In vitro activities of garenoxacin (BMS-284756) against 170 clinical isolates of nine Pasteurella species

The in vitro susceptibilities of 170 clinical isolates plus 12 American Type Culture Collection strains of Pasteurella species comprising nine species and three Pasteurella multocida subspecies were studied by an agar dilution method. Garenoxacin (BMS-284756), a new des-fluoro(6) quinolone, was active at 90% of the strains susceptible to 相似文献   

In vitro susceptibilities to and bactericidal activities of garenoxacin (BMS-284756) and other antimicrobial agents against human mycoplasmas and ureaplasmas

The in vitro susceptibilities to garenoxacin (BMS-284756), an investigational des-fluoroquinolone, and eight other agents were determined for 63 Mycoplasma pneumoniae, 45 Mycoplasma hominis, 15 Mycoplasma fermentans, and 68 Ureaplasma sp. isolates. Garenoxacin was the most active quinolone, inhibiting all isolates at 相似文献   

Activities of garenoxacin (BMS-284756) and other agents against anaerobic clinical isolates

A total of 590 clinical isolates consisting of 33 species of both gram-positive and gram-negative anaerobes were collected from nine centers in the Chicago area in 1998-1999. The largest number of isolates (330 isolates, 56%) belonged to the Bacteroides group. Isolates were tested by agar dilution against garenoxacin (BMS-284756, T-3811 ME), trovafloxacin, moxifloxacin, clindamycin, imipenem, piperacillin-tazobactam, and cefoxitin. All but one species (2% of Bacteroides vulgatus isolates) were fully susceptible to piperacillin-tazobactam and imipenem. A number of species were resistant to clindamycin. Among the fluoroquinolones, garenoxacin and trovafloxacin had an MIC at which 90% of the isolates tested were inhibited of <4 micro g/ml for all but two species (Fusobacterium mortiferum/varium and Peptostreptococcus anaerobius).     

Postantibiotic effects of garenoxacin (BMS-284756) against 12 gram-positive or -negative organisms

Conventional in vitro methods were used to determine the postantibiotic effects (PAEs), sub-MIC effects (SMEs), and postantibiotic sub-MIC effects (PA-SMEs) of garenoxacin for a range of organisms. The mean PAEs of garenoxacin for pneumococci, staphylococci, and enterococci were 0.3 to 2.2 h. For Escherichia coli and Pseudomonas aeruginosa, the PAEs were 0.9 to 1.6 h. The mean PA-SMEs (0.4 times the MIC) for pneumococci, staphylococci, and enterococci were 3.0 to >10 h, 1.8 to >10.7 h, and 5.8 h, respectively, while those for E. coli and P. aeruginosa were 7.6 and 4.4 h, respectively.     

In vitro activities of garenoxacin (BMS-284756) against Streptococcus pneumoniae, viridans group streptococci, and Enterococcus faecalis compared to those of six other quinolones

The activity of garenoxacin, a new quinolone, was determined in comparison with other quinolones against different strains of S. pneumoniae, viridans group streptococci (VGS), and Enterococcus faecalis. Strains were quinolone-susceptible clinical isolates and quinolone-resistant strains with defined mechanisms of resistance obtained from either clinical isolates or derivatives of S. pneumoniae R6. Clinical quinolone-susceptible strains of S. pneumoniae, VGS and E. faecalis showed garenoxacin MICs within a range of 0.03 microg/ml to 0.25 micro g/ml. Garenoxacin MICs increased two- to eightfold when one mutation was present in the ParC quinolone resistance-determining region (QRDR), fourfold when one mutation was present in the GyrA QRDR (S. pneumoniae), 8- to 64-fold when two or three mutations were associated in ParC and GyrA QRDR, and 2,048-fold when two mutations were present in both the GyrA and ParC QRDRs (Streptococcus pneumoniae). Increased active efflux had a moderate effect on garenoxacin MICs for S. pneumoniae and VGS. Against S. pneumoniae, garenoxacin behaved like moxifloxacin and sparfloxacin, being more affected by a single gyrA mutation than by a single parC mutation. Although garenoxacin was generally two- to fourfold more active than moxifloxacin against the different wild-type or mutant strains of S. pneumoniae, VGS, and E. faecalis, it was two- to fourfold less active than gemifloxacin. At four times the respective MIC for each strain, the bactericidal effect of garenoxacin, observed at 6 h for S. pneumoniae and at 24 h for S. oralis and E. faecalis, was not influenced by the presence of mutation either in the ParC or in both the ParC and GyrA QRDRs.     

In vitro activities of Garenoxacin (BMS 284756) against 108 clinical isolates of Gardnerella vaginalis

Garenoxacin (BMS 284756) was active against 105 of 108 (97%) recent clinical Gardnerella vaginalis isolates at < or =2 micro g/ml by using the reference agar dilution method for anaerobes. Twenty-eight percent of isolates (31 of 108) were resistant to metronidazole, and 44% were resistant to doxycycline. All were susceptible to clindamycin and ampicillin-sulbactam.     

In vitro activities of cefotaxime and moxalactam (LY127935) against Haemophilus influenzae

The in vitro activities of two new beta-lactam antibiotics, cefotaxime and moxalactam (LY127935), were compared with those of cefamandole, cefoxitin, cefuroxime, and ampicillin against both beta-lactamase-producing and non-beta-lactamase-producing isolates of Haemophilus influenzae. Both cefotaxime and LY127935 were highly active against all isolates irrespective of beta-lactamase production.     

In vitro activities of piperacillin against beta-lactamase-negative ampicillin-resistant Haemophilus influenzae

The in vitro activities of piperacillin (PIP) against beta-lactamase-negative ampicillin (AMP)-resistant (BLNAR) Haemophilus influenzae were compared with those of cefotaxime (CTX) and ceftriaxone (CRO), and the potency of PIP as therapy for meningitis caused by BLNAR is also discussed. PIP showed good activity (MIC at which 90% of strains are inhibited, 0.25 micro g/ml) against 69 BLNAR strains, and its activity was comparable to that of CRO and superior to that of CTX. No significant correlation was observed between the MICs of PIP and CTX or CRO or AMP, whereas a high correlation was observed between the MICs of CTX and CRO. In the killing study, PIP showed potent bactericidal activity compared with those of CTX and CRO. By microscopic examination, PIP caused the formation of a spindle and short filamentous cells with bulges and induced cell lysis in BLNAR strains, while treatment with CTX and CRO resulted in the formation of large, spherical cells without any obvious lysis. The affinity of Bocillin FL, a fluorescent penicillin used for determination of the 50% inhibitory concentration (IC(50)s) for penicillin-binding proteins (PBPs), to PBPs 3a and 3b of BLNAR strains was drastically decreased compared with that to an AMP-susceptible strain (ATCC 33391). In the case of the BLNAR strains, the IC(50)s for PBPs 1a, 1b, and 2 were similar to those for the PBPs of ATCC 33391. Since the affinity of binding to PBPs 3a and 3b of the BLNAR strains decreased drastically, the second targets among the PBPs were PBP 2 for PIP, PBP1 (1a and 1b) for CTX and CRO. In conclusion, PIP showed excellent activities against BLNAR strains in a manner different from those of cephem antibiotics, suggesting that it could be a candidate therapeutic agent for the treatment of meningitis caused by BLNAR strains.     

In vitro susceptibility study of BMS-284756 against Legionella species.

Legionella organisms are often associated with respiratory infections, and Legionella pneumonia results in significant mortality unless it is promptly and effectively treated. The present study was undertaken to compare the in vitro activity of BMS-284756 (T-3811ME), a novel des-F(6)-quinolone, against Legionella species versus the activity of other fluoroquinolones (levofloxacin, moxifloxacin, and ciprofloxacin) and of the macrolides erythromycin, clarithromycin, and azithromycin. The most potent agents tested against Legionella pneumophila serogroup 1, the largest group tested, were BMS-284756, moxifloxacin, and levofloxacin (MIC(90) = 0.016 mg/L). The MIC(90) range for BMS-284756 was 0.008-0.03 mg/L against the total panel of L pneumophila serogroups 1-9 and 12, with the lowest MIC(90) observed for serogroup 7 and the highest for serogroup 2. BMS-284756 was one of the most potent agents tested against isolates of L micdadei, L longbeachae, and other Legionella species (MIC(90) range: 0.008-0.06 mg/L). These results and the high intrinsic activity of BMS-284756 against other respiratory pathogens support its use as empiric monotherapy for a wide range of respiratory infections.     

In vitro activities of ravuconazole (BMS-207147) against 541 clinical isolates of Cryptococcus neoformans

The in vitro activities of the new triazole, ravuconazole (BMS-207147), were compared to those of fluconazole and itraconazole against 541 clinical isolates of Cryptococcus neoformans. Isolates were obtained from cerebrospinal fluid (396), blood (116), and miscellaneous clinical specimens (29). Overall, ravuconazole (MIC at which 90% of the isolates are inhibited [MIC(90)], 0.25 microg/ml) was more active than either itraconazole (MIC(90), 0.5 microg/ml) or fluconazole (MIC(90), 8 microg/ml). Among the isolates inhibited by > or =16 microg of fluconazole/ml, 90.2% were inhibited by < or =1 microg of ravuconazole/ml. On the basis of our findings and the favorable pharmacokinetic properties of ravuconazole, we suggest that ravuconazole may be useful for the treatment of infectious diseases due to C. neoformans and that further clinical studies to confirm these promising in vitro results are warranted.     

Bactericidal activity of garenoxacin against in vitro biofilm formed by nontypeable Haemophilus influenzae

Using β-lactamase-negative ampicillin (ABPC)-susceptible (BLNAS) and β-lactamase-negative ABPC-resistant (BLNAR) nontypeable Haemophilus influenzae (NTHi) strains isolated from otological patients, colony biofilm was prepared on membrane filter substrates. Bactericidal activities of garenoxacin (GRNX), levofloxacin (LVFX), cefditoren (CDTR), and clavulanic acid/amoxicillin (CVA/AMPC) were examined by counting viable cells after drug exposure to biofilm cells for 6 and 24 h and by observation under a scanning electron microscope (SEM). After exposure of biofilm to the 100-fold MIC of GRNX or LVFX for 24 h, GRNX and LVFX showed potent bactericidal activity (?log₁₀ CFU/ml, ≥5.1). In this case, the drug-exposure AUC, exposure concentration × 24 μg h/ml, was 64–128 % for GRNX and 121 % for LVFX of free AUC at the clinical dosage in humans, respectively. CDTR and CVA/AMPC at 100-fold MIC exhibited little bactericidal activity against biofilm cells. Under an SEM, after exposure of BLNAS and BLNAR biofilms to GRNX or LVFX, most of the biofilm matrices were transformed. Quinolones such as GRNX show potent bactericidal activity against biofilm-forming NTHi at the usual clinical dosage.     

Antimicrobial activities of garenoxacin (BMS 284756) against Asia-Pacific region clinical isolates from the SENTRY program, 1999 to 2001

Between 1999 and 2001, 16,731 isolates from the Asia-Pacific Region were tested in the SENTRY Program for susceptibility to six fluoroquinolones including garenoxacin. Garenoxacin was four- to eightfold less active against Enterobacteriaceae than ciprofloxacin, although both drugs inhibited similar percentages at 1 microg/ml. Garenoxacin was more active against gram-positive species than all other fluoroquinolones except gemifloxacin. For Staphylococcus aureus, oxacillin resistance was high in many participating countries (Japan, 67%; Taiwan, 60%; Hong Kong, 55%; Singapore, 52%), with corresponding high levels of ciprofloxacin resistance (57 to 99%) in oxacillin-resistant S. aureus (ORSA). Of the ciprofloxacin-resistant ORSA isolates, the garenoxacin MIC was >4 microg/ml for only 9% of them. For Streptococcus pneumoniae, penicillin nonsusceptibility and macrolide resistance were high in many countries. No relationship was seen between penicillin and garenoxacin susceptibility, with all isolates being susceptible at <2 microg/ml. There was, however, a partial correlation between ciprofloxacin and garenoxacin MICs. For ciprofloxacin-resistant isolates for which garenoxacin MICs were 0.25 to 1 microg/liter, mutations in both the ParC and GyrA regions of the quinolone resistance-determining region could be demonstrated. No mutations conferring high-level resistance were detected. Garenoxacin shows useful activity against a wide range of organisms from the Asia-Pacific region. In particular, it has good activity against S. aureus and S. pneumoniae, although there is evidence that low-level resistance is present in those organisms with ciprofloxacin resistance.     

In vitro activity of rosoxacin against Haemophilus influenzae

The in vitro activity of rosoxacin was compared to that of ampicillin, cefoxitin, chloramphenicol, and rifampin, against 94 clinical isolates of Haemophilus influenzae. The results indicated that rosoxacin had significantly better in vitro activity against H. influenzae than the other antibiotics evaluated in this study. In addition, rosoxacin was an effective antimicrobial agent against isolates of H. influenzae that were resistant to ampicillin due to beta-lactamase production.     

In vitro and in vivo efficacies of T-3811ME (BMS-284756) against Mycoplasma pneumoniae

T-3811, the free base of T-3811ME (BMS-284756), a new des-F(6)-quinolone, showed a potent in vitro activity (MIC at which 90% of the isolates tested are inhibited [MIC(90)], 0.0313 microg/ml) against Mycoplasma pneumoniae. The MIC(90) of T-3811 was 4-fold higher than that of clarithromycin but was 4- to 8-fold lower than those of trovafloxacin, gatifloxacin, gemifloxacin, and moxifloxacin and was 16- to 32-fold lower than those of levofloxacin, ciprofloxacin, and minocycline. In an experimental M. pneumoniae pneumonia model in hamsters, after the administration of T-3811ME (20 mg/kg of body weight as T-3811, once daily, orally) for 5 days, the reduction of viable cells of M. pneumoniae in bronchoalveolar lavage fluid was greater than those of trovafloxacin, levofloxacin, and clarithromycin (20 and 40 mg/kg, orally) (P < 0.05).     

In vitro activities and targets of three cephem antibiotics against Haemophilus influenzae.

The antimicrobial activities of cefixime, cefpodoxime, and ceftibuten were determined with 18 ampicillin-susceptible (Amps), 13 ampicillin-resistant beta-lactamase-producing (AmprBLP), and 7 ampicillin-resistant non-beta-lactamase-producing (AmprNBLP) strains of Haemophilus influenzae. An effect of inoculum density on apparent MIC, the bactericidal activity of these agents, and the targets of the three cephems were determined. The MICs of cefixime, cefpodoxime, and ceftibuten for 90% of the Amps and AmprBLP isolates were 0.04, 0.08, and 0.08 microgram/ml, respectively. In contrast, the MICs for 90% of the AmprNBLP strains were 0.96, 1.92, and 7.68 micrograms/ml. No significant inoculum effect was observed for any group of strains comparing inocula of 10(3) and 10(5) CFU, whereas only the AmprNBLP isolates showed a marked effect at an inoculum of 10(6) CFU. Although bactericidal levels were achieved for the Amps and AmprBLP strains, tolerance to cefixime and ceftibuten was observed. The bactericidal activity for the AmprNBLP strains was limited, with cefixime showing the highest activity of the three cephems. Penicillin-binding proteins 2, 4, and 5 revealed high affinity, with 50% inhibitory concentration levels below the MIC for all three cephems, suggesting that these are important targets of these agents in H. influenzae. We conclude that the cephems are highly active in vitro against Amps and AmprBLP strains of H. influenzae, but less so against AmprNBLP isolates.     

Antimicrobial activity of a novel des-fluoro (6) quinolone,garenoxacin (BMS-284756), compared to other quinolones,against clinical isolates from cancer patients

The in vitro spectrum of a novel des-fluoro (6) quinolone, garenoxacin (BMS-284756), was compared with that of ciprofloxacin, levofloxacin, and trovafloxacin against 736 clinical isolates from cancer patients. Garenoxacin was the most active agent overall against Gram-positive organisms, with potent activity against Aerococcus spp., Micrococcus spp., Rhodococcus equi, Stomatococcus mucilaginous, Bacillus spp., Enterococcus faecalis, Listeria monocytogenes, methicillin-susceptible Staphylococcus spp., and all beta-hemolytic and viridans streptococci. Although ciprofloxacin was the most active agent tested against the Enterobacteriaceae garenoxacin inhibited the majority of these isolates at 相似文献