Therapeutic effect of ethylenediaminetetraacetic acid irrigation solution against wound infection with drug-resistant bacteria in a rat model: an animal study

Deng, Ziwei; Liu, Fengxian; Li, C.

doi:10.1302/2046-3758.85.bjr-2018-0280.r3

Cited by 18 publications

(12 citation statements)

References 40 publications

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“…Although the efficacy of EDTA-NS solution has been well established by previous studies, 22 - 25 to the best of our knowledge it was unknown if one concentration of EDTA-NS is superior to others for reducing SSIs. In the present study, we evaluated a range of EDTA-NS concentrations to determine if there was an optimal concentration that was effective and safe in reducing infections in three rat models: 1) soft-skin defect, 2) bone exposed, and 3) intra-articular implant.…”

Section: Discussionmentioning

confidence: 93%

“…Pseudomonas aeruginosa, Enterococcus , Acinetobacter baumannii , Enterobacter, and Proteus mirabilis ). 22 - 25 For those modelling arthroplasties with an intra-articular implant, wound irrigation with EDTA-reduced infection caused no adverse effects, and was superior to povidone-iodine, benzalkonium chloride, and NS. In the above studies, 1 mM was the concentration of EDTA used in irrigation solutions.…”

Section: Introductionmentioning

confidence: 99%

“…In the above studies, 1 mM was the concentration of EDTA used in irrigation solutions. 23 , 24 25 However, it is unknown whether 1 mM EDTA in irrigation solutions is an optimal concentration for reducing or preventing bacterial SSIs. In the present study, we evaluated the cell toxicity of different concentrations of ethylenediaminetetraacetic acid dissolved in normal saline (EDTA-NS) and the efficacy of different concentrations of EDTA as an additive to NS irrigation solutions in preventing infection in three different rat models, with the goal of identifying an optimal concentration.…”

Section: Introductionmentioning

confidence: 99%

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Optimal concentration of ethylenediaminetetraacetic acid as an irrigation solution additive to reduce infection rates in rat models of contaminated wound

Lin

Gao

Wei

et al. 2021

Bone & Joint Research

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Aims In wound irrigation, 1 mM ethylenediaminetetraacetic acid (EDTA) is more efficacious than normal saline (NS) in removing bacteria from a contaminated wound. However, the optimal EDTA concentration remains unknown for different animal wound models. Methods The cell toxicity of different concentrations of EDTA dissolved in NS (EDTA-NS) was assessed by Cell Counting Kit-8 (CCK-8). Various concentrations of EDTA-NS irrigation solution were compared in three female Sprague-Dawley rat models: 1) a skin defect; 2) a bone exposed; and 3) a wound with an intra-articular implant. All three models were contaminated with Staphylococcus aureus or Escherichia coli. EDTA was dissolved at a concentration of 0 (as control), 0.1, 0.5, 1, 2, 5, 10, 50, and 100 mM in sterile NS. Samples were collected from the wounds and cultured. The bacterial culture-positive rate (colony formation) and infection rate (pus formation) of each treatment group were compared after irrigation and debridement. Results Cell viability intervened below 10 mM concentrations of EDTA-NS showed no cytotoxicity. Concentrations of 1, 2, and 5 mM EDTA-NS had lower rates of infection and positive cultures for S. aureus and E. coli compared with other concentrations in the skin defect model. For the bone exposed model, 0.5, 1, and 2 mM EDTA-NS had lower rates of infection and positive cultures. For intra-articular implant models 10 and 50 mM, EDTA-NS had the lowest rates of infection and positive cultures. Conclusion The concentrations of EDTA-NS below 10 mM are safe for irrigation. The optimal concentration of EDTA-NS varies by type of wound after experimental inoculation of three types of wound. Cite this article: Bone Joint Res 2021;10(1):68–76.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Optimal concentration of ethylenediaminetetraacetic acid as an irrigation solution additive to reduce infection rates in rat models of contaminated wound

Lin

Gao

Wei

et al. 2021

Bone & Joint Research

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“…Similarly, the amount of EDTA typically used in nebulized bronchodilators does not induce bronchospasm ( Asmus et al, 2001 ). Some additional benefits of EDTA is that it can disperse and kill mature PA in biofilms ( Banin et al, 2006 ) and can achieve complete eradication of 7 bacterial pathogens (including 5 ESKAPE members) in skin, bone, implant infections ( Deng et al, 2019 ). In UTI’s, based upon the low pH of morning voided urine, the acidification of nitrite has been shown to kill nitrate reducing bacteria such as E. coli and PA ( Carlsson et al, 2003 , 2005 ).…”

Section: Why Inhaled or Topical No Is Likely Not Nearly As Effective As Ab569mentioning

confidence: 99%

The Bactericidal Tandem Drug, AB569: How to Eradicate Antibiotic-Resistant Biofilm Pseudomonas aeruginosa in Multiple Disease Settings Including Cystic Fibrosis, Burns/Wounds and Urinary Tract Infections

et al. 2021

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The life-threatening pandemic concerning multi-drug resistant (MDR) bacteria is an evolving problem involving increased hospitalizations, billions of dollars in medical costs and a remarkably high number of deaths. Bacterial pathogens have demonstrated the capacity for spontaneous or acquired antibiotic resistance and there is virtually no pool of organisms that have not evolved such potentially clinically catastrophic properties. Although many diseases are linked to such organisms, three include cystic fibrosis (CF), burn/blast wounds and urinary tract infections (UTIs), respectively. Thus, there is a critical need to develop novel, effective antimicrobials for the prevention and treatment of such problematic infections. One of the most formidable, naturally MDR bacterial pathogens is Pseudomonas aeruginosa (PA) that is particularly susceptible to nitric oxide (NO), a component of our innate immune response. This susceptibility sets the translational stage for the use of NO-based therapeutics during the aforementioned human infections. First, we discuss how such NO therapeutics may be able to target problematic infections in each of the aforementioned infectious scenarios. Second, we describe a recent discovery based on years of foundational information, a novel drug known as AB569. AB569 is capable of forming a “time release” of NO from S-nitrosothiols (RSNO). AB569, a bactericidal tandem consisting of acidified NaNO2 (A-NO2–) and Na2-EDTA, is capable of killing all pathogens that are associated with the aforementioned disorders. Third, we described each disease state in brief, the known or predicted effects of AB569 on the viability of PA, its potential toxicity and highly remote possibility for resistance to develop. Finally, we conclude that AB569 can be a viable alternative or addition to conventional antibiotic regimens to treat such highly problematic MDR bacterial infections for civilian and military populations, as well as the economical burden that such organisms pose.

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“…In addition, bactericidal concentrations of AB569 were non-toxic to primary adult human skin (dermal) fibroblasts. Regarding human use, both the NaNO 2 and/or EDTA component(s) of AB569 have separately proven to be safe in studies related to the treatment of urinary tract infection [ 33 ], burn wounds [ 34 ], cystic fibrosis lung infection [ 35 ], chelation therapy [ 36 ], soaps [ 37 ] and cosmetics [ 38 ]. Thus, our results suggest that AB569 has great potential as a therapeutic agent form the treatment of battlefield wound/burn/blast infections as well as problematic ventilator-associated pneumonia (VAP) infections by Ab .…”

Section: Introductionmentioning

confidence: 99%

AB569, a non-toxic combination of acidified nitrite and EDTA, is effective at killing the notorious Iraq/Afghanistan combat wound pathogens, multi-drug resistant Acinetobacter baumannii and Acinetobacter spp.

et al. 2021

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Multi-drug resistant (MDR) Acinetobacter baumannii (Ab) and Acinetobacter spp. present monumental global health challenges. These organisms represent model Gram-negative pathogens with known antibiotic resistance and biofilm-forming properties. Herein, a novel, nontoxic biocide, AB569, consisting of acidified nitrite (A-NO2-) and ethylenediaminetetraacetic acid (EDTA), demonstrated bactericidal activity against all Ab and Acinetobacter spp. strains, respectively. Average fractional inhibitory concentrations (FICs) of 0.25 mM EDTA plus 4 mM A-NO2- were observed across several clinical reference and multiple combat wound isolates from the Iraq/Afghanistan wars. Importantly, toxicity testing on human dermal fibroblasts (HDFa) revealed an upper toxicity limit of 3 mM EDTA plus 64 mM A-NO2-, and thus are in the therapeutic range for effective Ab and Acinetobacter spp. treatment. Following treatment of Ab strain ATCC 19606 with AB569, quantitative PCR analysis of selected genes products to be responsive to AB569 revealed up-regulation of iron regulated genes involved in siderophore production, siderophore biosynthesis non-ribosomal peptide synthetase module (SBNRPSM), and siderophore biosynthesis protein monooxygenase (SBPM) when compared to untreated organisms. Taken together, treating Ab infections with AB569 at inhibitory concentrations reveals the potential clinical application of preventing Ab from gaining an early growth advantage during infection followed by extensive bactericidal activity upon subsequent exposures.

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Therapeutic effect of ethylenediaminetetraacetic acid irrigation solution against wound infection with drug-resistant bacteria in a rat model: an animal study

Cited by 18 publications

References 40 publications

Optimal concentration of ethylenediaminetetraacetic acid as an irrigation solution additive to reduce infection rates in rat models of contaminated wound

Optimal concentration of ethylenediaminetetraacetic acid as an irrigation solution additive to reduce infection rates in rat models of contaminated wound

The Bactericidal Tandem Drug, AB569: How to Eradicate Antibiotic-Resistant Biofilm Pseudomonas aeruginosa in Multiple Disease Settings Including Cystic Fibrosis, Burns/Wounds and Urinary Tract Infections

AB569, a non-toxic combination of acidified nitrite and EDTA, is effective at killing the notorious Iraq/Afghanistan combat wound pathogens, multi-drug resistant Acinetobacter baumannii and Acinetobacter spp.

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