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Antimicrobial Agents and Chemotherapy, June 1999, p. 1475-1479, Vol. 43, No. 6
R. M. Alden Research Laboratory, Santa
Monica-UCLA Medical Center, Santa Monica, California
90404,1 and UCLA School of Medicine, Los
Angeles, California 900242
Received 23 October 1998/Returned for modification 21 February
1999/Accepted 14 March 1999
The activity of gatifloxacin against 308 aerobes and 112 anaerobes
isolated from bite wound infections was studied. Gatifloxacin was
active at Approximately 5 million Americans
are bitten annually by animals (2, 7, 21, 25), and many
bites become infected with a wide variety of fastidious aerobic
bacteria and anaerobic veterinary bacteria (1, 3, 4, 8, 15, 20,
25). These unusual isolates are not included in published
susceptibility testing surveys of newer antimicrobial compounds
(9, 10). A clinician must rely on published studies to guide
both empirical and subsequent specific antimicrobial therapeutic choices.
Gatifloxacin (BMS-206584; AM-1155) is a new
8-methoxy fluoroquinolone [1-cyclopropyl-6-fluoro-1,4-dihydro-8-meth-oxy-7-(3-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid) with R and S enantiomers that
have identical pharmacokinetics after oral and intravenous
administration and a broad spectrum of activity (5, 13, 14,
26). In order to determine its activity against various
pathogenic species, we compared the susceptibilities of 420 recent
clinical bite wound isolates to gatifloxacin and five other fluoroquinolones.
The strains were previously isolated from bite wounds and identified by
standard criteria (11, 12, 16, 17, 24). The specific bite
sources (n) were dogs (146), cats (208), humans (23), and
other (24). Twelve bovine respiratory strains, especially Pasteurella haemolytica, were included for comparative
purposes; 7 American Type Culture Collection (ATCC) strains and 6 control strains were also tested. The numbers and species of isolates tested are shown in Table
1.
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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
ABSTRACT
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0.016 µg/ml against all 148 Pasteurella
isolates (eight species and three subspecies) tested and all other
aerobes tested, including Actinobacillus-Haemophilus spp.,
Eikenella corrodens, Neisseria weaveri,
Weeksella zoohelcum, staphylococci, and streptococci. Fusobacteria were sometimes resistant. Gatifloxacin MICs at which 90%
of the isolates were inhibited were 0.125 µg/ml against
Bacteroides tectum and Prevotella spp., 0.25 µg/ml against Porphyromonas spp., and 0.5 µg/ml against peptostreptococci.
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TABLE 1.
Comparative in vitro activities of gatifloxacin,
levofloxacin, trovafloxacin, sparfloxacin, ciprofloxacin,
grepafloxacin, and amoxicillin-clavulanate against 420 aerobic and
anaerobic skin and soft tissue animal and human bite wound pathogens
Standard laboratory powders were supplied as follows: gatifloxacin, Bristol Myers Squibb, Wallingford, Conn.; trovafloxacin, Pfizer Inc., New York, N.Y.; ciprofloxacin, Bayer Inc., West Haven, Conn.; levofloxacin, R. W. Johnson Pharmaceutical Research Institute, Raritan, N.J.; grepafloxacin, Glaxo-Wellcome Inc., Research Triangle Park, N.C.; sparfloxacin, Rhone-Poulenc Rorer, Collegeville, Pa.; and amoxicillin-clavulanate, SmithKline Beecham Pharmaceuticals, Philadelphia, Pa.
Susceptibility testing was performed by use of National Committee for Clinical Laboratory Standards (NCCLS) methods (18, 19). Brucella agar supplemented with hemin, vitamin K1, and 5% laked sheep blood was the basal medium used for anaerobic species and for Eikenella corrodens and Weeksella zoohelcum. Mueller-Hinton agar was used for staphylococci, and Mueller-Hinton agar supplemented with 5% sheep blood was used for the remainder of the organisms. Serial dilutions of antimicrobial agents were reconstituted according to the manufacturers' instructions on the day of the test and added to the agar media at various concentrations.
The agar plates were inoculated with a Steers replicator (Craft Machine Inc., Chester, Pa.). An inoculum of 104 CFU per spot was used for aerobes, and 105 CFU per spot was used for E. corrodens and anaerobes. E. corrodens, W. zoohelcum, and streptococci were incubated in 5% CO2, anaerobic bacteria were incubated in an anaerobic chamber for 48 h; and other organisms were incubated in ambient air at 37°C for 24 h prior to examination.
The control strains tested included Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922, Bacteroides fragilis ATCC 25285, Bacteroides thetaiotaomicron ATCC 29761, and Eubacterium lentum ATCC 43055. In addition, P. haemolytica ATCC 33396, Pasteurella multocida subsp. gallicida ATCC 51689, P. multocida subsp. septica ATCC 51688, Pasteurella stomatis ATCC 43327, Pasteurella dagmatis ATCC 43325, Pasteurella canis ATCC 43326, and Neisseria canis ATCC 14687 were used.
The activities of gatifloxacin and the other agents tested against the
bite wound isolates are shown in Table 1. Gatifloxacin was active at
0.125 µg/ml against all aerobic bite wound isolates, with the
exception of some streptococci (MIC at which 90% of the isolates were
inhibited [MIC90], 1 µg/ml; range, <0.03 to 2 µg/ml). All six fluoroquinolones tested were active at 0.125
µg/ml against all 148 Pasteurella isolates (eight species
and three P. multocida subspecies).
The other aerobic genera and species tested were also susceptible to
0.125 µg of gatifloxacin per ml, with the exception of
streptococci, which varied by species: all Streptococcus
mitis isolates were susceptible to 0.5 µg/ml, 10 isolates of
Streptococcus mutans and other species were susceptible to
1 µg/ml, but 2 µg/ml was required for inhibition of 1 of 4 isolates of Streptococcus intermedius.
Gatifloxacin was active against Bacteroides tectum (MIC90, 0.125 µg/ml), Prevotella heparinolytica (MIC90, 0.125 µg/ml), other Prevotella and Porphyromonas spp. (MIC90, 0.25 µg/ml), and peptostreptococci (MIC90, 0.5 µg/ml). Gatifloxacin was slightly more active against Prevotella spp. than was trovafloxacin but otherwise was generally equivalent to trovafloxacin. Consistent with our findings, Ednie et al. (5), using an unspecified NCCLS agar dilution method, reported gatifloxacin to have an MIC50 and an MIC90 of 0.5 and 1 µg/ml, respectively, for 55 peptostreptococcal isolates. Schaumann et al. (22) reported an MIC90 of 0.25 µg/ml for peptostreptococci by using a broth microdilution method, which may account for the disparity.
Fusobacterium species (MIC50 and
MIC90, 
8 µg/ml], including Fusobacterium
nucleatum (MIC50, 0.25 µg/ml; MIC90, 8
µg/ml), were sometimes resistant to gatifloxacin as well as to the
other quinolones. Ednie et al. (5) reported gatifloxacin to
have an MIC50 and an MIC90 of 0.5 µg/ml for
F. nucleatum and Fusobacterium mortiferum, 0.5 and 1 µg/ml, respectively, for Fusobacterium necrophorum, and 4 µg/ml for Fusobacterium varium. Schaumann et al.
(22) tested 17 Fusobacterium species by a broth
microdilution method and reported an MIC90 of 8 µg/ml.
Erwin et al. (6) studied Fusobacterium species by
an unspecified NCCLS agar dilution method and reported an
MIC90 of 0.19 µg/ml for gatifloxacin, which they noted to
be more active than trovafloxacin. In contrast, we found that
trovafloxacin had an MIC90 of 4 µg/ml against
fusobacteria; this value was generally within one dilution of the
gatifloxacin results. Also in contrast to our findings, Wexler et al.
(27) and Spangler et al. (23) noted trovafloxacin
MIC90s of 0.5 and 0.25 mg/liter, respectively, for F. nucleatum and MIC90s of 0.5 and 1.0 µg/ml,
respectively, for other Fusobacterium spp. Since the same
methods were used by us and by Wexler et al. (27), the
reason for this disparity is unclear, except that we studied veterinary
isolates recovered from human infections, while Wexler et al.
used human isolates recovered from other sources. The different medium
used by Spangler et al. (23), supplemented
Wilkins-Chalgren agar, may account for some variation.
Gatifloxacin appears to be more active than older quinolones against a spectrum of pathogens isolated from human and animal bite wounds and merits further clinical evaluation.
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ACKNOWLEDGMENTS |
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We thank Judee H. Knight, Alice E. Goldstein, and David Talan for various forms of assistance.
This study was funded in part by an educational grant from Bristol Myers Squibb, Wallingford, Conn.
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FOOTNOTES |
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* Corresponding author. Mailing address: 2021 Santa Monica Blvd., Suite 640E, Santa Monica, CA 90404. Phone: (310) 315-1511. Fax: (310) 315-3662. E-mail: EJCGMD{at}aol.com.
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Antimicrobial Agents and Chemotherapy, June 1999, p. 1475-1479, Vol. 43, No. 6
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