In vitro activity of EDTA and TOL-463 against Neisseria gonorrhoeae

Nash, Evelyn E.; Henning, Tara; Pham, Cau D.; Pettus, Kevin; Sharpe, Samera; Kersh, Ellen N.

doi:10.1016/j.diagmicrobio.2018.10.021

Cited by 2 publications

(2 citation statements)

References 18 publications

(18 reference statements)

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“…Salicylamide successfully inhibited the growth of the 40 clinical isolates of N. gonorrhoeae tested (MIC values ranged from 8 to 32 g/ml). Salicylamide (at 5ϫ MIC) exhibited bactericidal activity against N. gonorrhoeae, successfully reducing the bacterial burden below the limit of detection after 10 h. Azithromycin, the current drug of choice for gonorrhea, achieved the same effect in 8 h, which is in agreement with previous reports (31,32). Due to the nature of gonococcal infection, a bactericidal drug is preferred over bacteriostatic drugs in quelling infection and preventing transmission.…”

Section: Discussionsupporting

confidence: 89%

Repurposing Salicylamide for Combating Multidrug-Resistant Neisseria gonorrhoeae

Alhashimi

Mayhoub

Seleem

2019

Antimicrob Agents Chemother

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The U.S. Centers for Disease Control and Prevention (CDC) lists Neisseria gonorrhoeae as one of the most urgent antibiotic-resistant threats in the United States. This is due to the emergence of clinical isolates that have developed resistance to nearly every antibiotic used to treat gonorrhea and highlights the critical need to find new therapeutics. The present study discovered salicylamide, an analgesic and antipyretic drug, has antibacterial activity against 40 different antibiotic-resistant strains of N. gonorrhoeae (MIC, 8 to 32 μg/ml) with low frequency of resistance <2.4 × 10−9. Interestingly, salicylamide did not inhibit growth of bacterial species in the vaginal microflora involved in defense against gonococcal infections, such as Lactobacillus gasseri, Lactobacillus jensenii, Lactobacillus johnsonii, and Lactobacillus crispatus. A time-kill assay revealed that salicylamide is a rapidly bactericidal drug, as it eradicated a high inoculum of N. gonorrhoeae within 10 h. Salicylamide was superior to the drug of choice, ceftriaxone, in reducing the burden of intracellular N. gonorrhoeae by 97% in infected endocervical cells. Furthermore, salicylamide outperformed ceftriaxone in reducing expression of the proinflammatory cytokine interleukin 8 (IL-8) from endocervical cells infected with N. gonorrhoeae. A checkerboard assay revealed that salicylamide exhibited a synergistic interaction with tetracycline and additive relationships with azithromycin, ciprofloxacin, and ceftriaxone. A more in-depth investigation of the structure-activity relationship of derivatives of salicylamide revealed the amide and hydroxyl groups are important for antigonorrheal activity. In conclusion, this study identified salicylamide as a promising candidate for further investigation as a novel treatment option for multidrug-resistant gonorrhea.

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Section: Discussionsupporting

confidence: 89%

Repurposing Salicylamide for Combating Multidrug-Resistant Neisseria gonorrhoeae

Alhashimi

Mayhoub

Seleem

2019

Antimicrob Agents Chemother

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“…Only by checkerboard assay would a definitive conclusion be made regarding the synergistic activity. EDTA is commonly reported to be a synergist for various antimicrobials [35][36][37][38] and should be more comprehensively evaluated in future work.…”

Section: Discussionmentioning

confidence: 99%

Antimicrobial Activity of a Vaginal Gel Formulation: Considerations Related to Vaginal Infection and Dysbiosis

Seta

Larsen

2021

Pathogens

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Many non-prescription preparations intended to treat or alleviate symptoms of vaginal infection are available in American and European markets, but many have scant preclinical or clinical research underpinning. Respecta®Balance Gel (RBG) is marketed as an adjunct to probiotic treatment and its relevant antimicrobial properties were studied. Key findings with the manufacturer-supplied gel showed reduced turbidity in broth-dilution tests by 50% against Candida albicans and Candida glabrata at RBG concentrations 0.2–0.4% of neat product, respectively. A 50% reduction in turbidity of Escherichia coli, Streptococcus agalactiae, Enterococcus faecalis ranged from 1.6–2.2% and Gardnerella vaginalis was shown by flow cytometry counts to undergo a 50% reduction at 0.3% RBG. Propidium iodide staining indicated a rapid reduction of cell integrity of G. vaginalis almost immediately while after 4 h 45% of E. coli cells were stained. The lactic acid in BHI inhibited bacteria and yeast at concentrations ranging from 0.2–1.8% but inhibition was not solely due to pH since a 1:4 dilution of RBG resulted in a pH near neutral (6.75). Other findings showed biofilm accumulation assessed after 10-days exposure of Candida spp. to RBG and was reduced by an average of one-third (community strains) to one-half (drug-resistant strains). One excipient of the RBG, disodium EDTA, inhibited the growth of bacteria and yeast at concentrations below those present in RBG and may accentuate the activity of the host defense factor, lactoferrin. We conclude that RBG is a potent inhibitor of vaginal microorganisms relevant to vaginitis or intrapartum infections and contains excipients that may contribute to its antimicrobial activity.

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In vitro activity of EDTA and TOL-463 against Neisseria gonorrhoeae

Cited by 2 publications

References 18 publications

Repurposing Salicylamide for Combating Multidrug-Resistant Neisseria gonorrhoeae

Repurposing Salicylamide for Combating Multidrug-Resistant Neisseria gonorrhoeae

Antimicrobial Activity of a Vaginal Gel Formulation: Considerations Related to Vaginal Infection and Dysbiosis

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