Synergic combinations of antimicrobial peptides (AMPs) against biofilms of methicillin-resistant Staphylococcus aureus (MRSA) on polystyrene and medical devices.

Abstract Objectives Antimicrobial research is being focused to look for more effective therapeutics against antibiotic-resistant infections caused by methicillin-resistantStaphylococcus aureus (MRSA). In this direction, antimicrobial peptides (AMP) appears 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 synergic activity against MRSA biofilms developed on polystyrene surface (PSS) and central venous catheter (CVC). Methods The research was subdivided into distinct phases to assess the ability of AMPs to inhibit biofilm formation, to identify a possible synergy between AMPs, and to eradicate preformed biofilms on PSS and CVC using AMPs alone or in combination. Results The activity of the AMPs was particularly evident in the inhibition of biofilm formation on PSS and on CVC, while the eradication of preformed biofilms was more difficult and was reached only after 24 h of contact. The synergic activity of AMPs combinations, selected by their FICI, has led to an improvement in the performance of all the molecules in the removal of different biofilms. Conclusions Overall, AMPs could represent the next generation of antimicrobial agents for a prophylactic or therapeutic tool to control biofilm of antibiotic-resistant and/or biofilm-associated infections on different medical devices

Role of Daptomycin in Cutaneous Wound Healing: A Narrative Review

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 resistanc

Effects of the Infusion of 4% or 20% Human Serum Albumin on the Skeletal Muscle Microcirculation in Endotoxemic Rats

Sepsis-induced microcirculatory alterations contribute to tissue hypoxia and organ dysfunction. In addition to its plasma volume expanding activity, human serum albumin (HSA) has anti-oxidant and anti-inflammatory properties and may have a protective role in the microcirculation during sepsis. The concentration of HSA infused may influence these effects. We compared the microcirculatory effects of the infusion of 4% and 20% HSA in an experimental model of sepsis

Activity of Antimicrobial Peptides and Conventional Antibiotics against Superantigen Positive Staphylococcus aureus Isolated from the Patients with Neoplastic and Inflammatory Erythrodermia

Superantigens are proteins comprising a group of molecules produced by various microorganisms. They are involved in pathogenesis of several human diseases. The aim of the study was the comparison of susceptibility to antibiotics and antimicrobial peptides (AMPs) of Staphylococcus aureus (SA) strains producing staphylococcal enterotoxins SEA, SEB, SEC, SED, and TSST-1 and nonproducing ones. In the group of the total 28 of the patients with erythrodermia the presence of SA was confirmed in 24 cases. The total of 14 strains of SA excreted enterotoxins SEA, SEC, SED, and TSST-1. We did not observe that strains producing mentioned superantigens were less susceptible to AMPs (aurein 1.2, citropin 1.1, lipopeptide, protegrin 1, tachyplesin 3, temporin A, and uperin 3.6). The opposite situation was observed in conventional antibiotics. SA strains excreting tested superantigens had higher MICs and MBCs than nonproducing ones. The interesting finding considering the high efficacy of AMPs, against all examined strains of SA, makes them attractive candidates for therapeutic implication

Temporin A as a prophylactic agent against methicillin sodium-susceptible and methicillin sodium-resistant Staphylococcus epidermidis vascular graft infection

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Clinical and microbiological features of ceftolozane/tazobactam-resistant Pseudomonas aeruginosa isolates in a university hospital in central Italy

Objectives: 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 surveil- lance study was conducted from October 2018 to March 2019 at the University Hospital ‘Ospedali Riuniti’ in Ancona, Italy. Methods: Minimum inhibitory concentrations (MICs) to C/T were determined by Etest strip. Resistant iso- lates were characterized by phenotypic (broth microdilution antimicrobial susceptibility testing and mod- ified 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. Results: 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 spec- trum 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. Conclusion: 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 clone

Characterization of a Multiresistance Plasmid Carrying the optrA and cfr Resistance Genes From an Enterococcus faecium Clinical Isolate

open13noEnterococcus 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.openMorroni, Gianluca; Brenciani, Andrea; Antonelli, Alberto; Maria D’Andrea, Marco; Di Pilato, Vincenzo; Fioriti, Simona; Mingoia, Marina; Vignaroli, Carla; Cirioni, Oscar; Biavasco, Francesca; Varaldo, Pietro E.; Rossolini, Gian Maria; Giovanetti, EleonoraMorroni, Gianluca; Brenciani, Andrea; Antonelli, Alberto; Maria D’Andrea, Marco; Di Pilato, Vincenzo; Fioriti, Simona; Mingoia, Marina; Vignaroli, Carla; Cirioni, Oscar; Biavasco, Francesca; Varaldo, Pietro E.; Rossolini, Gian Maria; Giovanetti, Eleonor

In-vitro activity of cationic peptides alone and in combination with clinically used antimicrobial agents against Pseudomonas aeruginosa.

The in-vitro activity of cecropin P1, indolicidin, magainin II, nisin and ranalexin alone and in combination with nine clinically used antimicrobial agents was investigated against a control strain, Pseudomonas aeruginosa ATCC 27853 and 40 clinical isolates of P. aeruginosa. Antimicrobial activities were measured by MIC, MBC and viable count. In the combination study, the clinically used antibiotics were used at concentrations close to their mean serum level in humans in order to establish the clinical relevance of the results. To select peptide-resistant mutants, P. aeruginosa ATCC 27853 was treated with consecutive cycles of exposure to each peptide at 1 x MIC. The peptides had a varied range of inhibitory values: all isolates were more susceptible to cecropin P1, while ranalexin showed the lowest activity. Nevertheless, synergy was observed when the peptides were combined with polymyxin E and clarithromycin. Consecutive exposures to each peptide at 1 x MIC resulted in the selection of stable resistant mutants. Cationic peptides might be valuable as new antimicrobial agents. Our findings show that they are effective against P. aeruginosa, and that their activity is enhanced when they are combined with clinically used antimicrobial agents, particularly with polymyxin E and clarithromycin

In vitro activities of polycationic peptides alone and in combination with clinically used antimicrobial agents against Rhodococcus equi.

The in vitro activities of magainin II, nisin, and ranalexin alone and in combination with other antimicrobial agents against six clinical isolates of Rhodococcus equi were investigated by MIC and time-kill studies. All isolates were more susceptible to nisin. A positive interaction was observed when the peptides were combined with ampicillin, ceftriaxone, rifabutin, rifampin, azithromycin, clarithromycin, and vancomycin