Efficacy of Skin and Nasal Povidone-Iodine Preparation and Iodine-Containing Formulations in Treating Methicillin-Resistant Staphylococcus aureus Colonization of Ex Vivo Mucosal Tissue Model

Methicillin resistant Staphylococcus aureus (MRSA) induced skin infections have become a challenging problem due to the escalating antibiotic resistance. Carvacrol (CAR) has been reported to be effective against MRSA. However, due to its characteristics, CAR exhibits low skin retention. In this study, CAR was formulated into site-specific nanoparticle (NPs) delivery system using poly(ε-caprolactone) (PCL), following incorporation into a hydrogel matrix to facilitate dermal delivery. The release study exhibited significantly higher release of CAR from PCL NPs in the presence of bacterial lipase, highlighting its potential for differential delivery. Moreover, encapsulation of CAR in PCL NPs resulted in a two-fold increase in its anti-MRSA activity. Dermatokinetic studies revealed that the NPs loaded hydrogel was able to enhance skin retention of CAR after 24 h (83.29 ± 3.15%), compared to free CAR-loaded hydrogel (0.85 ± 0.14%). Importantly, this novel approach exhibited effective antimicrobial activity in an ex-vivo skin infection model. Hence, these findings have proven the concept that the loading of CAR into a responsive NPs system can lead to sustained antimicrobial effect at the desired site, and may provide a novel effective approach for treatment of MRSA induced skin infections. However, further studies must be conducted to investigate in-vivo efficacy of the developed system in an appropriate infection model.

Download Full-text

Impact of Bicarbonate-β-Lactam Exposures on Methicillin-Resistant Staphylococcus aureus (MRSA) Gene Expression in Bicarbonate-β-Lactam-Responsive vs. Non-Responsive Strains

Genes ◽

10.3390/genes12111650 ◽

2021 ◽

Vol 12 (11) ◽

pp. 1650

Author(s):

Selvi C. Ersoy ◽

Blake M. Hanson ◽

Richard A. Proctor ◽

Cesar A. Arias ◽

Truc T. Tran ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Cell Wall ◽

Methicillin Resistant Staphylococcus Aureus ◽

Ex Vivo ◽

In Vivo Models ◽

Methicillin Resistant ◽

Genetic Perturbations ◽

Functional Relevance

Methicillin-resistant Staphylococcus aureus (MRSA) infections represent a difficult clinical treatment issue. Recently, a novel phenotype was discovered amongst selected MRSA which exhibited enhanced β-lactam susceptibility in vitro in the presence of NaHCO3 (termed ‘NaHCO3-responsiveness’). This increased β-lactam susceptibility phenotype has been verified in both ex vivo and in vivo models. Mechanistic studies to-date have implicated NaHCO3-mediated repression of genes involved in the production, as well as maturation, of the alternative penicillin-binding protein (PBP) 2a, a necessary component of MRSA β-lactam resistance. Herein, we utilized RNA-sequencing (RNA-seq) to identify genes that were differentially expressed in NaHCO3-responsive (MRSA 11/11) vs. non-responsive (COL) strains, in the presence vs. absence of NaHCO3-β-lactam co-exposures. These investigations revealed that NaHCO3 selectively repressed the expression of a cadre of genes in strain 11/11 known to be a part of the sigB-sarA-agr regulon, as well as a number of genes involved in the anchoring of cell wall proteins in MRSA. Moreover, several genes related to autolysis, cell division, and cell wall biosynthesis/remodeling, were also selectively impacted by NaHCO3-OXA exposure in the NaHCO3-responsive strain MRSA 11/11. These outcomes provide an important framework for further studies to mechanistically verify the functional relevance of these genetic perturbations to the NaHCO3-responsiveness phenotype in MRSA.

Download Full-text

Infection prevention versus antimicrobial stewardship: Does nasal povidone-iodine interfere with methicillin-resistant Staphylococcus aureus (MRSA) screening?

Infection Control and Hospital Epidemiology ◽

10.1017/ice.2021.152 ◽

2021 ◽

pp. 1-2

Author(s):

Cecelia Harrison ◽

Robie Zent ◽

Elyse Schneck ◽

Cynthia E. Flynn ◽

Marci Drees

Keyword(s):

Staphylococcus Aureus ◽

Antimicrobial Stewardship ◽

Infection Prevention ◽

Methicillin Resistant Staphylococcus Aureus ◽

Povidone Iodine ◽

Methicillin Resistant

Download Full-text

Ex vivo efficacy of gemifloxacin in experimental keratitis induced by methicillin-resistant Staphylococcus aureus

International Journal of Antimicrobial Agents ◽

10.1016/j.ijantimicag.2016.06.026 ◽

2016 ◽

Vol 48 (4) ◽

pp. 395-400 ◽

Cited By ~ 4

Author(s):

Andreana Marino ◽

Anna Rita Blanco ◽

Giovanna Ginestra ◽

Antonia Nostro ◽

Giuseppe Bisignano

Keyword(s):

Staphylococcus Aureus ◽

Methicillin Resistant Staphylococcus Aureus ◽

Ex Vivo ◽

Methicillin Resistant ◽

Experimental Keratitis

Download Full-text

Bacterial Membrane-Derived Vesicles Attenuate Vancomycin Activity against Methicillin-Resistant Staphylococcus aureus

Microorganisms ◽

10.3390/microorganisms9102055 ◽

2021 ◽

Vol 9 (10) ◽

pp. 2055

Author(s):

Monika Kumaraswamy ◽

Kamilla Wiull ◽

Bishnu Joshi ◽

George Sakoulas ◽

Armin Kousha ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Antibiotic Resistance ◽

Whole Blood ◽

Methicillin Resistant Staphylococcus Aureus ◽

Ex Vivo ◽

Membrane Vesicles ◽

World Health ◽

Human Neutrophils ◽

Methicillin Resistant

Methicillin-resistant Staphylococcus aureus (MRSA) has evolved numerous antimicrobial resistance mechanisms and is identified as a serious public health threat by the World Health Organization and U.S. Centers for Disease Control and Prevention. The glycopeptide vancomycin (VAN) remains a cornerstone of therapy for severe MRSA infections despite increasing reports of therapeutic failure in hospitalized patients with bacteremia or pneumonia. Recently, the role of released bacterial-derived membrane vesicles (MVs) in antibiotic resistance has garnered attention. Here we examined the effect of exogenous MRSA-derived MVs on VAN activity against MRSA in vitro, using minimum inhibitory concentration and checkerboard assays, and ex vivo, incorporating components of host innate immunity such as neutrophils and serum complement present in blood. Additionally, the proteome of MVs from VAN-exposed MRSA was characterized to determine if protein expression was altered. The presence of MVs increased the VAN MIC against MRSA to values where clinical failure is commonly observed. Furthermore, the presence of MVs increased survival of MRSA pre-treated with sub-MIC concentrations of VAN in whole blood and upon exposure to human neutrophils but not human serum. Unbiased proteomic analysis also showed an elevated expression of MV proteins associated with antibiotic resistance (e.g., marR) or proteins that are functionally linked to cell membrane/wall metabolism. Together, our findings indicate MRSA-derived MVs are capable of lowering susceptibility of the pathogen to VAN, whole-blood- and neutrophil-mediated killing, a new pharmacodynamic consideration for a drug increasingly linked to clinical treatment failures.

Download Full-text