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Chemical Compound Review

CLINAFLOXACIN     7-(3-aminopyrrolidin-1-yl)-8- chloro-1...

Synonyms: Bay-v-3545, SureCN33959, AGN-PC-00C6C1, CHEMBL278255, CI-960, ...
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Disease relevance of CI-960


High impact information on CI-960


Chemical compound and disease context of CI-960


Biological context of CI-960

  • Absolute bioavailability of orally administered clinafloxacin was approximately 90% and did not change with increasing dose [8].
  • High-level resistance to all of the compounds except clinafloxacin was associated with two or more amino acid substitutions involving both GyrA (Ser-81 to Phe) and ParC (Ser-79 to Phe or Ser-80 to Pro and Asp-83 to Tyr) [16].
  • Further morphological studies during the PAE showed that the first division of the filamentous cell was asymmetrical, and both bacterial cell division and septation were delayed after exposure to 0.5 MIC of CI-960 [17].

Anatomical context of CI-960

  • We evaluated the effects of the quinolone CI-960 (Parke-Davis) on primary or repeated chlamydial infection in the monkey salpinx pocket model [18].
  • No modification of the MIC was observed after 20 successive infections of HeLa cells and contact with subinhibitory concentrations of clinafloxacin, levofloxacin, and sparfloxacin for 24 h [19].
  • The concentrations of clinafloxacin in alveolar macrophages, epithelial lining fluid, bronchial mucosa and serum after administration of single 200 mg oral doses to patients undergoing fibre-optic bronchoscopy [20].
  • After three days of therapy, significant reduction of bacterial concentrations were found in vegetations, kidneys, and spleens of animals treated with clinafloxacin [21].
  • Altering the medium pH, adding divalent cations (magnesium), and increasing the inoculum concentration to 10(6) colony-forming units per spot adversely effected the activity of both PD127391 and PD131628 [22].

Associations of CI-960 with other chemical compounds


Gene context of CI-960

  • Given the susceptibility of defined gyrA or parC mutants, the results suggested that clinafloxacin displays comparable if unequal targeting of gyrase and topoisomerase IV [4].
  • Clinafloxacin was highly active against S. pneumoniae 7785 (MIC, 0.125 microg/ml), and neither gyrA nor parC quinolone resistance mutations alone had much effect on this activity [4].
  • The MIC of clinafloxacin for strains with no mutation in either gyrA or parC genes ranged from 0.008 to 0.25 mg/L [24].
  • A combination of both mutations was needed to register resistance, suggesting that both gyrase and topoisomerase IV are clinafloxacin targets in vivo [4].
  • Overall, the NFQs and clinafloxacin were less susceptible than the other quinolones to existing mechanisms of quinolone resistance in staphylococci [25].

Analytical, diagnostic and therapeutic context of CI-960


  1. Activity of clinafloxacin against multidrug-resistant Enterococcus faecium. Burney, S., Landman, D., Quale, J.M. Antimicrob. Agents Chemother. (1994) [Pubmed]
  2. Antistaphylococcal activity of WCK 771, a tricyclic fluoroquinolone, in animal infection models. Patel, M.V., De Souza, N.J., Gupte, S.V., Jafri, M.A., Bhagwat, S.S., Chugh, Y., Khorakiwala, H.F., Jacobs, M.R., Appelbaum, P.C. Antimicrob. Agents Chemother. (2004) [Pubmed]
  3. CI-960, a new fluoroquinolone, for therapy of experimental ciprofloxacin-susceptible and -resistant Staphylococcus aureus endocarditis. Kaatz, G.W., Seo, S.M., Lamp, K.C., Bailey, E.M., Rybak, M.J. Antimicrob. Agents Chemother. (1992) [Pubmed]
  4. DNA gyrase and topoisomerase IV are dual targets of clinafloxacin action in Streptococcus pneumoniae. Pan, X.S., Fisher, L.M. Antimicrob. Agents Chemother. (1998) [Pubmed]
  5. Antimicrobial activities of two investigational fluoroquinolones (CI-960 and E4695) against over 100 Legionella sp. isolates. Gooding, B.B., Erwin, M.E., Barrett, M.S., Johnson, D.M., Jones, R.N. Antimicrob. Agents Chemother. (1992) [Pubmed]
  6. Results of a clinical trial of clinafloxacin versus imipenem/cilastatin for intraabdominal infections. Solomkin, J.S., Wilson, S.E., Christou, N.V., Rotstein, O.D., Dellinger, E.P., Bennion, R.S., Pak, R., Tack, K. Ann. Surg. (2001) [Pubmed]
  7. In vitro development of resistance to six quinolones in Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus. Boos, M., Mayer, S., Fischer, A., Köhrer, K., Scheuring, S., Heisig, P., Verhoef, J., Fluit, A.C., Schmitz, F.J. Antimicrob. Agents Chemother. (2001) [Pubmed]
  8. Pharmacokinetics of clinafloxacin after single and multiple doses. Randinitis, E.J., Brodfuehrer, J.I., Eiseman, I., Vassos, A.B. Antimicrob. Agents Chemother. (2001) [Pubmed]
  9. Clinafloxacin versus piperacillin-tazobactam in treatment of patients with severe skin and soft tissue infections. Siami, G., Christou, N., Eiseman, I., Tack, K.J. Antimicrob. Agents Chemother. (2001) [Pubmed]
  10. Drug interactions with clinafloxacin. Randinitis, E.J., Alvey, C.W., Koup, J.R., Rausch, G., Abel, R., Bron, N.J., Hounslow, N.J., Vassos, A.B., Sedman, A.J. Antimicrob. Agents Chemother. (2001) [Pubmed]
  11. In vitro evaluation of ABT-719, a novel DNA gyrase inhibitor. Flamm, R.K., Vojtko, C., Chu, D.T., Li, Q., Beyer, J., Hensey, D., Ramer, N., Clement, J.J., Tanaka, S.K. Antimicrob. Agents Chemother. (1995) [Pubmed]
  12. Comparison of a rabbit model of bacterial endocarditis and an in vitro infection model with simulated endocardial vegetations. Hershberger, E., Coyle, E.A., Kaatz, G.W., Zervos, M.J., Rybak, M.J. Antimicrob. Agents Chemother. (2000) [Pubmed]
  13. Comparative activities of ciprofloxacin, clinafloxacin, gatifloxacin, gemifloxacin, levofloxacin, moxifloxacin, and trovafloxacin against epidemiologically defined Acinetobacter baumannii strains. Heinemann, B., Wisplinghoff, H., Edmond, M., Seifert, H. Antimicrob. Agents Chemother. (2000) [Pubmed]
  14. Activities of three investigational fluoroquinolones (BAY y 3118, DU-6859a, and clinafloxacin) against Neisseria gonorrhoeae isolates with diminished susceptibilities to ciprofloxacin and ofloxacin. Carlyn, C.J., Doyle, L.J., Knapp, C.C., Ludwig, M.D., Washington, J.A. Antimicrob. Agents Chemother. (1995) [Pubmed]
  15. Analysis of macromolecular biosynthesis to define the quinolone-induced postantibiotic effect in Escherichia coli. Guan, L., Blumenthal, R.M., Burnham, J.C. Antimicrob. Agents Chemother. (1992) [Pubmed]
  16. Activities of newer fluoroquinolones against Streptococcus pneumoniae clinical isolates including those with mutations in the gyrA, parC, and parE loci. Jorgensen, J.H., Weigel, L.M., Ferraro, M.J., Swenson, J.M., Tenover, F.C. Antimicrob. Agents Chemother. (1999) [Pubmed]
  17. Postantibiotic effect of CI-960, enoxacin and ciprofloxacin on Escherichia coli: effect on morphology and haemolysin activity. Guan, L., Burnham, J.C. J. Antimicrob. Chemother. (1992) [Pubmed]
  18. Effects of quinolone analog CI-960 in a monkey model of Chlamydia trachomatis salpingitis. Patton, D.L., Cosgrove, Y.T., Kuo, C.C., Campbell, L.A. Antimicrob. Agents Chemother. (1993) [Pubmed]
  19. Comparative activities of new fluoroquinolones, alone or in combination with amoxicillin, trimethoprim-sulfamethoxazole, or rifampin, against intracellular Listeria monocytogenes. Michelet, C., Avril, J.L., Arvieux, C., Jacquelinet, C., Vu, N., Cartier, F. Antimicrob. Agents Chemother. (1997) [Pubmed]
  20. The concentrations of clinafloxacin in alveolar macrophages, epithelial lining fluid, bronchial mucosa and serum after administration of single 200 mg oral doses to patients undergoing fibre-optic bronchoscopy. Honeybourne, D., Andrews, J.M., Cunningham, B., Jevons, G., Wise, R. J. Antimicrob. Chemother. (1999) [Pubmed]
  21. Treatment of experimental endocarditis due to multidrug-resistant Enterococcus faecium with clinafloxacin and penicillin. Zaman, M.M., Landman, D., Burney, S., Quale, J.M. J. Antimicrob. Chemother. (1996) [Pubmed]
  22. Antimicrobial activity evaluations of two new quinolones, PD127391 (CI-960 and AM-1091) and PD131628. Barrett, M.S., Jones, R.N., Erwin, M.E., Johnson, D.M., Briggs, B.M. Diagn. Microbiol. Infect. Dis. (1991) [Pubmed]
  23. Comparative activities of eight quinolones against members of the Bacteroides fragilis group. Borobio, M.V., Conejo, M., Ramirez, E., Suarez, A.I., Perea, E.J. Antimicrob. Agents Chemother. (1994) [Pubmed]
  24. Activity of clinafloxacin, compared with six other quinolones, against Acinetobacter baumannii clinical isolates. Vila, J., Ribera, A., Marco, F., Ruiz, J., Mensa, J., Chaves, J., Hernandez, G., Jimenez De Anta, M.T. J. Antimicrob. Chemother. (2002) [Pubmed]
  25. Quinolone resistance in Staphylococci: activities of new nonfluorinated quinolones against molecular targets in whole cells and clinical isolates. Roychoudhury, S., Catrenich, C.E., McIntosh, E.J., McKeever, H.D., Makin, K.M., Koenigs, P.M., Ledoussal, B. Antimicrob. Agents Chemother. (2001) [Pubmed]
  26. Clinafloxacin pharmacokinetics in subjects with various degrees of renal function. Randinitis, E.J., Koup, J.R., Rausch, G., Abel, R., Bron, N.J., Hounslow, N.J., Vassos, A.B., Sedman, A.J. Antimicrob. Agents Chemother. (2001) [Pubmed]
  27. Comparative therapeutic efficacy of clinafloxacin in a Pseudomonas aeruginosa mouse renal abscess model. Shapiro, M.A., Sesnie, J.C., Desaty, T.M., Griffin, T.J., Heifetz, C.L. J. Antimicrob. Chemother. (1998) [Pubmed]
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