scholarly journals In VitroandIn Vivoactivity of a novel catheter lock solution against bacterial and fungal biofilms

2018 ◽  
Author(s):  
Jyotsna Chandra ◽  
Lisa Long ◽  
Nancy Isham ◽  
Pranab K Mukherjee ◽  
Gino DiSciullo ◽  
...  
Keyword(s):  
Rabbit Model ◽  
Bloodstream Infections ◽  
Central Line ◽  
Saline Control ◽  
Resistant Bacteria ◽  
Lock Solution ◽  
Catheter Lock ◽  
Adhesion Phase

Central line associated bloodstream infections (CLABSIs) are increasingly recognized to be associated with intralumenal microbial biofilms, and effective measures for the prevention and treatment of BSI remain lacking. This report evaluates a new commercially developed antimicrobial catheter lock solution (ACL) containing trimethoprim (5 mg/ml) and ethanol (25%) and CA-EDTA 3% for activity against bacterial and fungal biofilms using in vitro and in vivo (rabbit) catheter biofilm models. Biofilms were formed with bacterial (seven different species including vancomycin-resistant enterococcus, VRE) or fungal (C. albicans) species on catheter materials. Biofilm formation was evaluated by quantitative culture (colony forming units, CFUs) and scanning electron microscopy (SEM). Treatment with ACL inhibited growth of adhesion phase biofilms in vitro after 60 min (VRE) or 15 min (all others), while mature biofilms were eradicated after exposure for 2 or 4 h, compared to control. Similar results were observed for drug-resistant bacteria. In the catheterized rabbit model, when compared against heparinized saline control, ACL lock therapy significantly reduced the catheter bacterial (3.49 ± 0.75 vs. 0.03 ± 0.06 log CFU/catheter, respectively; P = 0.001) and fungal burden (2.48 ± 1.60 vs. 0.55 ± 1.19 log CFU/catheter segment, respectively; P = 0.012). SEM also demonstrated eradication of bacterial and fungal biofilms in vivo on catheters exposed to ACL, while vigorous biofilms were observed on untreated control catheters. Our results demonstrate that ACL was efficacious against both adhesion phase and mature biofilms formed by bacteria and fungi in vitro as well as in vivo.

scholarly journals In Vitro and In Vivo Activity of a Novel Catheter Lock Solution against Bacterial and Fungal Biofilms

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
J. Chandra ◽  
L. Long ◽  
N. Isham ◽  
P. K. Mukherjee ◽  
G. DiSciullo ◽  
...  
Keyword(s):  
Rabbit Model ◽  
Bloodstream Infections ◽  
Central Line ◽  
Resistant Bacteria ◽  
Content Type ◽  
Lock Solution ◽  
Catheter Lock ◽  
Adhesion Phase

ABSTRACT Central-line-associated bloodstream infections are increasingly recognized to be associated with intraluminal microbial biofilms, and effective measures for the prevention and treatment of bloodstream infections remain lacking. This report evaluates a new commercially developed antimicrobial catheter lock solution (ACL), containing trimethoprim (5 mg/ml), ethanol (25%), and calcium EDTA (Ca-EDTA) (3%), for activity against bacterial and fungal biofilms, using in vitro and in vivo (rabbit) catheter biofilm models. Biofilms were formed by bacterial (seven different species, including vancomycin-resistant Enterococcus [VRE]) or fungal (Candida albicans) species on catheter materials. Biofilm formation was evaluated by quantitative culture (CFU) and scanning electron microscopy (SEM). Treatment with ACL inhibited the growth of adhesion-phase biofilms in vitro after 60 min (VRE) or 15 min (all others), while mature biofilms were completely inhibited after exposure for 2 or 4 h, compared to control. Similar results were observed for drug-resistant bacteria. Compared to the heparinized saline controls, ACL lock therapy significantly reduced the catheter bacterial (3.49 ± 0.75 versus 0.03 ± 0.06 log CFU/catheter; P = 0.016) and fungal (2.48 ± 1.60 versus 0.55 ± 1.19 log CFU/catheter segment; P = 0.013) burdens in the catheterized rabbit model. SEM also demonstrated eradication of bacterial and fungal biofilms in vivo on catheters exposed to ACL, while vigorous biofilms were observed on untreated control catheters. Our results demonstrated that ACL was efficacious against both adhesion-phase and mature biofilms formed by bacteria and fungi in vitro and in vivo.

scholarly journals Minocycline-EDTA-Ethanol Antimicrobial Catheter Lock Solution Is Highly Effective In Vitro for Eradication of Candida auris Biofilms

2020 ◽  
Vol 64 (4) ◽  
Author(s):  
Ruth A. Reitzel ◽  
Joel Rosenblatt ◽  
Bahgat Z. Gerges ◽  
Nylev Vargas-Cruz ◽  
Issam I. Raad
Keyword(s):  
Therapeutic Option ◽  
Bloodstream Infections ◽  
Central Line ◽  
Emerging Pathogen ◽  
Candida Auris ◽  
Content Type ◽  
Lock Solution ◽  
Highly Effective ◽  
Catheter Lock

ABSTRACT Candida auris is an emerging pathogen that can cause virulent central-line-associated bloodstream infections. Catheter salvage through the eradication of biofilms is a desirable therapeutic option. We compared taurolidine and minocycline-EDTA-ethanol (MEE) catheter lock solutions in vitro for the eradication of biofilms of 10 C. auris strains. MEE fully eradicated all C. auris biofilms, while taurolidine lock partially eradicated all of the C. auris biofilms. The superiority was significant for all C. auris strains tested (P = 0.002).

scholarly journals Nitroglycerin-Citrate-Ethanol Catheter Lock Solution Is Highly Effective for In Vitro Eradication of Candida auris Biofilm

2019 ◽  
Vol 63 (7) ◽  
Author(s):  
Nylev Vargas-Cruz ◽  
Ruth A. Reitzel ◽  
Joel Rosenblatt ◽  
Anne-Marie Chaftari ◽  
Rita Wilson Dib ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Bloodstream Infections ◽  
Central Line ◽  
Candida Auris ◽  
Content Type ◽  
Lock Solution ◽  
Amphotericin B Deoxycholate ◽  
Catheter Lock

ABSTRACT Candida auris poses emerging risks for causing severe central line-associated bloodstream infections. We tested in vitro the ability of antifungal lock solutions to rapidly eradicate C. auris biofilms. Liposomal amphotericin B, amphotericin B deoxycholate, fluconazole, voriconazole, micafungin, caspofungin, and anidulafungin failed to completely eradicate all 10 tested C. auris biofilms. Conversely, nitroglycerin-citrate-ethanol (NiCE) catheter lock solution completely eradicated all replicates for all of C. auris biofilms tested.

Advances in the prevention and management of central-line–associated bloodstream infections: The role of chelator-based catheter locks

2019 ◽  
Vol 40 (9) ◽  
pp. 1036-1045 ◽  
Author(s):  
Anne-Marie Chaftari ◽  
George M. Viola ◽  
Joel Rosenblatt ◽  
Ray Hachem ◽  
Issam Raad
Keyword(s):  
Antimicrobial Agents ◽  
Low Cost ◽  
Bloodstream Infections ◽  
Central Line ◽  
In Vivo Studies ◽  
Central Lines ◽  
Antiplatelet Aggregation ◽  
Catheter Lock

AbstractThe proper functioning of central lines is imperative for the management of patients with cancer or on hemodialysis. However, these lifelines can become infected and can malfunction.Chelators such as citrate and EDTA have been widely studied alone or in combination with other antimicrobial agents in catheter lock solutions to prevent catheter-related bloodstream infections and to maintain catheter patency. Given their anticoagulation, antiplatelet aggregation, antibiofilm, antimicrobial activity, safety profile, as well as their low cost, chelators have long been considered alternatives to heparin and a vital component of catheter lock solutions. In this review, we present a detailed summary of the properties of chelators and in vitro and in vivo studies of chelator-containing lock solutions.

scholarly journals A Novel Nonantibiotic Nitroglycerin-Based Catheter Lock Solution for Prevention of Intraluminal Central Venous Catheter Infections in Cancer Patients

2017 ◽  
Vol 61 (7) ◽  
Author(s):  
Anne-Marie Chaftari ◽  
Ray Hachem ◽  
Ariel Szvalb ◽  
Mahnaz Taremi ◽  
Bruno Granwehr ◽  
...  
Keyword(s):  
Adverse Events ◽  
Cancer Patients ◽  
Randomized Clinical Trials ◽  
Residual Effect ◽  
Bloodstream Infections ◽  
Venous Catheter ◽  
Central Line ◽  
Current Standard ◽  
Lock Solution ◽  
Catheter Lock

ABSTRACT For long-term central lines (CL), the lumen is the major source of central line-associated bloodstream infections (CLABSI). The current standard of care for maintaining catheter patency includes flushing the CL with saline or heparin. Neither agent has any antimicrobial activity. Furthermore, heparin may enhance staphylococcal biofilm formation. We evaluated the safety and efficacy of a novel nonantibiotic catheter lock solution for the prevention of CLABSI. Between November 2015 and February 2016, we enrolled 60 patients with hematologic malignancies who had peripherally inserted central catheters (PICC) to receive the study lock solution. The study lock consisted of 15 or 30 μg/ml of nitroglycerin in combination with 4% sodium citrate and 22% ethanol. Each lumen was locked for at least 2 h once daily prior to being flushed. After enrollment of 10 patients at the lower nitroglycerin dose without evidence of toxicity, the dose was escalated to the higher dose (30 μg/ml). There were no serious related adverse events or episodes of hypotension with lock administration. Two patients experienced mild transient adverse events (one headache and one rash) possibly related to the lock and that resolved without residual effect. The CLABSI rate was 0 on lock days versus 1.6/1,000 catheter days (CD) off lock prophylaxis, compared with a rate of 1.9/1,000 CD at the institution in the same patient population. In conclusion, the nitroglycerin-based lock prophylaxis is safe and well tolerated. It may prevent CLABSI when given daily to cancer patients. Large, prospective, randomized clinical trials are needed to validate these findings. (This study has been registered at ClinicalTrials.gov under identifier NCT02577718.)

scholarly journals Successful Salvage of Central Venous Catheters in Patients with Catheter-Related or Central Line-Associated Bloodstream Infections by Using a Catheter Lock Solution Consisting of Minocycline, EDTA, and 25% Ethanol

2016 ◽  
Vol 60 (6) ◽  
pp. 3426-3432 ◽  
Author(s):  
Issam Raad ◽  
Anne-Marie Chaftari ◽  
Ramia Zakhour ◽  
Mary Jordan ◽  
Zanaib Al Hamal ◽  
...  
Keyword(s):  
Animal Studies ◽  
Bloodstream Infections ◽  
Central Line ◽  
Infectious Complications ◽  
Central Venous Catheters ◽  
Control Group ◽  
Central Venous ◽  
Systemic Antibiotic Therapy ◽  
Lock Solution

In cancer patients with long-term central venous catheters (CVC), removal and reinsertion of a new CVC at a different site might be difficult because of the unavailability of accessible vascular sites.In vitroand animal studies showed that a minocycline-EDTA-ethanol (M-EDTA-EtOH) lock solution may eradicate microbial organisms in biofilms, hence enabling the treatment of central line-associated bloodstream infections (CLABSI) while retaining the catheterin situ. Between April 2013 and July 2014, we enrolled 30 patients with CLABSI in a prospective study and compared them to a historical group of 60 patients with CLABSI who had their CVC removed and a new CVC inserted. Each catheter lumen was locked with an M-EDTA-EtOH solution for 2 h administered once daily, for a total of 7 doses. Patients who received locks had clinical characteristics that were comparable to those of the control group. The times to fever resolution and microbiological eradication were similar in the two groups. Patients with the lock intervention received a shorter duration of systemic antibiotic therapy than that of the control patients (median, 11 days versus 16 days, respectively;P< 0.0001), and they were able to retain their CVCs for a median of 74 days after the onset of bacteremia. The M-EDTA-EtOH lock was associated with a significantly decreased rate of mechanical and infectious complications compared to that of the CVC removal/reinsertion group, who received a longer duration of systemic antimicrobial therapy. (This study has been registered at ClinicalTrials.gov under registration no. NCT01539343.)

scholarly journals Successful Therapy of Experimental Endocarditis Caused by Vancomycin-Resistant Staphylococcus aureus with a Combination of Vancomycin and β-Lactam Antibiotics

2006 ◽  
Vol 50 (9) ◽  
pp. 2951-2956 ◽  
Author(s):  
Paige M. Fox ◽  
Russell J. Lampen ◽  
Katrina S. Stumpf ◽  
Gordon L. Archer ◽  
Michael W. Climo
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Rabbit Model ◽  
Bloodstream Infections ◽  
Aberrant Cell ◽  
Trial Treatment ◽  
Vancomycin Resistant ◽  
Vancomycin Treatment

ABSTRACT VRS1 is the first isolated strain of vancomycin-resistant Staphylococcus aureus (VRSA) found to carry the vanA gene complex previously described in Enterococcus. Under vancomycin pressure, VRS1 makes aberrant cell walls consisting of stem tetrapeptide and depsipeptide that lack the terminal d-Ala-d-Ala residues targeted by vancomycin. Previous data have suggested that this aberrant cell wall is not cross-linked by PBP2a, the enzyme responsible for cell wall transpeptidation in the presence of β-lactam antibiotics. We examined the efficacy of treating VRS1 with a combination of vancomycin and β-lactam antibiotics in vitro and in vivo. We found that the MIC of oxacillin for VRS1 decreased from >256 μg/ml to <1 μg/ml in the presence of vancomycin. Using the rabbit model of endocarditis, we treated VRS1-infected rabbits with nafcillin alone, vancomycin alone, or a combination of nafcillin and vancomycin. Treatment with nafcillin in combination with vancomycin cleared bloodstream infections within 24 h and sterilized 12/13 spleens (92%), as well as 8/13 kidneys (62%), following 3 days of treatment. Mean aortic valve vegetation counts were reduced 3.48 log10 CFU/g with the combination therapy (compared to untreated controls) and were significantly lower than with either vancomycin or nafcillin given alone. VRS1 was extremely virulent in this model, as no untreated rabbits survived the 3-day trial. Treatment of clinical infections due to VRSA with the combination of vancomycin and β-lactams may be an option, based on these results.

Effects of Probiotics in the Management of Infected Chronic Wounds: From Cell Culture to Human Studies

2020 ◽  
Vol 15 (3) ◽  
pp. 193-206
Author(s):  
Brognara Lorenzo ◽  
Salmaso Luca ◽  
Mazzotti Antonio ◽  
Di M. Alberto ◽  
Faldini Cesare ◽  
...  
Keyword(s):  
Chronic Wounds ◽  
Animal Experiments ◽  
Multidrug Resistant ◽  
Preliminary Evidence ◽  
Human Studies ◽  
In Vivo Studies ◽  
Resistant Bacteria ◽  
Keywords Probiotics

Background: Chronic wounds are commonly associated with polymicrobial biofilm infections. In the last years, the extensive use of antibiotics has generated several antibiotic-resistant variants. To overcome this issue, alternative natural treatments have been proposed, including the use of microorganisms like probiotics. The aim of this manuscript was to review current literature concerning the application of probiotics for the treatment of infected chronic wounds. Methods: Relevant articles were searched in the Medline database using PubMed and Scholar, using the keywords “probiotics” and “wound” and “injuries”, “probiotics” and “wound” and “ulcer”, “biofilm” and “probiotics” and “wound”, “biofilm” and “ulcer” and “probiotics”, “biofilm” and “ulcer” and “probiotics”, “probiotics” and “wound”. Results: The research initially included 253 articles. After removal of duplicate studies, and selection according to specific inclusion and exclusion criteria, 19 research articles were included and reviewed, accounting for 12 in vitro, 8 in vivo studies and 2 human studies (three articles dealing with animal experiments included also in vitro testing). Most of the published studies about the effects of probiotics for the treatment of infected chronic wounds reported a partial inhibition of microbial growth, biofilm formation and quorum sensing. Discussion: The application of probiotics represents an intriguing option in the treatment of infected chronic wounds with multidrug-resistant bacteria; however, current results are difficult to compare due to the heterogeneity in methodology, laboratory techniques, and applied clinical protocols. Lactobacillus plantarum currently represents the most studied strain, showing a positive application in burns compared to guideline treatments, and an additional mean in chronic wound infections. Conclusions: Although preliminary evidence supports the use of specific strains of probiotics in certain clinical settings such as infected chronic wounds, large, long-term clinical trials are still lacking, and further research is needed.

scholarly journals β-elemene alleviates airway stenosis via the ILK/Akt pathway modulated by MIR143HG sponging miR-1275

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Guoying Zhang ◽  
Cheng Xue ◽  
Yiming Zeng
Keyword(s):  
Cell Cycle ◽  
Cell Viability ◽  
Cell Model ◽  
Protective Efficacy ◽  
Rabbit Model ◽  
Akt Pathway ◽  
Loss Of Function ◽  
Airway Stenosis

Abstract Background We have previously found that β-elemene could inhibit the viability of airway granulation fibroblasts and prevent airway hyperplastic stenosis. This study aimed to elucidate the underlying mechanism and protective efficacy of β-elemene in vitro and in vivo. Methods Microarray and bioinformatic analysis were used to identify altered pathways related to cell viability in a β-elemene-treated primary cell model and to construct a β-elemene-altered ceRNA network modulating the target pathway. Loss of function and gain of function approaches were performed to examine the role of the ceRNA axis in β-elemene's regulation of the target pathway and cell viability. Additionally, in a β-elemene-treated rabbit model of airway stenosis, endoscopic and histological examinations were used to evaluate its therapeutic efficacy and further verify its mechanism of action. Results The hyperactive ILK/Akt pathway and dysregulated LncRNA-MIR143HG, which acted as a miR-1275 ceRNA to modulate ILK expression, were suppressed in β-elemene-treated airway granulation fibroblasts; β-elemene suppressed the ILK/Akt pathway via the MIR143HG/miR-1275/ILK axis. Additionally, the cell cycle and apoptotic phenotypes of granulation fibroblasts were altered, consistent with ILK/Akt pathway activity. In vivo application of β-elemene attenuated airway granulation hyperplasia and alleviated scar stricture, and histological detections suggested that β-elemene's effects on the MIR143HG/miR-1275/ILK axis and ILK/Akt pathway were in line with in vitro findings. Conclusions MIR143HG and ILK may act as ceRNA to sponge miR-1275. The MIR143HG/miR-1275/ILK axis mediates β-elemene-induced cell cycle arrest and apoptosis of airway granulation fibroblasts by modulating the ILK/Akt pathway, thereby inhibiting airway granulation proliferation and ultimately alleviating airway stenosis.

scholarly journals Development of Triamcinolone Acetonide-Loaded Microemulsion as a Prospective Ophthalmic Delivery System for Treatment of Uveitis: In Vitro and In Vivo Evaluation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 444
Author(s):  
Alaa Mahran ◽  
Sayed Ismail ◽  
Ayat A. Allam
Keyword(s):  
Triamcinolone Acetonide ◽  
Delivery System ◽  
Histopathological Examination ◽  
Rabbit Model ◽  
Subconjunctival Injection ◽  
In Vivo Evaluation ◽  
Ternary Phase Diagrams ◽  
Ophthalmic Delivery

Treatment of uveitis (i.e., inflammation of the uvea) is challenging due to lack of convenient ophthalmic dosage forms. This work is aimed to determine the efficiency of triamcinolone acetonide (TA)-loaded microemulsion as an ophthalmic delivery system for the treatment of uveitis. Water titration method was used to construct different pseudo-ternary phase diagrams. Twelve microemulsion formulations were prepared using oleic acid, Cremophor EL, and propylene glycol. Among all tested formulations, Formulation F3, composed of oil: surfactant-co-surfactant (1:1): water (15:35:50% w/w, respectively), was found to be stable and showed acceptable pH, viscosity, conductivity, droplet size (211 ± 1.4 nm), and zeta potential (−25 ± 1.7 mV) and almost complete in vitro drug release within 24 h. The in vivo performance of the optimized formulation was evaluated in experimentally uveitis-induced rabbit model and compared with a commercial TA suspension (i.e., Kenacort®-A) either topically or by subconjunctival injection. Ocular inflammation was evaluated by clinical examination, white blood cell count, protein content measurement, and histopathological examination. The developed TA-loaded microemulsion showed superior therapeutic efficiency in the treatment of uveitis with high patient compliance compared to commercial suspension. Hence, it could be considered as a potential ocular treatment option in controlling of uveitis.

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