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. 1996 Mar;40(3):776–779. doi: 10.1128/aac.40.3.776

Pharmacokinetics of sparfloxacin and serum bactericidal activity against pneumococci.

M Trautmann 1, M Ruhnke 1, K Borner 1, J Wagner 1, P Koeppe 1
PMCID: PMC163197  PMID: 8851610

Abstract

Sparfloxacin, a new fluorinated quinolone, exhibits higher in vitro activity against pneumococci than do ciprofloxacin and ofloxacin. Since up to 30% of cases of pneumococcal pneumonia are associated with bacteremia, and since an increasing percentage of pneumococci are resistant against penicillin, we studied the serum bactericidal activity of sparfloxacin against pneumococci in eight healthy, middle-aged volunteers. Pharmacokinetics in serum and urine after a 400-mg oral dose of sparfloxacin were comparable to those described by other authors. Inhibitory and bactericidal activities in serum were measured for four pneumococcal isolates representing penicillin-susceptible (one isolate), intermediately resistant (two isolates), and highly resistant (one isolate) strains. Geometric mean inhibitory titers ranged between 1:2.4 and 1:6.3 and bactericidal titers ranged between 1:1.3 and 1:3.6 during a time period of 1 to 6 h after drug intake. Although such titers were not sufficient to predict a clinical response based on previous pharmacodynamic studies using quinolone antibiotics, data obtained with volunteers may only partially reflect the clinical situation in which a rise of humoral antibodies directed against pneumococcal antigens may help to reinforce the bactericidal action of the antibiotic.

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Selected References

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  1. Ausina V., Coll P., Sambeat M., Puig I., Condom M. J., Luquin M., Ballester F., Prats G. Prospective study on the etiology of community-acquired pneumonia in children and adults in Spain. Eur J Clin Microbiol Infect Dis. 1988 Jun;7(3):342–347. doi: 10.1007/BF01962334. [DOI] [PubMed] [Google Scholar]
  2. Barry B., Gehanno P., Blumen M., Boucot I. Clinical outcome of acute otitis media caused by pneumococci with decreased susceptibility to penicillin. Scand J Infect Dis. 1994;26(4):446–452. doi: 10.3109/00365549409008618. [DOI] [PubMed] [Google Scholar]
  3. Blaser J., Stone B. B., Groner M. C., Zinner S. H. Comparative study with enoxacin and netilmicin in a pharmacodynamic model to determine importance of ratio of antibiotic peak concentration to MIC for bactericidal activity and emergence of resistance. Antimicrob Agents Chemother. 1987 Jul;31(7):1054–1060. doi: 10.1128/aac.31.7.1054. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Borner K., Borner E., Lode H. Determination of sparfloxacin in serum and urine by high-performance liquid chromatography. J Chromatogr. 1992 Sep 2;579(2):285–289. doi: 10.1016/0378-4347(92)80393-5. [DOI] [PubMed] [Google Scholar]
  5. Cantón E., Pemán J., Jimenez M. T., Ramón M. S., Gobernado M. In vitro activity of sparfloxacin compared with those of five other quinolones. Antimicrob Agents Chemother. 1992 Mar;36(3):558–565. doi: 10.1128/aac.36.3.558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chin N. X., Gu J. W., Yu K. W., Zhang Y. X., Neu H. C. In vitro activity of sparfloxacin. Antimicrob Agents Chemother. 1991 Mar;35(3):567–571. doi: 10.1128/aac.35.3.567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Echols R., Weinstein M. P., O'Keeffe B., Shah A., Heller A. H. Comparative crossover assessment of serum bactericidal activity and pharmacokinetics of ciprofloxacin and ofloxacin. J Antimicrob Chemother. 1994 Jan;33(1):111–118. doi: 10.1093/jac/33.1.111. [DOI] [PubMed] [Google Scholar]
  8. Forrest A., Nix D. E., Ballow C. H., Goss T. F., Birmingham M. C., Schentag J. J. Pharmacodynamics of intravenous ciprofloxacin in seriously ill patients. Antimicrob Agents Chemother. 1993 May;37(5):1073–1081. doi: 10.1128/aac.37.5.1073. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Friedland I. R., McCracken G. H., Jr Management of infections caused by antibiotic-resistant Streptococcus pneumoniae. N Engl J Med. 1994 Aug 11;331(6):377–382. doi: 10.1056/NEJM199408113310607. [DOI] [PubMed] [Google Scholar]
  10. Fuchs P. C., Barry A. L., Pfaller M. A., Allen S. D., Gerlach E. H. Multicenter evaluation of the in vitro activities of three new quinolones, sparfloxacin, CI-960, and PD 131,628, compared with the activity of ciprofloxacin against 5,252 clinical bacterial isolates. Antimicrob Agents Chemother. 1991 Apr;35(4):764–766. doi: 10.1128/aac.35.4.764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Goldstein F. W., Garau J. Resistant pneumococci: a renewed threat in respiratory infections. Scand J Infect Dis Suppl. 1994;93:55–62. [PubMed] [Google Scholar]
  12. Hackbarth C. J., Chambers H. F., Sande M. A. Serum bactericidal titer as a predictor of outcome in endocarditis. Eur J Clin Microbiol. 1986 Feb;5(1):93–97. doi: 10.1007/BF02013476. [DOI] [PubMed] [Google Scholar]
  13. Hammerschlag M. R., Hyman C. L., Roblin P. M. In vitro activities of five quinolones against Chlamydia pneumoniae. Antimicrob Agents Chemother. 1992 Mar;36(3):682–683. doi: 10.1128/aac.36.3.682. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Johnson J. H., Cooper M. A., Andrews J. M., Wise R. Pharmacokinetics and inflammatory fluid penetration of sparfloxacin. Antimicrob Agents Chemother. 1992 Nov;36(11):2444–2446. doi: 10.1128/aac.36.11.2444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kaku M., Ishida K., Irifune K., Mizukane R., Takemura H., Yoshida R., Tanaka H., Usui T., Tomono K., Suyama N. In vitro and in vivo activities of sparfloxacin against Mycoplasma pneumoniae. Antimicrob Agents Chemother. 1994 Apr;38(4):738–741. doi: 10.1128/aac.38.4.738. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Klastersky J., Daneau D., Swings G., Weerts D. Antibacterial activity in serum and urine as a therapeutic guide in bacterial infections. J Infect Dis. 1974 Feb;129(2):187–193. doi: 10.1093/infdis/129.2.187. [DOI] [PubMed] [Google Scholar]
  17. Koeppe P., Hamann C. A program for non-linear regression analysis to be used on desk-top computers. Comput Programs Biomed. 1980 Dec;12(2-3):121–128. doi: 10.1016/0010-468x(80)90058-6. [DOI] [PubMed] [Google Scholar]
  18. Lee B. L., Padula A. M., Kimbrough R. C., Jones S. R., Chaisson R. E., Mills J., Sande M. A. Infectious complications with respiratory pathogens despite ciprofloxacin therapy. N Engl J Med. 1991 Aug 15;325(7):520–521. doi: 10.1056/nejm199108153250719. [DOI] [PubMed] [Google Scholar]
  19. Liñares J., Pallares R., Alonso T., Perez J. L., Ayats J., Gudiol F., Viladrich P. F., Martin R. Trends in antimicrobial resistance of clinical isolates of Streptococcus pneumoniae in Bellvitge Hospital, Barcelona, Spain (1979-1990). Clin Infect Dis. 1992 Jul;15(1):99–105. doi: 10.1093/clinids/15.1.99. [DOI] [PubMed] [Google Scholar]
  20. Malmborg A. S., Ahlén S. In vitro activity of sparfloxacin compared with ciprofloxacin and ofloxacin against respiratory tract pathogens. Chemotherapy. 1993;39(1):32–35. doi: 10.1159/000238970. [DOI] [PubMed] [Google Scholar]
  21. Pallares R., Gudiol F., Liñares J., Ariza J., Rufi G., Murgui L., Dorca J., Viladrich P. F. Risk factors and response to antibiotic therapy in adults with bacteremic pneumonia caused by penicillin-resistant pneumococci. N Engl J Med. 1987 Jul 2;317(1):18–22. doi: 10.1056/NEJM198707023170104. [DOI] [PubMed] [Google Scholar]
  22. Platt R., Ehrlich S. L., Afarian J., O'Brien T. F., Pennington J. E., Kass E. H. Moxalactam therapy of infections caused by cephalothin-resistant bacteria: influence of serum inhibitory activity on clinical response and acquisition of antibiotic resistance during therapy. Antimicrob Agents Chemother. 1981 Sep;20(3):351–355. doi: 10.1128/aac.20.3.351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Prober C. G., Yeager A. S. Use of the serum bactericidal titer to assess the adequacy of oral antibiotic therapy in the treatment of acute hematogenous osteomyelitis. J Pediatr. 1979 Jul;95(1):131–135. doi: 10.1016/s0022-3476(79)80106-7. [DOI] [PubMed] [Google Scholar]
  24. Pérez-Trallero E., Garcia-Arenzana J. M., Jimenez J. A., Peris A. Therapeutic failure and selection of resistance to quinolones in a case of pneumococcal pneumonia treated with ciprofloxacin. Eur J Clin Microbiol Infect Dis. 1990 Dec;9(12):905–906. doi: 10.1007/BF01967510. [DOI] [PubMed] [Google Scholar]
  25. Reller L. B., Stratton C. W. Serum dilution test for bactericidal activity. II. Standardization and correlation with antimicrobial assays and susceptibility tests. J Infect Dis. 1977 Aug;136(2):196–204. doi: 10.1093/infdis/136.2.196. [DOI] [PubMed] [Google Scholar]
  26. Shimada J., Nogita T., Ishibashi Y. Clinical pharmacokinetics of sparfloxacin. Clin Pharmacokinet. 1993 Nov;25(5):358–369. doi: 10.2165/00003088-199325050-00002. [DOI] [PubMed] [Google Scholar]
  27. Simor A. E., Fuller S. A., Low D. E. Comparative in vitro activities of sparfloxacin (CI-978; AT-4140) and other antimicrobial agents against staphylococci, enterococci, and respiratory tract pathogens. Antimicrob Agents Chemother. 1990 Nov;34(11):2283–2286. doi: 10.1128/aac.34.11.2283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Spangler S. K., Jacobs M. R., Appelbaum P. C. Susceptibilities of 177 penicillin-susceptible and -resistant pneumococci to FK 037, cefpirome, cefepime, ceftriaxone, cefotaxime, ceftazidime, imipenem, biapenem, meropenem, and vancomycin. Antimicrob Agents Chemother. 1994 Apr;38(4):898–900. doi: 10.1128/aac.38.4.898. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Standiford H. C., Tatem B. A. Technical aspects and clinical correlations of the serum bactericidal test. Eur J Clin Microbiol. 1986 Feb;5(1):79–87. doi: 10.1007/BF02013474. [DOI] [PubMed] [Google Scholar]
  30. Sánchez C., Armengol R., Lite J., Mir I., Garau J. Penicillin-resistant pneumococci and community-acquired pneumonia. Lancet. 1992 Apr 18;339(8799):988–988. doi: 10.1016/0140-6736(92)91560-u. [DOI] [PubMed] [Google Scholar]
  31. Weinstein M. P., Stratton C. W., Ackley A., Hawley H. B., Robinson P. A., Fisher B. D., Alcid D. V., Stephens D. S., Reller L. B. Multicenter collaborative evaluation of a standardized serum bactericidal test as a prognostic indicator in infective endocarditis. Am J Med. 1985 Feb;78(2):262–269. doi: 10.1016/0002-9343(85)90436-x. [DOI] [PubMed] [Google Scholar]

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