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Antimicrobial Agents and Chemotherapy, September 1998, p. 2459-2462, Vol. 42, No. 9
Department of Pathology (Clinical
Microbiology), Hershey Medical Center, Hershey, Pennsylvania
17033,1 and
Department of Pathology,
Case Western Reserve University, Cleveland, Ohio
441062
Received 13 March 1998/Returned for modification 2 June
1998/Accepted 15 June 1998
The agar dilution MIC was used to compare activities of
gatifloxacin with those of ciprofloxacin, sparfloxacin, trovafloxacin, ampicillin, ampicillin-sulbactam, clindamycin, and metronidazole against 351 anaerobes. Overall MICs at which 50% of the isolates are
inhibited and MICs at which 90% of the isolates are inhibited (in
micrograms per milliliter) were as follows: gatifloxacin, 0.5 and 4; ciprofloxacin, 2 and 32; sparfloxacin, 2 and 8; trovafloxacin, 1 and 4; ampicillin, 1 and 64; ampicillin-sulbactam, 0.5 and 4; clindamycin, 0.125 and 8; and metronidazole, 1 and >16, respectively. Gatifloxacin MICs were similar to those of trovafloxacin in all organism groups.
Anaerobes are becoming increasingly
resistant to Quinolones such as ciprofloxacin, ofloxacin, fleroxacin, pefloxacin,
enoxacin, and lomefloxacin are inactive or only marginally active
against anaerobes (6-10, 16, 17). Newer quinolones with
increased antianaerobic activities include (i) those with slightly
increased activities (sparfloxacin, grepafloxacin, and levofloxacin)
and (ii) those with significantly improved antianaerobic activities (trovafloxacin, clinafloxacin, moxifloxacin, and DU-6859a) (6-10, 16, 17).
Gatifloxacin (AM-1155, CG 5501) is a broad-spectrum quinolone which
shares with sparfloxacin and grepafloxacin a methyl piperazinyl side chain at position 7 and a cyclopropyl substituent at position 1 (9, 11-13, 19, 21). The current study used standardized agar dilution methodology to examine the activities of gatifloxacin compared with those of ciprofloxacin, sparfloxacin, trovafloxacin, ampicillin, ampicillin-sulbactam, clindamycin, and metronidazole against 351 anaerobes.
All anaerobes were clinical strains isolated during the past 4 years
identified by standard procedures (18) and kept frozen in
200 g of skim milk (dehydrated skim milk; Difco Laboratories, Detroit, Mich.) per liter at Among anaerobic gram-negative bacilli, 86.3% of B. fragilis
group isolates, 61.2% of Prevotella-Porphyromonas
isolates, and 5.0% of fusobacteria produced
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Copyright © 1998, American Society for Microbiology. All rights reserved.
Activities of Gatifloxacin Compared to Those of
Seven Other Agents against Anaerobic Organisms
ABSTRACT
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-lactams due to -lactamase production and
other mechanisms. Although -lactamase production, as well as
concomitant resistance to -lactams, is the norm among the
Bacteroides fragilis group, other anaerobic gram-negative
bacilli in the genera Prevotella, Porphyromonas, and Fusobacterium have increasingly become -lactamase
positive. -Lactamase production also has been described for
clostridia. Metronidazole resistance in organisms other than
non-spore-forming gram-positive bacilli has been described elsewhere,
as has clindamycin resistance in anaerobic gram-negative bacilli
(1-5).
70°C until use. Prior to testing, strains were subcultured three times onto enriched sheep blood agar
plates. Gatifloxacin Susceptibility powder was obtained from Bristol-Myers Squibb Laboratories, Wallingford, Conn., and
other drugs were obtained from their respective manufacturers.
-Lactamase testing was performed by the nitrocefin disk
method (Cefinase; BBL Microbiology Systems,
Cockeysville, Md.) (1, 2). Agar dilution
susceptibility testing was performed according to the latest
method (approved but not yet published) recommended by the
National Committee for Clinical Laboratory Standards (15), with brucella agar with 5% sterile defibrinated laked sheep
blood for non-B. fragilis group strains; sulbactam was added
to ampicillin at a fixed ratio of 1:2. All quality control
gram-negative and -positive strains (15) recommended by the
National Committee for Clinical Laboratory Standards were included with
each run; in every case, results (where available) were in
control.
-lactamase. Results of
MIC testing are presented in Table
1.
Overall, MICs at which 50% of the isolates are inhibited
(MIC50s) and MIC90s (in micrograms per
milliliter) were as follows: gatifloxacin, 0.5 and 4;
ciprofloxacin, 2 and 32; sparfloxacin, 2 and 8; trovafloxacin, 1 and 4;
ampicillin, 1 and 64; ampicillin-sulbactam, 0.5 and 4;
clindamycin, 0.125 and 8; and metronidazole, 1 and >16,
respectively.
TABLE 1.
MICs (micrograms per milliliter) of agents
Gatifloxacin and trovafloxacin had the lowest MICs of all quinolones tested, followed by sparfloxacin and ciprofloxacin. MICs of the former two compounds were similar, with trovafloxacin MICs tending to be 1 or 2 dilutions lower than those of gatifloxacin. Gatifloxacin and trovafloxacin MICs were lower for non-B. fragilis group anaerobic gram-negative bacilli other than Prevotella bivia and Fusobacterium varium and for gram-positive anaerobes. One each of three strains (Bacteroides thetaiotaomicron, F. varium, and Lactobacillus spp.) yielded gatifloxacin and trovafloxacin MICs of >8 µg/ml.
Addition of sulbactam enhanced the activities of ampicillin against
-lactamase-producing anaerobic gram-negative bacilli. Although
most strains tested were susceptible (MICs of 
2 µg/ml) to
clindamycin, resistance was seen in some members of most groups tested.
With the exception of one strain of Prevotella
denticola with a metronidazole MIC of 16 µg/ml, the only
anaerobes resistant to metronidazole were the anaerobic gram-positive
bacilli.
All strains with unexpectedly high gatifloxacin, trovafloxacin, and metronidazole MICs were tested three times; in each case, results were identical.
Kato and coworkers (13) reported in vitro activity of
gatifloxacin against a wide range of anaerobes. MIC90s of
3.13 to 6.25 µg/ml were found for all members of the B. fragilis group. MIC90s for P. bivia were
6.25 µg/ml. By comparison, gatifloxacin was more active against
Prevotella intermedia, Porphyromonas
gingivalis, Fusobacterium species, peptostreptococci,
and Clostridium perfringens, with MIC90s of
0.39 µg/ml for all species except Peptostreptococcus asaccharolyticus. Gatifloxacin was not active against
Clostridium difficile (MIC90 of 25 µg/ml)
(13). Gatifloxacin MICs were several dilutions lower
than those of ciprofloxacin, ofloxacin, tosufloxacin, temafloxacin, and sparfloxacin (13). By contrast,
Bauernfeind (9), in a preliminary study, has reported a
MIC90 of 2 µg/ml for C. difficile.
In general, our results with gatifloxacin are similar to those reported by Kato et al. (13) and Bauernfeind (9). However, in contrast to findings by Kato et al. (13), we found lower gatifloxacin MICs, similar to those reported by Bauernfeind (9) against C. difficile. Although Kato et al. (13) found MIC90s of 0.39 µg/ml against 13 fusobacteria, the species of these strains was not reported. Wexler and coworkers (20) have reported elevated trovafloxacin MICs against F. varium compared to those of the same drug against other fusobacteria, and it is probable that the same applies for gatifloxacin. This needs to be confirmed by others.
Antianaerobic activities of ciprofloxacin, sparfloxacin,
and trovafloxacin are similar to those reported previously
(7-10, 16, 17, 20). Slightly higher trovafloxacin
MICs obtained in this study may be dependent on the composition
of strains tested compared to those in other reports by us and others
(16, 20). Activities of ampicillin-sulbactam, clindamycin,
and metronidazole reflect well-known patterns obtained with these
drugs, with ampicillin-sulbactam being very active against
-lactamase-producing strains, clindamycin being active
against all strains except some clostridia (especially C. difficile), and metronidazole being active against all
strains except anaerobic gram-positive bacilli. High
-lactam MICs for -lactamase-negative fusobacteria have been
described before (1-5). We do not have an explanation for
the metronidazole resistance encountered in one strain of
P. denticola; this phenomenon is currently under
investigation.
Nakashima and coworkers (14) have reported maximum concentrations of drug in serum in healthy human volunteers of 0.873, 1.71, 3.35, and 5.41 µg/ml after single oral doses of 100, 200, 400, and 600 mg, respectively. Values for area under the concentration-time curve after the four doses were 7.0, 14.5, 32.4, and 53.5 µg · h/ml, respectively. Serum concentrations reached a peak between 1 and 2 h (14). With the above pharmacokinetic data considered with the MIC data presented above as well as its known activity against members of the family Enterobacteriaceae (9, 11, 12, 21), gatifloxacin shows promise in treatment of mixed anaerobic infections, especially of those of the respiratory tract, ear, nose and throat, skin and soft tissue, and bite wounds. Clinical studies will be necessary to validate these hypotheses.
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ACKNOWLEDGMENTS |
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This study was supported by a grant from Bristol-Myers Squibb Laboratories.
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FOOTNOTES |
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* Corresponding author. Mailing address: Department of Pathology, Hershey Medical Center, 500 University Dr., Hershey, PA 17033. Phone: (717) 531-5113. Fax: (717) 531-7953. E-mail: pappelbaum{at}psghs.edu.
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REFERENCES |
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|
Top
Abstract
Text
References
|
|---|
| 1. |
Appelbaum, P. C.,
A. Philippon,
M. R. Jacobs,
S. K. Spangler, and L. Gutmann.
1990.
Characterization of -lactamases from non-Bacteroides fragilis group Bacteroides spp. belonging to seven species and their role in -lactam resistance.
Antimicrob. Agents Chemother.
34:2169-2176 |
| 2. | Appelbaum, P. C., S. K. Spangler, and M. R. Jacobs. 1990. Evaluation of two methods for rapid testing for beta-lactamase production in Bacteroides and Fusobacterium. Eur. J. Clin. Microbiol. Infect. Dis. 9:47-50[Medline]. |
| 3. |
Appelbaum, P. C.,
S. K. Spangler, and M. R. Jacobs.
1990.
-Lactamase production and susceptibilities to amoxicillin, amoxicillin-clavulanate, ticarcillin, ticarcillin-clavulanate, cefoxitin, imipenem, and metronidazole of 320 non-Bacteroides fragilis Bacteroides isolates and 129 fusobacteria from 28 U.S. centers.
Antimicrob. Agents Chemother.
34:1546-1550 |
| 4. |
Appelbaum, P. C.,
S. K. Spangler, and M. R. Jacobs.
1993.
Susceptibility of 539 gram-positive and -negative anaerobes to new agents, including RP 59500, biapenem, trospectomycin and piperacillin/tazobactam.
J. Antimicrob. Chemother.
32:223-231 |
| 5. |
Appelbaum, P. C.,
S. K. Spangler,
G. A. Pankuch,
A. Philippon,
M. R. Jacobs,
R. Shiman,
E. J. C. Goldstein, and D. Citron.
1994.
Characterization of a -lactamase from Clostridium clostridioforme.
J. Antimicrob. Chemother.
33:33-40 |
| 6. |
Barry, A. L., and P. C. Fuchs.
1991.
In vitro activities of sparfloxacin, tosufloxacin, ciprofloxacin, and fleroxacin.
Antimicrob. Agents Chemother.
35:955-960 |
| 7. |
Barry, A. L.,
P. C. Fuchs,
D. M. Citron,
S. D. Allen, and H. M. Wexler.
1993.
Methods for testing the susceptibility of anaerobic bacteria to two fluoroquinolone compounds, PD 131628 and clinafloxacin.
J. Antimicrob. Chemother.
31:893-900 |
| 8. |
Bauernfeind, A.
1993.
Comparative in vitro activities of the new quinolone, Bay y 3118, and ciprofloxacin, sparfloxacin, tosufloxacin, CI-960 and CI-990.
J. Antimicrob. Chemother.
31:505-522 |
| 9. |
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 |
| 10. |
Goldstein, E. J. C., and D. M. Citron.
1992.
Comparative activity of ciprofloxacin, ofloxacin, sparfloxacin, temafloxacin, CI-960, CI-990, and Win 57273 against anaerobic bacteria.
Antimicrob. Agents Chemother.
36:1158-1162 |
| 11. |
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 |
| 12. |
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 |
| 13. |
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 |
| 14. | Nakashima, M., T. Uematsu, K. Kosuge, H. Kusajima, T. Ooie, Y. Masuda, R. Ishida, and H. Uchida. 1995. Single- and multiple-dose pharmacokinetics of AM-1155, a new 6-fluoro-8-methoxy quinolone, in humans. Antimicrob. Agents Chemother. 39:2635-2640[Abstract]. |
| 15. | National Committee for Clinical Laboratory Standards. 1993. Methods for antimicrobial susceptibility testing of anaerobic bacteria, 3rd ed. In Approved standard. NCCLS publication no. M11-A3. National Committee for Clinical Laboratory Standards, Villanova, Pa. |
| 16. |
Spangler, S. K.,
M. R. Jacobs, and P. C. Appelbaum.
1994.
Activity of CP 99,219 compared with those of ciprofloxacin, grepafloxacin, metronidazole, cefoxitin, piperacillin, and piperacillin-tazobactam against 489 anaerobes.
Antimicrob. Agents Chemother.
38:2471-2476 |
| 17. |
Spangler, S. K.,
M. R. Jacobs, and P. C. Appelbaum.
1997.
Bactericidal activity of DU-6859a compared to activities of three quinolones, three -lactams, clindamycin, and metronidazole against anaerobes as determined by time-kill methodology.
Antimicrob. Agents Chemother.
41:847-849[Abstract].
|
| 18. | Summanen, P., E. J. Baron, D. M. Citron, C. A. Strong, H. M. Wexler, and S. M. Finegold. 1993. Wadsworth anaerobic bacteriology manual, 5th ed. Star Publishing Co., Belmont, Calif. |
| 19. |
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 |
| 20. | 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]. |
| 21. |
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, September 1998, p. 2459-2462, Vol. 42, No. 9
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Copyright © 1998, American Society for Microbiology. All rights reserved.
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