Susceptibility of Staphylococcus species and subspecies to fleroxacin

Abstract

Twenty-four Staphylococcus species or subspecies were examined for their susceptibilities to the fluoroquinolone fleroxacin (Ro 23-6240) by disk diffusion (5-jig disk) and by agar dilution for the determination of MICs.Resistant strains were further tested for their susceptibilities to oxacillin and the fluoroquinolone ciprofloxacin. Reference strains of the novobiocin-resistant species (Staphylococcus saprophyticus, Staphylococcus cohnii, Staphylococcus xylosus, Staphylococcus arlettae, and Staphylococcus gallinarum) had an intrinsic intermediate susceptibility (MIC,4 ,ug/ml) to fleroxacin. Fleroxacin resistance was not observed in the reference strains of the novobiocin-susceptible species (MIC, 0.5 to 2.0 ,uglml). Clinical isolates of coagulase-negative species were generally less susceptible to fleroxacin than were reference strains. Fleroxacin (Ro 23-6240) is a new orally and intravenously administered trifluoroquinolone with a half-life of 9 to 10 h in humans and peak levels of 2.3 VLg/ml in serum after a single 200-mg oral dose (12). The drug has shown excellent activity against most members of the family Enterobacteriaceae, inhibiting 90% of isolates per species at concentrations of <1 p.g/ml (2, 3). Because of its broad spectrum of activity, fleroxacin may also have use for treating staphylococcal infections; a previous report has shown the in vitro effectiveness of fleroxacin against two species of staphylococci (9). In the current study, 24 Staphylococcus species or subspecies were tested for their susceptibilities to fleroxacin by disk diffusion and by agar dilution for determination of MICs. The resistant strains were further tested for their susceptibilities to oxacillin and to the fluoroquinolone ciprofloxacin.(A preliminary report of this work was presented previ-Reference strains of the 24 Staphylococcus species or subspecies were obtained from our laboratory's collection of isolates from the skin of healthy human volunteers or from animals. Clinical strains used in this study were isolated from April 1989 to February 1990 from a variety of patients at Rex Hospital, Raleigh, N.C. All the clinical strains were identified by using the criteria of Kloos and coworkers (4, 5). The reference and clinical strains were maintained on P agar (11) at 4°C for up to 2 months and preserved by desiccation on steatite fish spine insulator beads at 4°C. These storage conditions do not alter the antibiograms or plasmid compositions of strains tested in this laboratory.Fleroxacin as powder and in 5-,ug disks was kindly provided by Hoffmann-La Roche, Inc. Md.). Disk diffusion susceptibility testing was performed by the procedure outlined by the National Committee for Clinical Laboratory Standards (7). Agar dilution susceptibility tests for fleroxacin and oxacillin were performed by the procedure outlined by the National Committee for Clinical Laboratory Standards (8) with Mueller-Hinton agar. Oxacillin plates were supplemented with 4% NaCl. The plates were inoculated by using the Steers replicator (10). Ciprofloxac...

Pharmacokinetics of [18F]fleroxacin in healthy human subjects studied by using positron emission tomography

“…Overall, the concentrations of fleroxacin achieved in human tissue appear quite promising compared with the sensitivity of a wide range of microorganisms to fleroxacin. Thus, while the MICs for 90% of strains tested (MIC90s) for virtually all members of the family Enterobacteriaceae are <0.5 ,g/ml (with the MIC90 for Serratia marcescens of <1 ,ug/ml and that for Providencia species of <2 ,ug/ml), peak concentration of fleroxacin are well over 5 ,ug/g in all extracranial tissues after a standard 400-mg dose, with a sustained concentration above the MIC90 in virtually all tissues for at least 6 to 8 h. In addition, the MIC90s for such organisms as Acinetobacter anitratus (4 ,ug/ml) and methicillin-sensitive and methicillin-resistant S. aureus (1 p,g/ml) are also within reach of the levels of fleroxacin achieved in tissues (2,6). Thus, this study suggests that fleroxacin should be particularly useful against urinary tract, gastrointestinal, hepatobiliary, skeletal, and pulmonary infections and that it has promise for the treatment of infections due to these organisms at other sites such as the prostate, uterus, and muscle.…”

“…Both in vitro and in animal models, fleroxacin's anti-gram-negative-bacterium activity has been shown to be comparable to that of the earlier fluoroquinolones (norfloxacin, pefloxacin, ciprofloxacin, and ofloxacin) (1,2,7,11,13,19,29,36,37,40). In addition, however, studies in endocarditis models, as well as in vitro, have shown that fleroxacin has significant activity against both methicillin-susceptible and -resistant Staphylococcus aureus (1,6,25,28).…”

Update on clinical significance of coagulase-negative staphylococci

“…However, with the increased use of this group of antibiotics, particularly ciprofloxacin, there have been reports of resistant CNS (21,23,72,101,181). Studies have indicated that resistance to one quinolone may predispose the isolate to become resistant to other quinolones (21,257,296,319).…”

“…However, with the increased use of this group of antibiotics, particularly ciprofloxacin, there have been reports of resistant CNS (21,23,72,101,181). Studies have indicated that resistance to one quinolone may predispose the isolate to become resistant to other quinolones (21,257,296,319). Some investigators have tried to induce resistance to the quinolones by serial passages in the presence of the antibiotics (23,224,284 (88).…”

“…The (167). The human isolates exhibiting intrinsic novobiocin resistance (S. saprophyticus, S. cohnii, and S. xylosus) show a slight intrinsic penicillin resistance (167) and decreased susceptibility to quinolone antibiotics (21). Fortunately, S. lugdunensis and S. schleiferi rarely appear to develop resistance to most antibiotics (84); however, antibiotic resistance in S. lugdunensis has begun to emerge (187).…”