scholarly journals Antibacterial activities of epiroprim, a new dihydrofolate reductase inhibitor, alone and in combination with dapsone.

1996 ◽  
Vol 40 (6) ◽  
pp. 1376-1381 ◽  
Author(s):  
H H Locher ◽  
H Schlunegger ◽  
P G Hartman ◽  
P Angehrn ◽  
R L Then
Keyword(s):  
Dihydrofolate Reductase ◽  
Biological Fluids ◽  
Pneumocystis Carinii ◽  
Antibacterial Activities ◽  
Gram Negative Bacteria ◽  
Highly Active ◽  
Excellent Activity ◽  
Resistant Strains ◽  
Better Than

Epiroprim (EPM; Ro 11-8958) is a new selective inhibitor of microbial dihydrofolate reductase. EPM displayed excellent activity against staphylococci, enterococci, pneumococci, and streptococci which was considerably better than that of trimethoprim (TMP). EPM was also active against TMP-resistant strains, although the MICs were still relatively high. Its combination with dapsone (DDS) was synergistic and showed as in vitro activity superior to that of the TMP combination with sulfamethoxazole (SMZ). The EPM-DDS (ratio, 1:19) combination inhibited more than 90% of all important gram-positive pathogens at a concentration of 2 + 38 micrograms/ml. Only a few highly TMP-resistant staphylococci and enterococci were not inhibited. EPM was also more active than TMP against Moraxella catarrhalis, Neisseria meningitidis, and Bacteroides spp., but it was less active than TMP against all other gram-negative bacteria tested. Atypical mycobacteria were poorly susceptible to EPM, but the combination with DDS was synergistic and active at concentrations most probably achievable in biological fluids (MICs from 0.25 +/- 4.75 to 4 + 76 micrograms/ml). EPM and the EPM-DDS combination were also highly active against experimental staphylococcal infections in a mouse septicemia model. The combination EPM-DDS has previously been shown to exhibit activity in Pneumocystis carinii and Toxoplasma models and, as shown in the present study, also shows good activity against a broad range of bacteria including many strains resistant to TMP and TMP-SMZ.

scholarly journals In Vitro and In Vivo Antibacterial Activities of S-4661, a New Carbapenem

1998 ◽  
Vol 42 (1) ◽  
pp. 94-99 ◽  
Author(s):  
Masakatsu Tsuji ◽  
Yoshikazu Ishii ◽  
Akira Ohno ◽  
Shuichi Miyazaki ◽  
Keizo Yamaguchi
Keyword(s):  
Antibacterial Activities ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
In Vitro Activity ◽  
Gram Positive ◽  
Highly Active ◽  
The Family ◽  
High Degree

ABSTRACT The in vitro and in vivo antibacterial activities of S-4661, a new 1β-methylcarbapenem, were compared with those of imipenem, meropenem, biapenem, cefpirome, and ceftazidime. The activity of S-4661 against methicillin-susceptible staphylococci and streptococci was comparable to that of imipenem, with an MIC at which 90% of the strains tested were inhibited (MIC90) equal to 0.5 μg/ml or less. S-4661 was highly active against members of the familyEnterobacteriaceae, Haemophilus influenzae, andMoraxella catarrhalis, with MIC90s ranging from 0.032 to 0.5 μg/ml. Against imipenem-resistant Pseudomonas aeruginosa, S-4661 was the most active among test agents (MIC90, 8 μg/ml). Furthermore, S-4661 displayed a high degree of activity against many ceftazidime-, ciprofloxacin-, and gentamicin-resistant isolates of P. aeruginosa. The in vivo efficacy of S-4661 against experimentally induced infections in mice caused by gram-positive and gram-negative bacteria, including penicillin-resistant Streptococcus pneumoniae and drug-resistant P. aeruginosa, reflected its potent in vitro activity and high levels in plasma in mice. We conclude that S-4661 is a promising new carbapenem for the treatment of infections caused by gram-positive and -negative bacteria, including penicillin-resistantS. pneumoniae and drug-resistant P. aeruginosa.

scholarly journals In Vitro and In Vivo Antibacterial Activities of DW-224a, a New Fluoronaphthyridone

2006 ◽  
Vol 50 (6) ◽  
pp. 2261-2264 ◽  
Author(s):  
Hee-Soo Park ◽  
Hyun-Joo Kim ◽  
Min-Jung Seol ◽  
Dong-Rack Choi ◽  
Eung-Chil Choi ◽  
...  
Keyword(s):  
Antibacterial Activities ◽  
The Other ◽  
Vitro Activity ◽  
Gram Negative Bacteria ◽  
In Vitro Activity ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria

ABSTRACT DW-224a showed the most potent in vitro activity among the quinolone compounds tested against clinical isolates of gram-positive bacteria. Against gram-negative bacteria, DW-224a was slightly less active than the other fluoroquinolones. The in vivo activities of DW-224a against gram-positive bacteria were more potent than those of other quinolones.

scholarly journals Characterization of Novel Antimicrobial Peptoids

1999 ◽  
Vol 43 (6) ◽  
pp. 1429-1434 ◽  
Author(s):  
Bob Goodson ◽  
Anton Ehrhardt ◽  
Simon Ng ◽  
John Nuss ◽  
Kirk Johnson ◽  
...  
Keyword(s):  
Antibacterial Activities ◽  
Membrane Disruption ◽  
Infection Model ◽  
Gram Negative Bacteria ◽  
Positional Isomers ◽  
Bacterial Growth Inhibition ◽  
Alpha Carbon

ABSTRACT Peptoids differ from peptides in that peptoids are composed of N-substituted rather than alpha-carbon-substituted glycine units. In this paper we report the in vitro and in vivo antibacterial activities of several antibacterial peptoids discovered by screening combinatorial chemistry libraries for bacterial growth inhibition. In vitro, the peptoid CHIR29498 and some of its analogues were active in the range of 3 to 12 μg/ml against a panel of gram-positive and gram-negative bacteria which included isolates which were resistant to known antibiotics. Peptoid antimicrobial activity againstStaphylococcus aureus was rapid, bactericidal, and independent of protein synthesis. β-Galactosidase and propidium iodide leakage assays indicated that the membrane is the most likely target of activity. Positional isomers of an active peptoid were also active, consistent with a mode of action, such as membrane disruption, that does not require a specific fit between the molecule and its target. In vivo, CHIR29498 protected S. aureus-infected mice in a simple infection model.

scholarly journals In vitro antibacterial activity of LY333328, a new semisynthetic glycopeptide.

1997 ◽  
Vol 41 (10) ◽  
pp. 2165-2172 ◽  
Author(s):  
F Biavasco ◽  
C Vignaroli ◽  
R Lupidi ◽  
E Manso ◽  
B Facinelli ◽  
...  
Keyword(s):  
Structural Analog ◽  
Clinical Isolates ◽  
Alkyl Derivative ◽  
Minimal Bactericidal Concentration ◽  
Highly Active ◽  
In Vitro Antibacterial Activity ◽  
Resistant Strains ◽  
Vancomycin Resistant ◽  
Time Kill

LY333328 is a semisynthetic N-alkyl derivative of LY264826, a naturally occurring structural analog of vancomycin. LY333328 was evaluated for its in vitro inhibitory and bactericidal activities in comparison with those of the two currently available glycopeptides (vancomycin and teicoplanin). Glycopeptide-susceptible test strains included a total of 311 isolates (most of clinical origin) from the genera Staphylococcus, Enterococcus, Streptococcus, Aerococcus, Gemella, Lactococcus, Listeria, Corynebacterium, and Clostridium. Test strains resistant or intermediate to vancomycin and/or teicoplanin included 56 clinical isolates of Enterococcus (of the VanA, VanB, and VanC phenotypes) and 32 clinical isolates of Staphylococcus (S. haemolyticus, S. epidermidis, and S. aureus), 31 strains of gram-positive genera outside the spectrum of activity of vancomycin (Leuconostoc, Pediococcus, Lactobacillus, and Erysipelothrix), and laboratory-derived organisms obtained after exposure of susceptible Staphylococcus isolates to teicoplanin (6 strains) or laboratory-derived organisms with resistance determinants received from VanA enterococci (2 Enterococcus and 25 Listeria transconjugants). LY333328 was highly active against staphylococci, enterococci, and listeriae (whether they were clinical or laboratory-derived strains) resistant to the currently available glycopeptides. In particular, the MICs of LY333328 did not vary substantially between teicoplanin-susceptible and teicoplanin-resistant staphylococci and between vancomycin-susceptible and vancomycin-resistant enterococci. LY333328 demonstrated fairly good inhibitory activity even against most strains of Leuconostoc, Pediococcus, and Erysipelothrix (MIC range, 1 to 8 microg/ml), whereas it proved less active (although much more active than vancomycin or teicoplanin) against Lactobacillus strains. In minimal bactericidal concentration (MBC) and time-kill studies, LY333328 demonstrated excellent bactericidal activity; enterococci, in particular, which were largely tolerant of vancomycin and teicoplanin, were uniformly killed by LY333328, with MBC-to-MIC ratios of 4 to 8 for most vancomycin-susceptible and vancomycin-resistant strains. In attempts to select for resistant clones, no survivors stably growing in the presence of 10 microg of LY333328 per ml were obtained from the Staphylococcus and Enterococcus test strains exposed to the drug.

Design and Synthesis of Novel Sulfonamide-Derived Triazoles and Bioactivity Exploration

2020 ◽  
Vol 16 (1) ◽  
pp. 104-118 ◽  
Author(s):  
Shi-Chao He ◽  
Hui-Zhen Zhang ◽  
Hai-Juan Zhang ◽  
Qing Sun ◽  
Cheng-He Zhou
Keyword(s):  
Chlorosulfonic Acid ◽  
Antibacterial Activities ◽  
Structural Features ◽  
The Novel ◽  
E Coli ◽  
Design And Synthesis ◽  
Chemical Studies ◽  
Antimicrobial Evaluation ◽  
Better Than

Objective: Due to the incidence of resistance, a series of sulfonamide-derived 1,2,4- triazoles were synthesized and evaluated. Method: The novel sulfonamide-derived 1,2,4-triazoles were prepared starting from commercial acetaniline and chlorosulfonic acid by sulfonylation, aminolysis, N-alkylation and so on. The antimicrobial activity of the synthesized compounds were evaluated in vitro by two-fold serial dilution technique. Results: In vitro antimicrobial evaluation found that 2-chlorobenzyl sulfonamide 1,2,4-triazole 7c exhibited excellent antibacterial activities against MRSA, B. subtilis, B. typhi and E. coli with MIC values of 0.02−0.16 μmol/mL, which were comparable or even better than Chloromycin. The preliminary mechanism suggested that compound 7c could effectively bind with DNA, and also it could bind with human microsomal heme through hydrogen bonds in molecular docking. Computational chemical studies were performed on compound 7c to understand the structural features that are essential for activity. Additionally, compound 7c could generate a small amount of reactive oxygen species (ROS). Conclusion: Compound 7c could serve as a potential clinical antimicrobial candidate.

scholarly journals In Vitro Activities of Isavuconazole and Other Antifungal Agents against Candida Bloodstream Isolates

2007 ◽  
Vol 51 (5) ◽  
pp. 1818-1821 ◽  
Author(s):  
H. Seifert ◽  
U. Aurbach ◽  
D. Stefanik ◽  
O. Cornely
Keyword(s):  
Amphotericin B ◽  
Antifungal Agents ◽  
Tertiary Care ◽  
Common Species ◽  
University Hospital ◽  
Phase Iii ◽  
Highly Active ◽  
Fluconazole Resistant ◽  
Resistant Strains

ABSTRACT Isavuconazole is the active component of the new azole antifungal agent BAL8557, which is entering phase III clinical development. This study was conducted to compare the in vitro activities of isavuconazole and five other antifungal agents against 296 Candida isolates that were recovered consecutively from blood cultures between 1995 and 2004 at a tertiary care university hospital. Microdilution testing was done in accordance with CLSI (formerly NCCLS) guideline M27-A2 in RPMI-1640 MOPS (morpholinepropanesulfonic acid) broth. The antifungal agents tested were amphotericin B, flucytosine, fluconazole, itraconazole, voriconazole, and isavuconazole. C. albicans was the most common species, representing 57.1% of all isolates. There was no trend found in favor of non-Candida albicans species over time. In terms of MIC50s, isavuconazole was more active (0.004 mg/liter) than amphotericin B (0.5 mg/liter), itraconazole (0.008 mg/liter), voriconazole (0.03 mg/liter), flucytosine (0.125 mg/liter), and fluconazole (8 mg/liter). For isavuconazole, MIC50s/MIC90s ranged from 000.2/0.004 mg/liter for C. albicans to 0.25/0.5 mg/liter for C. glabrata. Two percent of isolates (C. glabrata and C. krusei) were resistant to fluconazole; C. albicans strains resistant to fluconazole were not detected. There were only two isolates with MICs for isavuconazole that were >0.5 mg/liter: both were C. glabrata isolates, and the MICs were 2 and 4 mg/liter, respectively. In conclusion, isavuconazole is highly active against Candida bloodstream isolates, including fluconazole-resistant strains. It was more active than itraconazole and voriconazole against C. albicans and C. glabrata and appears to be a promising agent against systemic Candida infections.

Antibacterial Activity and Chemical Composition of the Essential Oil of Grammosciadium platycarpum Boiss. from Iran

2005 ◽  
Vol 60 (1-2) ◽  
pp. 30-34 ◽  
Author(s):  
Ali Sonboli ◽  
Fereshteh Eftekhar ◽  
Morteza Yousefzadi ◽  
Mohammad Reza Kanani
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibacterial Activity ◽  
Chemical Composition ◽  
Essential Oil ◽  
Essential Oils ◽  
Antibacterial Activities ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Two Samples

The chemical composition of the essential oils obtained from two samples (GP1 and GP2) of Grammosciadium platycarpum Boiss. was analyzed by GC and GC-MS. The analysis of the oils resulted in the identification of twenty-two constituents. Linalool (79.0% - GP1, 81.8% - GP2) and limonene (10.0%, 5.8%) were found to be the major components, respectively. The in vitro antibacterial activities of these oils and their main compounds against seven Gram-positive and Gram-negative bacteria were investigated. The results exhibited that the total oils and their major components possess strong to moderate activities against all the tested bacteria except for Pseudomonas aeruginosa.

scholarly journals In Vitro Activities of Several Diaminomethylpyridopyrimidines against Mycobacterium avium Complex

1998 ◽  
Vol 42 (12) ◽  
pp. 3315-3316 ◽  
Author(s):  
Carolyn M. Shoen ◽  
Olga Choromanska ◽  
Robert C. Reynolds ◽  
James R. Piper ◽  
Cheryl A. Johnson ◽  
...  
Keyword(s):  
Dihydrofolate Reductase ◽  
Mycobacterium Avium ◽  
Mycobacterium Avium Complex ◽  
Dhfr Inhibitors ◽  
Better Than

ABSTRACT Three recently synthesized dihydrofolate reductase (DHFR) inhibitors designated SoRI 8890, 8895, and 8897 were evaluated for their in vitro activities against 25 isolates of Mycobacterium avium complex. The MICs at which 50 and 90% of isolates were inhibited were 1 and 2, 4 and 8, and 4 and 8 μg/ml for SoRI 8890, 8895, and 8897, respectively. Although the addition of dapsone at 0.5 μg/ml did not significantly enhance the in vitro activities of these compounds, their activities alone were comparable to, if not better than, results seen with other DHFR inhibitors, such as pyrimethamine or WR99210.

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