| 1. |
- Jacobsson, Susanne, 1974-, et al.
(author)
-
High in vitro activity of DIS-73285, a novel antimicrobial with a new mechanism of action, against MDR and XDR Neisseria gonorrhoeae
- 2020
-
In: Journal of Antimicrobial Chemotherapy. - : Oxford University Press. - 0305-7453 .- 1460-2091. ; 75:11, s. 3244-3247
-
Journal article (peer-reviewed)abstract
- 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.
|
|
| 2. |
- Jacobsson, Susanne, 1974-, et al.
(author)
-
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?
- 2019
-
In: Journal of Antimicrobial Chemotherapy. - : Oxford University Press. - 0305-7453 .- 1460-2091. ; 74:6, s. 1591-1594
-
Journal article (peer-reviewed)abstract
- 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.
|
|
| 3. |
- Meo, Paul, et al.
(author)
-
IN-VITRO ACTIVITY OF SMT-571 AND COMPARATORS AGAINST CLINICAL ISOLATES AND REFERENCE STRAINS OF NEISSERIA GONORRHOEAE
- 2019
-
In: Sexually Transmitted Infections. - : BMJ Publishing Group Ltd. - 1368-4973 .- 1472-3263. ; 95:Suppl. 1, s. A295-A295
-
Journal article (other academic/artistic)abstract
- Background: The emergence and spread of multidrug resistance to antibiotics used to treat gonorrhoea has resulted in a dramatic loss of effective regimens for the condition. Currently, the extended spectrum cephalosporin, ceftriaxone, is the only viable monotherapy option available, however, resistance to this last line treatment is now emerging globally. Herein, we assessed the in vitro activity of a novel small molecule antimicrobial with a new mechanism of action, SMT-571, against a large collection of N. gonorrhoeae clinical isolates and reference strains including numerous MDR and XDR gonococcal isolates.Methods: MICs (mg/L) of SMT-571 were determined by agar dilution according to current CLSI guidelines. The MICs of ceftriaxone, cefixime, azithromycin, ciprofloxacin, spectinomycin, tetracycline, and ampicillin were determined using the Etest method (AB bioMérieux, Marcy l’Etoile, France).Results: SMT-571 showed potent in vitro activity against all the tested N. gonorrhoeae isolates (n=262) with MICs ranging from 0.064 to 0.125 mg/L, and the MIC50, MIC90 and modal MIC were all 0.125 mg/L. The compound was not influenced by pre-existing resistance mechanisms with no cross-resistance or correlation between the MICs of SMT-571 and comparator agents being observed.Conclusion: This study is the first broad evaluation of the in vitro activities of a new mechanism, novel small molecule anti-microbial for the treatment of gonorrhoea. SMT-571 demonstrated highin vitroactivity against a large geographically, temporally and genetically diverse collection of clinical N. gonorrhoeae isolates and international reference strains, including various types of high-level resistant, MDR and XDR gonococcal isolates.
|
|
