Allizond, Valeria

Banche, Giuliana

Cuffini, Annamaria

Musso, Tiziana

Scutera, Sara

Sparti, Rosaria

English

Scutera, Sara Agata Caterina

Institutional Research Information System University of Turin

O0920 The in vitro interplay between dalbavancin and human phagocytes againststaphylococci causing skin and skin-structure infectionsValeria Allizond*1, Giuliana Banche1, Sara Scutera2, Rosaria Sparti2, Tiziana Musso2, Anna Maria Cuffini11 Bacteriology Laboratory, Department of Public Health and Pediatrics, University of Torino, Turin, Italy., 2Immunology Laboratory, Department of Public Health and Pediatrics, University of Torino, Turin, Italy.Background: The skin and soft tissue infections (SSTIs) increase represents a major concern in both communityand hospital setting, carrying a significant economic burden, as well as morbidity and mortality, especially whencaused by methicillin-resistant Staphylococcus aureus (MRSA). Dalbavancin (DAL), a lipoglycopeptide, is indicatedfor the treatment of SSTIs, and has a broad spectrum of action against most microorganisms, including thoseresistant to other antimicrobials. The aim of this study was to determine the straightforward performance of DALupon the binomial antibiotic resistant staphylococci and host defenses, to establish its potentialimmunomodulating activity.Materials/methods: DAL effect (at 1xMIC or 2xMIC) on human polymorphonuclear cells (PMNs) functionalactivities (microbicidal activity and cytokine release profile) was investigated by incubating MRSA and phagocytesfor different incubation times. To differentiate between any separate effect of DAL on the bacteria and PMNs, invitro DAL pretreatment assays were also performed by the exposure of each of them to DAL (at 1xMIC) for 1 h,before they were incubated together.Results: Our results evidenced in DAL presence an enhanced MRSA killing activity by PMNs in comparison withDAL-free controls, within 90 minutes of incubation. In fact, in control condition PMNs were able to scanty killingested MRSA, whereas with the addition of DAL at 1xMIC or 2XMIC, significantly (p<0.01) enhanced theirstaphylococcal killing (Figure 1A). The assays with DAL pre-treated MRSA or PMNs highlighted a similar trend: animproved staphylococcal killing due to DAL direct effect on both staphylococci and PMNs within 90 minutes ofincubation (Figure 1 B). In parallel a decreased level of TNF-α was observed in DAL-treated PMNs in presence ofMRSA.Conclusions: Neutrophil-mediated killing is a crucial defense system against S. aureus, however the pathogen hasevolved many strategies to resist killing. In the present study, we highlighted that DAL acts in synergism withneutrophils by modulating both staphylococcal killing and cytokine release. A role of TNF in apoptosis regulationhas been observed that could indirectly influence the killing capacity. These preliminary results draw attention tothe need of a deeper understanding of the mechanisms exerted by DAL on neutrophil functional activities.29TH ECCMID13-16 APRIL 2019 AMSTERDAM, NETHERLANDS POWERED BY M-ANAGE.COM 

The in vitro interplay between dalbavancin and human phagocytes against staphylococci causing skin and skin-structure infections

https://iris.unito.it/bitstream/2318/1702525/1/O0920_Allizond.pdf

The in vitro interplay between dalbavancin and human phagocytes against staphylococci causing skin and skin-structure infections

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