linezolid and quinupristin-dalfopristin

The activity of telavancin and comparators was assessed against a contemporary (2007 and 2008) global collection of 10,000 isolates of Staphylococcus aureus. Telavancin was very active against methicillin-susceptible and -resistant S. aureus (MSSA and MRSA, respectively; MIC(50/90) for both, 0.12/0.25 microg/ml; 100.0% susceptible). This agent was 2-, 4-, and 8-fold more potent than daptomycin (MIC(90), 0.5 microg/ml), vancomycin or quinupristin-dalfopristin (MIC(90), 1 microg/ml), and linezolid (MIC(90), 2 microg/ml) against MRSA, respectively. These data show a potent activity of telavancin tested against a current global collection of S. aureus.

Topics: Acetamides; Aminoglycosides; Anti-Bacterial Agents; Daptomycin; Drug Resistance, Bacterial; Humans; In Vitro Techniques; Linezolid; Lipoglycopeptides; Methicillin Resistance; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Oxazolidinones; Staphylococcal Infections; Staphylococcus aureus; Vancomycin; Virginiamycin

TD-1792 is a glycopeptide-cephalosporin heterodimer antibiotic with activity against a broad spectrum of gram-positive pathogens that includes methicillin-susceptible and -resistant Staphylococcus aureus. The objective of the present study was to evaluate the in vitro activity of TD-1792 against a collection of clinical isolates of vancomycin-intermediate Staphylococcus spp. (VISS), heteroresistant VISS (hVISS), and vancomycin-resistant S. aureus (VRSA). The TD-1792, vancomycin, daptomycin, linezolid, and quinupristin-dalfopristin MICs and minimum bactericidal concentrations (MBCs) were determined for 50 VISS/hVISS isolates and 3 VRSA isolates. Time-kill experiments (TKs) were then performed over 24 h with two vancomycin-intermediate S. aureus strains and two VRSA strains, using each agent at multiples of the MIC. TD-1792 and daptomycin were also evaluated in the presence and absence of 50% human serum to determine the effects of the proteins on their activities. Most of the VISS/hVISS isolates were susceptible to all agents except vancomycin. TD-1792 exhibited the lowest MIC values (MIC(90) = 0.125 microg/ml), followed by quinupristin-dalfopristin and daptomycin (MIC(90) = 1 microg/ml) and then linezolid (MIC(90) = 2 microg/ml). The presence of serum resulted in a 2- to 8-fold increase in the TD-1792 and daptomycin MIC values. In TKs, QD demonstrated bactericidal activity at multiples of the MIC that simulated therapeutic levels, whereas linezolid was only bacteriostatic. Both TD-1792 and daptomycin demonstrated rapid bactericidal activities against all isolates tested. The presence of proteins had only a minimal impact on the activity of TD-1792 in TKs. TD-1792 exhibited significant in vitro activity against multidrug-resistant Staphylococcus isolates and represents a promising candidate for the treatment of infections caused by gram-positive organisms.

Topics: Acetamides; Anti-Bacterial Agents; Cephalosporins; Daptomycin; Glycopeptides; Linezolid; Microbial Sensitivity Tests; Oxazolidinones; Staphylococcus; Staphylococcus aureus; Vancomycin; Vancomycin Resistance; Virginiamycin

Antibacterial agents are used in malaria therapy due to their effect on two prokaryote organelles, the mitochondrion and the apicoplast. We demonstrate here that the ribosome-blocking antibiotics telithromycin and quinupristin-dalfopristin, but not linezolid, inhibit the growth of Plasmodium falciparum. Both drugs induce delayed death in the parasite, suggesting that their effect involves the impairment of apicoplast translation processes.

Topics: Animals; Humans; Ketolides; Malaria, Falciparum; Parasitic Sensitivity Tests; Plasmodium falciparum; Protein Biosynthesis; Protein Synthesis Inhibitors; Time Factors; Virginiamycin

Among 203 strains of Staphylococcus aureus, the MICs of CG400549 were 0.06 to 1.0 microg/ml, with MIC(50) and MIC(90) values of 0.25 microg/ml each. All strains were susceptible to linezolid and quinupristin-dalfopristin (MICs, 0.25 to 2.0 microg/ml). The daptomycin MICs were 0.25 to 2.0 microg/ml for methicillin-susceptible and 0.25 to 4.0 microg/ml against methicillin-resistant strains (including vancomycin-intermediate strains). Single-passage selection testing showed low resistance frequencies with CG400549, but multistep analysis showed that CG400549 yielded resistant mutants after 14 to 17 days in all strains tested.

Topics: Acetamides; Anti-Bacterial Agents; Daptomycin; Drug Resistance, Multiple, Bacterial; Enoyl-(Acyl-Carrier-Protein) Reductase (NADH); Enzyme Inhibitors; Linezolid; Methicillin Resistance; Microbial Sensitivity Tests; Molecular Structure; Oxazolidinones; Pyridines; Staphylococcus aureus; Thienopyridines; Thiophenes; Virginiamycin