Commercial Broth Microdilution Panel Validation and Reproducibility Trials for Garenoxacin(BMS-284756) a Novel Desfluoroquinolone
The JONES Group/JMI Laboratories, North Liberty, Iowa,1 Tufts University School of Medicine, Boston, Massachusetts2;, http://www.100md.com
Received 13 February 2003/ Returned for modification 14 May 2003/ Accepted 24 May 2003;, http://www.100md.com
ABSTRACT;, http://www.100md.com
Results from garenoxacin dry-form broth microdilution MIC panels prepared commercially (Sensititre, TREK Diagnostics) were compared to reference frozen-form MICs to ensure the validity of the longer-shelf-life product. A total of 1,078 organisms from seven major organism groups were used in this trial. All commercial MIC results were within ± one log2 dilution of reference garenoxacin values, and reproducibility trials produced identical MIC results for 90.5 to 92.1% of garenoxacin MIC comparisons. Control quinolones (ciprofloxacin and gatifloxacin) also performed at a similarly high level of accuracy.;, http://www.100md.com
TEXT;, http://www.100md.com
Because of a combination of several characteristics, including favorable pharmacokinetics, the ability to be given orally or parenterally, and spectrum of activity, the quinolones as a class have been extensively used to treat a wide range of bacterial infections. Garenoxacin (formerly BMS-284756) is a novel des-fluoro(6) quinolone. Relative to other fluoroquinolones, nearly complete bioavailability and lower toxicity in animal models have been documented for garenoxacin (9; M. Takahata, J. Mitsuyama, Y. Yamashiro, H. Araki, H. Yamada, H. Hayakawa, Y. Todo, S. Minami, Y. Watanabe, and H. Narita, Abstr. 37th Intersci. Conf. Antimicrob. Agents Chemother., abstr. T-3811, 1997). Garenoxacin has also demonstrated potent in vitro activity against a wide variety of bacterial pathogens, including many gram-positive bacterial species (2, 3, 8, 9). Similarly, other reports have shown the potential utility of garenoxacin against multidrug-resistant gram-positive pathogens, including many methicillin-resistant Staphylococcus aureus or Staphylococcus epidermidis organisms and penicillin-resistant Streptococcus pneumoniae (2, 9). Garenoxacin potency is comparable to that of other newer quinolones against gram-negative organisms and has proven to be active against Mycobacterium tuberculosis, Mycoplasma pneumoniae, and Chlamydia trachomatis (9).
Appropriate disk diffusion and MIC quality control (QC) ranges for garenoxacin have been previously established (1). These QC ranges were determined for seven commonly used American Type Culture Collection (ATCC) control strains, which were tested over a 10-day period by more than seven laboratories using reference methods (5). With QC ranges established for garenoxacin, and as this compound nears completion of Phase III clinical trials and advances into clinical use, routine susceptibility testing using commercially prepared MIC products will be necessary. To validate the garenoxacin MIC results derived from commercially prepared products with extended shelf lives, a comparison (validation) study conforming to the National Committee for Clinical Laboratory Standards (NCCLS) guidelines was performed (6).an22+w3, 百拇医药
In accordance with NCCLS M7-A6 methods (5) and established precedent (4), a minimum of 100 isolates per organism group listed in the M100-S13 document (7) tables for which garenoxacin has proven activity were tested. The spectrum of garenoxacin activity was determined for the following seven organism groups: Staphylococcus spp. (153 strains), Streptococcus spp. (141 strains; viridans group and ß-hemolytic streptococcal species), S. pneumoniae (167 strains), Enterococcus spp. (102 strains), Haemophilus influenzae (308 strains), Enterobacteriaceae (105 strains), and other gram-negative bacilli (102 strains). Garenoxacin susceptibility was determined by using both commercial dry-form (Sensititre/TREK Diagnostics, Cleveland, Ohio) and frozen broth microdilution panels. All frozen-form reference panels were processed using the manufacturer's package insert procedures (also produced by TREK Diagnostics) and were maintained at -70°C or below until used. All panels were inoculated with a final concentration of 5 x 105 CFU/ml. The panels were incubated in ambient air at 35°C and were interpreted at 16 to 20 h for gram-negative rapid-growing species or 20 to 24 h for gram-positive and fastidious organisms (5). Gatifloxacin was tested concurrently as an internal QC quinolone agent for this MIC validation study. The tested range for garenoxacin on both the reference and commercial dry-form panels was 0.008 to 16 µg/ml. The tested gatifloxacin concentration range on commercial dry-form panels was 0.03 to 4 µg/ml, and it was 0.004 to 8 µg/ml for frozen-form panels.
Commercial MIC panel reproducibility was assessed for garenoxacin by testing 14 strains. These strains included 10 commonly used ATCC strains: Escherichia coli ATCC 25922 and ATCC 35218, Klebsiella pneumoniae ATCC 13883, Pseudomonas aeruginosa ATCC 27853, S. aureus ATCC 29213 and ATCC 25923, Enterococcus faecalis ATCC 29212, H. influenzae ATCC 49247 and ATCC 49766, and S. pneumoniae ATCC 49619, as well as four clinical isolates. Susceptibility testing was performed three times daily for 3 days, generating a total of 126 determinations. Ciprofloxacin was utilized as the control antimicrobial agent for this portion of the study. The acceptable agreement definition for susceptibility test reproducibility was that 95% of MIC results be within ±1 log2 dilution step. All MIC results for QC strains were within published NCCLS M100-S13 ranges (7).#[&+h30, 百拇医药
Table 1 summarizes the validation phase results for testing garenoxacin and gatifloxacin to compare reference NCCLS frozen panels (5) to commercial dry-form panels. Garenoxacin MIC results were slightly less variable than gatifloxacin test comparisons. All dry-form MIC results for garenoxacin were within ±1 log2 dilution. The gatifloxacin MICs for six strains were 2 log2 dilutions higher or lower than the reference method MIC.
fig.ommitted@2, 百拇医药
TABLE 1. Variations of garenoxacin MIC results performed on commercially prepared dry-form panels versus reference frozen-form broth microdilution panels@2, 百拇医药
Table 1 also includes a subset analysis for MIC data pairs that had on-scale values. A trend toward a higher (0.5-log2 dilution) MIC was observed for garenoxacin. With the on-scale results, 48% of MIC determinations were at a twofold-higher value. Likewise, gatifloxacin commercial-panel MICs trended higher, with 42% being twofold greater but <1% being fourfold higher. Slightly elevated dry-form garenoxacin and gatifloxacin MIC results were common for all species groups tested, but among S. pneumoniae strains, MICs were equal on both test panels for only 4% of strains. Gatifloxacin dry-form panel MIC results were also elevated for S. pneumoniae isolates (data not shown). On-scale garenoxacin MICs for the Streptococcus spp. demonstrated that 62.4% of the dry-form MIC results were equal to the matched frozen-form MIC results. Among the Staphylococcus spp. with on-scale values, garenoxacin MICs were identical for 74.3% of isolates (59% for gatifloxacin). With the Enterococcus sp. isolates, garenoxacin and gatifloxacin had identical on-scale MICs for 57.1 and 57.4% of isolates, respectively.
Garenoxacin MICs for the Enterobacteriaceae also demonstrated a slight shift towards a 1-log2-higher dilution for on-scale dry-form values than with frozen-form panels. Identical MICs occurred in 44.8% of tests with Enterobacteriaceae, while 50.7% of MICs were twofold higher. Among the nonfermentative gram-negative bacilli, identical MICs occurred for 53.4% of isolates, and 43.1% of tests demonstrated a twofold-higher MIC. All garenoxacin MICs for H. influenzae were within ±1 log2 dilution, with no significant shift or trend toward either higher or lower values. When all MIC results were analyzed for gatifloxacin, MICs for only 1.3% of the isolates were observed to be beyond the ±1-log2-dilution range.-\7w, 百拇医药
Garenoxacin MIC results for the commercial dry-form panel reproducibility studies are listed in Table 2. Garenoxacin had a slightly greater same-day MIC reproducibility result, with 92.1% being identical versus 90.5% for the ciprofloxacin control. The MICs were identical for 90.5% of garenoxacin between-day replicates, compared to 88.9% for ciprofloxacin. There was no clear tendency for the MIC of either quinolone skewing towards higher or lower values or for unacceptable low levels of reproducibility. Ciprofloxacin MIC comparison results were on-scale for 8 of the 14 organisms tested, while garenoxacin demonstrated on-scale MIC results for 12 of the 14 strains tested. For both garenoxacin and ciprofloxacin, all replicate MICs were within ±1 log2 dilution for same-day and for between-day testing, meeting the definition of acceptable reproducibility.
fig.ommitted\o&3r/&, 百拇医药
TABLE 2. Garenoxacin dry-form MIC panel reproducibility results testing three replicates daily for 3 days (126 total results)\o&3r/&, 百拇医药
The purpose of this study was to provide method and MIC endpoint validation for commercially prepared, dry-form panels containing garenoxacin when compared to the NCCLS frozen-form reference broth microdilution test (5). All MIC comparisons for garenoxacin between commercial and reference broth microdilution MIC results showed equality within ±1 log2 dilution. However, garenoxacin and the gatifloxacin control demonstrated a slight trend toward higher MICs on the dry-form panels, and this was most pronounced for S. pneumoniae. All reproducibility results obtained were within ±1 log2 dilution for the 14 organisms tested.\o&3r/&, 百拇医药
Garenoxacin, a novel des-fluoro(6) quinolone, has proven to be a potent antimicrobial agent in vitro, with a wide spectrum of activity, especially against gram-positive organisms and fastidious respiratory tract pathogens (2, 3, 8, 9; Takahata et al., 37th ICAAC). The study results reported here demonstrate that garenoxacin can be accurately and reproducibly tested following the Food and Drug Administration release of this product by using commercial dry-form (Sensititre, TREK Diagnostics) reagents and can be controlled by methods and QC ranges found in contemporary NCCLS tables (1, 5, 7).
ACKNOWLEDGMENTSigm, http://www.100md.com
We thank Bristol-Myers Squibb for the educational/research grant that made this project possible.igm, http://www.100md.com
We also extend our thanks to K. Meyer, T. Anderegg, M. Beach, and D. Biedenbach for their technical support in the preparation of the manuscript and the execution of this comparative trial.igm, http://www.100md.com
REFERENCESigm, http://www.100md.com
Biedenbach, D. J., R. N. Jones, and The Quality Control Working Group. 2001. Assessment of BMS284756 MIC and 5-µg disk diffusion quality control studies tested against seven American Type Culture Collection strains. Diagn. Microbiol. Infect. Dis. 41:225-228.igm, http://www.100md.com
Fung-Tomc, J. C., B. Minassian, B. Kolek, E. Huczko, L. Aleksunes, T. Stickle, T. Washo, E. Gradelski, L. Valera, and D. P. Bonner. 2000. Antibacterial spectrum of a novel des-fluoro(6) quinolone, BMS284756. Antimicrob. Agents Chemother. 44:3351-3356.igm, http://www.100md.com
Gordon, K. A., M. A. Pfaller, R. N. Jones, and 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. J. Antimicrob. Chemother. 49:851-855.
Jones, R. N., T. R. Anderegg, and D. J. Biedenbach. Validation of commercial dry-form broth microdilution panels for susceptibility testing of AZD2563, a new long-acting oxazolidinone. Clin. Microbiol. Infect., in press.%, 百拇医药
National Committee for Clinical Laboratory Standards. 2003. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Document M7-A6. National Committee for Clinical Laboratory Standards, Wayne, Pa.%, 百拇医药
National Committee for Clinical Laboratory Standards. 2001. Development of in vitro susceptibility testing criteria and quality control parameters. Approved guideline M23-A2. National Committee for Clinical Laboratory Standards, Wayne, Pa.%, 百拇医药
National Committee for Clinical Laboratory Standards. 2003. Performance standards for antimicrobial susceptibility testing M100-S13. National Committee for Clinical Laboratory Standards, Wayne, Pa.%, 百拇医药
Pfaller, M. A., M. L. Beach, K. A. Gordon, and R. N. Jones. 2002. Comparative antimicrobial spectrum and activity of BMS284756 (T-3811; a desfluoroquinolone) tested against an international collection of staphylococci and enterococci, including in vitro test development and intermethod comparisons. J. Chemother. 14:13-18.%, 百拇医药
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.(Kelley A. Gordon Paul R. Rhomberg and Ronald N. Jones)
Received 13 February 2003/ Returned for modification 14 May 2003/ Accepted 24 May 2003;, http://www.100md.com
ABSTRACT;, http://www.100md.com
Results from garenoxacin dry-form broth microdilution MIC panels prepared commercially (Sensititre, TREK Diagnostics) were compared to reference frozen-form MICs to ensure the validity of the longer-shelf-life product. A total of 1,078 organisms from seven major organism groups were used in this trial. All commercial MIC results were within ± one log2 dilution of reference garenoxacin values, and reproducibility trials produced identical MIC results for 90.5 to 92.1% of garenoxacin MIC comparisons. Control quinolones (ciprofloxacin and gatifloxacin) also performed at a similarly high level of accuracy.;, http://www.100md.com
TEXT;, http://www.100md.com
Because of a combination of several characteristics, including favorable pharmacokinetics, the ability to be given orally or parenterally, and spectrum of activity, the quinolones as a class have been extensively used to treat a wide range of bacterial infections. Garenoxacin (formerly BMS-284756) is a novel des-fluoro(6) quinolone. Relative to other fluoroquinolones, nearly complete bioavailability and lower toxicity in animal models have been documented for garenoxacin (9; M. Takahata, J. Mitsuyama, Y. Yamashiro, H. Araki, H. Yamada, H. Hayakawa, Y. Todo, S. Minami, Y. Watanabe, and H. Narita, Abstr. 37th Intersci. Conf. Antimicrob. Agents Chemother., abstr. T-3811, 1997). Garenoxacin has also demonstrated potent in vitro activity against a wide variety of bacterial pathogens, including many gram-positive bacterial species (2, 3, 8, 9). Similarly, other reports have shown the potential utility of garenoxacin against multidrug-resistant gram-positive pathogens, including many methicillin-resistant Staphylococcus aureus or Staphylococcus epidermidis organisms and penicillin-resistant Streptococcus pneumoniae (2, 9). Garenoxacin potency is comparable to that of other newer quinolones against gram-negative organisms and has proven to be active against Mycobacterium tuberculosis, Mycoplasma pneumoniae, and Chlamydia trachomatis (9).
Appropriate disk diffusion and MIC quality control (QC) ranges for garenoxacin have been previously established (1). These QC ranges were determined for seven commonly used American Type Culture Collection (ATCC) control strains, which were tested over a 10-day period by more than seven laboratories using reference methods (5). With QC ranges established for garenoxacin, and as this compound nears completion of Phase III clinical trials and advances into clinical use, routine susceptibility testing using commercially prepared MIC products will be necessary. To validate the garenoxacin MIC results derived from commercially prepared products with extended shelf lives, a comparison (validation) study conforming to the National Committee for Clinical Laboratory Standards (NCCLS) guidelines was performed (6).an22+w3, 百拇医药
In accordance with NCCLS M7-A6 methods (5) and established precedent (4), a minimum of 100 isolates per organism group listed in the M100-S13 document (7) tables for which garenoxacin has proven activity were tested. The spectrum of garenoxacin activity was determined for the following seven organism groups: Staphylococcus spp. (153 strains), Streptococcus spp. (141 strains; viridans group and ß-hemolytic streptococcal species), S. pneumoniae (167 strains), Enterococcus spp. (102 strains), Haemophilus influenzae (308 strains), Enterobacteriaceae (105 strains), and other gram-negative bacilli (102 strains). Garenoxacin susceptibility was determined by using both commercial dry-form (Sensititre/TREK Diagnostics, Cleveland, Ohio) and frozen broth microdilution panels. All frozen-form reference panels were processed using the manufacturer's package insert procedures (also produced by TREK Diagnostics) and were maintained at -70°C or below until used. All panels were inoculated with a final concentration of 5 x 105 CFU/ml. The panels were incubated in ambient air at 35°C and were interpreted at 16 to 20 h for gram-negative rapid-growing species or 20 to 24 h for gram-positive and fastidious organisms (5). Gatifloxacin was tested concurrently as an internal QC quinolone agent for this MIC validation study. The tested range for garenoxacin on both the reference and commercial dry-form panels was 0.008 to 16 µg/ml. The tested gatifloxacin concentration range on commercial dry-form panels was 0.03 to 4 µg/ml, and it was 0.004 to 8 µg/ml for frozen-form panels.
Commercial MIC panel reproducibility was assessed for garenoxacin by testing 14 strains. These strains included 10 commonly used ATCC strains: Escherichia coli ATCC 25922 and ATCC 35218, Klebsiella pneumoniae ATCC 13883, Pseudomonas aeruginosa ATCC 27853, S. aureus ATCC 29213 and ATCC 25923, Enterococcus faecalis ATCC 29212, H. influenzae ATCC 49247 and ATCC 49766, and S. pneumoniae ATCC 49619, as well as four clinical isolates. Susceptibility testing was performed three times daily for 3 days, generating a total of 126 determinations. Ciprofloxacin was utilized as the control antimicrobial agent for this portion of the study. The acceptable agreement definition for susceptibility test reproducibility was that 95% of MIC results be within ±1 log2 dilution step. All MIC results for QC strains were within published NCCLS M100-S13 ranges (7).#[&+h30, 百拇医药
Table 1 summarizes the validation phase results for testing garenoxacin and gatifloxacin to compare reference NCCLS frozen panels (5) to commercial dry-form panels. Garenoxacin MIC results were slightly less variable than gatifloxacin test comparisons. All dry-form MIC results for garenoxacin were within ±1 log2 dilution. The gatifloxacin MICs for six strains were 2 log2 dilutions higher or lower than the reference method MIC.
fig.ommitted@2, 百拇医药
TABLE 1. Variations of garenoxacin MIC results performed on commercially prepared dry-form panels versus reference frozen-form broth microdilution panels@2, 百拇医药
Table 1 also includes a subset analysis for MIC data pairs that had on-scale values. A trend toward a higher (0.5-log2 dilution) MIC was observed for garenoxacin. With the on-scale results, 48% of MIC determinations were at a twofold-higher value. Likewise, gatifloxacin commercial-panel MICs trended higher, with 42% being twofold greater but <1% being fourfold higher. Slightly elevated dry-form garenoxacin and gatifloxacin MIC results were common for all species groups tested, but among S. pneumoniae strains, MICs were equal on both test panels for only 4% of strains. Gatifloxacin dry-form panel MIC results were also elevated for S. pneumoniae isolates (data not shown). On-scale garenoxacin MICs for the Streptococcus spp. demonstrated that 62.4% of the dry-form MIC results were equal to the matched frozen-form MIC results. Among the Staphylococcus spp. with on-scale values, garenoxacin MICs were identical for 74.3% of isolates (59% for gatifloxacin). With the Enterococcus sp. isolates, garenoxacin and gatifloxacin had identical on-scale MICs for 57.1 and 57.4% of isolates, respectively.
Garenoxacin MICs for the Enterobacteriaceae also demonstrated a slight shift towards a 1-log2-higher dilution for on-scale dry-form values than with frozen-form panels. Identical MICs occurred in 44.8% of tests with Enterobacteriaceae, while 50.7% of MICs were twofold higher. Among the nonfermentative gram-negative bacilli, identical MICs occurred for 53.4% of isolates, and 43.1% of tests demonstrated a twofold-higher MIC. All garenoxacin MICs for H. influenzae were within ±1 log2 dilution, with no significant shift or trend toward either higher or lower values. When all MIC results were analyzed for gatifloxacin, MICs for only 1.3% of the isolates were observed to be beyond the ±1-log2-dilution range.-\7w, 百拇医药
Garenoxacin MIC results for the commercial dry-form panel reproducibility studies are listed in Table 2. Garenoxacin had a slightly greater same-day MIC reproducibility result, with 92.1% being identical versus 90.5% for the ciprofloxacin control. The MICs were identical for 90.5% of garenoxacin between-day replicates, compared to 88.9% for ciprofloxacin. There was no clear tendency for the MIC of either quinolone skewing towards higher or lower values or for unacceptable low levels of reproducibility. Ciprofloxacin MIC comparison results were on-scale for 8 of the 14 organisms tested, while garenoxacin demonstrated on-scale MIC results for 12 of the 14 strains tested. For both garenoxacin and ciprofloxacin, all replicate MICs were within ±1 log2 dilution for same-day and for between-day testing, meeting the definition of acceptable reproducibility.
fig.ommitted\o&3r/&, 百拇医药
TABLE 2. Garenoxacin dry-form MIC panel reproducibility results testing three replicates daily for 3 days (126 total results)\o&3r/&, 百拇医药
The purpose of this study was to provide method and MIC endpoint validation for commercially prepared, dry-form panels containing garenoxacin when compared to the NCCLS frozen-form reference broth microdilution test (5). All MIC comparisons for garenoxacin between commercial and reference broth microdilution MIC results showed equality within ±1 log2 dilution. However, garenoxacin and the gatifloxacin control demonstrated a slight trend toward higher MICs on the dry-form panels, and this was most pronounced for S. pneumoniae. All reproducibility results obtained were within ±1 log2 dilution for the 14 organisms tested.\o&3r/&, 百拇医药
Garenoxacin, a novel des-fluoro(6) quinolone, has proven to be a potent antimicrobial agent in vitro, with a wide spectrum of activity, especially against gram-positive organisms and fastidious respiratory tract pathogens (2, 3, 8, 9; Takahata et al., 37th ICAAC). The study results reported here demonstrate that garenoxacin can be accurately and reproducibly tested following the Food and Drug Administration release of this product by using commercial dry-form (Sensititre, TREK Diagnostics) reagents and can be controlled by methods and QC ranges found in contemporary NCCLS tables (1, 5, 7).
ACKNOWLEDGMENTSigm, http://www.100md.com
We thank Bristol-Myers Squibb for the educational/research grant that made this project possible.igm, http://www.100md.com
We also extend our thanks to K. Meyer, T. Anderegg, M. Beach, and D. Biedenbach for their technical support in the preparation of the manuscript and the execution of this comparative trial.igm, http://www.100md.com
REFERENCESigm, http://www.100md.com
Biedenbach, D. J., R. N. Jones, and The Quality Control Working Group. 2001. Assessment of BMS284756 MIC and 5-µg disk diffusion quality control studies tested against seven American Type Culture Collection strains. Diagn. Microbiol. Infect. Dis. 41:225-228.igm, http://www.100md.com
Fung-Tomc, J. C., B. Minassian, B. Kolek, E. Huczko, L. Aleksunes, T. Stickle, T. Washo, E. Gradelski, L. Valera, and D. P. Bonner. 2000. Antibacterial spectrum of a novel des-fluoro(6) quinolone, BMS284756. Antimicrob. Agents Chemother. 44:3351-3356.igm, http://www.100md.com
Gordon, K. A., M. A. Pfaller, R. N. Jones, and 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. J. Antimicrob. Chemother. 49:851-855.
Jones, R. N., T. R. Anderegg, and D. J. Biedenbach. Validation of commercial dry-form broth microdilution panels for susceptibility testing of AZD2563, a new long-acting oxazolidinone. Clin. Microbiol. Infect., in press.%, 百拇医药
National Committee for Clinical Laboratory Standards. 2003. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Document M7-A6. National Committee for Clinical Laboratory Standards, Wayne, Pa.%, 百拇医药
National Committee for Clinical Laboratory Standards. 2001. Development of in vitro susceptibility testing criteria and quality control parameters. Approved guideline M23-A2. National Committee for Clinical Laboratory Standards, Wayne, Pa.%, 百拇医药
National Committee for Clinical Laboratory Standards. 2003. Performance standards for antimicrobial susceptibility testing M100-S13. National Committee for Clinical Laboratory Standards, Wayne, Pa.%, 百拇医药
Pfaller, M. A., M. L. Beach, K. A. Gordon, and R. N. Jones. 2002. Comparative antimicrobial spectrum and activity of BMS284756 (T-3811; a desfluoroquinolone) tested against an international collection of staphylococci and enterococci, including in vitro test development and intermethod comparisons. J. Chemother. 14:13-18.%, 百拇医药
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.(Kelley A. Gordon Paul R. Rhomberg and Ronald N. Jones)