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

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).

2019 ◽  
Vol 63 (7) ◽  
Author(s):  
Nylev Vargas-Cruz ◽  
Ruth A. Reitzel ◽  
Joel Rosenblatt ◽  
Anne-Marie Chaftari ◽  
Rita Wilson Dib ◽  
...  

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.


2018 ◽  
Vol 62 (8) ◽  
Author(s):  
J. Chandra ◽  
L. Long ◽  
N. Isham ◽  
P. K. Mukherjee ◽  
G. DiSciullo ◽  
...  

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.


2018 ◽  
Author(s):  
Jyotsna Chandra ◽  
Lisa Long ◽  
Nancy Isham ◽  
Pranab K Mukherjee ◽  
Gino DiSciullo ◽  
...  

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.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S416-S416
Author(s):  
Ruth A Reitzel ◽  
Joel Rosenblatt ◽  
Bahgat Gerges ◽  
Nylev Vargas-Cruz ◽  
Ray Y Hachem ◽  
...  

Abstract Background Bloodstream infections due to Candida auris are an emerging public health concern due to high prevalence of antifungal resistance and significant rates of patient mortality. C. auris is typically azole-resistant; however, several strains have been identified with elevated MICs to all major classes of antifungals. Previously we reported that a synergistic combination of MEDTA+EtOH was highly effective in a clinical trial that evaluated salvage of catheters in patients with bacterial CLABSI. We have also previously reported in vitro studies that demonstrated this combination was capable of eradicating ordinary yeast CLABSI pathogens. In this study we evaluated the ability MEDTA+EtOH lock to rapidly eradicate C. auris biofilms. Methods Biofilm eradication of C. auris was evaluated in 10 strains. Candida auris biofilm was grown on silicone discs for 24 hours. Discs were then washed to remove any nonadherent organisms and exposed for 60 minutes to 1 mg/mL Minocycline + 30 mg/mL EDTA + 25% Ethanol (MEDTA+EtOH) lock solution. 1.35% Taurolidine + 3.5% Citrate + 1000U Heparin (TCH) lock solution was used as a comparator. Discs were exposed to Muller–Hinton broth as a control. Subsequently discs were sonicated for 15 minutes in 5 mL of saline and quantitatively cultured onto sabouraud dextrose agar. Plates were incubated at 37°C for 48 hours and counted for growth. All testing was conducted with 6 replicates. Results Median and range of recovered viable colonies are presented below. MEDTA+EtOH was significantly more efficacious compared with control (P = 0.002 for all strains) in completely eradicating all replicates in all 10 strains of C. auris tested. MEDTA+EtOH was also superior compared with TCH lock solution (P = 0.002) for all strains. Conclusion MEDTA+EtOH is highly effective and was superior to TCH and positive control in the rapid in vitro eradication of all 10 strains of C. auris biofilms tested. Disclosures All authors: No reported disclosures.


2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S616-S616
Author(s):  
Joel Rosenblatt ◽  
Ruth Reitzel ◽  
Nylev Vargas-Cruz ◽  
Ray Y Hachem ◽  
Anne-Marie Chaftari ◽  
...  

2017 ◽  
Vol 61 (7) ◽  
Author(s):  
Anne-Marie Chaftari ◽  
Ray Hachem ◽  
Ariel Szvalb ◽  
Mahnaz Taremi ◽  
Bruno Granwehr ◽  
...  

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.)


2016 ◽  
Vol 60 (6) ◽  
pp. 3426-3432 ◽  
Author(s):  
Issam Raad ◽  
Anne-Marie Chaftari ◽  
Ramia Zakhour ◽  
Mary Jordan ◽  
Zanaib Al Hamal ◽  
...  

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.)


2013 ◽  
Vol 57 (4) ◽  
pp. 1998-2000 ◽  
Author(s):  
R. Estes ◽  
J. Theusch ◽  
A. Beck ◽  
D. Pitrak ◽  
Kathleen M. Mullane

ABSTRACTCentral venous catheters commonly develop central line-associated bloodstream infections.In vitroantibiotic lock therapy (ALT) was simulated on 10 methicillin-resistantStaphylococcus aureus(MRSA) clinical isolates imbedded in biofilm-coated silicon disks. Five days of 4-h daily exposures to daptomycin (2.5 mg/ml) in 25% ethanol or minocycline (3 mg/ml) plus 25% ethanol and 30 mg/ml EDTA resulted in significantly greater elimination of MRSA colonization than treatment with minocycline alone.


Sign in / Sign up

Export Citation Format

Share Document