rifampin 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

1. Interspecies allometry scaling for prediction of human excretory amounts in urine or feces was performed for numerous antibacterials. Antibacterials used for urinary scaling were: rifapentine, pefloxacin, trovafloxacin (Gr1/low; <10%); miloxacin, linezolid, PNU-142300 (Gr2/medium; 10-40%); aztreonam, carumonam, cefozopran, doripenem, imipenem, and ceftazidime (Gr3/high; >50%). Rifapentine, cabotegravir, and dolutegravir was used for fecal scaling (high; >50%). 2. The employment of allometry equation: Y = aW(b) enabled scaling of urine/fecal amounts from animal species. Corresponding predicted amounts were converted into % recovery by considering the respective human dose. Comparison of predicted/observed values enabled fold difference and error calculations (mean absolute error [MAE] and root mean square error [RMSE]). Comparisons were made for urinary/fecal data; and qualitative assessment was made amongst Gr1/Gr2/Gr3 for urine. 3. Average correlation coefficient for the allometry scaling was >0.995. Excretory amount predictions were largely within 0.75- to 1.5-fold differences. Average MAE and RMSE were within ±22% and 23%, respectively. Although robust predictions were achieved for higher urinary/fecal excretion (>50%), interspecies scaling was applicable for low/medium excretory drugs. 4. Based on the data, interspecies scaling of urine or fecal excretory amounts may be potentially used as a tool to understand the significance of either urinary or fecal routes of elimination in humans in early development.

Topics: Animals; Anti-Bacterial Agents; Aztreonam; Carbapenems; Cefozopran; Ceftazidime; Cephalosporins; Doripenem; Feces; Fluoroquinolones; Heterocyclic Compounds, 3-Ring; Humans; Imipenem; Linezolid; Naphthyridines; Oxazines; Oxolinic Acid; Pefloxacin; Piperazines; Pyridones; Retrospective Studies; Rifampin

Topics: Anti-Infective Agents; Arthritis, Infectious; Cefazolin; Cephalosporins; Drug Therapy, Combination; Fluoroquinolones; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Naphthyridines; Rifampin; Sacroiliac Joint; Staphylococcal Infections; Staphylococcus aureus; Sulfamethoxazole; Trimethoprim

The susceptibility of 140 Legionella spp isolates (106 clinical and 34 environmental isolates) to trovafloxacin (TRFX), levofloxacin (LEVX), moxifloxacin (MOFX), ciprofloxacin (CIPX), ofloxacin (OFLX), erythromycin (ERY), azithromycin (AZI) and rifampicin (RIF) was studied using a standard microdilution method and buffered yeast extract broth (BYE) supplemented with 0.1% alpha-ketoglutarate. The post-antibiotic effects (PAEs) of the study drugs against 10 clinical isolates of Legionella pneumophila sg.1 were compared. The MIC inhibiting 90% of strains tested on BYEalpha broth were 0.008, 0.016, 0.016, 0.06, 0.125, 0.5, 0.5, and 0.004 mg/l for TRFX, LEVX, MOXX, CIP, OFLX, ERY, AZI, and RIF, respectively. The MBC/MIC ratios ranged from one to eight depending on the antibiotic tested: TRFX [1x-2 x MIC], LEVX, MOFX, CIPX and OFLX [1x-4 x MIC], RIF [2x-4 x MIC], ERY and AZI [2x-8 x MIC]. TRFX, RIF, LEVX, MOFX, CIPX, OFLX, ERY and AZI showed similar activity against Legionella species other than L. pneumophila. One-hour exposures to the study antimicrobial agents at a concentration of 4 x MIC resulted in PAEs as follows (average in hours): TRFX: 2.68 h; RIF: 2.63 h; CIPX: 2.62 h; MOFX: 2.56 h; LEVX: 2.41 h; OFLX: 2.25 h; AZI: 1.65 h; and ERY: 1.54 h. In conclusion, our in vitro data confirm that trovafloxacin, levofloxacin, moxifloxacin and rifampicin have excellent bacteriostatic and bactericidal activity against Legionella spp and show significant post-antibiotic effect.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Aza Compounds; Fluoroquinolones; Humans; Legionella; Legionellosis; Levofloxacin; Microbial Sensitivity Tests; Moxifloxacin; Naphthyridines; Ofloxacin; Quinolines; Rifampin

This study evaluated whether certain antimicrobial agents used in the treatment of community-acquired respiratory infection were effective against the pathogen Neisseria meningitidis, whose natural habitat is the nasopharyngeal mucosa. Antimicrobial agents commonly use in primary healthcare (betalactams, cephalosporins and macrolides), quinolones and rifampicin were studied by determining minimal inhibitory and bactericidal concentrations, time-kill curves and postantibiotic effect. All of them showed bactericidal activity 24 h after incubation. We therefore believe that they are able to empirically eliminate the causative agent of meningococcal meningitis. However, the only antimicrobial agents capable of inducing a significant postantibiotic effect in the tested strain were the quinolones, which slowed down the growth of the microorganism for over 1 h.

Topics: Amoxicillin; Anti-Infective Agents; Ciprofloxacin; Clarithromycin; Community-Acquired Infections; Drug Resistance; Fluoroquinolones; Humans; Meningococcal Infections; Microbial Sensitivity Tests; Naphthyridines; Nasopharynx; Neisseria meningitidis; Respiratory Tract Infections; Rifampin; Time Factors

Pneumococci can enter and survive inside human lung alveolar carcinoma cells. We examined the activity of azithromycin, gentamicin, levofloxacin, moxifloxacin, penicillin G, rifampin, telithromycin, and trovafloxacin against pneumococci inside and outside cells. We found that moxifloxacin, trovafloxacin, and telithromycin were the most active, but only telithromycin killed all intracellular organisms.

Topics: Anti-Bacterial Agents; Aza Compounds; Azithromycin; Fluoroquinolones; Gentamicins; Humans; Ketolides; Levofloxacin; Macrolides; Microbial Sensitivity Tests; Moxifloxacin; Naphthyridines; Ofloxacin; Penicillin G; Quinolines; Rifampin; Streptococcus pneumoniae; Tumor Cells, Cultured

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

Sitafloxacin (DU-6859a) and trovafloxacin are novel quinolones potent on methicillin-resistant Staphylococcus aureus (MRSA) that are designed for once daily administration. In order to define the adequacy of the above regimen for the therapy of infections by multiple drug-resistant MRSA, their postantibiotic effect (PAE), their bactericidal activity, and their interactions with rifampin were determined on 14 MRSA isolates resistant to both ciprofloxacin and rifampin. PAE was defined after 1-h exposure to 1x, 4x, and 10x MIC and the killing effect after exposure to 1x and 4x MIC. Rifampin was applied for interactive studies at a concentration of 2 micrograms/mL, which is equal to its mean serum level. Median PAEs produced by 1x, 4x, and 10x MIC of sitafloxacin were 1.39, 3.75, and 6.61 h respectively, and by 1x, 4x, and 10x MIC of trovafloxacin 0.87, 2.07, and 2.23 h respectively. PAEs achieved by sitafloxacin were statistically shown to be longer than those achieved by trovafloxacin; PAEs achieved by a concentration of 10x MIC of each quinolone did not differ significantly from those achieved by a concentration of 4x MIC. Both the 4x and 10x MIC concentrations produced a more prolonged PAE than the 1x MIC concentration. A rapid bactericidal activity was expressed over the first 6 h of growth by each quinolone involving 80% of isolates enhanced in some isolates by their interaction with rifampin. The above findings revealed an extended PAE and a rapid killing effect of both sitafloxacin and trovafloxacin on MRSA resistant to ciprofloxacin and to rifampin, thus supporting their once daily administration in the therapy of infections by multiple drug-resistant MRSA. However little in vitro benefit is derived by their interaction with rifampin.

Topics: Anti-Infective Agents; Drug Interactions; Fluoroquinolones; Humans; Methicillin Resistance; Microbial Sensitivity Tests; Naphthyridines; Rifampin; Staphylococcus aureus

The killing activities of trovafloxacin alone and in combination with beta-lactam agents (extended-spectrum cephalosporins, meropenem), rifampin, or vancomycin were evaluated against 20 genotypically characterized Streptococcus pneumoniae isolates for which amoxicillin MICs were >/=4 microg/ml (cefotaxime MICs, >/=4 microg/ml for six strains) at concentrations clinically achievable in cerebrospinal fluid. At 6 h the mean killing activity of trovafloxacin alone (range, 2.6 to 2.9 log(10) CFU/ml) did not vary significantly according to the susceptibility of the strains to beta-lactam agents. The activities of trovafloxacin or vancomycin added to the beta-lactam agents and the combination trovafloxacin-vancomycin were additive or indifferent. Against the ceftriaxone-resistant isolates, the killing activity of the combination of a beta-lactam agent and trovafloxacin did not differ significantly from that of a beta-lactam agent and vancomycin.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antitubercular; Cephalosporin Resistance; Cephalosporins; Drug Interactions; Fluoroquinolones; Humans; Microbial Sensitivity Tests; Naphthyridines; Rifampin; Streptococcus pneumoniae; Vancomycin

The in vitro bactericidal interaction of trovafloxacin and rifampin against Enterococcus spp. has indicated that antagonism occurs between these two antimicrobial agents. This drug combination was examined in vivo in rats with experimental pyelonephritis. The rats received trovafloxacin, rifampin, or both drugs. On the basis of the mean log10 CFU of Enterococcus faecalis from the kidneys, there was no evidence that trovafloxacin and rifampin were antagonistic in vivo.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Drug Interactions; Drug Therapy, Combination; Enterococcus faecalis; Female; Fluoroquinolones; Gram-Positive Bacterial Infections; Naphthyridines; Pyelonephritis; Rats; Rats, Sprague-Dawley; Rifampin

The fluoroquinolone trovafloxacin was bactericidal (0.47 +/- 0.23 delta log10 CFU/ml x h after 10 mg/kg of body weight and 0.78 +/- 0.15 delta log10 CFU/ml x h after 30 mg/kg) in the treatment of experimental meningitis caused by a highly penicillin-resistant (MIC and minimum bactericidal concentration = 4 and 4 microg/ml) strain of Streptococcus pneumoniae. Combinations with ampicillin and rifampin were indifferent compared to single drugs.

Topics: Ampicillin; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Ceftriaxone; Fluoroquinolones; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Naphthyridines; Penicillin Resistance; Rabbits; Rifampin; Streptococcus pneumoniae

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