minocycline and dalfopristin

Multi-antibiotic resistant Gram-positive cocci represent emerging pathogens especially in the setting of the immunocompromised, hospitalized patients, in particular when surgery, invasive procedures, or prosthetic implants are of concern, patients are admitted in intensive care units, or underlying chronic disorders and immunodeficiency are of concern, and broad-spectrum antibiotics and/or immunosuppressive drugs are widely administered. The spectrum of available antimicrobial compounds for an effective management of these relevant infections is significantly impaired in selection and clinical efficacy by the emerging and spread of methicillin-resistant and more recently glycopeptide-resistant Gram-positive microbial strains linezolid, together with the recently licensed quinupristin-dalfopristin, daptomycin and tigecycline, followed by a number of glycopeptides, fluoroquinolones, and other experimental compounds represent an effective response to these concerns, due to their innovative mechanisms of action, their maintained or enhanced activity against multiresistant pathogens, their effective pharmacokinetic/pharmacodynamic properties, their frequent possibility of synergistic activity with other compounds effective against Gram-positive pathogens, and a diffuse potential for a safe and easy administration, also when compromised patients are of concern. The main problems related to the epidemiological and clinical features of multiresistant Gram-positive infection, the potential clinical indications of all recently available compounds compared with the standard of treatment of resistant Gram-positive infections, and updated data on efficacy and tolerability of linezolid have to be clarified.

Topics: Acetamides; Administration, Oral; Anti-Infective Agents; Daptomycin; Drug Resistance, Multiple, Bacterial; Enterococcus; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Injections, Intravenous; Linezolid; Microbial Sensitivity Tests; Minocycline; Oxazolidinones; Practice Guidelines as Topic; Staphylococcus aureus; Streptococcus pneumoniae; Teicoplanin; Tigecycline; Time Factors; Vancomycin; Virginiamycin

Topics: Acetamides; Bacteria; Drug Design; Drug Resistance, Bacterial; Humans; Linezolid; Minocycline; Oxazolidinones; Tetracyclines; Tigecycline; Virginiamycin

Inhalation of water contaminated with Naegleria fowleri may lead to a potentially fatal infection of the central nervous system known as primary amebic meningoencephalitis (PAM). Amphotericin B (AMB), an antifungal drug, is the only agent with established clinical efficacy in the treatment of PAM, though therapy with this drug is not always effective and has been associated with adverse effects on the kidneys and other organs. We investigated the activity of various therapeutic agents against N. fowleri in an attempt to identify other useful agents for treating PAM. Several of these agents exhibited in vitro activity against the Lee (M67) strain of N. fowleri. The minimum inhibitory concentrations of these agents were 0.1 microg/ml (ketoconazole), 1 microg/ml (liposomal AMB), and 10 microg/ml (minocycline, quinupristin-dalfopristin, and trifluoperazine). Other agents had a minimum inhibitory concentration > 10 microg/ml (linezolid) or > 100 microg/ml (rifampin). In a mouse model of PAM, none of the untreated control mice survived, whereas the survival of treated animals was 50% (quinupristin-dalfopristin), 30% (ketoconazole and liposomal AMB), 20% (trifluoperazine), and 10% (linezolid and minocycline). Further studies are needed to ascertain whether these agents have synergistic activity with AMB in vitro and in vivo.

Topics: Acetamides; Adolescent; Amebiasis; Amebicides; Amphotericin B; Animals; Central Nervous System Protozoal Infections; Disease Models, Animal; Drug Therapy, Combination; Female; Humans; Ketoconazole; Linezolid; Liposomes; Male; Mice; Minocycline; Naegleria fowleri; Oxazolidinones; Trifluoperazine; Virginiamycin

The susceptibilities of Mycoplasma hominis, Mycoplasma pneumoniae, and Ureaplasma urealyticum to eight new antimicrobial agents were determined by agar dilution. M. pneumoniae was susceptible to the new glycylcycline GAR-936 at 0.12 microg/ml and evernimicin at 4 microg/ml, but it was resistant to linezolid. It was most susceptible to dirithromycin, quinupristin-dalfopristin, telithromycin, reference macrolides, and josamycin. M. hominis was susceptible to linezolid, evernimicin, and GAR-936. It was resistant to macrolides and the ketolide telithromycin but susceptible to quinupristin-dalfopristin and josamycin. U. urealyticum was susceptible to evernimicin (8 to 16 microg/ml) and resistant to linezolid. It was less susceptible to GAR-936 (4.0 microg/ml) than to tetracycline (0.5 microg/ml). Telithromycin and quinupristin-dalfopristin were the most active agents against ureaplasmas (0.06 microg/ml). The new quinolone gatifloxacin was active against M. pneumoniae and M. hominis at 0.12 to 0.25 microg/ml and active against ureaplasmas at 1.0 microg/ml. The MICs of macrolides were markedly affected by pH, with an 8- to 32-fold increase in the susceptibility of M. pneumoniae as the pH increased from 6.9 to 7.8. A similar increase in susceptibility with increasing pH was also observed with ureaplasmas. Tetracyclines showed a fourfold increase of activity as the pH decreased 1 U, whereas GAR-936 showed a fourfold decrease in activity with a decrease in pH.

Topics: 4-Quinolones; Acetamides; Aminoglycosides; Anti-Bacterial Agents; Aza Compounds; Erythromycin; Fluoroquinolones; Gatifloxacin; Humans; Hydrogen-Ion Concentration; Ketolides; Linezolid; Macrolides; Microbial Sensitivity Tests; Minocycline; Moxifloxacin; Mycoplasma hominis; Mycoplasma pneumoniae; Oxazolidinones; Quinolines; Tetracyclines; Tigecycline; Ureaplasma urealyticum; Virginiamycin