scholarly journals Abyssomicins—A 20-Year Retrospective View

Marine Drugs ◽  
2021 ◽  
Vol 19 (6) ◽  
pp. 299
Author(s):  
Hans-Peter Fiedler
Keyword(s):  
Selective Inhibition ◽  
The Sea Of Japan ◽  
Gram Positive Bacteria ◽  
New Family ◽  
Retrospective View ◽  
Marine Actinomycete ◽  
Actinomycete Strain ◽  
Resistant Strains ◽  
Vancomycin Resistant ◽  
Acid Pathway

Abyssomicins represent a new family of polycyclic macrolactones. The first described compounds of the abyssomicin family were abyssomicin B, C, atrop-C, and D, produced by the marine actinomycete strain Verrucosispora maris AB-18-032, which was isolated from a sediment collected in the Sea of Japan. Among the described abyssomicins, only abyssomicin C and atrop-abyssomicin C show a high antibiotic activity against Gram-positive bacteria, including multi-resistant and vancomycin-resistant strains. The inhibitory activity is caused by a selective inhibition of the enzyme 4-amino-4-deoxychorismate synthase, which catalyzes the transformation of chorismate to para-aminobenzoic acid, an intermediate in the folic acid pathway.

scholarly journals Antimicrobial Activities of Mefloquine and a Series of Related Compounds

2000 ◽  
Vol 44 (4) ◽  
pp. 848-852 ◽  
Author(s):  
C. M. Kunin ◽  
W. Y. Ellis
Keyword(s):  
Staphylococcus Epidermidis ◽  
Antimicrobial Activities ◽  
Walter Reed Army Institute ◽  
Gram Negative Bacteria ◽  
Antimicrobial Drugs ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Resistant Strains ◽  
Vancomycin Resistant ◽  
Related Compounds

ABSTRACT Mefloquine was found to have bactericidal activity against methicillin- and fluoroquinolone-susceptible and -resistant strains ofStaphylococcus aureus and Staphylococcus epidermidis and gentamicin- and vancomycin-resistant strains ofEnterococcus faecalis and Enterococcus faecium. The MICs were 16 μg/ml, and the minimal bactericidal concentrations (MBCs) were 16 to 32 μg/ml. These concentrations cannot be achieved in serum. Mefloquine was active at a more achievable concentration against penicillin-susceptible and -resistant Streptococcus pneumoniae, with MICs of 0.2 to 1.5 μg/ml. Mefloquine was not active against gram-negative bacteria and yeasts. In an attempt to find more active derivatives, 400 mefloquine-related compounds were selected from the chemical inventory of The Walter Reed Army Institute of Research. We identified a series of compounds containing a piperidine methanol group attached to pyridine, quinoline, and benzylquinoline ring systems. These had activities similar to that of mefloquine against S. pneumoniae but were far more active against other gram-positive bacteria (MICs for staphylococci, 0.8 to 6.3 μg/ml). They had activities similar to that of amphotericin B againstCandida spp. and Cryptococcus neoformans. Combinations of the compounds with gentamicin and vancomycin were additive against staphylococci and pneumococci. The MIC and MBC of gentamicin were decreased by four- to eightfold when this drug was combined with limiting dilutions of the compounds. There was no antagonism with other antimicrobial drugs. The compounds were rapidly bactericidal. They appear to act by disrupting cell membranes. Combinations of the compounds with aminoglycoside antibiotics may have potential for therapeutic use.

Development, Optimization, and Validation of a Green and Stability-Indicating HPLC Method for Determination of Daptomycin in Lyophilized Powder

2015 ◽  
Vol 98 (5) ◽  
pp. 1276-1285 ◽  
Author(s):  
Eliane Gandolpho Tótoli ◽  
Hérida Regina Nunes Salgado
Keyword(s):  
Mobile Phase ◽  
Hplc Method ◽  
Pharmaceutical Dosage Form ◽  
Stability Indicating ◽  
Gram Positive Bacteria ◽  
Stress Degradation ◽  
Resistant Strains ◽  
Vancomycin Resistant ◽  
Toxic Organic Solvents

Abstract Daptomycin is an antimicrobial that plays an important role in clinical practice today because it is considered a promising drug to combat resistant strains, such as methicilin and vancomycin-resistant Gram-positive bacteria. Considering the analysis of daptomycin in a pharmaceutical dosage form, the only method found in literature uses potentially toxic organic solvents. Therefore, the objective of this work was to develop a green and stability-indicating HPLC method for determination of daptomycin in lyophilized powder. The mobile phase was ethanol–water (55 + 45, v/v) at pH 4.5 pumped at a flow rate of 0.6 mL/min. A C18 column was used, and UV detection was performed at 221 nm. Stress degradation studies were conducted in order to demonstrate the specificity and stability-indicating capability of the method. The method was validated according to International Conference on Harmonization guidelines, proving to be linear (r = 0.9996), precise, accurate, robust (demonstrated by the Plackett-Burman model), and specific within the range 20–70 μg/mL. The retention time of daptomycin was 5.8 min. It can be concluded that the validated method can be a fast, safe, and environmentally friendly alternative for the analysis of daptomycin.

Antimicrobial-Resistant Gram-Positive Bacteria in PD Peritonitis and the Newer Antibiotics Used to Treat Them

2005 ◽  
Vol 25 (4) ◽  
pp. 313-319 ◽  
Author(s):  
William Salzer
Keyword(s):  
Methicillin Resistant Staphylococcus Aureus ◽  
Natural Habitat ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
The Past ◽  
Vancomycin Resistant Enterococci ◽  
Resistant Strains ◽  
Vancomycin Resistant ◽  
Novel Antibiotics

The incidence of resistant gram-positive bacteria in nosocomial and, more recently, community-acquired infections is increasing. Staphylococci, because of their natural habitat on the skin, have always been the leading cause of peritonitis in patients receiving peritoneal dialysis (PD). These organisms have demonstrated a remarkable ability to develop resistance to antibiotics, first with penicillin, then antistaphylococcal penicillins (methicillin-resistant Staphylococcus aureus), and more recently, strains expressing resistance to vancomycin (vancomycin-intermediate and vancomycin-resistant S. aureus) have emerged. Enterococci are normal inhabitants of the gastrointestinal tract and occasionally cause PD peritonitis. In the past 15 years, vancomycin-resistant enterococci have emerged as significant pathogens in many areas. In the past 5 years, novel antibiotics that have activity on gram-positive bacteria, including vancomycin-resistant strains, have become available. The problem of resistant gram-positive bacteria in PD peritonitis, their therapy, and the role of these newer agents, quinupristin/dalfopristin, linezolid, and daptomycin, are reviewed.

scholarly journals Pharmacodynamics of Telavancin (TD-6424), a Novel Bactericidal Agent, against Gram-Positive Bacteria

2004 ◽  
Vol 48 (8) ◽  
pp. 3043-3050 ◽  
Author(s):  
Sharath S. Hegde ◽  
Noe Reyes ◽  
Tania Wiens ◽  
Nicole Vanasse ◽  
Robert Skinner ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Gram Positive ◽  
Time Curve ◽  
Once Daily ◽  
Gram Positive Bacteria ◽  
Resistant Strains ◽  
Vancomycin Resistant ◽  
Dose Dependent

ABSTRACT Telavancin (TD-6424) is a novel lipoglycopeptide that produces rapid and concentration-dependent killing of clinically relevant gram-positive organisms in vitro. The present studies evaluated the in vivo pharmacodynamics of telavancin in the mouse neutropenic thigh (MNT) and mouse subcutaneous infection (MSI) animal models. Pharmacokinetic-pharmacodynamic studies in the MNT model demonstrated that the 24-h area under the concentration-time curve (AUC)/MIC ratio was the best predictor of efficacy. Telavancin produced dose-dependent reduction of thigh titers of several organisms, including methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA), penicillin-susceptible and -resistant strains of Streptococcus pneumoniae, and vancomycin-resistant Enterococcus faecalis. The 50% effective dose (ED50) estimates for telavancin ranged from 0.5 to 6.6 mg/kg of body weight (administered intravenously), and titers were reduced by up to 3 log10 CFU/g from pretreatment values. Against MRSA ATCC 33591, telavancin was 4- and 30-fold more potent (on an ED50 basis) than vancomycin and linezolid, respectively. Against MSSA ATCC 13709, telavancin was 16- and 40-fold more potent than vancomycin and nafcillin, respectively. Telavancin, vancomycin, and linezolid were all efficacious and more potent against MRSA ATCC 33591 in the MSI model compared to the MNT model. This deviation in potency was, however, disproportionately greater for vancomycin and linezolid than for telavancin, suggesting that activity of telavancin is less affected by the immune status. The findings of these studies collectively suggest that once-daily dosing of telavancin may provide an effective approach for the treatment of clinically relevant infections with gram-positive organisms.

scholarly journals Williamsia maris sp. nov., a novel actinomycete isolated from the Sea of Japan

2004 ◽  
Vol 54 (1) ◽  
pp. 191-194 ◽  
Author(s):  
James E. M. Stach ◽  
Luis A. Maldonado ◽  
Alan C. Ward ◽  
Alan T. Bull ◽  
Michael Goodfellow
Keyword(s):  
New Species ◽  
Type Strain ◽  
Gene Tree ◽  
The Sea Of Japan ◽  
Rrna Gene ◽  
Phenotypic Properties ◽  
Phenotypic Data ◽  
Marine Actinomycete ◽  
Actinomycete Strain ◽  
Taxonomic Approach

The taxonomic position of a marine actinomycete, strain SJS0289/JS1T, was determined using a polyphasic taxonomic approach. The organism, which had phenotypic properties consistent with its classification in the genus Williamsia, formed a distinct clade in the 16S rRNA gene tree together with the type strain of Williamsia muralis, but was readily distinguished from this species using DNA–DNA relatedness and phenotypic data. The genotypic and phenotypic data show that the organism merits recognition as a new species of Williamsia. The name proposed for the new species is Williamsia maris; the type strain is SJS0289/JS1T (=DSM 44693T=JCM 12070T=KCTC 9945T=NCIMB 13945T).

scholarly journals Mode of Action of Van-M-02, a Novel Glycopeptide Inhibitor of Peptidoglycan Synthesis, in Vancomycin-Resistant Bacteria

2009 ◽  
Vol 54 (2) ◽  
pp. 960-962 ◽  
Author(s):  
Kenji Miura ◽  
Hidenori Yamashiro ◽  
Kouichi Uotani ◽  
Satoshi Kojima ◽  
Takashi Yutsudo ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Inhibitory Activity ◽  
Mode Of Action ◽  
Resistant Bacteria ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Peptidoglycan Synthesis ◽  
Vancomycin Resistant Enterococci ◽  
Resistant Strains ◽  
Vancomycin Resistant

ABSTRACT Van-M-02, a novel glycopeptide, was revealed to exert potent activities against Gram-positive bacteria, including vancomycin-resistant enterococci (VRE) and vancomycin-resistant Staphylococcus aureus (VRSA). A crude assay system was then used to study the mode of action of Van-M-02 as a peptidoglycan synthesis model of both vancomycin-susceptible and -resistant strains. The results suggested that Van-M-02 inhibits the synthesis of lipid intermediates irrespective of their termini. This inhibitory activity may contribute to the anti-VRE and anti-VRSA activities observed.

scholarly journals In Vitro Activities of Daptomycin, Vancomycin, Linezolid, and Quinupristin-Dalfopristin against Staphylococci and Enterococci, Including Vancomycin- Intermediate and -Resistant Strains

2000 ◽  
Vol 44 (4) ◽  
pp. 1062-1066 ◽  
Author(s):  
Michael J. Rybak ◽  
Ellie Hershberger ◽  
Tabitha Moldovan ◽  
Richard G. Grucz
Keyword(s):  
Multidrug Resistant ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Vancomycin Resistant Enterococci ◽  
Alternative Drug ◽  
Potential Alternative ◽  
Resistant Strains ◽  
Vancomycin Resistant ◽  
Time Kill

ABSTRACT The in vitro activity of daptomycin was compared with those of vancomycin, linezolid, and quinupristin-dalfopristin against a variety (n = 203) of gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and S. epidermidis (MRSA and MRSE, respectively), vancomycin-resistant enterococci (VRE), and vancomycin-intermediate S. aureus(VISA). Overall, daptomycin was more active against all organisms tested, except Enterococcus faecium and VISA, against which its activity was similar to that of quinupristin-dalfopristin. In time-kill studies with MRSA, MRSE, VRE, and VISA, daptomycin demonstrated greater bactericidal activity than all other drugs tested, killing ≥3 log CFU/ml by 8 h. Daptomycin may be a potential alternative drug therapy for multidrug-resistant gram-positive organisms and warrants further investigation.

scholarly journals Antibacterial Activity of REP8839, a New Antibiotic for Topical Use

2005 ◽  
Vol 49 (10) ◽  
pp. 4247-4252 ◽  
Author(s):  
Ian A. Critchley ◽  
Casey L. Young ◽  
Kimberley C. Stone ◽  
Urs A. Ochsner ◽  
Joseph Guiles ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Trna Synthetase ◽  
Inoculum Size ◽  
Neutral Medium ◽  
Gram Positive Bacteria ◽  
Resistant Strains ◽  
Mupirocin Resistance ◽  
Vancomycin Resistant ◽  
High Level ◽  
Methionyl Trna Synthetase

ABSTRACT REP8839 is a novel methionyl-tRNA synthetase (MetS) inhibitor with potent antibacterial activity against clinical isolates of Staphylococcus aureus, Streptococcus pyogenes, and other clinically important gram-positive bacteria but little activity against gram-negative bacteria. All isolates of S. aureus, including strains resistant to methicillin, mupirocin, vancomycin, and linezolid were susceptible to REP8839 at concentrations of ≤0.5 μg/ml. REP8839 was also active against Staphylococcus epidermidis, including multiply resistant strains (MIC, ≤0.25 μg/ml). All S. pyogenes isolates were susceptible to REP8839 at concentrations of ≤0.25 μg/ml, suggesting that MetS2, a second enzyme previously identified in Streptococcus pneumoniae, was not present in this organism. REP8839 was highly bound to the protein of human serum, and activity was not greatly influenced by inoculum size but was affected by pH, exhibiting optimal antibacterial activity in a neutral medium rather than a weak acidic medium. Like mupirocin, REP8839 exhibited bacteriostatic activity against key pathogens. The emergence of mupirocin resistance in S. aureus highlights the need for a new topical antibiotic with the ability to inhibit high-level mupirocin-resistant strains and other emerging phenotypes, such as vancomycin-resistant and community-acquired methicillin-resistant isolates.

A light-up probe with aggregation-induced emission characteristics (AIE) for selective imaging, naked-eye detection and photodynamic killing of Gram-positive bacteria

2015 ◽  
Vol 51 (62) ◽  
pp. 12490-12493 ◽  
Author(s):  
Guangxue Feng ◽  
Youyong Yuan ◽  
Hu Fang ◽  
Ruoyu Zhang ◽  
Bengang Xing ◽  
...  
Keyword(s):  
Selective Recognition ◽  
Emission Characteristics ◽  
Eye Detection ◽  
Gram Positive ◽  
Aggregation Induced Emission ◽  
Gram Positive Bacteria ◽  
Naked Eye ◽  
Resistant Strains ◽  
Vancomycin Resistant ◽  
Naked Eye Detection

We report a multifunctional light-up probe based on AIEgens for selective recognition, naked-eye identification, and photodynamic killing of Gram-positive bacteria including vancomycin-resistant strains.

scholarly journals Antistaphylococcal Activity of Ceftobiprole, a New Broad-Spectrum Cephalosporin

2005 ◽  
Vol 49 (10) ◽  
pp. 4210-4219 ◽  
Author(s):  
Tatiana Bogdanovich ◽  
Lois M. Ednie ◽  
Stuart Shapiro ◽  
Peter C. Appelbaum
Keyword(s):  
Active Component ◽  
Serial Passage ◽  
Coagulase Negative Staphylococci ◽  
Low Frequencies ◽  
Methicillin Resistant ◽  
Gram Positive Bacteria ◽  
Antistaphylococcal Activity ◽  
Amoxicillin Clavulanate ◽  
Resistant Strains ◽  
Vancomycin Resistant

ABSTRACT Ceftobiprole (formerly BAL9141), the active component of the prodrug BAL5788 (ceftobiprole medocaril), is a novel cephalosporin with expanded activity against gram-positive bacteria. Among 152 Staphylococcus aureus isolates, including 5 vancomycin-intermediate and 2 vancomycin-resistant strains, MIC50 and MIC90 values for ceftobiprole were each 0.5 μg/ml against methicillin-susceptible strains and 2 μg/ml against methicillin-resistant strains. Against 151 coagulase-negative staphylococci (including 4 vancomycin-intermediate strains), MIC50 and MIC90 values were, respectively, 0.125 μg/ml and 1 μg/ml against methicillin-susceptible and 1 μg/ml and 2 μg/ml against methicillin-resistant strains. Teicoplanin was less active than vancomycin against coagulase-negative strains. Linezolid, quinupristin-dalfopristin, and daptomycin were active against all strains, whereas increased MICs for amoxicillin-clavulanate, cefazolin, minocycline, gentamicin, trimethoprim-sulfamethoxazole, levofloxacin, rifampin, mupirocin, fusidic acid, and fosfomycin were sometimes observed. At 2× MIC, ceftobiprole was bactericidal against 11 of 12 test strains by 24 h. Prolonged serial passage in the presence of subinhibitory concentrations of ceftobiprole failed to select for clones with MICs >4 times those of the parents; the maximum MIC achieved for ceftobiprole after 50 passages (in 1 of 10 strains) was 8 μg/ml. Single-passage selections showed very low frequencies of resistance to ceftobiprole irrespective of genotype or phenotype; the maximal ceftobiprole MIC of recovered clones was 8 μg/ml.

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