In vitro evaluation of a novel ketolide antimicrobial agent, RU-64004.

1997 ◽  
Vol 41 (2) ◽  
pp. 454-459 ◽  
Author(s):  
C Jamjian ◽  
D J Biedenbach ◽  
R N Jones
Keyword(s):  
Moraxella Catarrhalis ◽  
In Vitro Tests ◽  
In Vitro Activity ◽  
Gram Positive ◽  
Beta Hemolytic Streptococcus ◽  
Serious Infections ◽  
Resistant Strains ◽  
Vancomycin Resistant

Ketolides, a novel macrolide subclass, possess a mode of action that is similar to that of structurally related macrolide-lincosamide-streptogramin (MLS) compounds. By using reference in vitro tests, the in vitro activity of RU-64004 was compared to those of six other MLS compounds against more than 800 clinical pathogens, including 356 gram-positive organisms. The spectrum of activity of the ketolide was most similar to that of clindamycin versus staphylococci and streptococci and superior to those of all macrolides tested against oxacillin-resistant staphylococci and vancomycin-resistant (vanA, vanB, and vanC) enterococcal isolates. The activity of the ketolide was greater than those of the macrolides, azalides, or clindamycin tested against vancomycin-susceptible enterococci (MICs at which 90% of isolates are inhibited [MIC90S], 0.25 to 4 micrograms/ml), penicillin-resistant pneumococci (MIC90, 0.25 micrograms/ml), and most beta-hemolytic streptococci. All Streptococcus pneumoniae and beta-hemolytic streptococcus strain were inhibited by ketolide concentrations of < or = 0.25 micrograms/ml. Against 165 erythromycin-resistant strains, RU-64004 inhibited (MICs, < or = 0.5 micrograms/ml) approximately one-third of staphylococci, all streptococci, and slightly more than one-half of the enterococci. Quinupristin-dalfopristin (a streptogramin combination) was active against all tested isolates with the exception of non-Enterococcus faecium enterococci, against which the ketolide exhibited greater potency (MIC50S, 0.03 to 2 micrograms/ml). The ketolide was also active against Haemophilus influenzae (MIC90, 2 micrograms/ml), Moraxella catarrhalis (MIC90, 0.12 micrograms/ml), pathogenic Neisseria spp. (MIC90, 0.5 micrograms/ml), and many gram-positive anaerobes (MIC90, 0.5 micrograms/ml). RU-64004 may enhance the role of macrolide drugs in the treatment of some serious infections caused by MLS-resistant gram-positive organisms.

scholarly journals Comparative In Vitro Activities of AC98-6446, a Novel Semisynthetic Glycopeptide Derivative of the Natural Product Mannopeptimycin α, and Other Antimicrobial Agents against Gram-Positive Clinical Isolates

2004 ◽  
Vol 48 (3) ◽  
pp. 739-746 ◽  
Author(s):  
Peter J. Petersen ◽  
T. Z. Wang ◽  
Russell G. Dushin ◽  
Patricia A. Bradford
Keyword(s):  
Natural Product ◽  
Bactericidal Activity ◽  
Antimicrobial Agents ◽  
Marked Decrease ◽  
Gram Positive ◽  
Novel Structure ◽  
Resistant Strains ◽  
Vancomycin Resistant ◽  
Further Development

ABSTRACT AC98-6446 is a novel semisynthetic cyclic glycopeptide antibiotic related to the natural product mannopeptimycin α (AC98-1). In the present study the activity of AC98-6446 was evaluated against a variety of recent clinical gram-positive pathogens including multiply resistant strains. AC98-6446 demonstrated similar potent activities against methicillin-susceptible and methicillin-resistant staphylococci and glycopeptide-intermediate staphylococcal isolates (MICs at which 90% of isolates are inhibited [MIC90s], 0.03 to 0.06 μg/ml). AC98-6446 also demonstrated good activities against both vancomycin-resistant and -susceptible strains of enterococci (MIC90s, 0.12 and 0.25 μg/ml, respectively) as well as against streptococcal strains (MIC90s, ≤ 0.008 to 0.03 μg/ml). AC98-6446 demonstrated bactericidal activity in terms of the reduction in the viable counts (>3 log10 CFU/ml) of staphylococcal and streptococcal isolates and a marked decrease in the viable counts of most enterococcal strains (from 0.2 to 2.5 log10 CFU/ml). Unlike vancomycin, which demonstrates time-dependent killing, AC98-6446 demonstrated concentration-dependent killing. The potent activity, novel structure, and bactericidal activity demonstrated by AC98-6446 make it an attractive candidate for further development.

scholarly journals In vitro activity of RU 64004, a new ketolide antibiotic, against gram-positive bacteria.

1997 ◽  
Vol 41 (5) ◽  
pp. 1196-1202 ◽  
Author(s):  
T Schülin ◽  
C B Wennersten ◽  
R C Moellering ◽  
G M Eliopoulos
Keyword(s):  
Vitro Activity ◽  
In Vitro Activity ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Agar Dilution ◽  
Resistant Strains ◽  
Erythromycin A

The comparative in vitro activity of RU 64004 (also known as HMR 3004), a new ketolide antibiotic, was tested by agar dilution against approximately 500 gram-positive organisms, including multiply resistant enterococci, streptococci, and staphylococci. All streptococci were inhibited by < or = 1 microg of RU 64004 per ml. The ketolide was more potent than other macrolides against erythromycin A-susceptible staphylococci and was generally more potent than clindamycin against erythromycin A-resistant strains susceptible to this agent. Clindamycin-resistant staphylococci (MIC, > 128 microg/ml) proved resistant to the ketolide, but some erythromycin A- and clindamycin-resistant enterococci remained susceptible to RU 64004.

scholarly journals In Vitro Activity and Killing Effect of Uperin 3.6 against Gram-Positive Cocci Isolated from Immunocompromised Patients

2005 ◽  
Vol 49 (9) ◽  
pp. 3933-3936 ◽  
Author(s):  
Andrea Giacometti ◽  
Oscar Cirioni ◽  
Wojciech Kamysz ◽  
Carmela Silvestri ◽  
Alberto Licci ◽  
...  
Keyword(s):  
Vitro Activity ◽  
Immunocompromised Patients ◽  
In Vitro Activity ◽  
Gram Positive ◽  
Killing Effect ◽  
Methicillin Resistant ◽  
Vancomycin Resistant Enterococci ◽  
Vancomycin Resistant ◽  
Gram Positive Cocci

ABSTRACT The in vitro activity of uperin 3.6, alone or combined with six antibiotics, against gram-positive cocci, including Rhodococcus equi, methicillin-resistant staphylococci, and vancomycin-resistant enterococci, was investigated. All isolates were inhibited at concentrations of 1 to 16 mg/liter. Synergy was demonstrated when uperin 3.6 was combined with clarithromycin and doxycycline.

scholarly journals In Vitro Antibacterial Activities of DQ-113, a Potent Quinolone, against Clinical Isolates

2002 ◽  
Vol 46 (3) ◽  
pp. 904-908 ◽  
Author(s):  
Mayumi Tanaka ◽  
Emi Yamazaki ◽  
Megumi Chiba ◽  
Kiyomi Yoshihara ◽  
Takaaki Akasaka ◽  
...  
Keyword(s):  
Streptococcus Pyogenes ◽  
Moraxella Catarrhalis ◽  
Antibacterial Agents ◽  
Antibacterial Activities ◽  
Clinical Isolates ◽  
Coagulase Negative Staphylococci ◽  
Vancomycin Resistant Enterococci ◽  
Resistant Strains ◽  
Vancomycin Resistant

ABSTRACT The antibacterial activity of DQ-113, formerly D61-1113, was compared with those of antibacterial agents currently available. MICs at which 90% of the isolates tested are inhibited (MIC90s) of DQ-113 against clinical isolates of methicillin-susceptible and -resistant Staphylococcus aureus and methicillin-susceptible and -resistant coagulase-negative staphylococci were 0.03, 0.008, 0.03, and 0.06 μg/ml, respectively. Moreover, DQ-113 showed the most potent activity against ofloxacin-resistant and methicillin-resistant S. aureus, with a MIC90 of 0.25μg/ml. DQ-113 inhibited the growth of all strains of Streptococcus pneumoniae, including penicillin-resistant strains, and Streptococcus pyogenes at 0.06 μg/ml, and DQ-113 was more active than the other quinolones tested against Enterococcus faecalis and Enterococcus faecium with MIC90s of 0.25 and 2 μg/ml, respectively. Against vancomycin-resistant enterococci, DQ-113 showed the highest activity among the reference compounds, with a MIC range from 0.25 to 2 μg/ml. DQ-113 also showed a potent activity against Haemophilus influenzae, including ampicillin-resistant strains (MIC90, 0.015 μg/ml), and Moraxella catarrhalis (MIC90, 0.03 μg/ml). The activity of DQ-113 was roughly comparable to that of levofloxacin against all species of Enterobacteriaceae. The MICs of DQ-113 against ofloxacin-susceptible Pseudomonas aeruginosa ranged from 0.25 to 2 μg/ml, which were four times higher than those of ciprofloxacin. From these results, DQ-113 showed the most potent activity against gram-positive pathogens among antibacterial agents tested.

scholarly journals Comparative In Vitro Activities of Daptomycin and Vancomycin against Resistant Gram-Positive Pathogens

2000 ◽  
Vol 44 (12) ◽  
pp. 3447-3450 ◽  
Author(s):  
D. R. Snydman ◽  
N. V. Jacobus ◽  
L. A. McDermott ◽  
J. R. Lonks ◽  
J. M. Boyce
Keyword(s):  
Staphylococcus Aureus ◽  
Antibacterial Activity ◽  
Streptococcus Pneumoniae ◽  
Calcium Concentration ◽  
In Vitro Activity ◽  
Gram Positive ◽  
Methicillin Resistant ◽  
Vancomycin Resistant ◽  
Gram Positive Cocci

ABSTRACT The in vitro activity of daptomycin against 224 current gram-positive clinical isolates including vancomycin-resistantEnterococcus faecium (VREF), methicillin-resistantStaphylococcus aureus (MRSA), methicillin-resistantStaphylococcus spp. (MRSS), and penicillin-resistantStreptococcus pneumoniae (PRSP) was evaluated. The MICs at which 90% of isolates are inhibited for daptomycin and vancomycin, respectively, were as follows: MRSA, 1 and 2 μg/ml; MRSS, 1 and 4 μg/ml; PRSP, 1 and 0.5 μg/ml; and VREF, 2 and >64 μg/ml. Daptomycin was bactericidal against 82% of 17 VREF isolates. The antibacterial activity of daptomycin was strongly dependent on the calcium concentration of the medium. Daptomycin was active against all gram-positive cocci tested.

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 In Vitro Activity and Potency of the Novel Oxazolidinone Contezolid (MRX-I) Tested against Gram-Positive Clinical Isolates from the United States and Europe

2020 ◽  
Vol 64 (11) ◽  
Author(s):  
Cecilia G. Carvalhaes ◽  
Leonard R. Duncan ◽  
Wen Wang ◽  
Helio S. Sader
Keyword(s):  
Antibacterial Agent ◽  
The United States ◽  
Clinical Development ◽  
Clinical Isolates ◽  
The Novel ◽  
In Vitro Activity ◽  
Gram Positive ◽  
Content Type ◽  
Vancomycin Resistant

ABSTRACT Contezolid, a new oxazolidinone antibacterial agent currently in development for the treatment of skin and skin structure infections, was susceptibility tested against Gram-positive clinical isolates (n = 1,211). Contezolid demonstrated potent activity against Staphylococcus aureus (MIC50/90, 0.5/1 mg/liter), coagulase-negative Staphylococcus (MIC50/90, 0.25/0.5 mg/liter), Enterococcus spp. (MIC50/90, 0.5/1 mg/liter), and streptococci (MIC50/90, 1/1 mg/liter). Moreover, methicillin-resistant S. aureus and vancomycin-resistant Enterococcus faecium isolates were all inhibited by contezolid at ≤1 mg/liter. These results support the clinical development of contezolid.

scholarly journals In Vitro Activity of the New Glycopeptide LY333328 against Multiply Resistant Gram-Positive Clinical Isolates

1998 ◽  
Vol 42 (9) ◽  
pp. 2452-2455 ◽  
Author(s):  
Fernando García-Garrote ◽  
Emilia Cercenado ◽  
Luis Alcalá ◽  
Emilio Bouza
Keyword(s):  
Vitro Activity ◽  
Clinical Isolates ◽  
In Vitro Activity ◽  
Gram Positive ◽  
Resistant Strains

ABSTRACT The in vitro activity of LY333328 was compared with those of vancomycin and teicoplanin against 425 gram-positive clinical isolates, including a variety of multiply resistant strains. LY333328 at ≤4 μg/ml inhibited all microorganisms tested, including methicillin- and teicoplanin-resistant staphylococci, glycopeptide-resistant enterococci, penicillin- and multiply resistant pneumococci, and viridans and beta-hemolytic streptococci.

scholarly journals In Vitro Activity of Omadacycline and Comparator Compounds Against Gram-positive Isolates Collected in the USA During 2016 as Part of a Global Surveillance Program

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S374-S374
Author(s):  
Michael D Huband ◽  
Michael a Pfaller ◽  
Helio S Sader ◽  
Robert K Flamm
Keyword(s):  
Resistance Mechanisms ◽  
Vitro Activity ◽  
Surveillance Program ◽  
Ionization Mass ◽  
In Vitro Activity ◽  
Coagulase Negative Staphylococci ◽  
Gram Positive ◽  
Resistant Strains ◽  
Research Grant

Abstract Background Omadacycline (OMC) is a broad spectrum aminomethylcycline antibacterial in late stage clinical development (PO and IV formulations) for treatment of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). OMC has potent in vitro activity against gram-positive (GP) pathogens expressing common resistance mechanisms to penicillins, tetracyclines, fluoroquinolones and macrolides. Methods A total of 4,122 GP isolates were collected in 2016 from 30 USA medical centers and included 2,366 staphylococci, 1,252 streptococci and 504 enterococci. A single isolate/patient/infection episode was included. Identifications were confirmed by matrix-assisted laser desorption/ionization mass spectrometry and susceptibility (S) testing was performed using reference broth microdilution methods. Results OMC was equally active against methicillin-susceptible (55.1% MSSA) and -resistant (44.9% MRSA) Staphylococcus aureus (SA; MIC50/90, 0.12/0.25 µg/mL). All SA were S to daptomycin (DAP), linezolid (LZD) and vancomycin (VAN). In MRSA, S was lower for levofloxacin (LEV; 28.2%), clindamycin (CLI; 69.9%), and erythromycin (ERY; 10.9%). OMC (MIC50/90, 0.12/0.5 µg/mL) and tigecycline (TGC; MIC50/90, 0.06/12 µg/mL) were the most active agents against coagulase-negative staphylococci (CoNS) and methicillin-R CoNS. S. pneumoniae (including penicillin- [12.8% resistant], ceftriaxone- and ERY-resistant strains), viridans group streptococci (VGS) and β-hemolytic streptococci (including ERY and tetracycline resistant strains) were inhibited by low levels of OMC (MIC50/90 0.06/0.06–0.12 µg/mL) and TGC (MIC50/90 0.03–0.06/0.06–0.12 µg/mL). OMC was highly potent against enterococci (MIC50/90 0.12/0.25 µg/mL) including vancomycin-R isolates. Vancomycin resistance rates were 4.3% and 66.5% in E. faecalis and E. faecium, respectively. Conclusion OMC demonstrated potent activity against susceptible and resistant GP pathogens often associated with ABSSSI and CABP including staphylococci, S. pneumoniae, β-hemolytic streptococci, VGS and enterococci. These data support further omadacycline clinical studies, especially in infections where resistant GP isolates occur. Disclosures M. D. Huband, Paratek Pharma, LLC: Research Contractor, Research grant; M. A. Pfaller, Paratek Pharma, LLC: Research Contractor, Research grant; H. S. Sader, Paratek Pharma, LLC: Research Contractor, Research grant R. K. Flamm, Paratek Pharma, LLC: Research Contractor, Research grant

scholarly journals In vitro activity of BAY 12-8039, a novel 8-methoxyquinolone, compared to activities of six fluoroquinolones against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.

1997 ◽  
Vol 41 (7) ◽  
pp. 1594-1597 ◽  
Author(s):  
A B Brueggemann ◽  
K C Kugler ◽  
G V Doern
Keyword(s):  
Streptococcus Pneumoniae ◽  
Haemophilus Influenzae ◽  
Moraxella Catarrhalis ◽  
Ambient Air ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Broth Microdilution ◽  
Agar Dilution ◽  
Resistant Strains

The in vitro activity of a novel 8-methoxyquinolone, BAY 12-8039, against recent clinical isolates of Streptococcus pneumoniae (n = 404), Haemophilus influenzae (n = 330), and Moraxella catarrhalis (n = 250) was evaluated. Activity was compared to those of six other fluoroquinolones: ciprofloxacin, clinafloxacin, levofloxacin, ofloxacin, sparfloxacin and trovafloxacin. BAY 12-8039 and clinafloxacin had the highest levels of activity against S. pneumoniae, both with a MIC at which 90% of the isolates were inhibited (MIC90) of 0.06 microg/ml. Trovafloxacin and sparfloxacin were the next most active agents versus S. pneumoniae (MIC90s = 0.12 microg/ml). No differences in activity against penicillin-susceptible, -intermediate, or -resistant strains of S. pneumoniae were noted for any of the fluoroquinolones tested. MIC90s for the seven fluoroquinolones ranged from 0.008 to 0.06 microg/ml versus H. influenzae and from 0.008 to 0.12 microg/ml for M. catarrhalis. The MICs for two strains of S. pneumoniae and one strain of H. influenzae were noted to be higher than those for the general population of organisms for all of the fluoroquinolones tested. Finally, the activity of BAY 12-8039 versus S. pneumoniae was found to be diminished when MIC determinations were performed with incubation of agar dilution plates or broth microdilution trays in 5 to 7% CO2 versus ambient air.

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