sultamicillin and trovafloxacin

Acinetobacter baumannii is an opportunistic pathogen associated with numerous nosocomial infections. In recent years it has shown extraordinary ease in developing resistance to most antimicrobial agents, which is a serious problem as it makes these infections difficult to treat. We determined the in vitro activity of eight quinolones, five betalactam agents and colistin in 160 clinical isolates of A. baumannii. In general, we observed a high rate of resistance to the quinolones (90%), excluding clinafloxacin (25%), and to ampicillin-sulbactam (61.25%) and imipenem (50%). Colistin is the agent with least resistance (13.125%), although its toxicity limits its therapeutic use. Clinafloxacin may be a good option to treat A. baumannii infections, especially in cases of therapeutic failure with other antimicrobial agents.

Topics: Acinetobacter; Acinetobacter Infections; Ampicillin; Anti-Infective Agents; Aza Compounds; Cefepime; Cephalosporins; Ciprofloxacin; Colistin; Fluoroquinolones; Gatifloxacin; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Moxifloxacin; Nalidixic Acid; Naphthyridines; Norfloxacin; Ofloxacin; Opportunistic Infections; Quinolines; Sulbactam; Thienamycins

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

Antibiotic-resistant enterococci are being increasingly identified as causal agents of infection. Trovafloxacin is a new fluoronaphthyridone with enhanced activity against gram-positive cocci and variable activity reported against Enterococcus spp. Twenty-one strains of vancomycin-resistant Enterococcus faecium and two strains of Enterococcus faecalis (one vancomycin resistant) were studied at an initial inoculum of 10(6) CFU/ml in time-kill assays with trovafloxacin (3 mg/liter), ampicillin-sulbactam (100/50 mg/liter), and the combination. Six strains of E. faecium (five vancomycin resistant) also were studied in an in vitro two-compartment dynamic model that mimics human pharmacokinetics with trovafloxacin simulated at 300 mg every 12 h (q12h), ampicillin-sulbactam at 2/1 g q6h, and the combination. Peripheral compartments were sampled q2h for 30 h for bacterial counts. Trovafloxacin MICs ranged from 0.5 to 32 mg/liter, and the nine strains of vancomycin-resistant E. faecium for which MICs were < or =2 mg/liter were more likely to show a reduction of 2 log units or more in viable counts in time-kill assays than were strains for which MICs were higher. Synergism with ampicillin-sulbactam was found for only one strain (trovafloxacin MIC, 16 mg/liter). Similar results were obtained in the pharmacokinetic model, with 2- to 4-log-unit reductions in viable bacteria for trovafloxacin-susceptible strains. Although no convincing evidence of synergism was found, ampicillin-sulbactam in combination minimized late bacterial regrowth of two trovafloxacin-susceptible strains. These data suggest that this high dose of trovafloxacin (with or without ampicillin-sulbactam) might be useful against strains of vancomycin-resistant E. faecium for which MICs were < or =2 mg/liter.

Topics: Ampicillin; Anti-Infective Agents; Drug Resistance, Microbial; Drug Synergism; Drug Therapy, Combination; Enterococcus faecalis; Enterococcus faecium; Fluoroquinolones; Gram-Positive Bacterial Infections; Microbial Sensitivity Tests; Naphthyridines; Sulbactam

We studied the effect of pH (7.1, 6.3, and 5.8) on the in vitro susceptibilities of 59 isolates of Bacteroides fragilis and 60 isolates of other B. fragilis group species to trovafloxacin, ciprofloxacin, clindamycin, ampicillin-sulbactam, piperacillin-tazobactam, imipenem, and meropenem. For each agent tested the geometric mean MIC was highest at pH 5.8, intermediate at pH 6.3, and lowest at pH 7.1. The magnitude of the pH effect varied greatly among different antibiotics. These data show that an acidic pH decreases the in vitro susceptibilities of the B. fragilis group to several antibiotics.

Topics: Ampicillin; Anti-Bacterial Agents; Anti-Infective Agents; Bacteroides fragilis; Ciprofloxacin; Clindamycin; Drug Therapy, Combination; Fluoroquinolones; Hydrogen-Ion Concentration; Imipenem; Meropenem; Microbial Sensitivity Tests; Naphthyridines; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sulbactam; Thienamycins

The activities of trovafloxacin and ciprofloxacin against 38 strains of non-beta-lactamase-producing enterococci, resistant to ampicillin, 34 strains susceptible to ampicillin, and 3 vancomycin-resistant enterococci were studied. Trovafloxacin was more active than ciprofloxacin against all the enterococci studied. The ampicillin-resistant strains were more susceptible than the ampicillin-susceptible strains to both agents. The effect of combining trovafloxacin with gentamicin, ampicillin-sulbactam, novobiocin, rifampin, teicoplanin, and vancomycin was determined for 17 strains by the checkerboard method. An additive effect by inhibition was seen with all antibiotics studied. The results by killing varied with the different agents studied. Gentamicin, ampicillin-sulbactam, and novobiocin produced an additive killing effect with trovafloxacin. Reduced killing was seen when rifampin, vancomycin, or teicoplanin were added to trovafloxacin.

Topics: Ampicillin; Ampicillin Resistance; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antitubercular; Ciprofloxacin; Dose-Response Relationship, Drug; Drug Resistance, Microbial; Drug Synergism; Drug Therapy, Combination; Enterococcus; Enterococcus faecalis; Fluoroquinolones; Gentamicins; Humans; Microbial Sensitivity Tests; Naphthyridines; Novobiocin; Rifampin; Sulbactam; Teicoplanin; Vancomycin