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Activity of the Investigational Fluoroquinolone Finafloxacin and Seven Other PD Dr Contact information: CORRESPONDING AUTHOR Activity of the Investigational Fluoroquinolone Finafloxacin and Seven Other PD Dr. Reiner Schaumann 49 th ICAAC Institute for Medical Microbiology and Epidemiology of Infectious Diseases San Francisco 2009 Antimicrobial Agents Against 83 Obligately Anaerobic Bacteria. University of Leipzig Liebigstr. 24 1 1 2 1 2 1 D-04103 Leipzig R. SCHAUMANN , G. H. GENZEL , W. STUBBINGS , C. S. STINGU , H. LABISCHINSKI , A. C. RODLOFF Germany E - 1973 Phone +49 341 97 15 200 1Inst. f. Med. Microbiology and Epidemiology of Infectious Diseases, Univ. of Leipzig, Leipzig, Germany; 2MerLion Pharmaceuticals GmbH, Berlin, Germany. Fax +49 341 97 15 209 E-Mail: [email protected] AbstractAbstract MethodsMethods ResultsResults andand DiscussionDiscussion Background: Finafloxacin (FIN) is a novel Bacterial Strains The Figures 2 and 3 show the scatter fluoroquinolone belonging to a 8-cyano subclass 83 obligately anaerobes including reference strains were taken from the histograms of MIC values obtained for FIN culture collection from the Institute for Medical Microbiology and and exhibits enhanced activity at slightly acidic and the seven other antimicrobial agents pH. FIN exhibited superior activity to comparator Epidemiology of Infectious Diseases, University of Leipzig, Germany. The fluoroquinolones in a wide range of rodent strains were collected from clinical specimens at the Institute and from against 83 obligately anaerobic bacteria infection models. With the present study the national and international studies and obtained in part from other included in this study. activity of FIN against 83 recently isolated strains laboratories. The following strains were used: Bacteroides fragils group of obligately anaerobic bacteria including (n=62): B. caccae (5); B. distasonis (10); B. eggerhtii (4); B. fragilis (6); B. pH was approx. 7.2 before incubation and reference strains was tested and compared to merdae (3); B. ovatus (7), B. stercoris (6); B. thetaiotaomicron (7); B. <0.03 5.0 to 7.5 after 48 h of incubation depending 0.06 uniformis (5); B. vulgatus (9) and Clostridium difficile (n=21). 0.125 35 various other antimicrobials. 0.25 on the strains tested and the growth of the 0.5 30 Methods: FIN was compared with moxifloxacin 1 25 bacteria. 2 20 (MOX), levofloxacin (LEV), ciprofloxacin (CIP), Antimicrobial Agents µg/ml 4 8 15 Antimicrobial agents were obtained as laboratory powders of known 16 10 clindamycin (CLI), imipenem (IMP), 32 5 >64 piperacillin/tazobactam (PIT) and metronidazole potency: FIN from MerLion Pharmaceuticals GmbH, Berlin, Germany; 0 The MIC values of the C. difficile strains and Fi Mo L Cip Cli Imipenem Pi Metronidazole nafl e p x v nd e metronidazole (MET) and clindamycin (CLI) from Sigma Chemical Co., St. i o ro r (MET) against 62 strains of the Bacteroides fragilis o floxaci fl f a a group 3 and 4 quinolones (Figure 3) seem to o loxacin my c x xacin i a ll c c in/T Louis, USA; moxifloxacin (MOX) and ciprofloxacin (CIP) from Bayer Vital in n in group and 21 Clostridium difficile strains. MICs a z display a bimodal distribution indicating ob a GmbH, Leverkusen, Germany; levofloxacin (LEV) from Aventis Pharma c were determined employing the microdilution tam that some strains are significantly less Frankfurt/M., Germany; imipenem (IMP) from MSD Sharp & Dohme GmbH, technique in Wilkens-Chalgren broth susceptible to these quinolones. supplemented with vitamin K1 and haemin. Haar, Germany; and piperacillin/tazobactam (PIT) from Sigma Chemical Co. and Otsuka Chemical Co. Ltd., Osaka, Japan, respectively. B. fragilis group, n=62 Results: The MIC 50 and MIC 90 values (µg/ml) are listed in the Table. Overall, FIN was particularly active against Conclusions: FIN has promising activity against Broth microdilution MIC determinations strains of the B. fragilis group (Figure 2) several pathogenic species of the B. fragilis group Tests were performed according to the recommendations of the Deutsches and C. difficile strains (Figure 3), where it and is slightly more active than MOX against the Institut für Normung (DIN) and standard DIN 58940-83. The bacterial inocula Figure 2 was equal to or more active than MOX and were prepared by suspending growth from 48 hour cultures grown on obligately anaerobic bacteria tested here. Further more active than LEV and CIP. work will be directed towards investigating the supplemented Columbia blood agar in Wilkins-Chalgren broth supplemented anti-anaerobic activity of finafloxacin under acidic with vitamin K 1 and haemin. After semi-automated inoculation (Dynatech conditions. MIC-2000-inoculator, Dynatech Laboratories, Inc., Chantilly, USA) resulting in a final dilution of approximately 1.0×10 5 CFU/well (1.0×10 6 CFU/ml), plates were incubated for 48 h at 37°C in an anaerobic chamber. The MIC was ConclusionsConclusions IntroductionIntroduction defined as the lowest antibiotic concentration that inhibited visible growth. In addition, pH of broth containing FIN was determined in part before and after incubation. FIN has promising activity against a number Finafloxacin (FIN; Fig. 1) is a novel of pathogenic species of the B. fragilis group fluoroquinolone belonging to a 8-cyano subclass and exhibits enhanced activity at slightly acidic ResultsResults andand DiscussionDiscussion and some C. difficile strains and is slightly pH. FIN exhibited superior activity to comparator more active than MOX against the obligately fluoroquinolones in a wide range of rodent Table 1: <0.03 anaerobic bacteria tested here. 0.06 infection models. With the present study the MIC /MIC (µg/ml) 0.125 B. fragilis group (n=62) C. difficile (n=21) 50 90 0.25 16 Further work will be directed towards 0.5 14 activity of FIN against 83 recently isolated strains of antimicrobials 12 Antimicrobial 1 investigating the anti-anaerobic activity of MIC MIC MIC MIC 2 10 of obligately anaerobic bacteria including Agent 50 90 50 90 against anaerobes µg/ml 4 8 8 6 finafloxacin under acidic conditions and reference strains was tested and compared to 16 4 FIN 0.5 2 1 16 32 2 >64 against additional obligately anaerobic various other antimicrobials. 0 F Mo L Cip Piperacillin/Tazobactam i e Clindamycin Im M naflo x vofloxacin ipen e bacteria. MOX 1 2 8 16 if ro tr l f o x o lo e n ac xa x m idazo cin ac in in le O O LEV 2 8 32 >64 F CIP 16 16 8 32 OH LiteratureLiterature H CLI 1 8 4 >64 H N N C. difficile , n=21 N H C l IMP 0.25 1 2 4 DIN, Deutsches Institut für Normung e.V. O H N Medizinische Mikrobiologie und Immunologie: PIT 0.5 4 0.5 2 Diagnostische Verfahren. Berlin, Wien, Zürich: Beuth MET 0.5 1 0.125 0.125 Figure 3 Verlag, 2004. Figure 1 Finafloxacin HCl.
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