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Chemotherapy 90;36:365-372

In vitro Activity of PD 127,391, a New Quinolone against Bacterial Isolates from Cancer Patients Kenneth V.I. Rolston, Dai Hsi Ho, Barbara LeBlanc, Gerald P. Bodey Section of Infectious Diseases, Department of Medical Specialties, The University of Texas M.D. Anderson Cancer Center, Houston, Tex., USA

Key Words. 4-Quinolones • PD127,391 • Broad antimicrobial spectrum

Introduction Bacterial infections continue to plague patients with neoplastic diseases despite tremendous advances in antimicrobial therapy [1], In recent years, a large number of 4-quinolone antimicrobial agents have been developed. Most of these agents in­ cluding norfloxacin, ciprofloxacin, enoxacin, ofloxacin, pefloxacin and fleroxacin are far more potent against aerobic gram­

negative bacilli than they are against gram-positive organisms. The two quinolones currently released for use in the Unit­ ed States (norfloxacin and ciprofloxacin) have both been used for infection preven­ tion in cancer patients, and ciprofloxacin has been used alone and in various anti­ microbial combinations for the therapy of established infections in such patients [2-6]. Current data indicate that these quinolones are effective in reducing gram­

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Abstract. The in vitro activity of PD 127,391, a new 4-quinolone, was compared to that of ciprofloxacin against common clinical bacterial isolates from patients with can­ cer. PD 127,391 was found to have a broad antimicrobial spectrum with excellent activ­ ity against gram-positive isolates (including multidrug-resistant organism such as Corynebacterium jeikeium, Enterococcus faecalis, Enterococcus faecium, methicillin-resistant Staphylococcus aureus and coagulase-negative Staphylococcus spp.). It was also ex­ tremely active against gram-negative bacilli including Pseudomonas aeruginosa. Against organisms such as Achromobacter xylosoxidans, Acinetobacter spp. and Xanthomonas maltophilia, which are frequently resistant to a variety of antimicrobial agents, PD 127,391 exhibited good activity, inhibiting all such isolates at a concentration of 0.5 pg/ml. Overall, PD127,391 was far more potent than ciprofloxacin against gram­ positive isolates and slightly more active against gram-negative isolates. No bacterium that we examined needed more than 2 pg/ml of PD 127,391 for inhibition.

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Materials and Methods Antimicrobial Agents Laboratory reference antimicrobial agents of known potency were obtained from the manufactur­ ers (PD127,391 from Warner-Lambert Pharmaceuti­ cal Research, Ann Arbor, Mich., and ciprofloxacin from Miles Pharmaceuticals, West Haven, Conn., USA). The powders were kept frozen at - 70°C until use. Bacterial Isolate A total of 798 gram-positive and gram-negative organisms, representing 37 bacterial species, was tested. All organisms were isolated from cancer pa­ tients admitted to our institution during the past 5

years, and the majority were blood culture isolates. These organisms are maintained using ultrafreezing methods and are renewed periodically as new iso­ lates become available. Only one isolate per patient was used in order to avoid duplication of strains. Staphylococcal species were identified according to the methods outlined by Kloos and Schleifer [9] and Kloos and Wolfsholl [10]. The streptococci were identified and grouped by the methods described by Facklam and Carey [11], Staphylococcus aureus iso­ lates were considered susceptible to penicillin G on the basis of a minimal inhibitory concentration of

In vitro activity of PD127,391, a new quinolone against bacterial isolates from cancer patients.

The in vitro activity of PD127,391, a new 4-quinolone, was compared to that of ciprofloxacin against common clinical bacterial isolates from patients ...
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