Caprylic Acid and Glyceryl Trinitrate Combination for Eradication of Biofilm

Abstract

There is a growing need for biocompatible, broad-spectrum, nonantibiotic, antimicrobial treatments because of the frequent ineffectiveness of antibiotics against biofilms and the increasing incidence of antibiotic resistance. In this study, we demonstrate rapid and complete biofilm eradication in an in vitro model with synergistic combinations of glyceryl trinitrate and caprylic acid against resistant Gram-positive, Gram-negative, and fungal biofilms.A n estimated 400,000 patients in the United States annually require medical treatment for anal fissures or rectal tears (1, 2). Wounds in microbially contaminated environments (such as the colon and rectum) can be difficult to heal due to the presence of biofilms. Furthermore, surgical site infections associated with implanted devices pose significant medical problems, frequently complicated by microbial biofilm formation on device surfaces (3). This, coupled with the increasing emergence of antibioticresistant biofilms (4), adversely impacts the outcomes of antibiotic wound therapies.Previously, we reported on the synergy of ethanol, citrate, and glyceryl trinitrate (GTN) as a novel nonantibiotic catheter lock solution (5). In other applications involving direct contact with tissues, the use of ethanol above trace concentrations can be undesirable due to potential irritation and cytotoxic responses from certain cell types. Additionally, in applications where bleeding occurs, chelator use can be undesirable, as it can interfere with blood coagulation, an essential step in initiating the healing response. Caprylic acid (CAP) is a medium-chain fatty acid naturally present in human breast milk. CAP has been used intravenously in some total parenteral nutrition formulations (6, 7). It is also readily absorbed following oral administration and yields significant blood concentrations (8). Protonated CAP has been reported to have antimicrobial properties (9, 10). Here, we studied biofilm eradication by the use of medical GTN plus CAP for potential use in medical applications where antimicrobial concentrations of ethanol might cause irritation and where the anticoagulant effects of citrate might be undesirable.The in vitro antimicrobial efficacy of GTN plus CAP was assessed in a well-established biofilm colonization model testing the eradication of biofilm following 2 h of antimicrobial agent exposure. This exposure duration was selected because previous studies showed solutions exhibiting biofilm eradication within 2 h that were also clinically effective (11). Biofilm eradication was assessed for clinical isolates of methicillinresistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), multidrug-resistant Pseudomonas aeruginosa, and Candida albicans, representative of key Gram-positive, Gram-negative, and infectious fungal pathogens (12). Briefly, 1-cm silicone discs were placed in 1 ml of human plasma and incubated overnight at 37°C. The plasma was replaced with 1 ml of 5.5 ϫ 10 5 CFU/ml of challenge organism inoculum and incubated f...

Eradication of Staphylococcus aureus Catheter-Related Biofilm Infections Using ML:8 and Citrox

“…Both agents also killed biofilms formed over 1, 3, and 5 days, suggesting the potential for ML:8 and Citrox to be used in the treatment of established staphylococcal biofilm infections, such as those that occur clinically when CRIs are diagnosed after establishment of biofilm. Our findings are consistent with research published on the antimicrobial potential of caprylic acid (7,8). A study examining the effect of ML:8-X10, a formulation similar to ML:8, and vancomycin showed equivalent activities of both agents against S. aureus (26).…”

“…ML:8 includes components previously approved for parenteral nutrition; the fatty acid caprylic acid is the main component and has been shown to be effective in the treatment of periodontal pathogens (7). The efficacy of caprylic acid against biofilms was also reported previously (8). Citrox is an antimicrobial formulation composed of flavonoids.…”

Glyceryl trinitrate is a novel inhibitor of quorum sensing in <i>Pseudomonas aeruginosa</i>

“…It was found to be an effective catherter lock solution in combination with ethanol and citrate 13,14 . Moreover, GTN combined with caprylic acid was able to eradicate biofilms of Staphylococcus aureus¸ Staphylococcus epidermidis, Pseudomonas aeruginosa and candida albicans 14 . GTN exerted antimicrobial activity against planktonic Candida albicans at high concentrations ranging from 0.15% to 0.3%…”

Proteomic Analysis of Horseweed (Conyza canadensis) Subjected to Caprylic Acid Stress

“…CAP forms an oily liquid that is marginally soluble in water and has a slightly unpleasant rancid‐like smell and taste. CAP can be used as an antimicrobial pesticide, a disinfectant, and algaecide . C8 fatty acid is also phytotoxic to velvetleaf ( Abutilon theophrasti ), giant foxtail ( Setaria faberi ), and common lambsquarters ( Chenopodium album ); esters of C6, C7, and C10 fatty acids are comparatively less effective than C8 fatty acid .…”

“…CAP can be used as an antimicrobial pesticide, a disinfectant, and algaecide. [7,8] C8 fatty acid is also phytotoxic to velvetleaf (Abutilon theophrasti), giant foxtail (Setaria faberi), and common lambsquarters (Chenopodium album); esters of C6, C7, and C10 fatty acids are comparatively less effective than C8 fatty acid. [9] An emulsifier from naturally occurring sources was found to be as effective as a phosphate ester emulsifier for enhancing CAP activity on velvetleaf, giant foxtail, and common lambsquarters.…”