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Antimicrobial Agents and Chemotherapy, November 1999, p. 2783-2786, Vol. 43, No. 11
Institute for Medical Microbiology and
Epidemiology of Infectious Diseases, University of Leipzig,
Leipzig, Germany
Received 26 October 1998/Returned for modification 26 March
1999/Accepted 18 August 1999
The activity of the new fluoroquinolone gatifloxacin was compared
with those of other quinolones and antimicrobial agents of other
classes against 294 anaerobes by the broth microdilution technique. For
all strains tested, gatifloxacin MICs at which 50 and 90% of the
isolates were inhibited were 0.5 and 2 mg/liter, respectively, and were
3 to 4 dilution steps lower than, e.g., ciprofloxacin.
Gatifloxacin (AM-1155) is a new
fluoroquinolone with a 3-methylpiperazine at position 7 of the
quinolone ring and a methoxy group at position 8. It is available
orally. Gatifloxacin has a broad spectrum against gram-positive and
gram-negative bacteria and is also effective against
Mycoplasma spp., Chlamydia spp., and mycobacteria
(2, 8-10, 14, 19-21, 25). In a study encompassing 404 anaerobic strains from Japan, the results for gatifloxacin were
described as "mediocre" (11). While this study was under revision, two other articles were published: Ednie et al. showed similar MICs of gatifloxacin and trovafloxacin by testing 351 strains
of anaerobes (5), while Goldstein et al. tested the in vitro
activities of gatifloxacin against 420 bite wound isolates, including
112 anaerobes. Gatifloxacin was active against all aerobes tested and
against Bacteroides tectum, Prevotella spp.,
Porphyromonas spp., and peptostreptococci. Fusobacteria were
sometimes resistant (7).
We compared the in vitro activities of gatifloxacin (Grünenthal
GmbH, Aachen, Germany) to those of trovafloxacin (Pfizer International
Pharmaceuticals Group, New York, N.Y.), ciprofloxacin (Bayer AG,
Leverkusen, Germany), metronidazole (Bayer AG), clindamycin (Sigma
Chemical Co., St. Louis, Mo.), imipenem (Merck & Co., Inc., West Point,
N.Y.), amoxicillin-clavulanate (10:1) (SmithKline Beecham Pharma GmbH,
Munich, Germany), and erythromycin (Serva Feinbiochemica GmbH & Co.,
Heidelberg, Germany) against 294 strains of obligately anaerobic
bacteria isolated from clinical specimens either in Germany or in
California. The species and numbers of isolates tested are shown in
Table 1. All strains were identified as
detailed previously by Claros et al. (3, 4).
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In Vitro Activities of Gatifloxacin, Two Other
Quinolones, and Five Nonquinolone Antimicrobials against
Obligately Anaerobic Bacteria
ABSTRACT
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TABLE 1.
In vitro activities of gatifloxacin and other
antimicrobial agents against
anaerobic bacteria
MICs were determined by the broth microdilution technique with 96-well
microdilution plates (Greiner GmbH, Frickenhausen, Germany). The plates
were filled semiautomatically (Quick Spense; Sandy Spring Instrument
Company, Inc., Germantown, Md.) with 100 µl of Wilkins-Chalgren
anaerobe broth (Oxoid Unipath Ltd., Basingstoke, United Kingdom)
containing the final antibiotic concentrations. The plates were stored
at 
80°C until use. For this study, the plates were thawed in an
anaerobic chamber (WA 6200; Heraeus Instruments, Hanau, Germany)
containing an atmosphere of 80% N2, 15% CO2,
and 5% H2. Then, the bacteria were delivered by a
semiautomated inoculator (MIC-2000; Dynatech Laboratories, Inc.,
Chantilly, Va.). The final inoculum was approximately 1.0 × 105 CFU/well. Incubation was usually for 48 h (96 h
for Bilophila wadsworthia) at 37°C in the anaerobic
chamber. The MIC was defined as the lowest antibiotic concentration
that inhibited visible growth.
Bacteroides fragilis ATCC 25285, B. fragilis ATCC 23745, Bacteroides ovatus ATCC 8483, Bacteroides vulgatus ATCC 8482, Bacteroides thetaiotaomicron ATCC 29148, Bacteroides caccae ATCC 43185, Fusobacterium mortiferum ATCC 9817, Fusobacterium varium ATCC 8501, and Peptostreptococcus magnus ATCC 14955 were used as reference strains. The MICs showed conformity with published results of the National Committee for Clinical Laboratory Standards and the German standard-setting organization Deutsches Institut für Normung (13, 15).
MIC distributions and MICs at which 50 or 90% of the isolates were
inhibited (MIC50 and MIC90, respectively) for
gatifloxacin, other quinolones, and nonquinolone antimicrobials are
given in Table 1. In addition, in Table 2
the results are shown as cumulative percentages of strains inhibited at
a given MIC. Overall, the MIC50 and MIC90 (in
milligrams per liter), respectively, for all strains were as follows:
imipenem, metronidazol, and trovafloxacin, 0.25 and 1; gatifloxacin,
0.5 and 2; clindamycin, 0.5 and 4; amoxicillin-clavulanate, 1 and 4;
ciprofloxacin, 4 and 32; erythromycin, 4 and >32. At a breakpoint
concentration of 
1 mg of gatifloxacin per liter, 83% of all strains
tested, 90% of the B. fragilis strains, and 81% of all
Bacteroides spp. were inhibited. The MIC50 and
MIC90 of gatifloxacin were 1 dilution step higher than
those of trovafloxacin with respect to all strains tested. In contrast,
gatifloxacin MIC50 and MIC90 were 3 to 4 dilution steps lower than those of ciprofloxacin. Gatifloxacin and
trovafloxacin MICs were significantly lower for anaerobic gram-negative
bacilli other than fusobacteria and Bilophila wadsworthia
than MICs of ciprofloxacin. For Clostridium spp., no major
disparities were found between gatifloxacin, trovafloxacin, and
ciprofloxacin MIC50, whereas the MIC90 for
ciprofloxacin was 3 dilution steps higher than those of gatifloxacin
and trovafloxacin.
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In comparison with other studies (1, 5, 6, 12, 16-18, 22-24), we found similar MIC50 and MIC90 of trovafloxacin, ciprofloxacin, metronidazole, clindamycin, imipenem, erythromycin, and amoxicillin-clavulanate. Like Pankuch et al. (16), we found a moderate level of clindamycin resistance for all strains tested (MICs for 10% of the strains were >4 mg/liter).
In general, our MICs of gatifloxacin against anaerobes have confirmed and extended the findings of previous reports (2, 5, 7, 9, 11, 21, 25). However, in contrast to the report of Wakabayashi et al., who tested 70 Japanese isolates, we found lower MIC50 and MIC90 of gatifloxacin against B. fragilis (21). Likewise, Kato et al. found higher MIC50 and MIC90 of gatifloxacin for B. fragilis and B. thetaiotaomicron by testing 404 Japanese isolates of anaerobic bacteria (11). Of the B. fragilis strains tested, only 76 and 83% were inhibited at concentrations of 0.78 and 1.56 mg of gatifloxacin per liter, respectively, whereas in our study, 90% of B. fragilis strains were inhibited at 1 mg/liter. However, our results for Bacteroides spp. are similar to those published by Ednie et al. (5). Moreover, in accordance with the results of Ednie et al., we found similar gatifloxacin MIC50 and MIC90 for fusobacteria, whereas Goldstein and coworkers found higher values and Kato et al. found lower values (5, 7, 11). In contrast to the findings of Ednie et al. and Goldstein et al., we found lower MIC90 for peptostreptococci (5, 7). The disparities might be due to technical differences, i.e., different media and our use of the broth microdilution technique rather than the agar dilution method.
It is recognized that the results of in vitro anaerobe susceptibility testing do not always correlate with in vivo findings. Although Kato et al. described "mediocre" in vitro activity of gatifloxacin against B. fragilis, they reported that gatifloxacin was effective against both B. fragilis and Escherichia coli in a mixed infection in a rat granuloma pouch in vivo (11). Hence, clinical studies are required to determine the roles of gatifloxacin in mixed and anaerobic infections.
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ACKNOWLEDGMENTS |
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This study was supported by a grant from Grünenthal (Aachen, Germany).
We gratefully acknowledge gifts of strains for this study from E. J. C. Goldstein (R. M. Alden Research Laboratory, Los Angeles, Calif.).
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FOOTNOTES |
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* Corresponding author. Mailing address: Institute for Medical Microbiology and Epidemiology of Infectious Diseases, University of Leipzig, Liebigstr. 24, D-04103 Leipzig, Germany. Phone: (0341) 97 15 200. Fax: (0341) 97 15 209. E-mail: schaur{at}medizin.uni-leipzig.de.
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REFERENCES |
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Abstract
Text
References
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| 1. | Aldridge, K. E., D. Ashcraft, and K. A. Bowman. 1997. Comparative in vitro activities of trovafloxacin (CP 99,219) and other antimicrobials against clinically significant anaerobes. Antimicrob. Agents Chemother. 41:484-487[Abstract]. |
| 2. |
Bauernfeind, A.
1997.
Comparison of the antibacterial activities of the quinolones Bay 12-8039, gatifloxacin (AM 1155), trovafloxacin, clinafloxacin, levofloxacin and ciprofloxacin.
J. Antimicrob. Chemother.
40:639-651 |
| 3. | Claros, M. C., D. M. Citron, S. Hunt Gerardo, E. J. C. Goldstein, G. Schönian, T. Montag, B. Hampel, and A. C. Rodloff. 1996. Characterization of indole-negative Bacteroides fragilis group species with use of polymerase chain reaction fingerprinting and resistance profiles. Clin. Infect. Dis. 23(Suppl. 1):S66-S72. |
| 4. | Claros, M. C., Y. Papke, N. Kleinkauf, D. Adler, D. M. Citron, S. Hunt-Gerardo, T. Montag, E. J. C. Goldstein, and A. C. Rodloff. Characteristics of Fusobacterium ulcerans, a new and unusual species compared to Fusobacterium varium and Fusobacterium mortiferum. Anaerobe, in press. |
| 5. |
Ednie, L. M.,
M. R. Jacobs, and P. C. Appelbaum.
1998.
Activities of gatifloxacin compared to those of seven other agents against anaerobic organisms.
Antimicrob. Agents Chemother.
42:2459-2462 |
| 6. |
Ednie, L. M.,
S. K. Spangler,
M. R. Jacobs, and P. C. Appelbaum.
1997.
Antianaerobic activity of the ketolide RU 64004 compared to activities of four macrolides, five  -lactams, clindamycin, and metronidazole.
Antimicrob. Agents Chemother.
41:1037-1041[Abstract].
|
| 7. |
Goldstein, E. J. C.,
D. M. Citron,
C. V. Merriam,
K. Tyrrell, and Y. Warren.
1999.
Activity of gatifloxacin compared to those of five other quinolones versus aerobic and anaerobic isolates from skin and soft tissue samples of human and animal bite wound infections.
Antimicrob. Agents Chemother.
43:1475-1479 |
| 8. |
Hosaka, M.,
S. Kinoshita,
A. Toyama,
M. Otsuki, and T. Nishino.
1995.
Antibacterial properties of AM-1155, a new 8-methoxy quinolone.
J. Antimicrob. Chemother.
36:293-301 |
| 9. |
Hosaka, M.,
T. Yasue,
H. Fukuda,
H. Tomizawa,
H. Aoyama, and K. Hirai.
1992.
In vitro and in vivo antibacterial activities of AM-1155, a new 6-fluoro-8-methoxy quinolone.
Antimicrob. Agents Chemother.
36:2108-2117 |
| 10. |
Ishida, K.,
M. Kaku,
K. Irifune,
R. Mizukane,
H. Takemura,
R. Yoshida,
H. Tanaka,
T. Usui,
K. Tomono,
N. Suyama,
H. Koga,
S. Kohno, and K. Hara.
1994.
In-vitro and in-vivo activity of a new quinolone, AM-1155, against Mycoplasma pneumoniae.
J. Antimicrob. Chemother.
34:875-883 |
| 11. |
Kato, N.,
H. Kato,
K. Tanaka-Bandoh,
K. Watanabe, and K. Ueno.
1997.
Comparative in-vitro and in-vivo activity of AM-1155 against anaerobic bacteria.
J. Antimicrob. Chemother.
40:631-637 |
| 12. |
MacGowan, A. P.,
K. E. Bowker,
H. A. Holt,
M. Wootton, and D. S. Reeves.
1997.
Bay 12-8039, a new 8-methoxy-quinolone: comparative in-vitro activity with nine other antimicrobials against anaerobic bacteria.
J. Antimicrob. Chemother.
40:503-509 |
| 13. | Medizinische Mikrobiologie und Immunologie: Normen und weitere Unterlagen. 1992. DIN, Deutsches Institut für Normung e. V., 2nd ed. Beuth, Berlin, Germany |
| 14. | Miyashita, N., Y. Niki, T. Kishimoto, M. Nakajima, and T. Matsushima. 1997. In vitro and in vivo activities of AM-1155, a new fluoroquinolone, against Chlamydia spp. Antimicrob. Agents Chemother. 41:1331-1334[Abstract]. |
| 15. | National Committee for Clinical Laboratory Standards. 1993. Methods for antimicrobial susceptibility testing of anaerobic bacteria, 3rd ed. Approved standard. NCCLS publication no. M11-A3. National Committee for Clinical Laboratory Standards, Wayne, Pa. |
| 16. |
Pankuch, G. A.,
M. R. Jacobs, and P. C. Appelbaum.
1993.
Susceptibilities of 428 gram-positive and -negative anaerobic bacteria to Bay  3118 compared with their susceptibilities to ciprofloxacin, clindamycin, metronidazole, piperacillin, piperacillin-tazobactam, and cefoxitin.
Antimicrob. Agents Chemother.
37:1649-1654 |
| 17. | Rodloff, A. C., H. Werner, M. Kresken, A. Jansen, and the German Bacteroides Study Group. 1992. German multicentre study on the in vitro susceptibility of Bacteroides species. Eur. J. Clin. Microbiol. Infect. Dis. 11:1074-1080[Medline]. |
| 18. | Spangler, S. K., M. R. Jacobs, and P. C. Appelbaum. 1996. Susceptibility of anaerobic bacteria to trovafloxacin: comparison with other quinolones and non-quinolone antibiotics. Infect. Dis. Clin. Pract. 5(Suppl. 3):S101-S109. |
| 19. |
Tomioka, H.,
H. Saito, and K. Sato.
1993.
Comparative antimycobacterial activities of the newly synthesized quinolone AM-1155, sparfloxacin, and ofloxacin.
Antimicrob. Agents Chemother.
37:1259-1263 |
| 20. |
Tomizawa, H.,
K. Tateda,
S. Miyazaki, and K. Yamaguchi.
1998.
Antibacterial activity of AM-1155 against penicillin-resistant Streptococcus pneumoniae.
J. Antimicrob. Chemother.
41:103-106 |
| 21. |
Wakabayashi, E., and S. Mitsuhashi.
1994.
In vitro antibacterial activity of AM-1155, a novel 6-fluoro-8-methoxy quinolone.
Antimicrob. Agents Chemother.
38:594-601 |
| 22. |
Wexler, H. M.,
E. Molitoris, and S. M. Finegold.
1993.
In vitro activity of Bay Y3118 against anaerobic bacteria.
Antimicrob. Agents Chemother.
37:2509-2513 |
| 23. | Wexler, H. M., E. Molitoris, D. Molitoris, and S. M. Finegold. 1996. In vitro activities of trovafloxacin against 557 strains of anaerobic bacteria. Antimicrob. Agents Chemother. 40:2232-2235[Abstract]. |
| 24. |
Wexler, H. M.,
E. Molitoris,
D. Reeves, and S. M. Finegold.
1994.
In vitro activity of DU-6859a against anaerobic bacteria.
Antimicrob. Agents Chemother.
38:2504-2509 |
| 25. |
Wise, R.,
N. P. Brenwald,
J. M. Andrews, and F. Boswell.
1997.
The activity of the methylpiperazinyl fluoroquinolone CG 5501: a comparison with other fluoroquinolones.
J. Antimicrob. Chemother.
39:447-452 |
Antimicrobial Agents and Chemotherapy, November 1999, p. 2783-2786, Vol. 43, No. 11
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Copyright © 1999, American Society for Microbiology. All rights reserved.
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