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In vitro activity of the novel oral antimicrobial SMT-571, with a new mechanism of action, against MDR and XDR Neisseria gonorrhoeae: future treatment option for gonorrhoea?
Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Sexually Transmitted Infections, Department of Laboratory Medicine.
Summit Therapeutics, Merrifield Centre, Rosemary Lane, Cambridge, UK.
Summit Therapeutics, Merrifield Centre, Rosemary Lane, Cambridge, UK.
Summit Therapeutics, Merrifield Centre, Rosemary Lane, Cambridge, UK.
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2019 (English)In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 74, no 6, p. 1591-1594Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Lack of effective treatment of gonorrhoea due to increasing antimicrobial resistance in Neisseria gonorrhoeae is a serious threat to the management and control of the infection. Novel antimicrobials are required to prevent the infection becoming untreatable.

OBJECTIVES: Herein, we investigated the in vitro activity of a novel small-molecule antimicrobial with a new mechanism of action, SMT-571, against a large collection of clinical N. gonorrhoeae isolates (n = 228) and international gonococcal reference strains (n = 34), including numerous MDR and XDR gonococcal isolates.

METHODS: MICs of SMT-571 were determined by agar dilution and MICs of ceftriaxone, cefixime, azithromycin, ciprofloxacin, ampicillin, spectinomycin and tetracycline were determined by Etest.

RESULTS: SMT-571 showed potent in vitro activity against all the tested N. gonorrhoeae isolates (n = 262). The MICs ranged from 0.064 to 0.125 mg/L and the MIC50, MIC90 and modal MIC were all 0.125 mg/L. No cross-resistance or correlation between the MICs of SMT-571 and comparator agents was seen.

CONCLUSIONS: SMT-571 demonstrated potent in vitro activity against all tested gonococcal isolates and no cross-resistance to previously and currently used antimicrobials was seen. With its promising supplementary in vitro and in vivo preclinical data, including high levels of oral bioavailability, SMT-571 could be an effective option for the oral treatment of gonorrhoea. Randomized controlled clinical trials for gonorrhoea that examine the treatment efficacy, pharmacokinetics/pharmacodynamics, toxicity and safety of SMT-571, and include urogenital and extragenital (rectal and pharyngeal) samples, are crucial.

Place, publisher, year, edition, pages
Oxford University Press, 2019. Vol. 74, no 6, p. 1591-1594
National Category
Infectious Medicine
Identifiers
URN: urn:nbn:se:oru:diva-72787DOI: 10.1093/jac/dkz060ISI: 000482076800021PubMedID: 30778550Scopus ID: 2-s2.0-85066281158OAI: oai:DiVA.org:oru-72787DiVA, id: diva2:1291818
Note

Funding Agencies:

Örebro County Council Research Committee, Örebro, Sweden  

Foundation for Medical Research at Örebro University Hospital, Örebro, Sweden  

Summit Therapeutics, Cambridge, UK 

Available from: 2019-02-26 Created: 2019-02-26 Last updated: 2019-08-29Bibliographically approved

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Jacobsson, SusanneUnemo, Magnus

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