Novel lipophosphonoxin-loaded polycaprolactone electrospun nanofiber dressing reduces Staphylococcus aureus induced wound infection in mice

AbstractActive wound dressings are attracting extensive attention in soft tissue repair and regeneration, including bacteria-infected skin wound healing. As the wide use of antibiotics leads to drug resistance we present here a new concept of wound dressings based on the polycaprolactone nanofiber scaffold (NANO) releasing second generation lipophosphonoxin (LPPO) as antibacterial agent. Firstly, we demonstrated in vitro that LPPO released from NANO exerted antibacterial activity while not impairing proliferation/differentiation of fibroblasts and keratinocytes. Secondly, using a mouse model we showed that NANO loaded with LPPO significantly reduced the Staphylococcus aureus counts in infected wounds as evaluated 7 days post-surgery. Furthermore, the rate of degradation and subsequent LPPO release in infected wounds was also facilitated by lytic enzymes secreted by inoculated bacteria. Finally, LPPO displayed negligible to no systemic absorption. In conclusion, the composite antibacterial NANO-LPPO-based dressing reduces the bacterial load and promotes skin repair, with the potential to treat wounds in clinical settings.

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Resveratrol-loaded peptide-hydrogels inhibit scar formation in wound healing through suppressing inflammation

Regenerative Biomaterials ◽

10.1093/rb/rbz041 ◽

2019 ◽

Cited By ~ 2

Author(s):

Chen-Chen Zhao ◽

Lian Zhu ◽

Zheng Wu ◽

Rui Yang ◽

Na Xu ◽

...

Keyword(s):

Wound Healing ◽

Damage Model ◽

Skin Wound ◽

Scar Formation ◽

Wound Dressings ◽

Skin Damage ◽

Skin Wound Healing ◽

Accelerate Wound Healing ◽

Peptide Hydrogels

Abstract Scar formation seriously affects the repair of damaged skin especially in adults and the excessive inflammation has been considered as the reason. The self-assembled peptide-hydrogels are ideal biomaterials for skin wound healing due to their similar nanostructure to natural extracellular matrix, hydration environment and serving as drug delivery systems. In our study, resveratrol, a polyphenol compound with anti-inflammatory effect, is loaded into peptide-hydrogel (Fmoc-FFGGRGD) to form a wound dressing (Pep/RES). Resveratrol is slowly released from the hydrogel in situ, and the release amount is controlled by the loading amount. The in vitro cell experiments demonstrate that the Pep/RES has no cytotoxicity and can inhibit the production of pro-inflammatory cytokines of macrophages. The Pep/RES hydrogels are used as wound dressings in rat skin damage model. The results suggest that the Pep/RES dressing can accelerate wound healing rate, exhibit well-organized collagen deposition, reduce inflammation and eventually prevent scar formation. The Pep/RES hydrogels supply a potential product to develop new skin wound dressings for the therapy of skin damage.

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Comparative Efficacies of Human Simulated Exposures of Telavancin and Vancomycin against Methicillin-Resistant Staphylococcus aureus with a Range of Vancomycin MICs in a Murine Pneumonia Model

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00062-10 ◽

2010 ◽

Vol 54 (12) ◽

pp. 5115-5119 ◽

Cited By ~ 36

Author(s):

Jared L. Crandon ◽

Joseph L. Kuti ◽

David P. Nicolau

Keyword(s):

Staphylococcus Aureus ◽

Bacterial Load ◽

Infection Model ◽

Time Curve ◽

Unbound Fraction ◽

Methicillin Resistant ◽

Vancomycin Mics ◽

Mrsa Strains

ABSTRACT Telavancin displays potent in vitro and in vivo activity against methicillin-resistant Staphylococcus aureus (MRSA), including strains with reduced susceptibility to vancomycin. We compared the efficacies of telavancin and vancomycin against MRSA strains with vancomycin MICs of ≥1 μg/ml in a neutropenic murine lung infection model. Thirteen clinical MRSA isolates (7 vancomycin-susceptible, 2 vancomycin-heteroresistant [hVISA], and 4 vancomycin-intermediate [VISA] isolates) were tested after 24 h, and 7 isolates (1 hVISA and 4 VISA isolates) were tested after 48 h of exposure. Mice were administered subcutaneous doses of telavancin at 40 mg/kg of body weight every 12 h (q12h) or of vancomycin at 110 mg/kg q12h; doses were designed to simulate the area under the concentration-time curve for the free, unbound fraction of drug (fAUC) observed for humans given telavancin at 10 mg/kg q24h or vancomycin at 1 g q12h. Efficacy was expressed as the 24- or 48-h change in lung bacterial density from pretreatment counts. At dose initiation, the mean bacterial load was 6.16 ± 0.26 log10 CFU/ml, which increased by averages of 1.26 ± 0.55 and 1.74 ± 0.68 log in untreated mice after 24 and 48 h, respectively. At both time points, similar CFU reductions were noted for telavancin and vancomycin against MRSA, with vancomycin MICs of ≤2 μg/ml. Both drugs were similarly efficacious after 24 and 48 h of treatment against the hVISA strains tested. Against VISA isolates, telavancin reduced bacterial burdens significantly more than vancomycin for 1 of 4 isolates after 24 h and for 3 of 4 isolates after 48 h. These data support the potential utility of telavancin for the treatment of MRSA pneumonia caused by pathogens with reduced susceptibility to vancomycin.

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In vitro studies of antibacterial and antifungal wound dressings comprising H2TiO3 and SiO2 nanoparticles

Polish Journal of Microbiology ◽

10.33073/pjm-2015-020 ◽

2015 ◽

Vol 64 (2) ◽

pp. 137-142 ◽

Cited By ~ 4

Author(s):

LUKASZ KROKOWICZ ◽

HANNA TOMCZAK ◽

ADAM BOBKIEWICZ ◽

JACEK MACKIEWICZ ◽

RYSZARD MARCINIAK ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Adult Population ◽

Antimicrobial Properties ◽

Wound Dressings ◽

Wound Management ◽

Current Standard ◽

Silicon Dioxide Nanoparticles ◽

Complex Wound ◽

Zones Of Inhibition

The incidence rate of the infected and complex wound is established at approximately 40,000/1 million of the world's adult population. The aim of this study was to assess the efficiency of three novel types of wound dressings comprising sodium chloride, metatitanic acid and silicon dioxide nanoparticles. The study design was to prove their antimicrobial properties against the microorganisms most commonly causing wound infections. The study evaluated the antimicrobial effect of tested dressings on referenced strains of bacteria (ATCC collection, Argenta, Poland) and strains of fungi species (our own collection of fungi cultured from patients). The dressings were tested with both bacterial and fungal strains on solid media (Mueller-Hinton, Sobouraud, bioMerieux, France) in the standard method. The results confirmed the inhibition of growth of bacteria and revealed zones of inhibition for Escherichia coli, Staphylococcus aureus and Enterococcus faecalis. Significant zones of inhibition were established for Staphylococcus aureus and for fungi species of the Candida sp. These results would be crucial due to the fact of the low availability of antifungal therapeutics for both systemic and topical usage. Moreover, the current standard of antifungal treatment is associated with high costs and high toxicity in general. The preliminary results are very promising but further studies are necessary. Based on the obtained results, the tested dressings may contribute to the development of the surgical armamentarium of complex wound management in the near future.

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Comparison of Effectiveness of Germania Honey Compared to Manuka Honey in Methicillin-Resistant Staphylococcus aureus (MRSA) Killing

The Open Microbiology Journal ◽

10.2174/1874285801913010021 ◽

2019 ◽

Vol 13 (1) ◽

pp. 21-27 ◽

Cited By ~ 1

Author(s):

Ali M. Bazzi ◽

Ali A. Rabaan ◽

Jaffar A. Al-Tawfiq ◽

Bilal M. Shannak

Keyword(s):

Staphylococcus Aureus ◽

Methicillin Resistant Staphylococcus Aureus ◽

Bacterial Species ◽

Wound Dressings ◽

Manuka Honey ◽

Bacterial Killing ◽

Methicillin Resistant ◽

Wound Culture ◽

Comparison Of Effectiveness

Purpose: Manuka honey is currently used in medical-grade sterile wound treatment products and has been shown to be effective in methicillin-resistant Staphylococcus aureus (MRSA) killing in vitro and in wound healing in a number of case studies and series. Locally produced honey in Pakistan and Chile have been proposed to be as effective as Manuka honey in bacterial killing in vitro, presenting potentially more accessible and affordable alternatives. In this study, we compared the effectiveness of a local Germania honey from Saudi Arabia to Manuka honey MGO 550 for in vitro killing of MRSA. Methodology: Overnight Muller Hinton broth cultures of 50 wound culture isolates of MRSA from 50 patients were incubated with a series of dilutions of Manuka honey MGO 550 and corresponding Germania honey dilutions for 24 h. Turbidity was assessed to determine whether bacterial growth had occurred, and no growth was confirmed by a further 24 h sub-culture on blood agar. Results/Key findings: Manuka honey MGO 550 was significantly more effective than Germania honey at MRSA killing at 100% v/v, 50% v/v and 25% v/v (p=0.025, 0.000265, and 0.000112 respectively) Conclusion: Manuka honey MGO 550 is significantly more effective in killing MRSA in vitro than Germania honey. Germania honey does not appear to be a promising locally produced alternative to Manuka honey for the development of honey-based wound dressings. Further experiments could determine if Germania honey is effective against other bacterial species.

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Impact of Inoculum Size and Heterogeneous Vancomycin-Intermediate Staphylococcus aureus (hVISA) on Vancomycin Activity and Emergence of VISA in an In Vitro Pharmacodynamic Model

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01009-08 ◽

2008 ◽

Vol 53 (2) ◽

pp. 805-807 ◽

Cited By ~ 22

Author(s):

Warren E. Rose ◽

Steven N. Leonard ◽

Kerri L. Rossi ◽

Glenn W. Kaatz ◽

Michael J. Rybak

Keyword(s):

Staphylococcus Aureus ◽

Bactericidal Activity ◽

Bacterial Load ◽

Inoculum Size ◽

Pharmacodynamic Model ◽

High Inoculum ◽

High Bacterial Load

ABSTRACT The activity of vancomycin against heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) and non-hVISA isolates, using an in vitro pharmacodynamic model, was reduced in the presence of a high inoculum amount (108 CFU/ml). A high bacterial load of >105 CFU/ml persisted for all strains with doses up to 5 g every 12 h against high inoculum amounts. No change in the vancomycin MIC was detected in any isolate at a moderate inoculum amount (106 CFU/ml), and bactericidal activity occurred only against the non-hVISA isolate (time to 99% kill, 7.5 h; P = 0.001).

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IB-367, a Protegrin Peptide with In Vitro and In Vivo Activities against the Microflora Associated with Oral Mucositis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.44.7.1803-1808.2000 ◽

2000 ◽

Vol 44 (7) ◽

pp. 1803-1808 ◽

Cited By ~ 62

Author(s):

Deborah A. Mosca ◽

Malinda A. Hurst ◽

Wendy So ◽

Beverly S. C. Viajar ◽

Craig A. Fujii ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Oral Mucositis ◽

Human Saliva ◽

Systemic Absorption ◽

Gram Positive ◽

Oral Flora ◽

Gram Negative ◽

Log Reduction

ABSTRACT Although the microflora associated with oral mucositis initiated by cytotoxic therapy is not well characterized, several studies suggest that reduction of the microbial load in the oral cavity has some clinical benefit. The MICs of IB-367, a synthetic protegrin analog, ranged from 0.13 to 64 μg/ml for gram-positive bacteria (Streptococcus mitis, Streptococcus sanguis,Streptococcus salivarius, and Staphylococcus aureus) and from 0.06 to 8 μg/ml for gram-negative species (Klebsiella, Escherichia, andPseudomonas). IB-367 exhibited rapid, microbicidal activity against both log- and stationary-phase cultures of methicillin-resistant Staphylococcus aureus (MRSA) andPseudomonas aeruginosa. At concentrations near the MICs for these two organisms (4 and 2 μg/ml, respectively), IB-367 reduced viability by more than 3 logs in less than 16 min. Similarly, IB-367 effected a 4-log reduction of the endogenous microflora in pooled human saliva within 2 min at 250 μg/ml, a concentration readily attained by local delivery. After nine serial transfers at 0.5× the MIC, the MIC of IB-367 for MRSA and P. aeruginosa increased only two to four times. In a phase I clinical study with healthy volunteers, IB-367 was well tolerated, with no detectable systemic absorption. One hour after treatment with 9 mg of IB-367, the prevalence of gram-negative bacteria and yeast was reduced, and the density of the predominant gram-positive oral flora was decreased 1,000 times. IB-367's properties (speed of killing, breadth of spectrum, and lack of resistance) make the compound a strong candidate for the prophylaxis of oral mucositis. Phase II clinical trials with IB-367 are under way for this indication in immunocompromised subjects.

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Bactericidal Effects of Low-Irradiance Low Level Light Therapy on Methicillin-Resistant Staphylococcus Aureus in Vitro

Fine Focus ◽

10.33043/ff.2.2.104-115 ◽

2016 ◽

Vol 2 (2) ◽

pp. 104-115

Author(s):

Patrick J. McMullan ◽

Jakob Krzyston ◽

Robert Osgood

Keyword(s):

Staphylococcus Aureus ◽

Methicillin Resistant Staphylococcus Aureus ◽

Bacterial Load ◽

Light Therapy ◽

Methicillin Resistant ◽

Low Level Light Therapy ◽

Bactericidal Properties ◽

Bactericidal Effects ◽

Total Fluence

Low Level Light Therapy (LLLT) within the visible blue spectrum (400-470 nanometers) is a well-documented therapeutic alternative to combat multidrug resistant organism infections through the generation of reactive oxygen species (ROS). However, one shortcoming of LLLT is that many studies deliver therapy through high powered lasers and lamps. High powered light sources not only require specialized staff to operate, but they also deliver the total light dose (fluence) at an exceptionally high intensity, or irradiance, which could consequently deplete the oxygen supplies required to promote LLLT’s bactericidal properties. To overcome these faults, low-irradiance LLLT, or delivering the same total fluence of LLLT over an extended period of time with decreased irradiance was evaluated in vitro. To further explore this alternative approach, the bactericidal effects of low-irradiance (10.44 mW/cm2) LLLT using wavelengths of 405-nm, 422-nm and 470-nm were studied on methicillin-resistant Staphylococcus aureus (MRSA) cultures. Among these wavelengths, it was determined that 405-nm LLLT provided the most effective reduction of bacterial load at the lowest total fluence (75 J/cm2) (94.50% reduction). The bactericidal effects of 405-nm low-irradiance LLLT were then further studied by treating MRSA cultures to 75 J/cm2 LLLT while using irradiances of 5.22 mW/cm2 and 3.48 mW/cm2. It was concluded that there was a greater reduction of MRSA bacterial load when samples were exposed to irradiances of 5.22 mW/cm2 (95.71% reduction) and 3.48 mW/cm2 (99.63% reduction). This study validates the bactericidal properties of low-irradiance LLLT on MRSA, and subsequent studies should be completed to optimize its full therapeutic potential.

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An in vitro test of the efficacy of silver-containing wound dressings against Staphylococcus aureus and Pseudomonas aeruginosa in simulated wound fluid

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2013.12.037 ◽

2014 ◽

Vol 462 (1-2) ◽

pp. 123-128 ◽

Cited By ~ 37

Author(s):

Jawal Said ◽

Cornelius C. Dodoo ◽

Michael Walker ◽

David Parsons ◽

Paul Stapleton ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Pseudomonas Aeruginosa ◽

Wound Dressings ◽

In Vitro Test ◽

Wound Fluid ◽

Vitro Test

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In Vitro and In Vivo Efficacies of Teicoplanin-Loaded Calcium Sulfate for Treatment of Chronic Methicillin-Resistant Staphylococcus aureus Osteomyelitis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01122-09 ◽

2009 ◽

Vol 54 (1) ◽

pp. 170-176 ◽

Cited By ~ 17

Author(s):

Wei-Tao Jia ◽

Shi-Hua Luo ◽

Chang-Qing Zhang ◽

Jian-Qiang Wang

Keyword(s):

Staphylococcus Aureus ◽

Antibacterial Activity ◽

Calcium Sulfate ◽

Release Kinetics ◽

Bacterial Load ◽

Rabbit Model ◽

Methicillin Resistant ◽

Group 2

ABSTRACT The i n vitro and in vivo therapeutic efficacies of teicoplanin-loaded calcium sulfate (TCS; 10% [wt] teicoplanin) were investigated in a rabbit model of chronic methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis. The in vitro elution characteristics of teicoplanin from TCS pellets were realized by carrying out an evaluation of the release kinetics, recovery rate, and antibacterial activity of the released teicoplanin. Chronic osteomyelitis was induced by inoculating 107 CFU of a MRSA strain into the tibial cavity of rabbits. After 3 weeks, the animals were treated by debridement followed by implantation of TCS pellets in group 1, calcium sulfate (CS) pellets alone in group 2, and intravenous (i.v.) teicoplanin (6 mg/kg of body weight every 12 h for three doses and then every 24 h up to 4 weeks) in group 3. Animals in group 4 were left untreated. After 6 weeks, the efficacy of the osteomyelitis treatment was evaluated by hematological, radiological, microbiological, and histological examinations. In vitro elution studies showed sustained release of teicoplanin at a therapeutic level over a time period of 3 weeks. The released teicoplanin maintained its antibacterial activity. In vivo, the best therapeutic effect was observed in animals treated with TCS pellets, resulting in significantly lower radiological and histological scores, lower positive rates of MRSA culture and bacterial load, and excellent bone regeneration compared with those treated by CS alone or i.v. teicoplanin, without any local or systemic adverse effects. TCS pellets are an effective alternative to i.v. teicoplanin for the treatment of chronic MRSA osteomyelitis, particularly because teicoplanin is delivered locally while the TCS pellets simultaneously promote bone defect repair.

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A Novel Qualitative and Quantitative Biofilm Assay Based on 3D Soft Tissue

International Journal of Biomaterials ◽

10.1155/2014/768136 ◽

2014 ◽

Vol 2014 ◽

pp. 1-5 ◽

Cited By ~ 11

Author(s):

Bodil Hakonen ◽

Linnea K. Lönnberg ◽

Eva Larkö ◽

Kristina Blom

Keyword(s):

Antimicrobial Activity ◽

Soft Tissues ◽

Bacterial Load ◽

Wound Dressings ◽

Rapid Screening ◽

Qualitative And Quantitative ◽

Development Of Resistance ◽

Novel Method

The lack of predictablein vitromethods to analyze antimicrobial activity could play a role in the development of resistance to antibiotics. Current used methods analyze planktonic cells but for the method to be clinically relevant, biofilm inin vivolike conditions ought to be studied. Hence, our group has developed a qualitative and quantitative method within vivolike 3D tissue for prediction of antimicrobial activity in reality. Devices (wound dressings) were applied on top ofPseudomonas aeruginosainoculated Muller-Hinton (MH) agar or 3D synthetic soft tissues (SST) and incubated for 24 hours. The antibacterial activity was then analyzed visually and by viable counts. On MH agar two out of three silver containing devices showed zone of inhibitions (ZOI) and on SST, ZOI were detected for all three. Corroborating results were found upon evaluating the bacterial load in SST and shown to be silver concentration dependent. In conclusion, a novel method was developed combining visual rapid screening and quantitative evaluation of the antimicrobial activity in both tissue and devices. It uses tissue allowing biofilm formation thus mimicking reality closely. These conditions are essential in order to predict antimicrobial activity of medical devices in the task to prevent device related infections.

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