giorgio Scalise, Marina Mingoia, Francesco Di Stanislao, and Pamela Barbadoro
- Subjects
medicine.medical_specialty ,business.industry ,medicine.drug_class ,Public health ,media_common.quotation_subject ,Antibiotics ,Antibiotic resistance ,Multidisciplinary approach ,Hygiene ,Epidemiology ,Medicine ,business ,Intensive care medicine ,media_common - Abstract
The global emergence of antibiotic-resistance, together with the lack of/reduced development of new antibiotic molecules, currently represents a serious public health problem as it can mean the return to a pre-antibiotic era in which infections caused by multiple-resistant pathogens are intractable. Since the beginnings, the interest of the Institutes of Microbiology, Hygiene and Public Health, and Infectious Diseases was focused on antibiotic resistance: from molecular mechanisms, through epidemiology and clinical issues, to prevention. Future perspectives include the search of new strategies and/or new compounds for prevention and control of difficult-to-treat pathogens in a multidisciplinary approach.
- Published
- 2020
29. New Perspectives on Old and New Therapies of Staphylococcal Skin Infections: The Role of Biofilm Targeting in Wound Healing
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Andrea Giacometti, Annamaria Offidani, Oriana Simonetti, Giulio Rizzetto, Giulia Radi, Oscar Cirioni, and Elisa Molinelli
- Subjects
Microbiology (medical) ,Chronic wound ,medicine.drug_class ,Antibiotics ,Antimicrobial peptides ,wound healing ,Review ,RM1-950 ,medicine.disease_cause ,Biochemistry ,Microbiology ,Antibiotic resistance ,medicine ,Pharmacology (medical) ,General Pharmacology, Toxicology and Pharmaceutics ,integumentary system ,business.industry ,staphylococcal skin infection ,biochemical phenomena, metabolism, and nutrition ,Antimicrobial ,antimicrobial molecules ,Infectious Diseases ,Staphylococcus aureus ,Immunology ,Therapeutics. Pharmacology ,medicine.symptom ,Wound healing ,business ,Staphylococcal Skin Infections - Abstract
Among the most common complications of both chronic wound and surgical sites are staphylococcal skin infections, which slow down the wound healing process due to various virulence factors, including the ability to produce biofilms. Furthermore, staphylococcal skin infections are often caused by methicillin-resistant Staphylococcus aureus (MRSA) and become a therapeutic challenge. The aim of this narrative review is to collect the latest evidence on old and new anti-staphylococcal therapies, assessing their anti-biofilm properties and their effect on skin wound healing. We considered antibiotics, quorum sensing inhibitors, antimicrobial peptides, topical dressings, and antimicrobial photo-dynamic therapy. According to our review of the literature, targeting of biofilm is an important therapeutic choice in acute and chronic infected skin wounds both to overcome antibiotic resistance and to achieve better wound healing.
- Published
- 2021
30. Antimicrobial Activity of Aztreonam in Combination with Old and New β-Lactamase Inhibitors against MBL and ESBL Co-Producing Gram-Negative Clinical Isolates: Possible Options for the Treatment of Complicated Infections
- Author
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Gianluca Morroni, Roberta Migliavacca, Francesco Comandatore, Francesco Luzzaro, Raffaela Bressan, Simona Fioriti, Luigi Principe, Stefano Di Bella, Gloria D’Achille, Cristina Lagatolla, Aurora Piazza, Carola Mauri, Oscar Cirioni, Marina Mingoia, Morroni, Gianluca, Bressan, Raffaela, Fioriti, Simona, D’Achille, Gloria, Mingoia, Marina, Cirioni, Oscar, Di Bella, Stefano, Piazza, Aurora, Comandatore, Francesco, Mauri, Carola, Migliavacca, Roberta, Luzzaro, Francesco, Principe, Luigi, and Lagatolla, Cristina
- Subjects
Microbiology (medical) ,Bacilli ,Avibactam ,RM1-950 ,MBL ,Aztreonam ,Biochemistry ,Microbiology ,Tazobactam ,Article ,β-lactamases inhibitors ,chemistry.chemical_compound ,synergism ,polycyclic compounds ,medicine ,Pharmacology (medical) ,General Pharmacology, Toxicology and Pharmaceutics ,aztreonam ,MBLs ,ESBL ,complicated infection ,difficult-to-treat pathogen ,Gram ,Vaborbactam ,biology ,Sulbactam ,biochemical phenomena, metabolism, and nutrition ,bacterial infections and mycoses ,Antimicrobial ,biology.organism_classification ,β-lactamases inhibitor ,Infectious Diseases ,chemistry ,Therapeutics. Pharmacology ,medicine.drug - Abstract
Metallo-β-lactamases (MBLs) are among the most challenging bacterial enzymes to overcome. Aztreonam (ATM) is the only β-lactam not hydrolyzed by MBLs but is often inactivated by co-produced extended-spectrum β-lactamases (ESBL). We assessed the activity of the combination of ATM with old and new β-lactamases inhibitors (BLIs) against MBL and ESBL co-producing Gram-negative clinical isolates. Six Enterobacterales and three non-fermenting bacilli co-producing MBL and ESBL determinants were selected as difficult-to-treat pathogens. ESBLs and MBLs genes were characterized by PCR and sequencing. The activity of ATM in combination with seven different BLIs (clavulanate, sulbactam, tazobactam, vaborbactam, avibactam, relebactam, zidebactam) was assessed by microdilution assay and time–kill curve. ATM plus avibactam was the most effective combination, able to restore ATM susceptibility in four out of nine tested isolates, reaching in some cases a 128-fold reduction of the MIC of ATM. In addition, relebactam and zidebactam showed to be effective, but with lesser reduction of the MIC of ATM. E. meningoseptica and C. indologenes were not inhibited by any ATM–BLI combination. ATM–BLI combinations demonstrated to be promising against MBL and ESBL co-producers, hence providing multiple options for treatment of related infections. However, no effective combination was found for some non-fermentative bacilli, suggesting the presence of additional resistance mechanisms that complicate the choice of an active therapy.
- Published
- 2021
31. Colistin enhances therapeutic efficacy of daptomycin or teicoplanin in a murine model of multiresistant Acinetobacter baumannii sepsis
- Author
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Maria Michela Cappelletti Trombettoni, Mauro Provinciali, Alessandra Barucca, Oriana Simonetti, Fiorenza Orlando, Oscar Cirioni, Maria Pelloni, Annamaria Offidani, Roberto Ghiselli, Mario Guerrieri, Andrea Giacometti, and Elisa Pierpaoli
- Subjects
Acinetobacter baumannii ,Male ,0301 basic medicine ,Microbiology (medical) ,030106 microbiology ,Microbial Sensitivity Tests ,Microbiology ,Sepsis ,03 medical and health sciences ,Daptomycin ,In vivo ,Drug Resistance, Multiple, Bacterial ,polycyclic compounds ,medicine ,Animals ,In vitro study ,Mice, Inbred BALB C ,biology ,Colistin ,Teicoplanin ,business.industry ,Drug Synergism ,General Medicine ,biochemical phenomena, metabolism, and nutrition ,bacterial infections and mycoses ,medicine.disease ,biology.organism_classification ,Survival Analysis ,Anti-Bacterial Agents ,Disease Models, Animal ,Treatment Outcome ,Infectious Diseases ,Murine model ,bacteria ,Drug Therapy, Combination ,lipids (amino acids, peptides, and proteins) ,business ,Acinetobacter Infections ,medicine.drug - Abstract
We investigated the efficacy of colistin combined with teicoplanin or daptomycin in an experimental mouse model of multiresistant Acinetobacter baumannii infection. Animal received intraperitoneally 1ml saline containing 2×1010CFU of A. baumannii. Colistin, daptomycin, teicoplanin, and colistin plus daptomycin or teicoplanin were given by intraperitoneal administration 2h after bacterial challenge. A control group received sodium chloride solution. In the in vitro study A. baumannii showed to be susceptible only to colistin with MIC of 2mg/l. In the in vivo study, colistin alone showed a good antimicrobial efficacy. When combined with teicoplanin or daptomycin, colistin produced the lowest bacterial and the best survival rates. In immunological studies, when colistin was associated to daptomycin or teicoplanin, both the number and the cytotoxic activity of NK cells increased. In conclusion, colistin combined with teicoplanin or daptomycin may improve the therapy of multiresistant A. baumannii infection.
- Published
- 2016
32. Spread of colistin resistance gene mcr-1 in Italy: characterization of the mcr-1.2 allelic variant in a colistin-resistant blood isolate of Escherichia coli
- Author
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Sefora Castelletti, Chiara Vincenzi, Gianluca Morroni, Serena Simoni, Marina Mingoia, Pietro E. Varaldo, Oscar Cirioni, Andrea Brenciani, and Eleonora Giovanetti
- Subjects
0301 basic medicine ,Microbiology (medical) ,030106 microbiology ,Microbial Sensitivity Tests ,Biology ,medicine.disease_cause ,Colistin resistance ,Microbiology ,03 medical and health sciences ,Plasmid ,Drug Resistance, Bacterial ,Escherichia coli ,medicine ,Humans ,Allele ,Gene ,Alleles ,Escherichia coli Infections ,Colistin ,Escherichia coli Proteins ,General Medicine ,Middle Aged ,Anti-Bacterial Agents ,Infectious Diseases ,Italy ,Female ,MCR-1 ,hormones, hormone substitutes, and hormone antagonists ,Plasmids ,medicine.drug - Abstract
mcr-1.2, an allelic variant of the transferable colistin resistance gene mcr-1, was characterized in a colistin-resistant blood isolate of Escherichia coli. It was harbored by an IncX4-type plasmid (33,293 bp). Despite its low prevalence, the potentially worrying spread of the mcr-1 gene, particularly its mcr-1.2 variant, in Italy requires increasing surveillance.
- Published
- 2018
33. High Rate of Ceftobiprole Resistance among Clinical Methicillin-Resistant Staphylococcus aureus Isolates from a Hospital in Central Italy
- Author
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Oscar Cirioni, Antonella Pocognoli, Marina Mingoia, Simona Fioriti, Andrea Brenciani, Lucia Brescini, Andrea Giacometti, Serena Simoni, Eleonora Giovanetti, Gianluca Morroni, and Francesco Barchiesi
- Subjects
0301 basic medicine ,Pharmacology ,High rate ,Penicillin binding proteins ,medicine.drug_class ,SCCmec ,030106 microbiology ,Cephalosporin ,Ceftobiprole ,biochemical phenomena, metabolism, and nutrition ,Biology ,medicine.disease_cause ,Methicillin-resistant Staphylococcus aureus ,Microbiology ,03 medical and health sciences ,Infectious Diseases ,Staphylococcus aureus ,polycyclic compounds ,medicine ,Therapeutic failure ,Pharmacology (medical) - Abstract
Ceftobiprole is a fifth-generation cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA). One-year surveillance at the Regional Hospital of Ancona (Italy) disclosed a 12% ceftobiprole resistance rate (12/102 isolates; MIC, ≥4 mg/liter). Epidemiological characterization demonstrated that the resistant isolates all belonged to different clones. Penicillin-binding protein (PBP) analysis showed substitutions in all PBPs and a novel insertion in PBP2a. The mecB and mecC genes were not detected. Ceftobiprole susceptibility screening is essential to avoid therapeutic failure and the spread of ceftobiprole-resistant strains.
- Published
- 2018
34. Enhanced Efficacy of Combinations of Pexiganan with Colistin Versus Acinetobacter Baumannii in Experimental Sepsis
- Author
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Andrea Giacometti, Daniele Minardi, Oriana Simonetti, Maria Pelloni, Annamaria Offidani, Mario Guerrieri, Maria Michela Cappelletti Trombettoni, Oscar Cirioni, Elisa Pierpaoli, Mauro Provinciali, Roberto Ghiselli, Fiorenza Orlando, and Alessandra Barucca
- Subjects
Acinetobacter baumannii ,Male ,0301 basic medicine ,medicine.medical_treatment ,030106 microbiology ,Pharmacology ,Critical Care and Intensive Care Medicine ,Bacterial counts ,Immunophenotyping ,Sepsis ,Mice ,03 medical and health sciences ,In vivo ,polycyclic compounds ,medicine ,Animals ,Saline ,Mice, Inbred BALB C ,biology ,Colistin ,business.industry ,Positive interaction ,biochemical phenomena, metabolism, and nutrition ,bacterial infections and mycoses ,biology.organism_classification ,medicine.disease ,Anti-Bacterial Agents ,030104 developmental biology ,Emergency Medicine ,bacteria ,lipids (amino acids, peptides, and proteins) ,business ,Bacteria ,Antimicrobial Cationic Peptides ,medicine.drug - Abstract
We investigated the efficacy of colistin combined with pexiganan in experimental mouse models of Acinetobacter baumannii infection.Adult male BALB/c mice received intraperitoneally 1 mL saline containing 2 × 10 CFU of susceptible and multiresistant A. baumannii. Two hours after bacterial challenge, animals received 1 mg/kg of colistin, 1 mg/kg of pexiganan, or 1 mg/kg of colistin plus 1 mg/kg of pexiganan.Blood culture positivity, the quantities of bacteria in the intra-abdominal fluid, the rate of lethality and immunological studies, such as immunophenotyping and NK cytotoxicity, were evaluated.In the in vitro study, A. baumannii showed susceptibility to colistin and pexiganan and a strong synergy was observed by testing colistin combined with pexiganan with fractionary inhibitory concentration index of 0.312 for both strains.In the in vivo study colistin or pexiganan alone showed a good antimicrobial efficacy. When colistin was combined with pexiganan, the positive interaction produced low bacterial counts that were statistically significant versus singly treated groups. For both strains the highest rate of survival was observed in combined-treated groups (90%).Pexiganan increased NK cytotoxic activity over the levels of infected and colistin-treated animals.In conclusion, pexiganan combined with colistin was found to be efficacious against A. baumannii infection.
- Published
- 2016
35. HIV-1 DNA dynamics and variations in HIV-1 DNA protease and reverse transcriptase sequences in multidrug-resistant patients during successful raltegravir-based therapy
- Author
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Silvia Baroncelli, Oscar Cirioni, Marco Floridia, Vincenzo Fragola, L. E. Weimer, Zuleika Michelini, Daniela Francisci, Andrea Cara, Nicoletta Ladisa, Clementina Maria Galluzzo, Angela Vivarelli, Anna Degli Antoni, and Maria Franca Pirillo
- Subjects
0301 basic medicine ,Mutation ,030106 microbiology ,virus diseases ,RNA ,Biology ,medicine.disease_cause ,Raltegravir ,Resistance mutation ,Virology ,Reverse transcriptase ,Raltegravir Potassium ,03 medical and health sciences ,chemistry.chemical_compound ,Infectious Diseases ,chemistry ,medicine ,Gene ,DNA ,medicine.drug - Abstract
There is limited information on the variations of HIV-1 DNA mutation profile in reverse transcriptase (RT) and protease (PR) genes during suppressive antiretroviral treatment (plasma HIV-1 RNA continuously 2.5 copies/ml). Integrated HIV-1 DNA did not show fluctuations during the study period. Sequencing of the PR and RT regions from HIV-1 DNA revealed changes in the resistance mutation profile in five patients. Total HIV-1 DNA declined after the introduction of RAL-based therapy, with a rebound after 2 years. No changes were observed in levels of integrated DNA, suggesting limited effect on archived HIV. The RT and PR sequence changes in archived HIV-1 DNA suggest that variation of the mutation profile can occur even in the absence of detectable HIV-1 RNA. J. Med. Virol. 88:2115-2124, 2016. © 2016 Wiley Periodicals, Inc.
- Published
- 2016
36. whISOBAXTM Inhibits Bacterial Pathogenesis and Enhances the Effect of Antibiotics
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Gianluca Morroni, Lucia Brescini, Reuven Rasooly, Hwang Yong Choi, Emmanouil Apostolidis, Paula Do, Andrea Giacometti, and Oscar Cirioni
- Subjects
witch hazel ,0301 basic medicine ,Microbiology (medical) ,medicine.drug_class ,030106 microbiology ,Antibiotics ,medicine.disease_cause ,checkerboard assay ,Biochemistry ,Microbiology ,Article ,Enterococcus faecalis ,03 medical and health sciences ,chemistry.chemical_compound ,Staphylococcus epidermidis ,biofilm inhibition ,medicine ,Pharmacology (medical) ,General Pharmacology, Toxicology and Pharmaceutics ,isobologram analysis ,whISOBAX ,biology ,Pseudomonas aeruginosa ,Chemistry ,lcsh:RM1-950 ,biology.organism_classification ,Ciprofloxacin ,antibacterial ,lcsh:Therapeutics. Pharmacology ,030104 developmental biology ,Infectious Diseases ,Staphylococcus aureus ,Linezolid ,staphylococcal enterotoxin inhibition ,Bacteria ,medicine.drug - Abstract
As bacteria are becoming more resistant to commonly used antibiotics, alternative therapies are being sought. whISOBAX (WH) is a witch hazel extract that is highly stable (tested up to 2 months in 37 °, C) and contains a high phenolic content, where 75% of it is hamamelitannin and traces of gallic acid. Phenolic compounds like gallic acid are known to inhibit bacterial growth, while hamamelitannin is known to inhibit staphylococcal pathogenesis (biofilm formation and toxin production). WH was tested in vitro for its antibacterial activity against clinically relevant Gram-positive and Gram-negative bacteria, and its synergy with antibiotics determined using checkerboard assays followed by isobologram analysis. WH was also tested for its ability to suppress staphylococcal pathogenesis, which is the cause of a myriad of resistant infections. Here we show that WH inhibits the growth of all bacteria tested, with variable efficacy levels. The most WH-sensitive bacteria tested were Staphylococcus epidermidis, Staphylococcus aureus, Enterococcus faecium and Enterococcus faecalis, followed by Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Streptococcus agalactiae and Streptococcus pneumoniae. Furthermore, WH was shown on S. aureus to be synergistic to linezolid and chloramphenicol and cumulative to vancomycin and amikacin. The effect of WH was tested on staphylococcal pathogenesis and shown here to inhibit biofilm formation (tested on S. epidermidis) and toxin production (tested on S. aureus Enterotoxin A (SEA)). Toxin inhibition was also evident in the presence of subinhibitory concentrations of ciprofloxacin that induces pathogenesis. Put together, our study indicates that WH is very effective in inhibiting the growth of multiple types of bacteria, is synergistic to antibiotics, and is also effective against staphylococcal pathogenesis, often the cause of persistent infections. Our study thus suggests the benefits of using WH to combat various types of bacterial infections, especially those that involve resistant persistent bacterial pathogens.
- Published
- 2020
37. Viscoelastic behaviour of hyaluronic acid formulations containing carvacrol prodrugs with antibacterial properties
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Ivana Cacciatore, Antonio Di Stefano, Gianluca Morroni, Andrea Giacometti, Lisa Marinelli, Piera Eusepi, Oscar Cirioni, and Giuseppe Di Biase
- Subjects
Keratinocytes ,Drug Compounding ,Enterococcus faecium ,Pharmaceutical Science ,Microbial Sensitivity Tests ,02 engineering and technology ,030226 pharmacology & pharmacy ,Enterococcus faecalis ,Viscoelasticity ,Excipients ,03 medical and health sciences ,Minimum inhibitory concentration ,chemistry.chemical_compound ,0302 clinical medicine ,Cell Movement ,Hyaluronic acid ,Humans ,Prodrugs ,Carvacrol ,Hyaluronic Acid ,Cells, Cultured ,Wound Healing ,Chromatography ,biology ,Viscosity ,Chemistry ,Prodrug ,021001 nanoscience & nanotechnology ,biology.organism_classification ,Antimicrobial ,Elasticity ,Anti-Bacterial Agents ,Drug Liberation ,Kinetics ,Solubility ,Cymenes ,0210 nano-technology - Abstract
In this paper, we report the development and viscoelastic properties of hyaluronic acid formulations (HA5, HA30, and HA60, containing 0.5, 3, and 6% HA, respectively) loaded with carvacrol prodrugs (WSCPS) with antibacterial properties. Notably, antimicrobial studies revealed that WSCP1-2 in both HA5 and HA30 formulations showed the best minimum inhibitory concentration (MIC) values against Enterococcus faecium (128 mg/L) and Enterococcus faecalis (256 mg/L) compared to those of carvacrol alone or in formulations with HA. Moreover, rheological analyses showed that HA30 composites exhibited a semi-solid consistency, while HA5 formulations possessed a fluid consistency. Considering these data, HA30 is a useful formulation which guarantees a good percentage of prodrug release (e.g., 30 and 60% for WSCP1 and 2, respectively) as well as a texture suitable for topical administration to treat wounds and/or skin infections.
- Published
- 2020
38. Witch Hazel Significantly Improves the Efficacy of Commercially Available Teat Dips
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Reuven Rasooly, Emmanouil Apostolidis, Paula Do, Andrea Giacometti, Gianluca Morroni, Oscar Cirioni, Adel Molnar, and Lucia Brescini
- Subjects
0301 basic medicine ,Microbiology (medical) ,escherichia coli ,Witch hazel ,medicine.drug_class ,030106 microbiology ,Antibiotics ,lcsh:Medicine ,pseudomonas aeruginosa ,mastitis ,medicine.disease_cause ,Article ,biofilm ,Microbiology ,03 medical and health sciences ,Escherichia coli ,medicine ,Immunology and Allergy ,Molecular Biology ,General Immunology and Microbiology ,biology ,Pseudomonas aeruginosa ,Chemistry ,lcsh:R ,technology, industry, and agriculture ,Biofilm ,biology.organism_classification ,030104 developmental biology ,Infectious Diseases ,witch hazel extract ,staphylococcus ,Antibacterial activity ,Staphylococcus ,Bacteria - Abstract
Bovine intramammary infections (IMIs) are the main cause of economic loss in milk production. Antibiotics are often ineffective in treating infections due to antimicrobial resistance and the formation of bacterial biofilms that enhance bacterial survival and persistence. Teat dips containing germicides are recommended to prevent new IMIs and improve udder health and milk quality. IMIs are often caused by staphylococci, which are Gram-positive bacteria that become pathogenic by forming biofilms and producing toxins. As a model for a teat dip (DIP), the BacStop iodine-based teat dip (DIP) was used. Witch hazel extract (whISOBAX (WH)) was tested because it contains a high concentration of the anti-biofilm/anti-toxin phenolic compound hamamelitannin. We found that the minimal inhibitory or bactericidal concentrations of DIP against planktonic S. epidermidis cells increased up to 160-fold in the presence of WH, and that DIP was 10-fold less effective against biofilm cells. While both DIP and WH are effective in inhibiting the growth of S. aureus, only WH inhibits toxin production (tested for enterotoxin-A). Importantly, WH also significantly enhances the antibacterial effect of DIP against Gram-negative bacteria that can cause IMIs, like Escherichia coli and Pseudomonas aeruginosa. Put together, these results suggest that the antibacterial activity of DIP combined with WH is significantly higher, and thus have potential in eradicating bacterial infections, both in acute (planktonic-associated) and in chronic (biofilm-associated) conditions.
- Published
- 2020
39. Efficacy of Pexiganan Combination with Tigecycline in a Mouse Model of Pseudomonas aeruginosa Sepsis
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Elżbieta Kamysz, Annamaria Offidani, Mauro Provinciali, Andrea Giacometti, Gianluca Morroni, Lucia Brescini, Fiorenza Orlando, Monia Orciani, Oriana Simonetti, Miriam Caffarini, Claudio Agostinelli, Elisa Pierpaoli, Oscar Cirioni, and Wojciech Kamysz
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Male ,medicine.drug_class ,Cell Survival ,Antibiotics ,Antimicrobial peptides ,Tigecycline ,Microbial Sensitivity Tests ,medicine.disease_cause ,Azithromycin ,01 natural sciences ,Microbiology ,Mice ,Structure-Activity Relationship ,Antibiotic resistance ,Drug Resistance, Multiple, Bacterial ,Sepsis ,Drug Discovery ,medicine ,Animals ,Humans ,Cell Proliferation ,Mice, Inbred BALB C ,Dose-Response Relationship, Drug ,business.industry ,Pseudomonas aeruginosa ,Broth microdilution ,General Medicine ,Antimicrobial ,0104 chemical sciences ,Anti-Bacterial Agents ,010404 medicinal & biomolecular chemistry ,Disease Models, Animal ,Drug Therapy, Combination ,business ,Injections, Intraperitoneal ,medicine.drug ,Antimicrobial Cationic Peptides ,HeLa Cells - Abstract
Background: Pseudomonas aeruginosa is a gram-negative pathogen, associated with a severe mortality rate. It is also difficult to treat due to numerous resistance mechanisms to a wide range of antibiotics. Objective: Evaluate the activity of pexiganan, an antimicrobial peptide, in combination with two clinical antibiotics (azithromycin and tigecycline) that are not active against P. aeruginosa. Methods: Ten clinical P. aeruginosa were isolated from urinary tract infections, blood culture, skin infections and respiratory tract infections. Minimum inhibitory concentrations (MICs) and synergies were evaluated by broth microdilution, checkerboard assays and time-kill studies. In vitro synergy was confirmed with an in vivo experiment using a murine model of sepsis. Results: Pexiganan MICs were included between 2 and 16 mg/L. Tigecycline and azithromycin MICs were high as expected (4-64 mg/L and 32-256 mg/L, respectively). Pexiganan and azithromycin combination resulted to be additive or indifferent while tigecycline and pexiganan combination was synergic against seven out of ten P. aeruginosa and additive against the other strains. In vivo experiment confirmed the in vitro synergy, denoting a significative reduction of bacteria in mice treated with pexiganan and tigecycline combination. Conclusion: Antimicrobial peptides are molecules that could be useful in the fight against infections and pexiganan seems to be one of the most promising. Our results demonstrated that, in association with tigecycline, pexiganan administration could overcome antibiotic resistance and increase the effectiveness of treatment against P. aeruginosa sepsis.
- Published
- 2018
40. High Rate of Ceftobiprole Resistance among Clinical Methicillin-Resistant
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Gianluca, Morroni, Andrea, Brenciani, Lucia, Brescini, Simona, Fioriti, Serena, Simoni, Antonella, Pocognoli, Marina, Mingoia, Eleonora, Giovanetti, Francesco, Barchiesi, Andrea, Giacometti, and Oscar, Cirioni
- Subjects
Methicillin-Resistant Staphylococcus aureus ,Microbial Sensitivity Tests ,biochemical phenomena, metabolism, and nutrition ,Staphylococcal Infections ,Hospitals ,Anti-Bacterial Agents ,Bacterial Typing Techniques ,Cephalosporins ,Italy ,Mechanisms of Resistance ,Drug Resistance, Multiple, Bacterial ,Mutation ,polycyclic compounds ,Humans ,Penicillin-Binding Proteins ,Multilocus Sequence Typing - Abstract
Ceftobiprole is a fifth-generation cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA). One-year surveillance at the Regional Hospital of Ancona (Italy) disclosed a 12% ceftobiprole resistance rate (12/102 isolates; MIC, ≥4 mg/liter). Epidemiological characterization demonstrated that the resistant isolates all belonged to different clones. Penicillin-binding protein (PBP) analysis showed substitutions in all PBPs and a novel insertion in PBP2a. The mecB and mecC genes were not detected. Ceftobiprole susceptibility screening is essential to avoid therapeutic failure and the spread of ceftobiprole-resistant strains.
- Published
- 2018
41. Characterization of a Multiresistance Plasmid Carrying the
- Author
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Gianluca, Morroni, Andrea, Brenciani, Alberto, Antonelli, Marco Maria, D'Andrea, Vincenzo, Di Pilato, Simona, Fioriti, Marina, Mingoia, Carla, Vignaroli, Oscar, Cirioni, Francesca, Biavasco, Pietro E, Varaldo, Gian Maria, Rossolini, and Eleonora, Giovanetti
- Published
- 2018
42. Characterization of a multiresistance plasmid carrying the optra and Cfr resistance genes from an enterococcus faecium clinical isolate
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Gianluca Morroni, Andrea Brenciani, Alberto Antonelli, Marco Maria D’Andrea, Vincenzo Di Pilato, Simona Fioriti, Marina Mingoia, Carla Vignaroli, Oscar Cirioni, Francesca Biavasco, Pietro E. Varaldo, Gian Maria Rossolini, and Eleonora Giovanetti
- Subjects
0301 basic medicine ,Microbiology (medical) ,Multiresistance plasmid ,030106 microbiology ,Enterococcus faecium ,lcsh:QR1-502 ,Context (language use) ,Settore BIO/19 - Microbiologia Generale ,Microbiology ,lcsh:Microbiology ,Enterococcus faecalis ,03 medical and health sciences ,Plasmid ,Staphylococcus sciuri ,Cfr gene ,Insertion sequence ,OptrA gene ,Genetics ,biology ,biology.organism_classification ,Settore MED/07 - Microbiologia e Microbiologia Clinica ,Oxazolidinone resistance ,Transformation (genetics) ,Composite transposon - Abstract
Enterococcus faecium E35048, a bloodstream isolate from Italy, was the first strain where the oxazolidinone resistance gene optrA was detected outside China. The strain was also positive for the oxazolidinone resistance gene cfr. WGS analysis revealed that the two genes were linked (23.1 kb apart), being co-carried by a 41,816-bp plasmid that was named pE35048-oc. This plasmid also carried the macrolide resistance gene erm(B) and a backbone related to that of the well-known Enterococcus faecalis plasmid pRE25 (identity 96%, coverage 65%). The optrA gene context was original, optrA being part of a composite transposon, named Tn6628, which was integrated into the gene encoding for the ζ toxin protein (orf19 of pRE25). The cfr gene was flanked by two ISEnfa5 insertion sequences and the element was inserted into an lnu(E) gene. Both optrA and cfr contexts were excisable. pE35048-oc could not be transferred to enterococcal recipients by conjugation or transformation. A plasmid-cured derivative of E. faecium E35048 was obtained following growth at 42°C, and the complete loss of pE35048-oc was confirmed by WGS. pE35048-oc exhibited some similarity but also notable differences from pEF12-0805, a recently described enterococcal plasmid from human E. faecium also co-carrying optrA and cfr; conversely it was completely unrelated to other optrA- and cfr-carrying plasmids from Staphylococcus sciuri. The optrA-cfr linkage is a matter of concern since it could herald the possibility of a co-spread of the two genes, both involved in resistance to last resort agents such as the oxazolidinones.
- Published
- 2018
43. In vitro and in vivo activity of fosfomycin alone and in combination with rifampin and tigecycline against Gram-positive cocci isolated from surgical wound infections
- Author
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Gianluca Morroni, Annamaria Offidani, Fiorenza Orlando, Oscar Cirioni, Mario Guerrieri, Andrea Giacometti, Mauro Provinciali, Roberto Ghiselli, Oriana Simonetti, Andrea Brenciani, and Ledia Xhuvelaj
- Subjects
0301 basic medicine ,Microbiology (medical) ,Male ,Methicillin-Resistant Staphylococcus aureus ,030106 microbiology ,Enterococcus faecium ,Minocycline ,Tigecycline ,Microbial Sensitivity Tests ,Biology ,Fosfomycin ,medicine.disease_cause ,Microbiology ,Enterococcus faecalis ,03 medical and health sciences ,Mice ,In vivo ,medicine ,Animals ,Humans ,Surgical Wound Infection ,Mice, Inbred BALB C ,Soft Tissue Infections ,General Medicine ,Skin Diseases, Bacterial ,biochemical phenomena, metabolism, and nutrition ,biology.organism_classification ,Antimicrobial ,Anti-Bacterial Agents ,Gram-Positive Cocci ,Staphylococcus aureus ,Rifampin ,Rifampicin ,medicine.drug - Abstract
Complicated skin and soft tissue infections constitute a heterogeneous group of severe disorders, with surgical site infections being the most common hospital-acquired ones. The aim of our study was to investigate the synergistic and bactericidal activities of antimicrobial combinations of fosfomycin with rifampicin and tigecycline against Enterococcus faecalis, Enterococcus faecium and methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates, and also to evaluate their in vivo effects in a mouse wound infection model. In in vitro studies, the combinations of fosfomycin with rifampicin and tigecycline were both synergistic. These synergies were confirmed in in vivo studies: the drug combinations showed the highest antimicrobial effects compared to monotherapy. In conclusion, the efficacy of fosfomycin combinations, also confirmed in our in vivo model, may suggest new directions in the treatment of infected skin and a possible alternative way to control bacterial skin infection.
- Published
- 2017
44. Role of Daptomycin on Burn Wound Healing in an Animal Methicillin-Resistant Staphylococcus aureus Infection Model
- Author
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Mario Guerrieri, Elisa Pierpaoli, Roberto Ghiselli, Andrea Giacometti, Mauro Provinciali, Annamaria Offidani, Oscar Cirioni, Pamela Castelli, Oriana Simonetti, Guendalina Lucarini, Roberto Di Primio, and Fiorenza Orlando
- Subjects
Male ,Methicillin-Resistant Staphylococcus aureus ,0301 basic medicine ,medicine.medical_specialty ,030106 microbiology ,Microbial Sensitivity Tests ,Fibroblast growth factor ,medicine.disease_cause ,Gastroenterology ,Cicatrix ,03 medical and health sciences ,Daptomycin ,In vivo ,Internal medicine ,Animals ,Medicine ,Pharmacology (medical) ,Rats, Wistar ,Mechanisms of Action: Physiological Effects ,Cell Proliferation ,Pharmacology ,Wound Healing ,business.industry ,Teicoplanin ,Epithelial Cells ,Staphylococcal Infections ,Methicillin-resistant Staphylococcus aureus ,Bacterial Load ,Thermal burn ,Anti-Bacterial Agents ,Rats ,ErbB Receptors ,Disease Models, Animal ,030104 developmental biology ,Infectious Diseases ,Staphylococcus aureus ,Wound Infection ,Fibroblast Growth Factor 2 ,Burns ,Wound healing ,business ,medicine.drug - Abstract
Prolonged hospitalization and antibiotic therapy are risk factors for the development of methicillin-resistant Staphylococcus aureus (MRSA) infections in thermal burn patients. We used a rat model to study the in vivo efficacy of daptomycin in the treatment of burn wound infections by S. aureus , and we evaluated the wound healing process through morphological and immunohistochemical analysis. A copper bar heated in boiling water was applied on a paraspinal site of each rat, resulting in two full-thickness burns. A small gauze was placed over each burn and inoculated with 5 × 10 7 CFU of S. aureus ATCC 43300. The study included two uninfected control groups with and without daptomycin treatment, an infected control group that did not receive any treatment, and two infected groups treated, respectively, with intraperitoneal daptomycin and teicoplanin. The main outcome measures were quantitative culture, histological evaluation of tissue repair, and immunohistochemical expression of wound healing markers: epidermal growth factor receptor (EGFR) and fibroblast growth factor 2 (FGF-2). The highest inhibition of infection was achieved in the group that received daptomycin, which reduced the bacterial load from 10 7 CFU/ml to about 10 3 CFU/g ( P < 0.01). The groups treated with daptomycin showed better overall healing with epithelialization and significantly higher collagen scores than the other groups, and these findings were also confirmed by immunohistochemical data. In conclusion, our results support the hypothesis that daptomycin is an important modulator of wound repair by possibly reducing hypertrophic burn scar formation.
- Published
- 2017
45. Supplementation with tocotrienols from Bixa orellana improves the in vivo efficacy of daptomycin against methicillin-resistant Staphylococcus aureus in a mouse model of infected wound
- Author
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Oriana Simonetti, Mauro Provinciali, Oscar Cirioni, Andrea Giacometti, Elisa Pierpaoli, and Fiorenza Orlando
- Subjects
0301 basic medicine ,Methicillin-Resistant Staphylococcus aureus ,medicine.drug_class ,medicine.medical_treatment ,030106 microbiology ,Antibiotics ,Pharmaceutical Science ,Microbial Sensitivity Tests ,medicine.disease_cause ,Microbiology ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Adjuvants, Immunologic ,Daptomycin ,In vivo ,Drug Discovery ,Medicine ,Animals ,030212 general & internal medicine ,Pharmacology ,Mice, Inbred BALB C ,business.industry ,Vitamin E ,Tocotrienols ,Bixaceae ,Staphylococcal Infections ,Methicillin-resistant Staphylococcus aureus ,Anti-Bacterial Agents ,Disease Models, Animal ,Complementary and alternative medicine ,Staphylococcus aureus ,Wound Infection ,Molecular Medicine ,business ,Wound healing ,medicine.drug - Abstract
Background Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of skin and soft-tissue infection worldwide. An adequate immune response acts as a first line of defence against infections and therefore plays an essential role in the maintenance of health. Tocotrienols (T3s), the lesser known isomers of vitamin E, possess many biological properties and have been recognized as immunomodulators. Purpose The aim of this study was to investigate whether the in vivo supplementation with a mixture of 87.1% δ- and 12.9% γ-T3s extract from seeds of Bixa orellana, (T3s) could be effective in increasing the effect of daptomycin (DAP) in a mouse model of wound infection due to MRSA. Study design/methods Bacteria were inoculated onto full-thickness wound on the dorsal side of BALB/c mice at 5 × 106 CFU per mouse. Mice were randomized into five groups: an uninfected group, an infected-untreated group, a T3s-pretreated group with no antibiotics given after challenge, a T3s-pretreated group plus DAP given after challenge, a group only given DAP after challenge. Main outcome measures were: bacterial load on the wounds, analysis of Natural Killer (NK) cytotoxicity, immunological phenotype and markers of tissue repair. Results Our results showed that bacterial load in wounds from mice receiving T3s or DAP alone was 1- or 3-log10 lower, respectively, compared with the infected-untreated group. T3s plus daptomycin showed the highest efficacy, achieving a 4-log10 decrease in bacterial load. This higher antimicrobial effect was associated with increased levels of NK cytotoxicity and markers of wound repair. Conclusion These data suggest that treatment with T3s may be useful for the management of infected wounds as immune adjuvants in combination with DAP.
- Published
- 2017
46. Relationship Between Health-Related Quality of Life Measures and High HIV Viral Load in HIV-Infected Triple-Class-Experienced Patients
- Author
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Vincenzo Fragola, Francesco Ortu, S. Donnini, Nicoletta Ladisa, Daniela Francisci, Rita Bellagamba, M Mannazzu, Massimiliano Digregorio, Mariagrazia Mancini, Giustino Parruti, Anna Degli Antoni, L. E. Weimer, Marco Floridia, Oscar Cirioni, Katherina Pugliese, Giovanni Guaraldi, Raffaella Bucciardini, Raffaella Libertone, and Zaira Maroccia
- Subjects
Adult ,Male ,medicine.medical_specialty ,Anti-HIV Agents ,HIV Infections ,HRQoL ,Young Adult ,Acquired immunodeficiency syndrome (AIDS) ,Quality of life ,Surveys and Questionnaires ,Internal medicine ,Hiv infected ,medicine ,Humans ,HIV infection ,viral load ,Pharmacology (medical) ,Depression (differential diagnoses) ,Aged ,Social functioning ,Health related quality of life ,business.industry ,virus diseases ,Middle Aged ,Viral Load ,medicine.disease ,humanities ,CD4 Lymphocyte Count ,Cross-Sectional Studies ,Infectious Diseases ,Quality of Life ,Physical therapy ,RNA, Viral ,Anxiety ,Female ,medicine.symptom ,business ,Viral load - Abstract
Health-related quality of life (HRQoL) has been recognized as a central measure of the overall health status in HIV patients. With the availability of different highly effective drug combinations, maximizing quality-adjusted survival has become a major target of HIV treatment. Although the association of HIV RNA and CD4 cell count with clinical HIV progression has been well established, the relation between these markers and HRQoL measures is still unclear.This cross-sectional study investigated the relationship linking HIV RNA and CD4 to HRQoL measures in 181 triple-class-experienced patients with advanced HIV disease. The instrument used was the ISSQoL, a self-administered and HIV-specific HRQoL questionnaire.Data showed no correlation between HRQoL measures and CD4 counts. Higher HIV RNA levels were, however, associated with poor HRQoL scores in 3 out of 9 scales of social functioning, depression and anxiety, and satisfaction with quality of life. In multivariable analyses, only the satisfaction with quality of life mean score remained significantly lower for the HIV RNA ≯100,000 copies/mL group compared to the HIV RNA 50 to 10,000 copies/mL group.Although other determinants of HRQoL in people with HIV should also be considered, this finding suggests a negative impact of high viral load on perceived HRQoL that adds to other described determinants of lower quality of life in people with HIV, such as lower social support and self-reported symptoms.
- Published
- 2014
47. In vitro activity and in vivo animal model efficacy of IB-367 alone and in combination with imipenem and colistin against Gram-negative bacteria
- Author
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Carmela Silvestri, Oriana Simonetti, Andrea Giacometti, Elżbieta Kamysz, Susanna Mazzocato, Annamaria Offidani, Mauro Provinciali, Wojciech Kamysz, Fiorenza Orlando, Mario Guerrieri, Roberto Ghiselli, and Oscar Cirioni
- Subjects
Acinetobacter baumannii ,Imipenem ,Gram-negative bacteria ,Physiology ,medicine.drug_class ,Administration, Topical ,Antibiotics ,Microbial Sensitivity Tests ,medicine.disease_cause ,Biochemistry ,Microbiology ,Cellular and Molecular Neuroscience ,Endocrinology ,In vivo ,Escherichia coli ,polycyclic compounds ,medicine ,Animals ,Humans ,Mice, Inbred BALB C ,biology ,Colistin ,Pseudomonas aeruginosa ,Pseudomonas ,biology.organism_classification ,Anti-Bacterial Agents ,Disease Models, Animal ,Klebsiella pneumoniae ,Drug Therapy, Combination ,Gram-Negative Bacterial Infections ,Injections, Intraperitoneal ,Antimicrobial Cationic Peptides ,medicine.drug - Abstract
The aim of our study was to evaluate the in vitro activity of IB-367 and its bactericidal effect for Pseudomonas aeruginosa and Escherichia coli, associated to a synergic study to test the antibiotic combinations between the peptide and colistin or imipenem. Minimum inhibitory concentrations (MICs), the minimum bactericidal concentrations (MBCs), the synergy test and killing study were carried out to evaluate the IB-367 activity. In the in vivo model, a wound was incised through the panniculus carnosus of BALB/c mice, and then inoculated with 5 × 107 colony-forming units of P. aeruginosa and E. coli. For each strain, the study included an infected or not infected group that did not receive any treatment, and five contaminated groups treated with local IB- 367, intraperitoneal imipenem, intraperitoneal colistin, topical IB-367 local plus intraperitoneal imipenem or intraperitoneal colistin. All isolates were inhibited by IB-367 at concentrations of 4-64 mg/l. Killing by IB-367 was shown to be very rapid: its activity on all Gram-negative bacteria was completed within a 40 min exposure period at a concentration of 2 × MIC/l. Synergy was demonstrated when IB-367 was combined with colistin or imipenem. In in vivo studies, the groups treated with topical IB-367 and intraperitoneal colistin showed the best results in terms of bacterial load inhibition either for Pseudomonas or for E. coli. The good in vitro activity and in vivo efficacy, as well as, the synergic interactions with antibiotics suggest that IB-367 is a promising candidate for potential application in the treatment of wound Gram-negative infections.
- Published
- 2014
48. Interindividual and Intra-Individual Variabilities of Darunavir and Ritonavir Plasma Trough Concentrations in Multidrug Experienced HIV Patients Receiving Salvage Regimens
- Author
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Daniela Francisci, Vincenzo Fragola, L. E. Weimer, Angela Vivarelli, Clementina Maria Galluzzo, Maria Franca Pirillo, Mario Regazzi, Paola Villani, Giustino Parruti, A. Cavalli, Laura Sighinolfi, Anna Volpe, Marco Floridia, Maria Cusato, Oscar Cirioni, Sara Tedeschi, Silvia Baroncelli, Federica Sozio, Baroncelli S., Villani P., Galluzzo C.M., Cavalli A., Volpe A., Francisci D., Vivarelli A., Sozio F., Tedeschi S., Cirioni O., Sighinolfi L., Cusato M., Pirillo M.F., Weimer L.E., Fragola V., Parruti G., Regazzi M., and Floridia M.
- Subjects
Adult ,Male ,medicine.medical_specialty ,Time Factors ,Genotype ,Coefficient of variation ,Salvage therapy ,HIV Infections ,Context (language use) ,Gastroenterology ,Young Adult ,Interquartile range ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,Chromatography, High Pressure Liquid ,Darunavir ,Ctrough ,Aged ,Salvage Therapy ,Pharmacology ,Sulfonamides ,Ritonavir ,business.industry ,Intraindividual variation ,HIV Protease Inhibitors ,Middle Aged ,Raltegravir ,Regimen ,HIV-1 ,RNA, Viral ,Drug Therapy, Combination ,Female ,business ,medicine.drug - Abstract
BACKGROUND:: There is no consensus on darunavir (DRV) target levels in plasma for clinical use, and information about variability in plasma concentrations is limited. AIM:: To investigate the variability in DRV plasma trough concentrations in the clinical setting, evaluating interindividual and intraindividual variabilities of plasma drug levels among HIV-infected patients receiving ritonavir (RTV)-boosted DRV (DRV/r) within salvage regimens, and evaluate the potential correlation between variability and virological response. METHODS:: Sixty-two patients taking DRV/r (600/100 mg twice a day) were evaluated for trough plasma concentrations and immunovirological parameters after 6 months from the start of the regimen. A subgroup of patients (n = 21) was also evaluated for intraindividual variability (expressed as coefficient of variation) on 2 samples taken at different time points. Drug concentrations were assayed by high-performance liquid chromatography with ultraviolet detection, and the values were expressed as medians with interquartile range (IQR). Genotypic sensitivity score and genotypic inhibitory quotient were calculated. RESULTS:: DRV/r was used with a median of 3 other antiretroviral drugs (raltegravir use 88.7%). Median plasma concentrations were 3.22 mcg/mL (IQR, 2.04-5.69) for DRV and 0.44 mcg/mL (IQR, 0.21-0.70) for RTV. Both drugs showed a high interindividual variability in plasma concentrations (61% and 99.3%, respectively). Only 3 patients (4.8%) had undetectable DRV plasma levels. DRV plasma concentrations showed a significant positive correlation with age (r = 0.298, P = 0.019), but no significant correlation between DRV genotypic inhibitory quotient and HIV-RNA plasma levels (P = 0.614) was found. Intraindividual coefficients of variation were 58.4% for DRV and 47.1% for RTV. Patients with undetectable HIV-RNA showed a trend for lower intraindividual coefficients of variation compared with patients with detectable HIV-RNA (55.9% versus 83.8%, P = 0.156). No major interaction effects with other antiretroviral drugs were found. CONCLUSIONS:: In a context of salvage therapy, both DRV and RTV plasma levels showed high interindividual and intraindividual variabilities. Lower intraindividual variability could be beneficial in maintaining viral suppression. Copyright © 2013 by Lippincott Williams & Wilkins.
- Published
- 2013
49. The Efficacy of the Quorum Sensing Inhibitor FS8 and Tigecycline in Preventing Prosthesis Biofilm in an Animal Model of Staphylococcal Infection
- Author
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Andrea Giacometti, Ivana Cacciatore, Erika Fornasari, Pamela Castelli, Oriana Simonetti, Federico Mocchegiani, Fiorenza Orlando, Carmela Silvestri, Oscar Cirioni, Mauro Provinciali, Marco Vivarelli, Annamaria Offidani, and Leonardo Baldassarre
- Subjects
Male ,Antibiotics ,FS8 ,Minocycline ,Tigecycline ,medicine.disease_cause ,lcsh:Chemistry ,Antibiotic prophylaxis ,lcsh:QH301-705.5 ,Spectroscopy ,Polyethylene Terephthalates ,Quorum Sensing ,General Medicine ,Staphylococcal Infections ,Antimicrobial ,Computer Science Applications ,Anti-Bacterial Agents ,Staphylococcus aureus ,tigecycline ,Oligopeptides ,medicine.drug ,Protein Binding ,Prosthesis-Related Infections ,medicine.drug_class ,Microbial Sensitivity Tests ,Biology ,Staphylococcal infections ,Catalysis ,Article ,Microbiology ,Inorganic Chemistry ,medicine ,Animals ,Amino Acid Sequence ,vascular graft infection ,Physical and Theoretical Chemistry ,Rats, Wistar ,Molecular Biology ,Microbial Viability ,Organic Chemistry ,Biofilm ,medicine.disease ,lipopeptides ,Rats ,Disease Models, Animal ,bacterial biofilm ,lcsh:Biology (General) ,lcsh:QD1-999 ,Biofilms - Abstract
We investigated the efficacy of tigecycline and FS8, alone or combined, in preventing prosthesis biofilm in a rat model of staphylococcal vascular graft infection. Graft infections were established in the back subcutaneous tissue of adult male Wistar rats by implantation of Dacron prostheses followed by topical inoculation with 2 x 107 colony-forming units of Staphylococcus aureus, strain Smith diffuse. The study included a control group, a contaminated group that did not receive any antibiotic prophylaxis, and three contaminated groups that received: (i) intraperitoneal tigecycline, (ii) FS8-soaked graft, and (iii) tigecycline plus FS8-soaked graft, respectively. Each group included 15 animals. The infection burden was evaluated by using sonication and quantitative agar culture. Moreover, an in vitro binding-study was performed to quantify the how much FS8 was coated to the surface of the prosthesis. Tigecycline, combined with FS8, against the adherent bacteria showed MICs (2.00 mg/L) and MBCs (4.00 mg/L) four-fold lower with respect to tigecycline alone in in vitro studies. The rat groups treated with tigecycline showed the lowest bacterial numbers (4.4 x 104 ± 1.2 x 104 CFU/mL). The FS8-treated group showed a good activity and significant differences compared to control group with bacterial numbers of 6.8 x 104 ± 2.0 x 104 CFU/mL. A stronger inhibition of bacterial growth was observed in rats treated with a combined FS8 and tigecycline therapy than in those that were singly treated with bacterial numbers of 101 CFU/mL graft. In conclusion, the ability to affect biofilm formation as well, its property to be an antibiotic enhancer suggests FS8 as alternative or additional agent to use in conjunction with conventional antimicrobial for prevention of staphylococcal biofilm related infection.
- Published
- 2013
50. Quorum sensing inhibitor FS3-coated vascular graft enhances daptomycin efficacy in a rat model of staphylococcal infection
- Author
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Marco Vivarelli, Carmela Silvestri, Erika Fornasari, Jacopo Vecchiet, Claudio Ucciferri, Leonardo Baldassarre, Ivana Cacciatore, Federico Mocchegiani, Mauro Provinciali, Oscar Cirioni, Pamela Castelli, Elena Orsetti, and Andrea Giacometti
- Subjects
Male ,Staphylococcus aureus ,Physiology ,medicine.drug_class ,Antibiotics ,Biology ,medicine.disease_cause ,Biochemistry ,Microbiology ,Cellular and Molecular Neuroscience ,Minimum inhibitory concentration ,Endocrinology ,Daptomycin ,In vivo ,medicine ,Animals ,Humans ,Antibiotic prophylaxis ,Minimum bactericidal concentration ,Biofilm ,Quorum Sensing ,Prostheses and Implants ,Staphylococcal Infections ,Rats ,Disease Models, Animal ,Vascular Grafting ,medicine.drug - Abstract
The aim of the study was to investigate the efficacy of the quorum sensing inhibitor FS3 and daptomycin in preventing prosthesis biofilm in a rat model of staphylococcal vascular graft infection. Graft infections were established in the back subcutaneous tissue of adult male Wistar rats by implantation of Dacron prostheses followed by topical inoculation with 2×10(7) colony-forming units of Staphylococcus aureus, strain Smith diffuse. The study included a control group, a contaminated group that did not receive any antibiotic prophylaxis and three contaminated groups that received: (i) intraperitoneal daptomycin, (ii) FS3-soacked graft, and (iii) daptomycin plus FS3-soaked graft, respectively. Each group included 15 animals. The infection burden was evaluated by using sonication and quantitative agar culture. Moreover, an in vitro binding-study was performed to quantify the how much FS3 was coated to the surface of the prosthesis. The in vitro studies showed, that minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values for daptomycin were lower in presence of FS3. In in vivo studies, when tested alone, daptomycin and FS3 showed good efficacies. Their combination showed efficacies significantly higher than that of each single compound. Daptomycin is an important candidate for prevention of staphylococcal biofilm related infection and FS3 could serve as an interesting anti-staphylococcal antibiotic enhancer.
- Published
- 2013
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