scholarly journals HighIn VitroSusceptibility to the Novel Spiropyrimidinetrione ETX0914 (AZD0914) among 873 Contemporary Clinical Neisseria gonorrhoeae Isolates from 21 European Countries from 2012 to 2014

2015 ◽  
Vol 59 (9) ◽  
pp. 5220-5225 ◽  
Author(s):  
Magnus Unemo ◽  
Johan Ringlander ◽  
Catherine Wiggins ◽  
Hans Fredlund ◽  
Susanne Jacobsson ◽  
...  
Keyword(s):  
Neisseria Gonorrhoeae ◽  
European Countries ◽  
Cross Resistance ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
The Novel ◽  
Content Type ◽  
Agar Dilution

ABSTRACTResistance inNeisseria gonorrhoeaeagainst all antimicrobials available for the treatment of gonorrhea has emerged. The first gonococcal strains with high-level resistance to ceftriaxone, the last option for first-line empirical antimicrobial monotherapy, were recently described. Consequently, new treatment options are essential. In this study, thein vitroactivity of the novel spiropyrimidinetrione ETX0914 (AZD0914), a DNA topoisomerase II inhibitor, was investigated among contemporary consecutive clinicalN. gonorrhoeaeisolates obtained in 21 European countries and compared to the activities of antimicrobials currently or previously recommended for treatment. Consecutive clinicalN. gonorrhoeaeisolates (n= 873) cultured in 21 European countries from 2012 to 2014 were examined for their susceptibility to ETX0914. The MICs of ETX0914 were determined using the agar dilution method. For comparison, the MICs of ceftriaxone, cefixime, azithromycin, and ciprofloxacin were determined using Etest or the agar dilution method. For ETX0914, the MIC range, modal MIC, MIC50, and MIC90were ≤0.002 to 0.25 mg/liter, 0.125 mg/liter, 0.064 mg/liter, and 0.125 mg/liter, respectively. The MIC values were substantially lower than those of the fluoroquinolone ciprofloxacin and most other antimicrobials examined. No cross-resistance with any other examined antimicrobial was observed. In conclusion, thein vitrosusceptibility to the novel spiropyrimidinetrione ETX0914 (AZD0914) among 873 contemporary clinical isolates from 21 European countries was high, and no cross-resistance to antimicrobials currently or previously used for gonorrhea treatment was indicated. Additional studies investigating thein vitroandin vivoinduction and mechanisms of ETX0914 resistance in gonococci, pharmacokinetics/pharmacodynamics in modeling/simulations and in humans, and performance in randomized controlled gonorrhea treatment trials are essential.

scholarly journals Variability in Azithromycin Susceptibility Results for Neisseria gonorrhoeae Obtained Using Gradient MIC Strip and Agar Dilution Techniques

2019 ◽  
Vol 57 (12) ◽  
Author(s):  
Gary N. McAuliffe ◽  
Marian Smith ◽  
Gavin Cooper ◽  
Rose F. Forster ◽  
Sally A. Roberts
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Susceptibility Testing ◽  
Geometric Mean ◽  
Test Strip ◽  
Clinical Isolates ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
Content Type ◽  
Test Strips ◽  
Agar Dilution

ABSTRACT Azithromycin is a component of empirical treatment regimens for Neisseria gonorrhoeae infections, but antimicrobial susceptibility testing for this agent is technically challenging. We compared the intertest variability, MIC values, and CLSI/EUCAST categorization of clinical and reference isolates of N. gonorrhoeae treated with azithromycin by testing 107 clinical isolates and nine reference isolates by agar dilution and in duplicates using MIC test strips (Liofilchem, Italy) and Etests (bioMérieux, France). Replicate isolate agreement within 1 log2 between duplicate tests was 87% for MIC test strips and 100% for Etests (P < 0.001). Essential agreement with the agar dilution method was higher for Etests (91%) than for MIC test strips (44%, P < 0.001). The geometric mean MIC was highest for MIC test strips (0.8 mg/liter) and significantly higher than both Etest (0.47 mg/liter, P < 0.001) and agar dilution (0.26 mg/liter, P < 0.001) methods. Etest MICs were higher than those obtained with agar dilution (P < 0.001). Agar dilution, MIC test strip, and Etest methods categorized 96%, 85%, and 95% (P = 0.003) of clinical isolates, respectively, as susceptible/wild type according to CLSI/EUCAST criteria. Our results illustrate the difficulties underlying azithromycin susceptibility testing for N. gonorrhoeae and demonstrate that results can vary using different methods. This variability could influence antimicrobial resistance reporting between laboratories involved in N. gonorrhoeae surveillance programs.

scholarly journals Emergence and Spread of Neisseria gonorrhoeae Strains with High-Level Resistance to Azithromycin in Taiwan from 2001 to 2018

2019 ◽  
Vol 63 (9) ◽  
Author(s):  
Yen-Hung Liu ◽  
Ya-Hui Wang ◽  
Chun-Hsing Liao ◽  
Po-Ren Hsueh
Keyword(s):  
Neisseria Gonorrhoeae ◽  
23S Rrna ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
Coding Region ◽  
Content Type ◽  
First Choice ◽  
Agar Dilution ◽  
High Level ◽  
Level Resistance

ABSTRACT A total of 598 Neisseria gonorrhoeae isolates obtained from patients in Taiwan from 2001 to 2018 were evaluated. The MICs of ceftriaxone (CRO) and azithromycin (AZM) against the isolates were determined by the agar dilution method. N. gonorrhoeae isolates with AZM MICs of ≥1 μg/ml were identified and characterized by the presence of AZM resistance determinants. For high-level AZM-resistant (AZM-HLR) isolates (MIC ≥ 256 μg/ml), genotyping was performed using multilocus sequence typing (MLST) and N. gonorrhoeae multiantigen sequence typing (NG-MAST). Among the N. gonorrhoeae isolates studied, 8.7% (52/598) exhibited AZM MICs of ≥1 μg/ml. Thirteen of the 52 isolates contained A2059G (23S rRNA NG-STAR type 1) or C2611T (23S rRNA NG-STAR type 2) mutations. The prevalence of the A2059G mutation was higher in AZM-HLR isolates (P < 0.001). The −35A deletion in the promoter region of the mtrR gene did not differ between AZM-HLR isolates (100%, 10/10) and the isolates with AZM MICs of 1 μg/ml to 64 μg/ml (95.2%, 40/42) (P = 1.000). The presence of mutations in the mtrR coding region was significantly different between these two groups at 90% (9/10) and 26.2% (11/42), respectively (P < 0.001). The AZM-HLR isolates, all carrying four mutated A2059G alleles, a −35A deletion, and G45D, were classified as MLST 12039/10899 and NG-MAST 1866/16497. In conclusion, Taiwan is among the countries reporting gonococci with high-level resistance to AZM so that a single dose of 1 g ceftriaxone intramuscularly as the first choice for management of N. gonorrhoeae infection should be evaluated.

An improved susceptibility test based on Amberlite reveals the potential antilisterial activity of fosfomycin in vitro

2013 ◽  
Vol 59 (4) ◽  
pp. 252-259 ◽  
Author(s):  
Lei Han ◽  
Jin'e Lei ◽  
Shaoshan Han ◽  
Li He ◽  
Chaofeng Ma ◽  
...  
Keyword(s):  
Brain Heart Infusion ◽  
Susceptibility Test ◽  
Host Cells ◽  
Clinical Isolates ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
Broth Microdilution Method ◽  
Agar Dilution

Listeria monocytogenes is resistant to fosfomycin in vitro but is susceptible in vivo due to increased expression of positive regulator factor A (PrfA) and its dependent factor, hexose phosphate transporter (Hpt), upon infection of host cells. Amberlite, a polymeric adsorbent resin, could induce PrfA-dependent gene expression and thus, in theory, improve the sensitivity of L. monocytogenes to fosfomycin in vitro. In the current study, an improved susceptibility test based on Amberlite was developed using reference strains. Thirty-five clinical isolates were further examined to verify those preliminary results. Briefly, Amberlite increased in vitro fosfomycin sensitivity of all strains. Optimal Amberlite concentrations, as evaluated through the expression of phospholipase B (PlcB) and Hpt, were 10% and 15% (w/v) in agar media and 3% (w/v) in broth media. Mueller–Hinton (MH) medium, tryptone soya (TS) medium, and brain heart infusion (BHI) medium were used to verify the results in the control strains using agar dilution and broth micro- and macro-dilution methods. Better listerial growth was shown in TS and BHI than in MH. Both broth dilution methods yielded lower minimal inhibitory concentration (MIC) of fosfomycin than the agar dilution method. The MIC of fosfomycin for 35 clinical isolates was 2–32 μg/mL, suggesting improved susceptibility. In conclusion, in vitro sensitivity of L. monocytogenes to fosfomycin was substantially improved in the presence of 3% Amberlite-supplemented TSB or BHIB and the broth microdilution method. This improved method revealed the potential antilisterial activity of fosfomycin in vitro and could facilitate the therapy of listeriosis using fosfomycin.

scholarly journals In vitro activities of eight macrolide antibiotics and RP-59500 (quinupristin-dalfopristin) against viridans group streptococci isolated from blood of neutropenic cancer patients.

1996 ◽  
Vol 40 (9) ◽  
pp. 2117-2120 ◽  
Author(s):  
F Alcaide ◽  
J Carratala ◽  
J Liñares ◽  
F Gudiol ◽  
R Martin
Keyword(s):  
Cancer Patients ◽  
High Rate ◽  
Cross Resistance ◽  
Macrolide Antibiotics ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
Agar Dilution ◽  
Resistant Strains ◽  
Viridans Group Streptococci

From January 1988 to December 1994, 66 consecutive blood culture isolates of viridans group streptococci collected from febrile neutropenic cancer patients were tested for antimicrobial susceptibilities by the agar dilution method. The antibiotics studied were erythromycin, clarithromycin, roxithromycin, dirithromycin, azithromycin, josamycin, diacetyl-midecamycin, spiramycin, and quinupristin-dalfopristin. A total of 26 (39.4%) strains were resistant to erythromycin with an MIC range of 0.5 to > 128 micrograms/ml. The strains were classified into three groups according to their penicillin susceptibility: 42 (63.6%) were susceptible, 8 (12.1%) were intermediately resistant, and 16 (24.3%) were highly resistant. The percentages of erythromycin-resistant strains in each group were 23.8, 62.5, and 68.8%, respectively. Streptococcus mitis was the species most frequently isolated (83.3%) and showed the highest rates of penicillin (40%) and erythromycin (43.6%) resistance. MICs of all macrolide antibiotics tested and of quinupristin-dalfopristin were higher for penicillin-resistant strains than for penicillin-susceptible strains. All macrolide antibiotics tested had cross-resistance to erythromycin, which was not observed with quinupristin-dalfopristin. Our study shows a high rate of macrolide resistance among viridans group streptococci isolated from blood samples of neutropenic cancer patients, especially those infected with penicillin-resistant strains. These findings make macrolides unsuitable prophylactic agents against viridans group streptococcal bacteremia in this patient population.

scholarly journals Antibiotic Susceptibility Pattern ofMycobacterium marinum

2000 ◽  
Vol 44 (11) ◽  
pp. 3133-3136 ◽  
Author(s):  
Alexandra Aubry ◽  
Vincent Jarlier ◽  
Sylvie Escolano ◽  
Chantal Truffot-Pernot ◽  
Emmanuelle Cambau
Keyword(s):  
Antibiotic Susceptibility ◽  
Geometric Mean ◽  
Multidrug Resistant ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
Susceptibility Pattern ◽  
Cutaneous Infections ◽  
Agar Dilution

ABSTRACT In vitro activities of 17 antibiotics against 53 clinical strains of Mycobacterium marinum, an atypical mycobacterium responsible for cutaneous infections, were determined using the reference agar dilution method. Rifampin and rifabutin were the most active drugs (MICs at which 90% of the isolates tested were inhibited [MIC90s], 0.5 and 0.6 μg/ml, respectively). MICs of minocycline (MIC90, 4 μg/ml), doxycycline (MIC90, 16 μg/ml), clarithromycin (MIC90, 4 μg/ml), sparfloxacin (MIC90, 2 μg/ml), moxifloxacin (MIC90, 1 μg/ml), imipenem (MIC90, 8 μg/ml), sulfamethoxazole (MIC90, 8 μg/ml) and amikacin (MIC90, 4 μg/ml) were close to the susceptibility breakpoints. MICs of isoniazid, ethambutol, trimethoprim, azithromycin, ciprofloxacin, ofloxacin, and levofloxacin were above the concentrations usually obtained in vivo. For each drug, the MIC50, geometric mean MIC, and modal MIC were very close, showing that all the strains had a similar susceptibility pattern. Percent agreement (within ±1 log2 dilution) between MICs yielded by the Etest method and by the agar dilution method used as reference were 83, 59, 43, and 24% for minocycline, rifampin, clarithromycin, and sparfloxacin, respectively. Reproducibility with the Etest was low, in contrast to that with the agar dilution method. In conclusion, M. marinum is a naturally multidrug-resistant species for which the agar dilution method is more accurate than the Etest for antibiotic susceptibility testing.

scholarly journals Sub-Inhibitory Concentrations of Chlorhexidine Induce Resistance to Chlorhexidine and Decrease Antibiotic Susceptibility in Neisseria gonorrhoeae

2021 ◽  
Vol 12 ◽  
Author(s):  
Jolein G. E. Laumen ◽  
Christophe Van Dijck ◽  
Sheeba S. Manoharan-Basil ◽  
Saïd Abdellati ◽  
Irith De Baetselier ◽  
...  
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Efflux Pump ◽  
Treatment Options ◽  
Fold Increase ◽  
Cross Resistance ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
Minimal Inhibitory Concentrations ◽  
Evolution Of Resistance

Objectives: Chlorhexidine digluconate (chlorhexidine) and Listerine® mouthwashes are being promoted as alternative treatment options to prevent the emergence of antimicrobial resistance in Neisseria gonorrhoeae. We performed in vitro challenge experiments to assess induction and evolution of resistance to these two mouthwashes and potential cross-resistance to other antimicrobials.Methods: A customized morbidostat was used to subject N. gonorrhoeae reference strain WHO-F to dynamically sustained Listerine® or chlorhexidine pressure for 18 days and 40 days, respectively. Cultures were sampled twice a week and minimal inhibitory concentrations (MICs) of Listerine®, chlorhexidine, ceftriaxone, ciprofloxacin, cefixime and azithromycin were determined using the agar dilution method. Isolates with an increased MIC for Listerine® or chlorhexidine were subjected to whole genome sequencing to track the evolution of resistance.Results: We were unable to increase MICs for Listerine®. Three out of five cultures developed a 10-fold increase in chlorhexidine MIC within 40 days compared to baseline (from 2 to 20 mg/L). Increases in chlorhexidine MIC were positively associated with increases in the MICs of azithromycin and ciprofloxacin. Low-to-higher-level chlorhexidine resistance (2–20 mg/L) was associated with mutations in NorM. Higher-level resistance (20 mg/L) was temporally associated with mutations upstream of the MtrCDE efflux pump repressor (mtrR) and the mlaA gene, part of the maintenance of lipid asymmetry (Mla) system.Conclusion: Exposure to sub-lethal chlorhexidine concentrations may not only enhance resistance to chlorhexidine itself but also cross-resistance to other antibiotics in N. gonorrhoeae. This raises concern regarding the widespread use of chlorhexidine as an oral antiseptic, for example in the field of dentistry.

scholarly journals In Vitro and In Vivo Evaluations of β-Lactam/β-Lactamase Mono- and Combined Therapies against Carbapenem-Nonsusceptible Enterobacteriaceae in Taiwan

2020 ◽  
Vol 8 (12) ◽  
pp. 1981
Author(s):  
Tsung-Ying Yang ◽  
Ya-Ju Hsieh ◽  
Li-Ting Kao ◽  
Guan-Hong Liu ◽  
Shao-Hsuan Lian ◽  
...  
Keyword(s):  
Carbapenem Resistance ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
Geographic Variations ◽  
C Elegans ◽  
Agar Dilution ◽  
Antibiotic Susceptibility Patterns ◽  
Resistance Rates

Increasing carbapenem resistance rates worldwide underscored the urgent need of novel antimicrobials. Ceftazidime–avibactam and aztreonam–avibactam combinations are developed to combat carbapenem resistance, but biological and geographic variations must be considered for antibiotic susceptibility patterns varied. Thus, we sought to assess the susceptibilities of ceftazidime–avibactam and aztreonam–avibactam against 660 carbapenem-nonsusceptible Enterobacteriaceae isolates (472 Klebsiella pneumoniae and 188 Escherichia coli) collected during an earlier Taiwan surveillance study. Agar dilution method was used to determine ceftazidime–avibactam and aztreonam–avibactam susceptibility. Metallo-carbapenemase’s contribution to resistance were investigated with EDTA addition. The in vivo efficacies were evaluated using a Caenorhabditis elegans model. High susceptibility rates were observed for ceftazidime–avibactam and aztreonam–avibactam against the 472 carbapenem-nonsusceptible K. pneumoniae (CnsKP) (85.2% and 95.3%, respectively) and 188 carbapenem-nonsusceptible E. coli (CnsEC) isolates (91.5% and 94.1%, respectively). For non-metallo-carbapenemase producers, the susceptibility rates for ceftazidime–avibactam were 93.6% for CnsKP and 97.7% for CnsEC, whereas only 7.1% CnsKP and 11.1% CnsEC in metallo-carbapenemase producers were susceptible to ceftazidime–avibactam. Of all isolates, 95.3% CnsKP and 94.1% CnsEC were susceptible to aztreonam–avibactam. In C. elegans model, ceftazidime–avibactam and aztreonam–avibactam revealed effective against a blaKPC-producing K. pneumoniae isolate in vivo. Our results propose a positive therapeutic approach for both combinations against carbapenem-nonsusceptible Enterobacteriaceae in Taiwan.

scholarly journals The Novel Arylamidine T-2307 MaintainsIn VitroandIn VivoActivity against Echinocandin-Resistant Candida albicans

2014 ◽  
Vol 59 (2) ◽  
pp. 1341-1343 ◽  
Author(s):  
Nathan P. Wiederhold ◽  
Laura K. Najvar ◽  
Annette W. Fothergill ◽  
Rosie Bocanegra ◽  
Marcos Olivo ◽  
...  
Keyword(s):  
Body Weight ◽  
Candida Albicans ◽  
Invasive Candidiasis ◽  
Placebo Control ◽  
The Novel ◽  
Content Type ◽  
Fungal Burden ◽  
Potential Use

ABSTRACTWe evaluated thein vitroandin vivoactivities of the investigational arylamidine T-2307 against echinocandin-resistantCandida albicans. T-2307 demonstrated potentin vitroactivity, and daily subcutaneous doses between 0.75 and 6 mg/kg of body weight significantly improved survival and reduced fungal burden compared to placebo control and caspofungin (10 mg/kg/day) in mice with invasive candidiasis caused by an echinocandin-resistant strain. Thus, T-2307 may have potential use in the treatment of echinocandin-resistantC. albicansinfections.

scholarly journals Antifungal and Antibacterial Metabolites from a French Poplar Type Propolis

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Séverine Boisard ◽  
Anne-Marie Le Ray ◽  
Anne Landreau ◽  
Marie Kempf ◽  
Viviane Cassisa ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Antifungal Activity ◽  
Antimicrobial Effect ◽  
Antibacterial Activities ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
Gram Positive ◽  
Weak Activity ◽  
Agar Dilution

During this study, thein vitroantifungal and antibacterial activities of different extracts (aqueous and organic) obtained from a French propolis batch were evaluated. Antifungal activity was evaluated by broth microdilution on three pathogenic strains:Candida albicans, C. glabrata, andAspergillus fumigatus. Antibacterial activity was assayed using agar dilution method on 36 Gram-negative and Gram-positive strains includingStaphylococcus aureus. Organic extracts showed a significant antifungal activity againstC. albicansandC. glabrata(MIC80between 16 and 31 µg/mL) but only a weak activity towardsA. fumigatus(MIC80= 250 µg/mL). DCM based extracts exhibited a selective Gram-positive antibacterial activity, especially againstS. aureus(SA) and several of its methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) strains (MIC10030–97 µg/mL). A new and active derivative of catechin was also identified whereas a synergistic antimicrobial effect was noticed during this study.

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