scholarly journals Impact of Frequent Administration of Bacteriophage on Therapeutic Efficacy in an A. baumannii Mouse Wound Infection Model

2020 ◽  
Vol 11 ◽  
Author(s):  
Michael D. Rouse ◽  
Joshua Stanbro ◽  
Jessica A. Roman ◽  
Michelle A. Lipinski ◽  
Anna Jacobs ◽  
...  
2012 ◽  
Vol 8 (8) ◽  
pp. 2932-2940 ◽  
Author(s):  
Akihiro Saito ◽  
Hiromi Miyazaki ◽  
Toshinori Fujie ◽  
Shinya Ohtsubo ◽  
Manabu Kinoshita ◽  
...  

2004 ◽  
Vol 48 (8) ◽  
pp. 2918-2923 ◽  
Author(s):  
Roderic M. K. Dale ◽  
Glen Schnell ◽  
Jonathan P. Wong

ABSTRACT “Nubiotics” are a novel class of proprietary protonated nucleic acid-based drugs shown to have potent in vitro antibacterial activities against a number of gram-positive and gram-negative bacteria. These nubiotics are evaluated here for their in vivo therapeutic efficacy for the treatment of burn wound infection caused by Pseudomonas aeruginosa. To achieve this, a burn wound infection model was established in mice by using a highly pathogenic burn wound clinical isolate of P. aeruginosa. Lethal doses of the bacteria were determined for two routes of infection (subcutaneous and topical), representing systemic and local forms of infection, respectively. Using this infection model, treatment with nubiotics by various routes of drug administration was evaluated and optimized. A total of 12 nubiotics and their analogues were tested and of these, Nu-2, -3, -4, and -5 were found to be extremely efficacious in the postexposure treatment of burn wound infection (60 to 100% survival rates versus 0% for untreated control [P < 0.05]). These nubiotics were effective when given either systemically by intravenous and/or subcutaneous administration or given locally to the affected site in the skin by topical application. Treatment by these two routes resulted in almost 100% survival rates and complete eradication of the bacteria from infection sites in the livers, spleens, and blood. These nubiotics were found to be as effective as intravenously administered ciprofloxacin, a potent and broad-spectrum fluoroquinolone. These results suggest that nubiotics may be a promising and effective approach for the treatment of burn wound infection caused by P. aeruginosa.


2012 ◽  
Vol 256 (2) ◽  
pp. 371-377 ◽  
Author(s):  
Kathleen M. Guthrie ◽  
Ankit Agarwal ◽  
Dana S. Tackes ◽  
Kevin W. Johnson ◽  
Nicholas L. Abbott ◽  
...  

2021 ◽  
Vol 9 (9) ◽  
pp. 1821
Author(s):  
Linda Pätzold ◽  
Alexandra Stark ◽  
Felix Ritzmann ◽  
Carola Meier ◽  
Thomas Tschernig ◽  
...  

The epithelial cytokine interleukin-17C (IL-17C) mediates inflammation through the interleukin 17 receptor E (IL-17RE). Prior studies showed a detrimental role of IL-17C in the pathogenesis of immune-mediated skin diseases (e.g., psoriasis). Here, we examined the role of IL-17C/IL-17RE in wound closure in a Staphylococcus aureus wound infection model. We demonstrate that wound closure is significantly delayed in IL-17RE (Il-17re−/−)- and 17C (Il-17c−/−)-deficient mice. There was no significant difference between WT, Il-17re−/−, and Il-17c−/− mice in the absence of infection. Deficiency for IL-17RE and IL-17C did not significantly affect the elimination of bacteria. IL-17C expression was increased in the epidermis of human S. aureus-infected skin. Our results indicate that the IL-17C/IL-17RE axis contributes to the closure of infected wounds but does not contribute to the elimination of S. aureus.


Antibiotics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1481
Author(s):  
John Jairo Aguilera-Correa ◽  
Sara Fernández-López ◽  
Iskra Dennisse Cuñas-Figueroa ◽  
Sandra Pérez-Rial ◽  
Hanna-Leena Alakomi ◽  
...  

Staphylococcus aureus is the most common cause of surgical site infections and its treatment is challenging due to the emergence of multi-drug resistant strains such as methicillin-resistant S. aureus (MRSA). Natural berry-derived compounds have shown antimicrobial potential, e.g., ellagitannins such as sanguiin H-6 and lambertianin C, the main phenolic compounds in Rubus seeds, have shown antimicrobial activity. The aim of this study was to evaluate the effect of sanguiin H-6 and lambertianin C fractionated from cloudberry seeds, on the MRSA growth, and as treatment of a MRSA biofilm development in different growth media in vitro and in vivo by using a murine wound infection model where sanguiin H-6 and lambertianin C were used to prevent the MRSA infection. Sanguiin H-6 and lambertianin C inhibited the in vitro biofilm development and growth of MRSA. Furthermore, sanguiin H-6 showed significant anti-MRSA effect in the in vivo wound model. Our study shows the possible use of sanguiin H-6 as a preventive measure in surgical sites to avoid postoperative infections, whilst lambertianin C showed no anti-MRSA activity.


2019 ◽  
Vol 27 (4) ◽  
pp. 360-365 ◽  
Author(s):  
Stephen C. Davis ◽  
Jie Li ◽  
Joel Gil ◽  
Cheyanne Head ◽  
Jose Valdes ◽  
...  

Antibiotics ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 679
Author(s):  
Maha M. Ismail ◽  
Reham Samir ◽  
Fatema R. Saber ◽  
Shaimaa R. Ahmed ◽  
Mohamed A. Farag

Bacterial biofilm contributes to antibiotic resistance. Developing antibiofilm agents, more favored from natural origin, is a potential method for treatment of highly virulent multidrug resistant (MDR) bacterial strains; The potential of Pimenta dioica and Pimenta racemosa essential oils (E.Os) antibacterial and antibiofilm activities in relation to their chemical composition, in addition to their ability to treat Acinetobacter baumannii wound infection in mice model were investigated; P. dioica leaf E.O at 0.05 µg·mL−1 efficiently inhibited and eradicated biofilm formed by A. baumannii by 85% and 34%, respectively. Both P. diocia and P. racemosa leaf E.Os showed a bactericidal action against A. baumanii within 6h at 2.08 µg·mL−1. In addition, a significant reduction of A. baumannii microbial load in mice wound infection model was found. Furthermore, gas chromatography mass spectrometry analysis revealed qualitative and quantitative differences among P. racemosa and P. dioica leaf and berry E.Os. Monoterpene hydrocarbons, oxygenated monoterpenes, and phenolics were the major detected classes. β-Myrcene, limonene, 1,8-cineole, and eugenol were the most abundant volatiles. While, sesquiterpenes were found as minor components in Pimenta berries E.O; Our finding suggests the potential antimicrobial activity of Pimenta leaf E.O against MDR A. baumannii wound infections and their underlying mechanism and to be further tested clinically as treatment for MDR A. baumannii infections.


Pharmaceutics ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 199 ◽  
Author(s):  
Iman S. Ahmed ◽  
Osama S. Elnahas ◽  
Nouran H. Assar ◽  
Amany M. Gad ◽  
Rania El Hosary

With the alarming rise in incidence of antibiotic-resistant bacteria and the scarcity of newly developed antibiotics, it is imperative that we design more effective formulations for already marketed antimicrobial agents. Fusidic acid (FA), one of the most widely used antibiotics in the topical treatment of several skin and eye infections, suffers from poor water-solubility, sub-optimal therapeutic efficacy, and a significant rise in FA-resistant Staphylococcus aureus (FRSA). In this work, the physico-chemical characteristics of FA were modified by nanocrystallization and lyophilization to improve its therapeutic efficacy through the dermal route. FA-nanocrystals (NC) were prepared using a modified nanoprecipitation technique and the influence of several formulation/process variables on the prepared FA-NC characteristics were optimized using full factorial statistical design. The optimized FA-NC formulation was evaluated before and after lyophilization by several in-vitro, ex-vivo, and microbiological tests. Furthermore, the lyophilized FA-NC formulation was incorporated into a cream product and its topical antibacterial efficacy was assessed in vivo using a rat excision wound infection model. Surface morphology of optimized FA-NC showed spherical particles with a mean particle size of 115 nm, span value of 1.6 and zeta potential of −11.6 mV. Differential scanning calorimetry and powder X-ray diffractometry confirmed the crystallinity of FA following nanocrystallization and lyophilization. In-vitro results showed a 10-fold increase in the saturation solubility of FA-NC while ex-vivo skin permeation studies showed a 2-fold increase in FA dermal deposition from FA-NC compared to coarse FA. Microbiological studies revealed a 4-fofd decrease in the MIC against S. aureus and S. epidermidis from FA-NC cream compared to commercial Fucidin cream. In-vivo results showed that FA-NC cream improved FA distribution and enhanced bacterial exposure in the infected wound, resulting in increased therapeutic efficacy when compared to coarse FA marketed as Fucidin cream.


PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e82800 ◽  
Author(s):  
Elisabeth M. Haisma ◽  
Marion H. Rietveld ◽  
Anna de Breij ◽  
Jaap T. van Dissel ◽  
Abdoelwaheb El Ghalbzouri ◽  
...  

2021 ◽  
Author(s):  
Wei Hong Tay ◽  
Ronni A.G. da Silva ◽  
Foo Kiong Ho ◽  
Kelvin K.L. Chong ◽  
Alexander Ludwig ◽  
...  

Enterococcus faecalis is a frequent opportunistic pathogen of wounds, whose infections are associated with biofilm formation, persistence, and recalcitrance toward treatment. We have previously shown that E. faecalis wound infection persists for at least 7 days. Here we report that viable E. faecalis are present within both immune and non-immune cells at the wound site up to 5 days after infection, raising the prospect that intracellular persistence contributes to chronic E. faecalis infection. Using an in vitro keratinocyte infection model, we show that a subpopulation of E. faecalis becomes internalized via macropinocytosis into single membrane-bound compartments, where they can survive and replicate. These intracellular E. faecalis can persist in late endosomes up to 72 hours after infection in the absence of colocalization with the lysosomal protease cathepsin D or apparent fusion with the lysosome, suggesting that E. faecalis blocks endosomal maturation. Indeed, intracellular E. faecalis infection results in a marked reduction in Rab7 expression, a small GTPase required for endosome-lysosome fusion. Finally, we demonstrate that intracellular E. faecalis derived from infected keratinocytes are significantly more efficient in reinfecting new keratinocytes. Together, these data suggest that intracellular proliferation of E. faecalis may contribute to its persistence in the face of a robust immune response, providing a primed reservoir of bacteria for subsequent reinfection.


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