The University of Illinois at Chicago, Department of Pharmacy Practice, Microbiology Research Laboratory, 833 South Wood Street, Chicago, IL 60612, USA
Sir,
Gatifloxacin, also known as BMS-206584, AM-1155 and CG-5501, is a novel 8-methoxy fluoroquinolone with activity against a broad-spectrum of bacteria. In the present study we have evaluated the in-vitro activity of this agent against Legionella spp. and compared it with that of the older fluoroquinolone, ciprofloxacin, which has previously been shown to be active in vitro against these pathogens and to be effective when used as treatment of patients with infections caused by them. 1,2
Gatifloxacin was obtained from Bristol-Myers Squibb (Wallingford, CT, USA) and was prepared according to the manufacturer's instructions with dimethylsulphoxide (DMSO) as the solvent and sterile distilled water as the diluent. Ciprofloxacin, which was obtained from United States Pharmacopeia (Rockville, MD, USA), was prepared according to guidelines of the National Committee for Clinical Laboratory Standards (NCCLS). 3 The organisms used in the study were provided by the University of Illinois Hospital (Chicago, IL, USA), Northwestern University Hospital (Chicago, IL, USA), Abbott Laboratories (Chicago, IL, USA), the Centers for Disease Control (Atlanta, GA, USA) and the American Type Culture Collection (ATCC) (Rockville, MD, USA), and included 41 non-replicate clinical isolates and five ATCC strains (Legionella pneumophila33152, Legionella bozemanii 33217, Legionella dumoffii 33279, Legionella gormanii 33297 and Legionella longbeachae 33462). Of the clinical isolates, 34 were identified as L. pneumophila and the remaining seven as L. bozemanii (n= 2), L. longbeachae (n= 2) and one each of L. dumoffii, Legionella erythra and Legionella micdadei.
MICs were determined by an agar dilution method recommended by the NCCLS.
3 The medium used was buffered charcoal yeast extract
(BCYE) (Oxoid-Unipath, Ogdensburg, NY, USA) but, as MICs determined with this
medium are often falsely high because of inactivation of the antibiotics by the charcoal,
4,5 we also carried out
susceptibility testing with a less inhibitory medium, buffered starch yeast extract (BSYE);
6 the antibiotic concentrations in the media ranged from
0.0005 to 8 mg/L in BCYE
and 0.00050.5 mg/L in BSYE. Inocula were prepared
by suspending organisms in sterile distilled water and adjusting the turbidity with a
spectrophotometer at 625 nm so that it was equivalent to that of a 0.5 McFarland standard. A
replicator device was used to inoculate approximately 8 µL of each suspension on to the
surfaces of the BSYE plates, giving final inocula of approximately 10
6 cfu/spot. The suspensions were then diluted 1:100 with sterile distilled water and
similarly inoculated on to the surfaces of the BCYE
plates, giving final inocula of
approximately 10
4 cfu/spot. Control plates of each medium containing DMSO and sterile distilled
water and blood agar plates (to ensure the purity of the inocula) were included. All tests were
performed in duplicate and the plates were incubated at 35°C for 48 h in a humidified
environment. The MIC was taken as the lowest concentration of each antibiotic that allowed no
growth or only a barely visible haze.
While all 46 strains grew well on BCYE agar, seven (two of L. pneumophila
and five of the non-pneumophila Legionella spp.) failed to grow on BSYE, even when
the higher inoculum was used. The use of DMSO as a solvent for gatifloxacin did not affect the
growth of any of the isolates.
The MICs of gatifloxacin and ciprofloxacin are summarized in the Table. The MIC90s of both quinolones for the L. pneumophila and
non-pneumophila Legionella spp. strains were 1 mg/L on BCYE and 0.03 mg/L
on BSYE. The lower MICs obtained with the non-charcoal-containing medium are believed to
more accurately reflectthe susceptibilities of Legionella spp. isolates. Unfortunately,
however, BSYE and other less antagonistic media do not support the growth of all strains.
4,5
|
In the light of the good in-vitro activity of gatifloxacin against Legionella spp. isolates, as demonstrated by a range of susceptibility testing methods, we believe that this antibiotic warrants further investigation as treatment of patients with infections caused by these organisms.
Acknowledgments
This work was supported by a grant from Bristol-Myers Squibb.
Notes
* Corresponding author. Tel: +1-312-996-8639; Fax:
+1-312-413-1797; E-mail: Pendland{at}uic.eduPendland@uic.edu
References
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