scholarly journals In Vitro Susceptibility to Closthioamide among Clinical and Reference Strains of Neisseria gonorrhoeae

2017 ◽  
Vol 61 (10) ◽  
Author(s):  
Victoria F. Miari ◽  
Priya Solanki ◽  
Yonek Hleba ◽  
Richard A. Stabler ◽  
John T. Heap
Keyword(s):  
Antimicrobial Resistance ◽  
Neisseria Gonorrhoeae ◽  
Related Species ◽  
Cross Resistance ◽  
Drug Resistant ◽  
In Vitro Susceptibility ◽  
Content Type ◽  
Reference Strains ◽  
Species Cross

ABSTRACT Neisseria gonorrhoeae is one of the leading antimicrobial resistance threats worldwide. This study determined the MICs of closthioamide to be 0.008 to 0.5 mg/liter for clinical N. gonorrhoeae strains and related species. Cross-resistance with existing antimicrobial resistance was not detected, indicating that closthioamide could be used to treat drug-resistant N. gonorrhoeae.

scholarly journals In Vitro Susceptibility of Neisseria gonorrhoeae Strains to Mupirocin, an Antibiotic Reformulated for Parenteral Administration in Nanoliposomes

2018 ◽  
Vol 62 (4) ◽  
Author(s):  
Ahuva Cern ◽  
Kristie L. Connolly ◽  
Ann E. Jerse ◽  
Yechezkel Barenholz
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Topical Administration ◽  
Parenteral Administration ◽  
Cross Resistance ◽  
Drug Resistant ◽  
Potential Treatment ◽  
In Vitro Susceptibility ◽  
Antibiotic Resistant ◽  
Content Type

ABSTRACT Neisseria gonorrhoeae is an urgent antibiotic-resistant threat. This study determined the MICs of mupirocin to be 0.0039 to 0.0625 μg/ml for 94 N. gonorrhoeae strains. Cross-resistance with other antibiotics was not detected. Mupirocin, which is currently limited to topical administration, demonstrated activity by injection when delivered in nanoliposomes. The nanoliposomal formulation of mupirocin is a potential treatment for drug-resistant N. gonorrhoeae .

scholarly journals In VitroActivity of Delafloxacin against Clinical Neisseria gonorrhoeae Isolates and Selection of Gonococcal Delafloxacin Resistance

2016 ◽  
Vol 60 (5) ◽  
pp. 3106-3111 ◽  
Author(s):  
Olusegun O. Soge ◽  
Stephen J. Salipante ◽  
David No ◽  
Erin Duffy ◽  
Marilyn C. Roberts
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Spontaneous Mutation ◽  
Efflux Pumps ◽  
Multidrug Resistant ◽  
Cross Resistance ◽  
Content Type ◽  
Resistant Mutants ◽  
Reference Strains ◽  
Selection Of

ABSTRACTWe evaluated thein vitroactivity of delafloxacin against a panel of 117Neisseria gonorrhoeaestrains, including 110 clinical isolates collected from 2012 to 2015 and seven reference strains, compared with the activities of seven antimicrobials currently or previously recommended for treatment of gonorrhea. We examined the potential for delafloxacin to select for resistant mutants in ciprofloxacin-susceptible and ciprofloxacin-resistantN. gonorrhoeae. We characterized mutations in thegyrA,gyrB,parC, andparEgenes and the multidrug-resistant efflux pumps (MtrC-MtrD-MtrE and NorM) by PCR and sequencing and by whole-genome sequencing. The MIC50, MIC90, and MIC ranges of delafloxacin were 0.06 μg/ml, 0.125 μg/ml, and ≤0.001 to 0.25 μg/ml, respectively. The frequency of spontaneous mutation ranged from 10−7to <10−9. The multistep delafloxacin resistance selection of 30 daily passages resulted in stable resistant mutants. There was no obvious cross-resistance to nonfluoroquinolone comparator antimicrobials. A mutant with reduced susceptibility to ciprofloxacin (MIC, 0.25 μg/ml) obtained from the ciprofloxacin-susceptible parental strain had a novel Ser91Tyr alteration in thegyrAgene. We also identified new mutations in thegyrAand/orparCandparEgenes and the multidrug-resistant efflux pumps (MtrC-MtrD-MtrE and NorM) of two mutant strains with elevated delafloxacin MICs of 1 μg/ml. Although delafloxacin exhibited potentin vitroactivity againstN. gonorrhoeaeisolates and reference strains with diverse antimicrobial resistance profiles and demonstrated a low tendency to select for spontaneous mutants, it is important to establish the correlation between these excellentin vitrodata and treatment outcomes through appropriate randomized controlled clinical trials.

scholarly journals High In Vitro Susceptibility to the First-in-Class Spiropyrimidinetrione Zoliflodacin among Consecutive Clinical Neisseria gonorrhoeae Isolates from Thailand and South Africa

2019 ◽  
Vol 63 (12) ◽  
Author(s):  
Susanne Jacobsson ◽  
Ranmini Kularatne ◽  
Rossaphorn Kittiyaowamarn ◽  
Venessa Maseko ◽  
Porntip Paopang ◽  
...  
Keyword(s):  
South Africa ◽  
Neisseria Gonorrhoeae ◽  
Cross Resistance ◽  
Controlled Clinical Trial ◽  
Phase 3 ◽  
In Vitro Susceptibility ◽  
Content Type ◽  
Randomized Controlled ◽  
Highly Active

ABSTRACT We evaluated the in vitro susceptibility to the first-in-class spiropyrimidinetrione zoliflodacin among recent consecutive clinical Neisseria gonorrhoeae isolates cultured in Thailand (n = 99) (in 2018) and South Africa (n = 100) (in 2015 to 2017). Zoliflodacin was highly active in vitro against all tested isolates (MIC range, 0.004 to 0.25 μg/ml; MIC50, 0.064 μg/ml; MIC90, 0.125 μg/ml), with no cross-resistance to any of the seven comparator antimicrobials. Our data support the initiation of the global phase 3 randomized controlled clinical trial of zoliflodacin for uncomplicated gonorrhea.

scholarly journals In Vitro Activity of the Novel Pleuromutilin Lefamulin (BC-3781) and Effect of Efflux Pump Inactivation on Multidrug-Resistant and Extensively Drug-Resistant Neisseria gonorrhoeae

2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Susanne Jacobsson ◽  
Susanne Paukner ◽  
Daniel Golparian ◽  
Jörgen S. Jensen ◽  
Magnus Unemo
Keyword(s):  
Efflux Pump ◽  
Multidrug Resistant ◽  
Cross Resistance ◽  
Drug Resistant ◽  
The Novel ◽  
Extensively Drug Resistant ◽  
Optimal Dosing ◽  
And Performance ◽  
Reference Strains

ABSTRACT We evaluated the activity of the novel semisynthetic pleuromutilin lefamulin, inhibiting protein synthesis and growth, and the effect of efflux pump inactivation on clinical gonococcal isolates and reference strains (n = 251), including numerous multidrug-resistant and extensively drug-resistant isolates. Lefamulin showed potent activity against all gonococcal isolates, and no significant cross-resistance to other antimicrobials was identified. Further studies of lefamulin are warranted, including in vitro selection and mechanisms of resistance, pharmacokinetics/pharmacodynamics, optimal dosing, and performance in randomized controlled trials.

scholarly journals Complete Genome Sequence of Acinetobacter radioresistens Strain LH6, a Multidrug-Resistant Bacteriophage-Propagating Strain

2018 ◽  
Vol 7 (5) ◽  
Author(s):  
Clay S. Crippen ◽  
Steven Huynh ◽  
William G. Miller ◽  
Craig T. Parker ◽  
Christine M. Szymanski
Keyword(s):  
Antimicrobial Resistance ◽  
Acinetobacter Baumannii ◽  
Genome Sequence ◽  
Complete Genome Sequence ◽  
Related Species ◽  
Complete Genome ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Content Type ◽  
Resistance Determinants

Antimicrobial resistance is a major problem worldwide. Understanding the interplay between drug-resistant pathogens, such as Acinetobacter baumannii and related species, potentially acting as environmental reservoirs is critical for preventing the spread of resistance determinants.

scholarly journals In VitroActivity of the New Fluoroketolide Solithromycin (CEM-101) against a Large Collection of Clinical Neisseria gonorrhoeae Isolates and International Reference Strains, Including Those with High-Level Antimicrobial Resistance: Potential Treatment Option for Gonorrhea?

2012 ◽  
Vol 56 (5) ◽  
pp. 2739-2742 ◽  
Author(s):  
Daniel Golparian ◽  
Prabhavathi Fernandes ◽  
Makoto Ohnishi ◽  
Jörgen S. Jensen ◽  
Magnus Unemo
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Treatment Option ◽  
Treatment Options ◽  
Effective Treatment Option ◽  
Content Type ◽  
New Treatment ◽  
High Level ◽  
Drug Resistant Strains ◽  
Reference Strains

ABSTRACTGonorrhea may become untreatable, and new treatment options are essential. We investigated thein vitroactivity of the first fluoroketolide, solithromycin. ClinicalNeisseria gonorrhoeaeisolates and reference strains (n= 246), including the two extensively drug-resistant strains H041 and F89 and additional isolates with clinical cephalosporin resistance and multidrug resistance, were examined. The activity of solithromycin was mainly superior to that of other antimicrobials (n= 10) currently or previously recommended for gonorrhea treatment. Solithromycin might be an effective treatment option for gonorrhea.

High susceptibility to zoliflodacin and conserved target (GyrB) for zoliflodacin among 1209 consecutive clinical Neisseria gonorrhoeae isolates from 25 European countries, 2018

2021 ◽  
Author(s):  
Magnus Unemo ◽  
Josefine Ahlstrand ◽  
Leonor Sánchez-Busó ◽  
Michaela Day ◽  
David Aanensen ◽  
...  
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Efflux Pump ◽  
Cross Resistance ◽  
Controlled Clinical Trial ◽  
European Economic Area ◽  
Resistance Mutations ◽  
Dilution Technique ◽  
In Vitro Susceptibility ◽  
Agar Dilution

Abstract Objectives Novel antimicrobials for treatment of gonorrhoea are imperative. The first-in-class spiropyrimidinetrione zoliflodacin is promising and currently in an international Phase 3 randomized controlled clinical trial (RCT) for treatment of uncomplicated gonorrhoea. We evaluated the in vitro activity of and the genetic conservation of the target (GyrB) and other potential zoliflodacin resistance determinants among 1209 consecutive clinical Neisseria gonorrhoeae isolates obtained from 25 EU/European Economic Area (EEA) countries in 2018 and compared the activity of zoliflodacin with that of therapeutic antimicrobials currently used. Methods MICs of zoliflodacin, ceftriaxone, cefixime, azithromycin and ciprofloxacin were determined using an agar dilution technique for zoliflodacin or using MIC gradient strip tests or an agar dilution technique for the other antimicrobials. Genome sequences were available for 96.1% of isolates. Results Zoliflodacin modal MIC, MIC50, MIC90 and MIC range were 0.125, 0.125, 0.125 and ≤0.004–0.5 mg/L, respectively. The resistance was 49.9%, 6.7%, 1.6% and 0.2% to ciprofloxacin, azithromycin, cefixime and ceftriaxone, respectively. Zoliflodacin did not show any cross-resistance to other tested antimicrobials. GyrB was highly conserved and no zoliflodacin gyrB resistance mutations were found. No fluoroquinolone target GyrA or ParC resistance mutations or mutations causing overexpression of the MtrCDE efflux pump substantially affected the MICs of zoliflodacin. Conclusions The in vitro susceptibility to zoliflodacin was high and the zoliflodacin target GyrB was conserved among EU/EEA gonococcal isolates in 2018. This study supports further clinical development of zoliflodacin. However, additional zoliflodacin data regarding particularly the treatment of pharyngeal gonorrhoea, pharmacokinetics/pharmacodynamics and resistance selection, including suppression, would be valuable.

scholarly journals 1H-Benzo[d]Imidazole Derivatives Affect MmpL3 in Mycobacterium tuberculosis

2019 ◽  
Vol 63 (10) ◽  
Author(s):  
Małgorzata Korycka-Machała ◽  
Albertus Viljoen ◽  
Jakub Pawełczyk ◽  
Paulina Borówka ◽  
Bożena Dziadek ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mycolic Acid ◽  
Cross Resistance ◽  
Metabolic Labeling ◽  
Drug Resistant ◽  
Content Type ◽  
Antitubercular Drugs ◽  
Imidazole Derivatives ◽  
Trehalose Dimycolate

ABSTRACT 1H-benzo[d]imidazole derivatives exhibit antitubercular activity in vitro at a nanomolar range of concentrations and are not toxic to human cells, but their mode of action remains unknown. Here, we showed that these compounds are active against intracellular Mycobacterium tuberculosis. To identify their target, we selected drug-resistant M. tuberculosis mutants and then used whole-genome sequencing to unravel mutations in the essential mmpL3 gene, which encodes the integral membrane protein that catalyzes the export of trehalose monomycolate, a precursor of the mycobacterial outer membrane component trehalose dimycolate (TDM), as well as mycolic acids bound to arabinogalactan. The drug-resistant phenotype was also observed in the parental strain overexpressing the mmpL3 alleles carrying the mutations identified in the resistors. However, no cross-resistance was observed between 1H-benzo[d]imidazole derivatives and SQ109, another MmpL3 inhibitor, or other first-line antitubercular drugs. Metabolic labeling and quantitative thin-layer chromatography (TLC) analysis of radiolabeled lipids from M. tuberculosis cultures treated with the benzoimidazoles indicated an inhibition of trehalose dimycolate (TDM) synthesis, as well as reduced levels of mycolylated arabinogalactan, in agreement with the inhibition of MmpL3 activity. Overall, this study emphasizes the pronounced activity of 1H-benzo[d]imidazole derivatives in interfering with mycolic acid metabolism and their potential for therapeutic application in the fight against tuberculosis.

scholarly journals In Vitro Activity of Clofazimine against Nontuberculous Mycobacteria Isolated in Beijing, China

2018 ◽  
Vol 62 (7) ◽  
Author(s):  
Jingjing Luo ◽  
Xia Yu ◽  
Guanglu Jiang ◽  
Yuhong Fu ◽  
Fengmin Huo ◽  
...  
Keyword(s):  
Nontuberculous Mycobacteria ◽  
Clinical Isolates ◽  
Natural Resistance ◽  
Cross Resistance ◽  
Mycobacterium Fortuitum ◽  
Strong Activity ◽  
Content Type ◽  
Beijing China ◽  
Reference Strains

ABSTRACT Due to the natural resistance of nontuberculous mycobacteria (NTM) to many antibiotics, the treatment of diseases caused by NTM is often long-term but unsuccessful. The main goal of this study was to evaluate the in vitro susceptibilities to clofazimine of 209 isolates consisting of different NTM species isolated in Beijing, China. Furthermore, 47 reference strains were also tested, including 30 rapidly growing mycobacterium (RGM) species and 17 slowly growing mycobacterium (SGM) species. The potential molecular mechanism contributing to clofazimine resistance of NTM was investigated as well. Clofazimine exhibited excellent activity against both reference strains and clinical isolates of different SGM species, and most of the strains had MICs far below 1 μg/ml. Although the majority of the clinical isolates of Mycobacterium abscessus and Mycobacterium fortuitum had MICs higher than 2 μg/ml, 17 out of the 30 reference strains of different RGM species had MICs below 1 μg/ml in vitro . According to the MIC distributions, the tentative epidemiological cutoff (ECOFF) values for Mycobacterium kansasii , Mycobacterium avium , and Mycobacterium intracellulare were defined at 0.5 μg/ml, 1 μg/ml, and 2 μg/ml, respectively. Intriguingly, single-direction cross-resistance between bedaquiline- and clofazimine (Cfz)-resistant isolates was observed among the tested NTM species. This study demonstrates that clofazimine had strong activity against most SGM species in vitro , as well as some RGM species. The data provide important insights into the possible clinical application of Cfz to treat NTM infections.

Sign in / Sign up

Export Citation Format

Share Document