This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fung-Tomc, J. C. Articles by Bonner, D. P. Search for Related Content PubMed PubMed Citation Articles by Fung-Tomc, J. C. Articles by Bonner, D. P.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, December 2000, p. 3351-3356, Vol. 44, No. 12
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Antibacterial Spectrum of a Novel Des-Fluoro(6) Quinolone, BMS-284756

Department of Microbiology, Bristol-Myers Squibb Company, Wallingford, Connecticut 06492

Received 23 June 2000/Returned for modification 3 August 2000/Accepted 21 September 2000

	ABSTRACT

Top Abstract Introduction Materials and Methods Results and Discussion References

The in vitro spectrum of a novel des-fluoro(6) quinolone, BMS-284756, was compared with those of five fluoroquinolones (trovafloxacin, moxifloxacin, levofloxacin, ofloxacin, and ciprofloxacin). BMS-284756 was among the most active and often was the most active quinolone against staphylococci (including methicillin-resistant strains), streptococci, pneumococci (including ciprofloxacin-nonsusceptible and penicillin-resistant strains), and Enterococcus faecalis. BMS-284756 inhibited 60 to 70% of the Enterococcus faecium (including vancomycin-resistant) strains and 90 to 100% of the Enterobacteriaceae strains and gastroenteric bacillary pathogens at the anticipated MIC susceptible breakpoint (4 µg/ml). Against the nonfermenters, BMS-284756 inhibited 90 to 100% of Pseudomonas fluorescens, Pseudomonas stutzeri, Stenotrophomonas maltophilia, Flavobacterium spp., and Acinetobacter spp. and 72% of Pseudomonas aeruginosa strains at 4 µg/ml. Against anaerobic bacteria, BMS-284756 was among the most active, inhibiting essentially all strains tested. It had very low MICs against the fastidious and atypical microbial species, in particular against mycoplasmas or ureaplasmas, Borrelia burgdorferi, chlamydia, and gonococci. These results indicate that with its broad antibacterial spectrum, BMS-284756 should be evaluated clinically for the treatment of community and nosocomial infections.

	INTRODUCTION

Top Abstract Introduction Materials and Methods Results and Discussion References

BMS-284756 is a novel des-fluoro(6) quinolone. This means that BMS-284756 differs from recently approved quinolones (i.e., the fluoroquinolones included in this study and gatifloxacin) in that BMS-284756 lacks a fluorine at the C-6 position. BMS-284756 (also known as T-3811ME) has antibacterial activity similar to those of fluorinated quinolones, but the des-F(6) derivatives are less acutely toxic in mice (K. Hayashi, Y. Todo, S. Hamamoto, K. Ojima, M. Yamada, T. Kito, M. Takahata, Y. Watanbe, and H. Narita, Abstr. 37th Intersci. Conf. Antimicrob. Agents Chemother., abstr. F-158, 1997).

Quinolones can differ in their antibacterial spectra and potencies. Notable potency differences among quinolones occur in their activities versus gram-positive bacteria, pseudomonads, anaerobic bacteria, and mycobacteria. In the present study, the antibacterial spectrum of BMS-284756 is compared to those of five fluoroquinolones against 1,150 strains representing 66 bacterial species. While the antibacterial activity of BMS-284756 was reported previously by Takahata et al. (9), the present study included additional bacterial species and was performed using NCCLS-recommended susceptibility test methods, whenever they were available for specific bacterial groups.

	MATERIALS AND METHODS

Top Abstract Introduction Materials and Methods Results and Discussion References

Antimicrobial agents. BMS-284756 was obtained from Toyama Chemical Co. Ltd., Toyama, Japan, and moxifloxacin (MFX) and ciprofloxacin (CIP) were obtained from Bayer Corporation, West Haven, Conn. Levofloxacin (LVX) and trovafloxacin (TVA) were extracted and purified from commercially available tablets and were determined to be 95% pure by high-performance liquid chromatography. Ofloxacin (OFX) was purchased from Sigma Chemical Co., St. Louis, Mo.

Bacterial strains. All bacterial strains used in this study were clinical isolates obtained from numerous sources of broad geographical distribution. Isolates were maintained frozen in liquid nitrogen. Some of the quinolone-resistant Neisseria gonorrhoeae strains were provided by Ronald Jones (University of Iowa, Iowa City).

Methicillin-susceptible (MS) Staphylococcus aureus was defined as strains for which oxacillin MICs were 2 µg/ml, and MS strains of Staphylococcus epidermidis and Staphylococcus haemolyticus were defined as strains for which oxacillin MICs were 0.25 µg/ml (4). Methicillin-resistant (MR) S. aureus strains were strains for which oxacillin MICs were 4 µg/ml, and MR S. epidermidis and S. haemolyticus strains were strains for which oxacillin MICs were 0.5 µg/ml. Because the oxacillin MIC interpretative breakpoint does not correlate with mecA carriage in Staphylococcus saprophyticus (2), MS and MR categorization in this species was based on mecA detection by PCR testing. All of the S. saprophyticus strains in this study were mecA negative.

Growth inhibitory activity. Determinations of the MICs for aerobic and anaerobic bacteria were performed by an agar dilution method in accordance with the procedure outlined by the NCCLS (4, 5). Other testing protocols used in this study were similar to those previously reported (1), with the following exceptions. Anaerobic bacterial susceptibility testing was done using brucella blood agar (5), Chlamydia pneumoniae with Hep-2 cells, and Borrelia burgdorferi with BSK H medium (Sigma).

The respective interpretative MIC breakpoints for strains susceptible, intermediate, and resistant to the quinolones are as follows: for TVA, 2, 4, and 8 µg/ml for general organisms (FDA-approved breakpoints), but 1, 2, and 4 µg/ml for Streptococcus pneumoniae and other streptococci (NCCLS-approved breakpoints), and 0.25 µg/ml for gonococci (susceptible breakpoint only); for MFX 2, 4, and 8 µg/ml for general organisms (FDA-approved breakpoints), but 1, 2, and 4 µg/ml for Streptococcus pneumoniae, with no interpretative MFX breakpoints for gonococci; for LVX and OFX, 2, 4, and 8 µg/ml for all organism groups (NCCLS-approved breakpoints), but for OFX only, 0.25, 0.5 to 1, and 2 µg/ml for gonococci; and for CIP, 1, 2, and 4 µg/ml for general organisms (NCCLS approved), with no interpretative criteria for Streptococcus pneumoniae and other streptococci, and 0.06, 0.12 to 0.5, and 1 µg/ml for gonococci (2).

The respective susceptible, intermediate, and resistant breakpoints used in the BMS-284756 clinical trials for this quinolone are 4, 8, and 16 µg/ml for the general organisms, 2, 4, and 8 µg/ml for MR S. aureus, and 2 (susceptible breakpoint only) for gonococci. The proposed 4-µg/ml susceptible breakpoint for BMS-284756 was based on a mean area under the curve (AUC) from 0 to infinity of 84.1 µg · h/ml following a single 400-mg oral dose of BMS-284756 (D. Gajjar, D. Grasela, A. Bello, Z. Ge, L. Christopher, Abstr. 40th Intersci. Conf. Antimicrob. Agents Chemother., abstr 2259, 2000); this breakpoint is compared to the susceptible breakpoints of quinolones (TVA, MFX, LVX, and OFX) of 2 µg/ml and AUCs of 30 to 50 µg · h/ml (3a) following a single standard dose. For quinolones, the pharmacodynamic parameter most predictive of efficacy is the AUC/MIC ratio (6, 8). In this paper, 4 µg/ml was used as a point of reference in discussing the BMS-284756 MIC data.

	RESULTS AND DISCUSSION

Top Abstract Introduction Materials and Methods Results and Discussion References

All of the results discussed in this section are listed in Table 1.

View this table: [in this window] [in a new window]   TABLE 1.   In vitro antibacterial activities of BMS-284756 and five comparative quinolones

Gram-positive aerobic bacteria. BMS-284756 was the most active quinolone against MS and MR staphylococci. BMS-284756 was generally 2-fold more active than TVA and MFX and 8- to 32-fold more active than LVX, OFX, and CIP. The quinolones inhibited MS staphylococci uniformly, with MICs at which 50% of the isolated were inhibited (MIC₅₀s) and MIC₉₀s generally being equal. By comparison, the quinolone MIC ranges were broader for MR staphylococci, with MIC₅₀s and MIC₉₀s differing by 32- to 64-fold. The fact that quinolone resistance is more commonly encountered among MR than MS staphylococcal clinical isolates accounts for the higher quinolone MIC₉₀s for MR strains (3, 7). In fact, for 40 to 50% of MR strains tested, CIP MICs were 2 µg/ml, compared with 0% of MS strains. For all the MR S. aureus strains, BMS-284756 MICs were 2 µg/ml.

The quinolones can be grouped by their streptococcal and pneumococcal potencies. BMS-284756, TVA, and MFX were about 10-fold more active than LVX, OFX, and CIP against these organisms. Along with BMS-284756 (MIC₉₀s = 0.12 to 0.25 µg/ml), LVX, TVA, and MFX covered all the streptococci and pneumococci at their susceptible breakpoints, but only BMS-284756 covered all Streptococcus pneumoniae strains with CIP MICs of 2 µg/ml (85% of which had OFX MICs of 4 µg/ml), and for 90% of the latter isolates BMS-284756 MICs were 0.5 µg/ml. As with streptococci, the enterococci were more susceptible to BMS-284756, TVA, and MFX than to LVX, OFX, and CIP. The quinolones were more active against Enterococcus faecalis than to Enterococcus faecium, the latter being more frequently resistant to quinolones. While BMS-284756, TVA, MFX, and LVX covered 90% or more of the E. faecalis and VanC enterococcal species (i.e., Enterococcus gallinarum and Enterococcus casseliflavus), only BMS-284756 covered >50% of E. faecium and VanA and VanB strains (comprised primarily of E. faecium) at 4 µg/ml.

Gram-negative aerobic bacteria. The quinolones have good activities against Enterobacteriaceae. Overall, CIP was the most active against Enterobacteriaceae, except Providencia spp. BMS-284756 was less active against the Enterobacteriaceae, but for almost all of the Enterobacteriaceae strains, BMS-284756 MICs were 4 µg/ml, levels that are achievable in plasma for this quinolone.

For bacterial species associated with gastroenteritis (Salmonella spp., Shigella spp., Yersinia enterocolitica, Aeromonas hydrophila, Vibrio cholerae, and Campylobacter jejuni), all the quinolones showed potent and generally similar activities.

Nonfermentative bacteria. Pseudomonal susceptibility to the quinolones is species dependent. Against Pseudomonas aeruginosa, CIP remained the most active. Approximately 90% of the P. aeruginosa strains were susceptible to CIP, TVA, and LVX, 72% were susceptible to OFX and BMS-284756 (at 4 µg/ml), and 28% were susceptible to MFX. All Pseudomonas stutzeri strains were susceptible to the six quinolones tested. All of the Pseudomonas fluorescens strains were susceptible to LVX, compared to the 87 to 93% of strains that were susceptible to CIP, TVA MFX, and BMS-284756 (at 4 µg/ml) and 67% that were susceptible to OFX.

In contrast, CIP was among the least active quinolones against the pseudomonas-related species, being inactive against Burkholderia cepacia, Stenotrophomonas maltophilia, and other nonfermenters (Flavobacterium and Acinetobacter spp.). While BMS-284756 MIC₉₀s for Stenotrophomonas maltophilia, Flavobacterium spp., and Acinetobacter spp. were 4 µg/ml, Burkholderia cepacia and Alcaligenes spp. were generally resistant.

Anaerobic bacteria. The broadest antianaerobic bacterial spectra were observed with BMS-284756, TVA, and MFX. BMS-284756 was very active against anaerobic bacteria, inhibiting all but one peptostreptococcal strain at 4 µg/ml.

Fastidious bacterial species. BMS-284756's exceptional antigonococcal activity extended to all CIP-nonsusceptible strains. Though the quinolones inhibited all CIP-susceptible N. gonorrhoeae strains, the BMS-284756 MIC₉₀ for CIP-nonsusceptible isolates was 0.25 µg/ml. While TVA was 10-fold more active than BMS-284756 against CIP-susceptible gonococci, the BMS-284756 MIC₉₀ for CIP-nonsusceptible strains was 2-fold better than that of TVA.

The quinolones were very active (MIC₉₀s, 0.1 µg/ml) against Neisseria meningitidis, Haemophilus influenzae, Moraxella catarrhalis, and Legionella spp., with good activities (MIC₉₀s, 0.5 µg/ml) also against Bordetella spp. and Helicobacter pylori. Included in the quinolones' spectra were all strains of Gardnerella vaginalis (except CIP), Mycoplasma pneumoniae (except CIP), and Bartonella spp. (except CIP and OFX). Only BMS-284756 and TVA inhibited all B. burgdorferi strains, with BMS-284756 MICs being 16-fold better than those of MFX, LVX, OFX, and CIP against the Lyme disease spirochete. BMS-284756, TVA, and MFX inhibited all Mycoplasma hominis and Ureaplasma urealyticum strains tested, with MIC₉₀s 10- to 100-fold better than those of LVX, OFX, and CIP against M. hominis and up to 30-fold better against U. urealyticum. This des-F(6) quinolone was the most active against chlamydia, with all strains being inhibited at 0.016 µg/ml; BMS-284756 was 100- to 1,000-fold more active than OFX and CIP, 50-fold more potent than LVX, and 10- to 50-fold better than MFX against chlamydia.

Of the quinolones tested, MFX was the most active against mycobacteria and CIP was the least active. BMS-284756 was comparable to OFX (MIC₉₀, 2 µg/ml) against Mycobacterium tuberculosis. BMS-284756 was previously reported to have good antitubercular activity, with a MIC₉₀ of 0.06 µg/ml (9). In the present study, the MIC₉₀ of BMS-284756 against M. tuberculosis was 2 µg/ml. The difference in these MIC₉₀ results against M. tuberculosis is likely due to susceptibility test differences. A broth macrodilution method was used in this study, whereas Takahata et al. (9) used a broth microdilution assay. Nevertheless, both studies concluded that the antitubercular activities of BMS-284756 and OFX are comparable. A recent study (E. J. Alvirez-Froitex and M. H. Cynamon, 9th Int. Congr. Infect. Dis., Abstr. 75.015, 2000), testing seven M. tuberculosis strains by a broth macrodilution test, yielded modal MICs of 1 µg/ml for BMS-284756 versus 0.5 and 0.06 µg/ml for LVX and MFX, respectively.

In summary, BMS-284756 is among the most active quinolones tested against gram-positive bacteria, particularly against MR S. aureus, S. epidermidis, and CIP-resistant S. pneumoniae. BMS-284756 had the broadest antianaerobic bacterial coverage, inhibiting almost all of the anaerobic bacterial strains tested. BMS-284756 was the most active quinolone against fastidious microbes (mycoplasmas, ureaplasmas, chlamydiae, CIP-nonsusceptible gonococci, and B. burgdorferi). It is active against the Enterobacteriaceae and most nonfermenters. The wide antibacterial spectrum of BMS-284756 supports its development for a broad range of indications.

	FOOTNOTES

^* Corresponding author. Mailing address: Bristol-Myers Squibb Company, Department of Microbiology-104, 5 Research Pkwy., Wallingford, CT 06492. Phone: (203) 677-6370. Fax: (203) 677-6771. E-mail: fungtomj{at}bms.com.

	REFERENCES

Top Abstract Introduction Materials and Methods Results and Discussion References

1.	Fung-Tomc, J., B. Minassian, B. Kolek, T. Washo, E. Huczko, and D. Bonner. 2000. In vitro antibacterial spectrum of a new broad-spectrum 8-methoxy fluoroquinolone, gatifloxacin. J. Antimicrob. Chemother. 45:437-446[Abstract/Free Full Text].
2.	Hussain, Z., B. Stoakes, V. Massey, D. Diagre, V. Fitzgerald, S. El Sayed, and R. Lannigan. 2000. Correlation of oxacillin MIC with mecA gene carriage in coagulase-negative staphylococci. J. Clin. Microbiol. 38:752-754[Abstract/Free Full Text].
3.	Issacs, R. D., P. J. Kunke, R. L. Cohen, and J. W. Smith. 1988. Ciprofloxacin resistance in epidemic methicillin-resistant Staphylococcus aureus. Lancet ii:843.
3a.	Medical Economics Co., Inc. 1996. Physicians' desk reference, 50th ed. Medical Economics Co., Inc., Montdale, N.J.
4.	National Committee for Clinical Laboratory Standards. 2000. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Document M7-A5. National Committee for Clinical Laboratory Standards, Wayne, Pa.
5.	National Committee for Clinical Laboratory Standards. 1997. Methods for antimicrobial susceptibility testing of anaerobic bacteria. Document M11-A4. National Committee for Clinical Laboratory Standards, Wayne, Pa.
6.	Preston, S. L., G. L. Drusano, A. L. Berman, C. L. Fowler, A. T. Chow, B. Dornseif, V. Reichi, J. Natarajan, and M. Corrado. 1998. Pharmacodynamics of levofloxacin, a new paradigm for early clinical trials. JAMA 279:125-129[Abstract/Free Full Text].
7.	Raviglione, M. C., J. F. Boyle, P. Mariuz, A. Pablos-Mendez, and A. Merlo. 1990. Ciprofloxacin-resistant methicillin-resistant Staphylococcus aureus in an acute-care hospital. Antimicrob. Agents Chemother. 34:2050-2054[Abstract/Free Full Text].
8.	Schentag, J. J., D. E. Nix, and M. H. Adelman. 1991. Mathematical examination of dual individualization principles (I): relationships between AUC above MIC and area under the inhibitory curve for cefmenoxime, ciprofloxacin, and tobramycin. DICP Ann. Pharmacother. 25:1050-1057.
9.	Takahata, M., J. Mitsuyama, Y. Yamashiro, M. Yonezawa, H. Araki, Y. Todo, S. Minami, Y. Watanabe, and H. Narita. 1999. In vitro and in vivo antimicrobial activities of T-3811ME, a novel des-F(6)-quinolone. Antimicrob. Agents Chemother. 43:1077-1084[Abstract/Free Full Text].

This article has been cited by other articles:

• Krishna, G., Kisicki, J. C., Olsen, S., Grasela, D. M., Wang, Z. (2007). The Effect of Omeprazole on the Bioavailability and Safety of Garenoxacin in Healthy Volunteers. J Clin Pharmacol 47: 628-632 [Abstract] [Full Text]  
• Lalucat, J., Bennasar, A., Bosch, R., Garcia-Valdes, E., Palleroni, N. J. (2006). Biology of Pseudomonas stutzeri. Microbiol. Mol. Biol. Rev. 70: 510-547 [Abstract] [Full Text]  
• Anguita-Alonso, P., Rouse, M. S., Piper, K. E., Steckelberg, J. M., Patel, R. (2006). Garenoxacin treatment of experimental endocarditis caused by viridans group streptococci.. Antimicrob. Agents Chemother. 50: 1263-1267 [Abstract] [Full Text]  
• Galbraith, K. M., Ng, A. C., Eggers, B. J., Kuchel, C. R., Eggers, C. H., Samuels, D. S. (2005). parC Mutations in Fluoroquinolone-Resistant Borrelia burgdorferi. Antimicrob. Agents Chemother. 49: 4354-4357 [Abstract] [Full Text]  
• Alyaseen, S. A., Piper, K. E., Rouse, M. S., Steckelberg, J. M., Patel, R. (2005). Selection of Cross-Resistance following Exposure of Pseudomonas aeruginosa Clinical Isolates to Ciprofloxacin or Cefepime. Antimicrob. Agents Chemother. 49: 2543-2545 [Abstract] [Full Text]  
• Van Wart, S., Phillips, L., Ludwig, E. A., Russo, R., Gajjar, D. A., Bello, A., Ambrose, P. G., Costanzo, C., Grasela, T. H., Echols, R., Grasela, D. M. (2004). Population Pharmacokinetics and Pharmacodynamics of Garenoxacin in Patients with Community-Acquired Respiratory Tract Infections. Antimicrob. Agents Chemother. 48: 4766-4777 [Abstract] [Full Text]  
• Pereyre, S., Renaudin, H., Bebear, C., Bebear, C. M. (2004). In Vitro Activities of the Newer Quinolones Garenoxacin, Gatifloxacin, and Gemifloxacin against Human Mycoplasmas. Antimicrob. Agents Chemother. 48: 3165-3168 [Abstract] [Full Text]  
• Yoo, B. K, Triller, D. M, Yong, C.-S., Lodise, T. P (2004). Gemifloxacin: A New Fluoroquinolone Approved for Treatment of Respiratory Infections. The Annals of Pharmacotherapy 38: 1226-1235 [Abstract] [Full Text]  
• Christiansen, K. J., Bell, J. M., Turnidge, J. D., Jones, R. N. (2004). Antimicrobial Activities of Garenoxacin (BMS 284756) against Asia-Pacific Region Clinical Isolates from the SENTRY Program, 1999 to 2001. Antimicrob. Agents Chemother. 48: 2049-2055 [Abstract] [Full Text]  
• Smith, R. P., Baltch, A. L., Ritz, W. J., Carpenter, A. N., Halse, T. A., Bopp, L. H. (2004). In Vitro Activities of Garenoxacin and Levofloxacin against Chlamydia pneumoniae Are Not Affected by Presence of Mycoplasma DNA. Antimicrob. Agents Chemother. 48: 2081-2084 [Abstract] [Full Text]  
• Jones, R. N., Gordon, K. A., Biedenbach, D. J. (2004). Comparisons of the in vitro susceptibility testing results for garenoxacin using six different national methods: report from the garenoxacin international bridging study. J Antimicrob Chemother 53: 258-265 [Abstract] [Full Text]  
• Entenza, J. M., Vouillamoz, J., Glauser, M. P., Moreillon, P. (2004). Efficacy of Garenoxacin in Treatment of Experimental Endocarditis Due to Staphylococcus aureus or Viridans Group Streptococci. Antimicrob. Agents Chemother. 48: 86-92 [Abstract] [Full Text]  
• Andes, D., Craig, W. A. (2003). Pharmacodynamics of the New Des-F(6)-Quinolone Garenoxacin in a Murine Thigh Infection Model. Antimicrob. Agents Chemother. 47: 3935-3941 [Abstract] [Full Text]  
• Perez-Vazquez, M., Roman, F., Aracil, B., Canton, R., Campos, J. (2003). In Vitro Activities of Garenoxacin (BMS-284756) against Haemophilus influenzae Isolates with Different Fluoroquinolone Susceptibilities. Antimicrob. Agents Chemother. 47: 3539-3541 [Abstract] [Full Text]  
• Grohs, P., Houssaye, S., Aubert, A., Gutmann, L., Varon, E. (2003). In Vitro Activities of Garenoxacin (BMS-284756) against Streptococcus pneumoniae, Viridans Group Streptococci, and Enterococcus faecalis Compared to Those of Six Other Quinolones. Antimicrob. Agents Chemother. 47: 3542-3547 [Abstract] [Full Text]  
• Liebetrau, A., Rodloff, A. C., Behra-Miellet, J., Dubreuil, L. (2003). In Vitro Activities of a New Des-Fluoro(6) Quinolone, Garenoxacin, against Clinical Anaerobic Bacteria. Antimicrob. Agents Chemother. 47: 3667-3671 [Abstract] [Full Text]  
• Hayakawa, H., Fukushima, Y., Kato, H., Fukumoto, H., Kadota, T., Yamamoto, H., Kuroiwa, H., Nishigaki, J., Tsuji, A. (2003). METABOLISM AND DISPOSITION OF NOVEL DES-FLUORO QUINOLONE GARENOXACIN IN EXPERIMENTAL ANIMALS AND AN INTERSPECIES SCALING OF PHARMACOKINETIC PARAMETERS. Drug Metab. Dispos. 31: 1409-1418 [Abstract] [Full Text]  
• Ricci, V., Piddock, L. (2003). Accumulation of garenoxacin by Bacteroides fragilis compared with that of five fluoroquinolones. J Antimicrob Chemother 52: 605-609 [Abstract] [Full Text]  
• Morosini, M.-I., Loza, E., del Campo, R., Almaraz, F., Baquero, F., Canton, R. (2003). Fluoroquinolone-Resistant Streptococcus pneumoniae in Spain: Activities of Garenoxacin against Clinical Isolates Including Strains with Altered Topoisomerases. Antimicrob. Agents Chemother. 47: 2692-2695 [Abstract] [Full Text]  
• Gordon, K. A., Rhomberg, P. R., Jones, R. N. (2003). Commercial Broth Microdilution Panel Validation and Reproducibility Trials for Garenoxacin (BMS-284756), a Novel Desfluoroquinolone. J. Clin. Microbiol. 41: 3967-3969 [Abstract] [Full Text]  
• Gajjar, D. A., Bello, A., Ge, Z., Christopher, L., Grasela, D. M. (2003). Multiple-Dose Safety and Pharmacokinetics of Oral Garenoxacin in Healthy Subjects. Antimicrob. Agents Chemother. 47: 2256-2263 [Abstract] [Full Text]  
• Ameyama, S., Shinmura, Y., Takahata, M. (2003). Inhibitory Activities of Quinolones against DNA Gyrase of Chlamydia pneumoniae. Antimicrob. Agents Chemother. 47: 2327-2329 [Abstract] [Full Text]  
• Credito, K. L., Jacobs, M. R., Appelbaum, P. C. (2003). Time-Kill Studies of the Antianaerobe Activity of Garenoxacin Compared with Those of Nine Other Agents. Antimicrob. Agents Chemother. 47: 1399-1402 [Abstract] [Full Text]  
• Hecht, D. W., Osmolski, J. R. (2003). Activities of Garenoxacin (BMS-284756) and Other Agents against Anaerobic Clinical Isolates. Antimicrob. Agents Chemother. 47: 910-916 [Abstract] [Full Text]  
• Pankuch, G. A., Jacobs, M. R., Appelbaum, P. C. (2003). Postantibiotic Effects of Garenoxacin (BMS-284756) against 12 Gram-Positive or -Negative Organisms. Antimicrob. Agents Chemother. 47: 1140-1142 [Abstract] [Full Text]  
• Andrews, J., Honeybourne, D., Jevons, G., Boyce, M., Wise, R., Bello, A., Gajjar, D. (2003). Concentrations of garenoxacin in plasma, bronchial mucosa, alveolar macrophages and epithelial lining fluid following a single oral 600 mg dose in healthy adult subjects. J Antimicrob Chemother 51: 727-730 [Abstract] [Full Text]  
• Waites, K. B., Crabb, D. M., Bing, X., Duffy, L. B. (2003). In Vitro Susceptibilities to and Bactericidal Activities of Garenoxacin (BMS-284756) and Other Antimicrobial Agents against Human Mycoplasmas and Ureaplasmas. Antimicrob. Agents Chemother. 47: 161-165 [Abstract] [Full Text]  
• Rodriguez-Cerrato, V., McCoig, C. C., Saavedra, J., Barton, T., Michelow, I. C., Hardy, R. D., Bowlware, K., Iglehart, J., Katz, K., McCracken, G. H. Jr (2003). Garenoxacin (BMS-284756) and Moxifloxacin in Experimental Meningitis Caused by Vancomycin-Tolerant Pneumococci. Antimicrob. Agents Chemother. 47: 211-215 [Abstract] [Full Text]  
• Lister, P. D. (2003). Impact of AUC/MIC ratios on the pharmacodynamics of the des-F(6) quinolone garenoxacin (BMS-284756) is similar to other fluoroquinolones. J Antimicrob Chemother 51: 199-202 [Full Text]  
• Goldstein, E. J. C., Citron, D. M., Merriam, C. V., Warren, Y. A., Tyrrell, K. L., Fernandez, H. T. (2002). In Vitro Activities of Garenoxacin (BMS 284756) against 108 Clinical Isolates of Gardnerella vaginalis. Antimicrob. Agents Chemother. 46: 3995-3996 [Abstract] [Full Text]  
• Ince, D., Zhang, X., Silver, L. C., Hooper, D. C. (2002). Dual Targeting of DNA Gyrase and Topoisomerase IV: Target Interactions of Garenoxacin (BMS-284756, T-3811ME), a New Desfluoroquinolone. Antimicrob. Agents Chemother. 46: 3370-3380 [Abstract] [Full Text]  
• Snydman, D. R., Jacobus, N. V., McDermott, L. A., Ruthazer, R., Goldstein, E., Finegold, S., Harrell, L., Hecht, D. W., Jenkins, S., Pierson, C., Venezia, R., Rihs, J., Gorbach, S. L. (2002). In Vitro Activities of Newer Quinolones against Bacteroides Group Organisms. Antimicrob. Agents Chemother. 46: 3276-3279 [Abstract] [Full Text]  
• Donati, M., Pollini, G. M., Sparacino, M., Fortugno, M. T., Laghi, E., Cevenini, R. (2002). Comparative in vitro activity of garenoxacin against Chlamydia spp.. J Antimicrob Chemother 50: 407-410 [Abstract] [Full Text]  
• Goldstein, E. J. C., Citron, D. M., Merriam, C. V., Warren, Y. A., Tyrrell, K. L., Fernandez, H. T. (2002). In Vitro Activities of Garenoxacin (BMS-284756) against 170 Clinical Isolates of Nine Pasteurella Species. Antimicrob. Agents Chemother. 46: 3068-3070 [Abstract] [Full Text]  
• Jones, M. E., Critchley, I. A., Karlowsky, J. A., Blosser-Middleton, R. S., Schmitz, F.-J., Thornsberry, C., Sahm, D. F. (2002). In Vitro Activities of Novel Nonfluorinated Quinolones PGE 9262932 and PGE 9509924 against Clinical Isolates of Staphylococcus aureus and Streptococcus pneumoniae with Defined Mutations in DNA Gyrase and Topoisomerase IV. Antimicrob. Agents Chemother. 46: 1651-1657 [Abstract] [Full Text]  
• Gordon, K. A., Pfaller, M. A., Jones, R. N., the SENTRY Participants Group, (2002). BMS284756 (formerly T-3811, a des-fluoroquinolone) potency and spectrum tested against over 10 000 bacterial bloodstream infection isolates from the SENTRY antimicrobial surveillance programme (2000). J Antimicrob Chemother 49: 851-855 [Abstract] [Full Text]  
• Schmitz, F.-J., Milatovic, D., Boos, M., Mayer, S., Fluit, A. C. (2002). In vitro activity of the novel des-F(6) quinolone BMS-284756 against genetically characterized clinical streptococcal isolates, including isolates with reduced quinolone susceptibility. J Antimicrob Chemother 49: 698-701 [Full Text]  
• Low, D. E., Muller, M., Duncan, C. L., Willey, B. M., de Azavedo, J. C., McGeer, A., Kreiswirth, B. N., Pong-Porter, S., Bast, D. J. (2002). Activity of BMS-284756, a Novel Des-Fluoro(6) Quinolone, against Staphylococcus aureus, Including Contributions of Mutations to Quinolone Resistance. Antimicrob. Agents Chemother. 46: 1119-1121 [Abstract] [Full Text]  
• Goldstein, E. J. C., Citron, D. M., Merriam, C. V., Warren, Y. A., Tyrrell, K. L., Fernandez, H. (2002). In Vitro Activities of the Des-Fluoro(6) Quinolone BMS-284756 against Aerobic and Anaerobic Pathogens Isolated from Skin and Soft Tissue Animal and Human Bite Wound Infections. Antimicrob. Agents Chemother. 46: 866-870 [Abstract] [Full Text]  
• Schmitz, F.-J., Boos, M., Mayer, S., Kohrer, K., Scheuring, S., C. Fluit, A. (2002). In Vitro Activities of Novel Des-Fluoro(6) Quinolone BMS-284756 against Mutants of Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus Selected with Different Quinolones. Antimicrob. Agents Chemother. 46: 934-935 [Full Text]  
• Schmitz, F.-J., Boos, M., Mayer, S., Jagusch, H., Fluit, A. C. (2002). Increased in vitro activity of the novel des-fluoro(6) quinolone BMS-284756 against genetically defined clinical isolates of Staphylococcus aureus. J Antimicrob Chemother 49: 283-287 [Abstract] [Full Text]  
• Lawrence, L. E., Frosco, M., Ryan, B., Chaniewski, S., Yang, H., Hooper, D. C., Barrett, J. F. (2002). Bactericidal Activities of BMS-284756, a Novel Des-F(6)-Quinolone, against Staphylococcus aureus Strains with Topoisomerase Mutations. Antimicrob. Agents Chemother. 46: 191-195 [Abstract] [Full Text]  
• Bassetti, M., Dembry, L. M., Farrel, P. A., Callan, D. A., Andriole, V. T. (2002). Antimicrobial Activities of BMS-284756 Compared with Those of Fluoroquinolones and {beta}-Lactams against Gram-Positive Clinical Isolates. Antimicrob. Agents Chemother. 46: 234-238 [Abstract] [Full Text]  
• Wise, R., Gee, T., Marshall, G., Andrews, J. M. (2002). Single-Dose Pharmacokinetics and Penetration of BMS 284756 into an Inflammatory Exudate. Antimicrob. Agents Chemother. 46: 242-244 [Abstract] [Full Text]  
• Pankuch, G. A., Nagai, K., Davies, T. A., Jacobs, M. R., Appelbaum, P. C. (2002). Antipneumococcal Activity of BMS 284756 Compared to Those of Six Other Agents. Antimicrob. Agents Chemother. 46: 251-254 [Abstract] [Full Text]  
• Weller, T. M. A., Andrews, J. M., Jevons, G., Wise, R. (2002). The in vitro activity of BMS-284756, a new des-fluorinated quinolone. J Antimicrob Chemother 49: 177-184 [Abstract] [Full Text]  
• Wu, P., Lawrence, L. E., Denbleyker, K. L., Barrett, J. F. (2001). Mechanism of Action of the Des-F(6) Quinolone BMS-284756 Measured by Supercoiling Inhibition and Cleavable Complex Assays. Antimicrob. Agents Chemother. 45: 3660-3662 [Abstract] [Full Text]  
• Rodriguez-Cerrato, V., Ghaffar, F., Saavedra, J., Michelow, I. C., Hardy, R. D., Iglehart, J., Olsen, K., McCracken, G. H. Jr. (2001). BMS-284756 in Experimental Cephalosporin-Resistant Pneumococcal Meningitis. Antimicrob. Agents Chemother. 45: 3098-3103 [Abstract] [Full Text]  
• Discotto, L. F., Lawrence, L. E., Denbleyker, K. L., Barrett, J. F. (2001). Staphylococcus aureus Mutants Selected by BMS-284756. Antimicrob. Agents Chemother. 45: 3273-3275 [Abstract] [Full Text]  
• Fung-Tomc, J., Valera, L., Minassian, B., Bonner, D., Gradelski, E. (2001). Activity of the novel des-fluoro(6) quinolone BMS-284756 against methicillin-susceptible and -resistant staphylococci. J Antimicrob Chemother 48: 735-738 [Full Text]  
• Schmitz, F.-J., Boos, M., Jagusch, H., Mayer, S., Fluit, A. C., Hafner, D. (2001). Induction of in vitro resistance to BMS-284756 by Streptococcus pneumoniae. J Antimicrob Chemother 48: 588-590 [Full Text]  
• Hartman-Neumann, S., DenBleyker, K., Pelosi, L. A., Lawrence, L. E., Barrett, J. F., Dougherty, T. J. (2001). Selection and Genetic Characterization of Streptococcus pneumoniae Mutants Resistant to the Des-F(6) Quinolone BMS-284756. Antimicrob. Agents Chemother. 45: 2865-2870 [Abstract] [Full Text]  
• Boswell, F. J., Andrews, J. M., Wise, R. (2001). Comparison of the in vitro activities of BMS-284756 and four fluoroquinolones against Streptococcus pneumoniae. J Antimicrob Chemother 48: 446-447 [Full Text]  
• Lawrence, L. E., Wu, P., Fan, L., Gouveia, K. E., Card, A., Casperson, M., Denbleyker, K., Barrett, J. F. (2001). The inhibition and selectivity of bacterial topoisomerases by BMS-284756 and its analogues. J Antimicrob Chemother 48: 195-201 [Abstract] [Full Text]  

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fung-Tomc, J. C. Articles by Bonner, D. P. Search for Related Content PubMed PubMed Citation Articles by Fung-Tomc, J. C. Articles by Bonner, D. P.