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High in vitro activity of DIS-73285, a novel antimicrobial with a new mechanism of action, against MDR and XDR Neisseria gonorrhoeae
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- Jacobsson, Susanne, 1974- (author)
- Örebro universitet,Institutionen för medicinska vetenskaper,Region Örebro län,WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Sexually Transmitted Infections, Department of Laboratory Medicine
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- Mason, Clive (author)
- Summit Therapeutics, Merrifield Centre, Rosemary Lane, Cambridge, UK
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- Khan, Nawaz (author)
- Summit Therapeutics, Merrifield Centre, Rosemary Lane, Cambridge, UK
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- 2020-07-26
- 2020
- English.
- In: Journal of Antimicrobial Chemotherapy. - : Oxford University Press. - 0305-7453 .- 1460-2091. ; 75:11, s. 3244-3247
- Journal article (peer-reviewed)
Abstract
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- BACKGROUND: The rising incidence of antimicrobial resistance in Neisseria gonorrhoeae may result in untreatable gonorrhoea in certain circumstances and development of novel antimicrobials is urgently needed.OBJECTIVES: To evaluate the in vitro activity of a novel small-molecule antimicrobial with a new mechanism of action, DIS-73285, against a large geographically, temporally and genetically diverse collection of clinical N. gonorrhoeae isolates and reference strains, including various types of high-level resistant, MDR and XDR gonococcal isolates (n = 262).METHODS: MICs (mg/L) of DIS-73285 were determined by agar dilution and by Etest for ceftriaxone, cefixime, azithromycin, ciprofloxacin, ampicillin, spectinomycin and tetracycline.RESULTS: DIS-73285 was substantially more potent than any of the currently or previously used therapeutic antimicrobials, with MICs ranging from ≤0.001 to 0.004 mg/L, and the MIC50, MIC90 and modal MIC all ≤0.001 mg/L (lowest MIC tested). No correlation with the MICs of DIS-73285 and the MICs of any of the currently or previously used antimicrobials was observed.CONCLUSIONS: The novel chemotype, small-molecule antimicrobial DIS-73285, demonstrated high in vitro potency against all tested N. gonorrhoeae isolates. Further in vitro and in vivo studies, evaluating efficacy, resistance emergence, pharmacokinetic/pharmacodynamic parameters, toxicity and safety, should be conducted to evaluate DIS-73285 as a therapy specifically for urogenital and extra-genital gonorrhoea.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
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