quinupristin-dalfopristin and trovafloxacin

Bacterial meningitis caused by Streptococcus pneumoniae is an important cause of neurological morbidity and mortality in both children and adults. With increasing antibiotic resistance in pneumococci and documented microbiological failure in treatment of pneumococcal meningitis with cefotaxime and ceftriaxone, the need for alternative antibiotic therapy is critical. Of the currently available options, vancomycin has shown the most promise, particularly when used in combination with ceftriaxone or cefotaxime. Rifampin, also used in combination with either ceftriaxone or cefotaxime, has demonstrated encouraging preliminary results against antibiotic-resistant pneumococci as well. Chloramphenicol has unexpectedly yielded discouraging clinical results in children with infection caused by penicillin-resistant strains. Of the investigational antibiotics currently in clinical trials for the treatment of meningitis, meropenem, a carbapenem-class antibiotic, has demonstrated increased activity against penicillin-resistant pneumococci compared with that of other beta-lactam antibiotics, while having a safety profile similar to that of the cephalosporins.

Topics: Adult; Anti-Bacterial Agents; Anti-Infective Agents; Child; Child, Preschool; Chloramphenicol; Clindamycin; Female; Fluoroquinolones; Humans; Infant; Infant, Newborn; Lactams; Male; Meningitis, Bacterial; Naphthyridines; Penicillin Resistance; Rifampin; Streptococcal Infections; Streptococcus pneumoniae; Vancomycin; Virginiamycin

The efficacy of different antibiotics was compared in an experimental model of aortic valve endocarditis in rabbits, using a serotype 19 strain of Streptococcus pneumoniae resistant to penicillin (MIC 12 mg/L) and ceftriaxone (MIC 12 mg/L). The results were compared with those of a control group, which received no treatment. One hundred and nineteen animals were treated with one of the following antibiotic regimens: im procaine penicillin G at a dosage of 300,000 U/kg weight/12 h (16 animals); iv trovafloxacin, 13.3 mg/kg/12 h (31 animals); iv ceftriaxone, 75 mg/kg/24 h (21 animals); iv vancomycin, 20 mg/kg/12 h (15 animals) and im quinupristin-dalfopristin, 30 mg/kg/8 h (20 animals). All the antibiotics used in this study proved to be efficient in reducing numbers of S. pneumoniae and in increasing the percentage of aortic vegetations that were rendered sterile compared with the control group. Penicillin at the dosage used in our study was capable of achieving serum concentrations two or three times greater than the MIC, thus demonstrating its effectiveness as an antibiotic for this endocarditis model. No significant difference was observed between the effects of vancomycin, quinupristin-dalfopristin and penicillin. Vancomycin proved to be more efficient than trovofloxacin in reducing the bacterial load and increasing the numbers sterilized. There was also a tendency for this antibiotic to be more effective than ceftriaxone in reducing the bacterial load of the vegetations. There was a statistically significant correlation between the weight of the vegetations and their bacterial load. In the light of these results, vancomycin and quinupristin-dalfopristin may be considered suitable alternatives to penicillin for the treatment of penicillin-resistant S. pneumoniae endocarditis.

Topics: Animals; Anti-Infective Agents; Ceftriaxone; Disease Models, Animal; Drug Resistance, Multiple; Endocarditis, Bacterial; Fluoroquinolones; Humans; Male; Naphthyridines; Penicillin Resistance; Penicillins; Pneumococcal Infections; Rabbits; Streptococcus pneumoniae; Vancomycin; Virginiamycin

The in vitro activities of the new agents linezolid, quinupristin-dalfopristin, moxifloxacin, and trovafloxacin were determined and compared with those of penicillin, clindamycin, and four macrolides against 53 erythromycin-resistant Streptococcus pneumoniae, 117 S. pyogenes (64 erythromycin-susceptible and 53 -resistant), and 101 S. agalactiae (53 erythromycin-susceptible and 48 -resistant) isolates. Differentiation of macrolide resistance phenotypes was performed by the double-disk method. The genetic basis for macrolide resistance in 52 strains was also determined. The M phenotype was found in 84.9, 6.3, and 1.9% of S. pyogenes, S. agalactiae, and S. pneumoniae isolates, respectively. These strains were susceptible to miocamycin and clindamycin. Strains with the inducible phenotype accounted for 27.1% of S. agalactiae isolates and 9.4% each of S. pyogenes and S. pneumoniae isolates. All erythromycin-resistant isolates were also resistant to the 14- and 15-membered macrolides tested. Strains with all three phenotypes were susceptible to

Topics: Acetamides; Anti-Bacterial Agents; Aza Compounds; Drug Resistance, Microbial; Drug Therapy, Combination; Erythromycin; Fluoroquinolones; Humans; Linezolid; Microbial Sensitivity Tests; Moxifloxacin; Naphthyridines; Oxazoles; Oxazolidinones; Quinolines; Streptococcus; Virginiamycin

To understand quinupristin-dalfopristin resistance among clinical isolates of gram-positive bacteria in Taiwan, where this agent is not yet available for clinical use, we evaluated 1,287 nonduplicate isolates recovered from January 1996 to December 1999 for in vitro susceptibility to quinupristin-dalfopristin and other newer antimicrobial agents. All methicillin-susceptible Staphylococcus aureus (MSSA) isolates were susceptible to quinupristin-dalfopristin. High rates of nonsusceptibility to quinupristin-dalfopristin (MICs, >/=2 microg/ml) were demonstrated for the following organisms: methicillin-resistant S. aureus (MRSA) (31%), coagulase-negative staphylococci (CoNS) (16%), Streptococcus pneumoniae (8%), viridans group streptococci (51%), vancomycin-susceptible enterococci (85%), vancomycin-resistant Enterococcus faecalis (100%), vancomycin-resistant Enterococcus faecium (66%), Leuconostoc spp. (100%), Lactobacillus spp. (50%), and Pediococcus spp. (87%). All isolates of MSSA, MRSA, S. pneumoniae, and viridans group streptococci were susceptible to vancomycin and teicoplanin. The rates of nonsusceptibility to vancomycin and teicoplanin were 5 and 7%, respectively, for CoNS, ranging from 12 and 18% for S. simulans to 0 and 0% for S. cohnii and S. auricularis. Moxifloxacin and trovafloxacin had good activities against these isolates except for ciprofloxacin-resistant vancomycin-resistant enterococci and methicillin-resistant staphylococci. In Taiwan, virginiamycin has been used in animal husbandry for more than 20 years, which may contribute to the high rates of quinupristin-dalfopristin resistance.

Topics: Acetamides; Anti-Bacterial Agents; Aza Compounds; Drug Resistance, Microbial; Drug Therapy, Combination; Fluoroquinolones; Gram-Positive Bacteria; Humans; Linezolid; Microbial Sensitivity Tests; Moxifloxacin; Naphthyridines; Oxazolidinones; Quinolines; Taiwan; Virginiamycin

The activities of eight fluoroquinolones and linezolid, quinupristin-dalfopristin (Synercid), gentamicin, and vancomycin were tested against 96 ciprofloxacin-susceptible and 205 ciprofloxacin-resistant Staphylococcus aureus strains. Overall, clinafloxacin, followed by moxifloxacin and trovafloxacin, was the most active quinolone tested. For all isolates, linezolid and quinupristin-dalfopristin showed activities that were at least comparable to vancomycin, with no cross-resistance to any other test compound.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Aza Compounds; Ciprofloxacin; Drug Resistance, Microbial; Fluoroquinolones; Gentamicins; Humans; Levofloxacin; Microbial Sensitivity Tests; Moxifloxacin; Naphthyridines; Ofloxacin; Piperazines; Quinolines; Quinolones; Staphylococcus aureus; Vancomycin; Virginiamycin

This in vitro study evaluated the activities of vancomycin, LY333328, and teicoplanin alone and in combination with gentamicin, rifampin, and RP59500 against Staphylococcus aureus isolates with intermediate susceptibilities to vancomycin. Ampicillin-sulbactam and trovafloxacin were also evaluated. LY333328 and ampicillin-sulbactam resulted in bactericidal activity against all isolates. The combination of gentamicin with glycopeptides showed synergistic activity, while rifampin had no added benefit.

Topics: Ampicillin; Anti-Bacterial Agents; Antibiotics, Antitubercular; Drug Therapy, Combination; Fluoroquinolones; Gentamicins; Glycopeptides; Lipoglycopeptides; Microbial Sensitivity Tests; Naphthyridines; Rifampin; Staphylococcus aureus; Sulbactam; Teicoplanin; Time Factors; Vancomycin; Virginiamycin

The antistaphylococcal activities of four newly developed antibiotics, moxifloxacin (an 8-methoxyfluoroquinolone), trovafloxacin (a naphthyridone), quinupristin/dalfopristin (a semisynthetic streptogramin) and linezolid (an oxazolidinone), were examined and compared with those of ciprofloxacin, vancomycin and teicoplanin, using an agar dilution method. A total of 245 clinical isolates of staphylococci, including a large number of clonally different methicillin-resistant strains, were tested. The new agents tested exhibited wide-spectrum antistaphylococcal activity against both methicillin-susceptible and methicillin-resistant strains. In contrast to the quinolones, the in-vitro activities of quinupristin/dalfopristin, linezolid and the glycopeptides remained almost unchanged, irrespective of the resistance phenotype for methicillin. A number of isolates with elevated quinolone MICs were observed.

Topics: Acetamides; Anti-Bacterial Agents; Aza Compounds; Fluoroquinolones; Humans; Linezolid; Methicillin Resistance; Microbial Sensitivity Tests; Moxifloxacin; Naphthyridines; Oxazoles; Oxazolidinones; Quinolines; Staphylococcal Infections; Staphylococcus; Virginiamycin

The antimicrobial activities of trovafloxacin, moxifloxacin, sanfetrinem, quinupristin-dalfopristin, and 14 other antimicrobial agents against 218 Bacteroides fragilis group strains were determined. A group of 10 imipenem-resistant strains were also tested. Imipenem, meropenem, and sanfetrinem had the lowest MICs of all of the beta-lactams. Quinupristin-dalfopristin inhibited all of the strains at 2 microg/ml. Overall, the MICs of trovafloxacin and moxifloxacin for 90% of the strains tested were 1 and 2 microg/ml, respectively.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Aza Compounds; Bacteroides fragilis; Fluoroquinolones; Lactams; Microbial Sensitivity Tests; Moxifloxacin; Naphthyridines; Quinolines; Virginiamycin

In the rabbit model of Streptococcus pneumoniae meningitis, treatment with rifabutin, quinupristin-dalfopristin, moxifloxacin and trovafloxacin led to smaller increases of the CSF concentrations of the pro-inflammatory cell wall components lipoteichoic and teichoic acids (LTA and TA) than did treatment with ceftriaxone. Low doses of moxifloxacin were associated with higher LTA and TA concentrations in CSF than were high doses.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Aza Compounds; Ceftriaxone; Cephalosporins; Disease Models, Animal; Fluoroquinolones; Immunoenzyme Techniques; Lipopolysaccharides; Meningitis, Pneumococcal; Moxifloxacin; Naphthyridines; Polysaccharides, Bacterial; Quinolines; Rabbits; Reference Values; Rifabutin; Teichoic Acids; Virginiamycin

The release of lipoteichoic acid (LTA) and teichoic acid (TA) from a Streptococcus pneumoniae type 3 strain during exposure to ceftriaxone, meropenem, rifampin, rifabutin, quinupristin-dalfopristin, and trovafloxacin in tryptic soy broth was monitored by a newly developed enzyme-linked immunosorbent assay. At a concentration of 10 microg/ml, a rapid and intense release of LTA and TA occurred during exposure to ceftriaxone (3,248+/-1,688 ng/ml at 3 h and 3,827+/-2,133 ng/ml at 12 h) and meropenem (2,464+/-1,081 ng/ml at 3 h and 2,900+/-1,364 ng/ml at 12 h). Three hours after exposure to rifampin, rifabutin, quinupristin-dalfopristin, and trovafloxacin, mean LTA and TA concentrations of less than 460 ng/ml were observed (for each group, P < 0.01 versus the concentrations after exposure to ceftriaxone). After 12 h of treatment, the LTA and TA concentrations were 463+/-126 ng/ml after exposure to rifampin, 669+/-303 ng/ml after exposure to rifabutin, and 1,236+/-772 ng/ml after exposure to quinupristin-dalfopristin (for each group, P < 0.05 versus the concentrations after exposure to ceftriaxone) and 1,745+/-1,185 ng/ml after exposure to trovafloxacin (P = 0.12 versus the concentration after exposure to ceftriaxone). At 10 microg/ml, bactericidal antibacterial agents that do not primarily affect cell wall synthesis reduced the amount of LTA and TA released during their cidal action against S. pneumoniae in comparison with the amount released after exposure to beta-lactams. Larger quantities of LTA and TA were released after treatment with low concentrations (1x the MIC and 1x the minimum bactericidal concentration) than after no treatment for all antibacterial agents except the rifamycins. This does not support the concept of using a low first antibiotic dose to prevent the release of proinflammatory cell wall components.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Enzyme-Linked Immunosorbent Assay; Fluoroquinolones; Lipopolysaccharides; Microscopy, Electron; Naphthyridines; Rifamycins; Streptococcus pneumoniae; Teichoic Acids; Virginiamycin

In a study designed to obtain data on compounds active against enterococci, the minimum inhibitory concentrations (MICs) of quinupristin/dalfopristin (RP 59500) and the novel quinolones DU-6859a, trovafloxacin, levofloxacin, and sparfloxacin were determined for 122 Enterococcus faecalis and seven Enterococcus faecium isolates. In addition, 15 Enterococcus faecalis isolates resistant to gentamicin, DU-6859a, and trovafloxacin were exposed over time to combinations of DU-6859a plus gentamicin and trovafloxacin plus gentamicin. DU-6859a and trovafloxacin were found to be the most active compounds against Enterococcus faecalis and DU-6859a and RP 59500 against Enterococcus faecium. Synergy between either DU-6859a or trovafloxacin and gentamicin was observed with 27 to 35% of the isolates. It is concluded that DU-6859a and trovafloxacin are very potent against enterococci, especially when combined with gentamicin.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Drug Resistance, Microbial; Drug Synergism; Drug Therapy, Combination; Enterococcus faecalis; Enterococcus faecium; Fluoroquinolones; Gentamicins; Levofloxacin; Microbial Sensitivity Tests; Naphthyridines; Ofloxacin; Quinolones; Virginiamycin

The in-vitro activities of five investigational antibiotics, RP59500 (a semisynthetic injectable streptogramin), CL 329,998 and CL 331,002 (two new glycylcyclines), trovafloxacin (a naphthyridone), and clinafloxacin (a dihalogenated quinolone), were examined and compared with those of minocycline, teicoplanin and vancomycin against 190 clinical isolates of Gram-positive cocci. The MICs for RP59500 against all isolates with the exception of Enterococcus faecalis were low. RP59500 was bactericidal against all except enterococcal isolates. CL 329,998 and CL 331,002 were significantly more active than minocycline against oxacillin-resistant Staphylococcus aureus (MIC90 0.25 versus 8 mg/L) and all enterococcal isolates (MIC90 0.125 versus 16 mg/L). Clinafloxacin was the most active agent against all staphylococcal isolates and was bactericidal. Trovafloxacin showed good activity against oxacillin-susceptible staphylococci and alpha-haemolytic streptococci (MIC90 < or = 0.125 mg/L). This study demonstrates the potential of the five investigational antibiotics as therapeutic agents for infections caused by Gram-positive cocci.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Fluoroquinolones; Gram-Positive Bacteria; Microbial Sensitivity Tests; Minocycline; Naphthyridines; Quinolones; Teicoplanin; Tetracyclines; Vancomycin; Virginiamycin

Two oxazolidinones (U100592 and U100766), trovafloxacin, and a streptogramin combination (dalfopristin-quinupristin) were highly active in vitro against Staphylococcus aureus and Staphylococcus epidermidis, including methicillin-resistant strains. Trovafloxacin was more active than ciprofloxacin. Time-kill synergy studies demonstrated indifference for the oxazolidinones combined with vancomycin and rifampin against methicillin-resistant staphylococci. Spontaneous resistance was observed with all agents.

Topics: Acetamides; Anti-Bacterial Agents; Drug Resistance, Microbial; Drug Synergism; Fluoroquinolones; Humans; Linezolid; Microbial Sensitivity Tests; Naphthyridines; Oxazoles; Oxazolidinones; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis; Time Factors; Virginiamycin

The results of susceptibility testing of 48 phenotyped strains of glycopeptide antibiotic-resistant enterococci are reported. Minimum inhibitory and bactericidal concentrations (MICs and MBCs) were determined for 27 vanA, 17 vanB, and 4 vanC strains. Antibiotics exhibiting the greatest activity included novobiocin (MIC90 = 8 micrograms/ml and MBC90 = 32 micrograms/ml), ramoplanin (MIC90 = 2 micrograms/ml and MBC90 = 4 micrograms/ml), and the streptogramin RP59500 (MIC90 = 4 micrograms/ml and MBC90 = 32 micrograms/ml). These antibiotics warrant further investigation as potentially useful agents, either alone or in combination, for treating enterococcal infections.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Ciprofloxacin; Depsipeptides; Drug Resistance, Microbial; Enterococcus; Fluoroquinolones; Fusidic Acid; Microbial Sensitivity Tests; Minocycline; Naphthyridines; Novobiocin; Peptides, Cyclic; Quinolones; Teicoplanin; Vancomycin; Virginiamycin