846 Effects of Ceragenins on Pseudomonas Aeruginosa Biofilm Formation in Burn Wounds in a Porcine Model

2020 ◽  
Vol 41 (Supplement_1) ◽  
pp. S262-S263
Author(s):  
Paul B Savage

Abstract Introduction Damage from burn wounds compromises the protective function of the skin, increasing susceptibility to bacterial and fungal infections and sepsis. Pseudomonas aeruginosa is commonly infects burn injuries and is associated with high morbidity, especially in large total burn surface area injuries. Silver sulfadiazine (SSD), the standard topical antimicrobial used for burn wounds, has been associated with irritation, scarring and other adverse effects creating a need for alternative treatment options. Ceragenins are small-molecule mimics of endogenous antimicrobial peptides. In this pilot study, two ceragenins, CSA-44 and CSA-144 were assessed for their ability to reduce P. aeruginosa in a porcine burn wound model. Methods One pathogen-free female pig was appropriately prepared and 48 burn wounds were generated, under general anesthesia, on the back and flank area by direct contact with a heated brass rod. Wounds were inoculated with P. aeruginosa and biofilm was allowed to form for 24 hours. Four of the wounds were analyzed 24 hours post inoculation to establish baseline bacterial counts. R emaining wounds were treated with a vehicle control, SSD (positive control) or formulations of CSA-44 and CSA-144 in gel, cream and aqueous forms. After 7 days of treatment, tissue samples from the wounds were excised and bacterial counts were determined (colony forming units per milliliter of tissue). Percent decreases in bacterial counts were evaluated for each wound. The wounds were also observed for erythema and irritation over the course of the study. Results The greatest reductions in bacterial counts after treatment were seen in wounds treated with aqueous CSA-44 at 0.05 % (99.6% reduction) and aqueous CSA-144 at 0.05% (98.4% reduction), which were both greater than the bacterial reductions seen in wounds treated with SSD. Additionally, after the second day of treatment, wounds treated with aqueous CSA-44 and CSA-144 showed reduced erythema, while wounds treated with SSD continued to show swelling and redness. Conclusions This study demonstrates the effective antimicrobial action of aqueous formulations of ceragenins CSA-44 and CSA-144. The bacterial reduction seen with aqueous CSA-44 and CSA-144 were greater than the positive control (SSD). Furthermore, treatment with CSA-44 showed reduced signs of irritation, which were not observed with SSD. Even within this small sample size, the superior antimicrobial ability of ceragenins, without the negative effects of SSD becomes apparent. Applicability of Research to Practice Ceragenins provide a means of replacing endogenous defenses against infection in burn wounds.

2011 ◽  
Vol 55 (5) ◽  
pp. 2325-2334 ◽  
Author(s):  
F. Jacobsen ◽  
C. Fisahn ◽  
M. Sorkin ◽  
I. Thiele ◽  
T. Hirsch ◽  
...  

ABSTRACTWound infection is a common risk for patients with chronic nonhealing wounds, causing high morbidity and mortality. Currently, systemic antibiotic treatment is the therapy of choice, despite often leading to several side effects and the risk of an insufficient tissue penetration due to impaired blood supply. If systemically delivered, moxifloxacin penetrates well into inflammatory blister fluid, muscle, and subcutaneous adipose tissues and might therefore be a possible option for the topical treatment of skin and infected skin wounds. In this study, topical application of moxifloxacin was investigated in comparison to mupirocin, linezolid, and gentamicin using a porcine wound infection and a rat burn infection model. Both animal models were performed either by an inoculation with methicillin-resistantStaphylococcus aureus(MRSA) orPseudomonas aeruginosa. Wound fluid, tissue, and blood samples were taken, and bacterial counts as well as the moxifloxacin concentration were determined for a 14-day follow-up. A histological comparison of the rat burn wound tissues was performed. Both strains were susceptible to moxifloxacin and gentamicin, whereas mupirocin and linezolid were effective only against MRSA. All antibiotics showed efficient reduction of bacterial counts, and except with MRSA, infected burn wounds reached bacterial counts below 105CFU/g tissue. Additionally, moxifloxacin was observed to promote wound healing as determined by histologic analysis, while no induction of bacterial resistance was observed during the treatment period. The use of topical antibiotics for the treatment of infected wounds confers many benefits. Moxifloxacin is therefore an ideal candidate, due to its broad antibacterial spectrum, its high efficiency, and its potential to promote wound healing.


2012 ◽  
Vol 57 (1) ◽  
pp. 466-474 ◽  
Author(s):  
Ping Liu

ABSTRACTTo evaluate the exposure-response relationships for efficacy and safety of intravenous anidulafungin in adult patients with fungal infections, a population pharmacokinetic-pharmacodynamic (PK-PD) analysis was performed with data from 262 patients in four phase 2/3 studies. The plasma concentration data were fitted with a previously developed population PK model. Anidulafungin exposures in patients with weight extremities (e.g., 40 kg and 150 kg) were simulated based on the final PK model. Since the patient population, disease status, and efficacy endpoints varied in these studies, the exposure-efficacy relationship was investigated separately for each study using logistic regression as appropriate. Safety data from three studies (n= 235) were pooled for analysis, and one study was excluded due to concomitant use of amphotericin B as a study treatment and different disease populations. The analysis showed that the same dosing regimen of anidulafungin can be administered to all patients regardless of body weight. Nonetheless, caution should be taken for patients with extremely high weight (e.g., >150 kg). There was a trend of positive association between anidulafungin exposure and efficacy in patients with esophageal candidiasis or invasive candidiasis, including candidemia (ICC); however, adequate characterization of the effect of anidulafungin exposure on response could not be established due to the relatively small sample size. No threshold value for exposure could be established, since patients with low exposure also achieved successful outcomes (e.g., area under the curve < 40 mg · h/liter in ICC patients). There was no association between anidulafungin exposure and the treatment-related adverse events or all-causality hepatic laboratory abnormalities.


2020 ◽  
Vol 2 (1) ◽  
pp. 31-38
Author(s):  
Fajrin Noviyanto ◽  
Siti Hodijah ◽  
Yusransyah Yusransyah

The bacteria that cause infections that can lead to high morbidity and mortality, the bacterium Pseudomonas aeruginosa. Bangle has a pharmacological activity as antibacterial, laxative, pancreatic lipase inhibitor, and protect cells from damage caused by oxidative stress. The purpose of this study are: to know the chemical constituents present in the extract of leaves bangle (Zingiber purpureum Roxb.) Can be efficacious as an antibacterial and knowing Minimal Inhibitory concentration (MIC) of the extracts of leaves bangle against Pseudomonas aeruginosa. Tests on the leaf extracts for antibacterial activity against Pseudomonas aeruginosa bangle made by the method of Kirby Bauer and solvents used are DMSO. Test solution with a concentration of leaf extract bangle 200, 400, 600, 800 and 1,000 ppm, the positive control solution (ciprofoxacin) and the solution negative control (DMSO). The results showed that the chemical constituents present in the extract of leaves bangle (Zingiber purpureum Roxb.) Are flavonoids, saponins, tannins, alkaloids and steroids. Value Minimum Inhibitory Concentration (MIC) of ethanol extract of the leaf bangle S bacteria Pseudomonas aeruginosa is a concentration of 40 % with an average diameter of 5.44 mm inhibitory. MIC extract ethanol extract of leaf bangle belonging to the bacterial activity that is strong enough..


2021 ◽  
Vol 26 (4) ◽  
Author(s):  
Dr.Fawzia Shalsh ◽  
Imad Ibrahim Ali Al-Sultana ◽  
Abdul Rahman Bin Azizc, ◽  
Salahudeen Muhamad Muhamad

Inarguably, in several developing and in-transition countries, human are threatened by the occurrence of rabies in domestic dogs and it is posing a major concern. However, the infection of rabies in domestic livestock could definitely have economic consequences. This study aimed to determine the occurrence of rabies among dogs in Kelantan by the use of Direct Fluorescent Antibody Test (DFAT) to determine presence of rabies infection in dogs. The detected rabies cases were 12.5% (1 out of 8 samples). The finding might be inconclusive due to small sample size. It was generally difficult to obtain a satisfactory large number representing high sample size. The positive control used in this research work is made up of inactivated rabies vaccine (Rabisin®) whose antigenic determinant is the viral glycoprotein. It was sufficient to be used although the use of live rabies virus for inoculation in brain tissue smear would be a better option for positive control. The finding from the florescence microscopy examination reveals a good brilliant green fluoresce of high grade (+4) for the positive control. The results of the samples show all negative at conjugate dilution 1:100.


2019 ◽  
Author(s):  
S.C. Davis ◽  
M. Solis ◽  
J. Gil ◽  
J. Valdes ◽  
A. Higa ◽  
...  

AbstractSilver has been incorporated into a variety of wound dressings and topical agents to prevent and combat wound infections. Pseudomonas aeruginosa is a common cause of burn wound infections and well-known biofilm producer. The objective of this study was to evaluate the effects of a panel of wound dressings containing different silver formulations on P. aeruginosa biofilms using an in vivo porcine burn wound model. Second-degree burns were created on the skin of specific pathogen-free pigs (n = 3) and inoculated with 2.14 × 105 cfu P. aeruginosa per wound. Biofilms were allowed to develop for 24 h, and then each wound was treated with one of 6 treatments: silver oxynitrate dressing (OXY), silver oxynitrate powder (POWD), nanocrystalline silver dressing (NANO), silver chloride dressing (AGCL), silver sulfadiazine (SSD), or a negative control polyurethane film with no silver-based formulation (NEG). Wounds were cultured at D3 post-infection (n = 3 per pig per treatment) and at D6 post-infection (n = 3 per pig per treatment) for quantification of bacteria. On D6, biopsies (n = 3 per treatment) were taken from POWD, SSD, and NEG wounds and wound healing progress was evaluated histologically. At the time of treatment initiation, 24 h post-infection, 8.71 log cfu P. aeruginosa were present in burn wounds. On D3 and D6, all treatments significantly reduced bacterial counts in wounds as compared to NEG, but POWD caused an approximately 7-log reduction in bacterial counts on both days and was the only treatment to reduce the bacterial counts to below the threshold for detecting bacteria. The OXY, NANO, and SSD treatments had similar reductions in bacterial recovery on D3 and D6 of approximately 2.5-4 log. The histological healing metrics of reepithelialization percentage, epithelial thickness, white cell infiltration, angiogenesis, and granulation tissue formation were similar among wounds from POWD, SSD, and NEG groups at 6 days post-infection. Silver oxynitrate powder reduced P. aeruginosa growth in burn wounds more effectively than other silver-based dressings but did not impact wound healing.


2012 ◽  
Vol 16 (2) ◽  
pp. 485-496 ◽  
Author(s):  
María Reinares ◽  
Adriane R. Rosa ◽  
Carolina Franco ◽  
José Manuel Goikolea ◽  
Kostas Fountoulakis ◽  
...  

Abstract Despite the high morbidity and mortality associated with bipolar depression, the optimal treatment for this phase is still a matter of debate. The aim of the current review was to provide updated evidence about the efficacy and tolerability of anticonvulsants in the treatment of acute bipolar depression. A comprehensive review of randomized controlled trials (RCTs) evaluating the use of anticonvulsants for the treatment of acute bipolar depression up to June 2011 was conducted by means of the PubMed-Medline database. Eligibility criteria included active comparator-controlled or placebo-controlled randomized studies involving monotherapy or combination therapy. A total of 18 RCTs fulfilled the inclusion criteria. Studies supported the efficacy of divalproex as monotherapy in acute bipolar depression but small sample size was a common methodological limitation. Findings were inconclusive for lamotrigine and carbamazepine although overall lamotrigine may have a beneficial but modest effect. Negative results were found for levetiracetam and gabapentin but the evidence base on these agents is scant. All anticonvulsants were generally well tolerated. No double-blind RCTs were found for the use of other anticonvulsants such as oxcarbazepine, licarbazepine, zonisamide, retigabine, pregabalin, tiagabine, felbamate and vigabatrine in the acute treatment of bipolar depression. To sum up, taking into consideration the efficacy and tolerability profiles of anticonvulsants, current evidence supports the use of divalproex and lamotrigine in the treatment of acute bipolar depression. However, available data for most other anticonvulsants are inconclusive and further RCTs with larger sample sizes are needed before drawing firm conclusions.


2018 ◽  
Vol 41 (3) ◽  
pp. E136-E143 ◽  
Author(s):  
Yazeed Toukan ◽  
Michal Gur ◽  
Fahed H Hakim ◽  
Yuval Geffen ◽  
Ronen Bar-Yoseph ◽  
...  

Introduction: CF pulmonary guidelines recommend alternate therapy (one month on, one month off) with inhaled tobramycin for chronic Pseudomonas aeruginosa colonization in cystic fibrosis (CF). Tobramycin-inhaled powder (TIP™) is increasingly replacing time-consuming nebulizer therapy. It is unclear whether laboratory parameters change during the month off period compared with the month on therapy. Purpose: Our aim was to assess whether spirometry, lung clearance index and circulating inflammatory markers differ between on/off treatment periods. Materials and methods: A prospective pilot study evaluating CF patients treated with TIP, on two consecutive months (on/off) therapy. The evaluations were performed at the end of a month off therapy (1-2 days before the initiation of TIP) and after 28 days of treatment with TIP (1-2 days after the end of the treatment cycle). Results: Nineteen CF patients (10 males) with a mean age of 18.7±9.7 years and BMI (body mass index) of 19.62±3.53 kg/m2 were evaluated. After a month off treatment with TIP, spirometry parameters and lung clearance index remained unchanged. IL-6 increased significantly (p=0.022) off treatment. There was a non-significant change in the other inflammatory cytokines off therapy [hs-CRP, IL-8,TNF-α, α1-antitrypsin (α1AT) and neutrophilic elastase]. Conclusions: The results of lung function parameters support the relative stability of CF patients during the month off therapy; however, the difference in serum IL-6 raises the possibility of ongoing higher degrees of inflammation during the month off therapy with TIP. The small sample size and the multiple parameters evaluated preclude firm conclusions; therefore, larger multicenter studies are needed to assess the on/off treatment strategy.


2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S86-S86
Author(s):  
C Hoang ◽  
M Flaws ◽  
N Moore ◽  
N Lerret

Abstract Introduction/Objective A common practice utilized by painters is licking their paint brush bristles to form a sharp point for fine lines and details. Literature details artists careless around their mediums have a higher incidence of becoming ill, yet if their brushes harbor any toxic substances or pathogenic bacteria it is currently unknown. Therefore, this study aims to determine if there is risk associated with brush licking, by determining if pathogenic bacteria and/or heavy metals are present on the brushes of volunteer artists. Methods We obtained 17 volunteer paint brushes and inoculated specialized collection and transport media (E- Swab, BD Biosciences, San Jose, CA) while the volunteer completed a qualitative de-identified survey indicating brush licking status. Brushes were swirled in the E-swab collection tube, then subbed to sheep blood agar plates and chocolate agar plates for bacteria growth analysis. Matrix-assisted laser desorption/ionization time-of-flight (MALDI- TOF) technology was used for identification. With the remaining E-Swab media, lead (3M, St. Paul, MN) and arsenic (HACH, Loveland, CO) testing using commercial kits was done. MALDI-TOF identification and heavy metal testing results were then compared to survey results. Results One of 17 specimens (6%) had pathogenic bacteria identified (Pseudomonas aeruginosa). This specimen’s survey also indicated routine brush licking. The sensitivity and specificity of MALDI-TOF for Pseudomonas aeruginosa is 96.67% and 97.87%, respectively. The remaining 16/17 (94%) had normal flora present. Importantly, the specimen containing Pseudomonas aeruginosa also had high levels of arsenic at 50 ppb. None of the specimen tested contained lead. Conclusion Our results indicated there is indeed some risk associated with brush licking. However, due to the small sample size, statistical significance could not be determined. Nonetheless, with the lack of knowledge surrounding this subject, it is beneficial to further explore and educate painters on the toxicities of brush licking.


Author(s):  
Conly L. Rieder ◽  
S. Bowser ◽  
R. Nowogrodzki ◽  
K. Ross ◽  
G. Sluder

Eggs have long been a favorite material for studying the mechanism of karyokinesis in-vivo and in-vitro. They can be obtained in great numbers and, when fertilized, divide synchronously over many cell cycles. However, they are not considered to be a practical system for ultrastructural studies on the mitotic apparatus (MA) for several reasons, the most obvious of which is that sectioning them is a formidable task: over 1000 ultra-thin sections need to be cut from a single 80-100 μm diameter egg and of these sections only a small percentage will contain the area or structure of interest. Thus it is difficult and time consuming to obtain reliable ultrastructural data concerning the MA of eggs; and when it is obtained it is necessarily based on a small sample size.We have recently developed a procedure which will facilitate many studies concerned with the ultrastructure of the MA in eggs. It is based on the availability of biological HVEM's and on the observation that 0.25 μm thick serial sections can be screened at high resolution for content (after mounting on slot grids and staining with uranyl and lead) by phase contrast light microscopy (LM; Figs 1-2).


Crisis ◽  
2020 ◽  
pp. 1-5
Author(s):  
Ruthmarie Hernández-Torres ◽  
Paola Carminelli-Corretjer ◽  
Nelmit Tollinchi-Natali ◽  
Ernesto Rosario-Hernández ◽  
Yovanska Duarté-Vélez ◽  
...  

Abstract. Background: Suicide is a leading cause of death among Spanish-speaking individuals. Suicide stigma can be a risk factor for suicide. A widely used measure is the Stigma of Suicide Scale-Short Form (SOSS-SF; Batterham, Calear, & Christensen, 2013 ). Although the SOSS-SF has established psychometric properties and factor structure in other languages and cultural contexts, no evidence is available from Spanish-speaking populations. Aim: This study aims to validate a Spanish translation of the SOSS-SF among a sample of Spanish-speaking healthcare students ( N = 277). Method: We implemented a cross-sectional design with quantitative techniques. Results: Following a structural equation modeling approach, a confirmatory factor analysis (CFA) supported the three-factor model proposed by Batterham and colleagues (2013) . Limitations: The study was limited by the small sample size and recruitment by availability. Conclusion: Findings suggest that the Spanish version of the SOSS-SF is a valid and reliable tool with which to examine suicide stigma among Spanish-speaking populations.


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