Summary
The therapeutic efficacy of ciprofloxacin, used alone and in combination with either ceftazidime or gentamicin, was evaluated in a model of experimentalKlebsiella pneumoniae septicemia in neutropenic mice. Therapeutic results were compared to those achieved by treatment with ceftazidime or gentamicin alone, as well as their combination. Infections were induced by i.v. injection of two strains ofK. pneumoniae. Therapy with i.m. antibiotics was performed in 8 h intervals for a total of 13 doses, and survival rates were recorded at the end of treatment as well as seven days later. Ciprofloxacin alone proved to be significantly more effective than ceftazidime and gentamicin, producing survival rates similar to the combination of ceftazidime plus gentamicin. Bacterial counts of spleens and blood confirmed the superior bactericidal activity of ciprofloxacin. Except for the combination of ciprofloxacin with ceftazidime, there was no apparent advantage of combinations of ciprofloxacin with the other agents compared to ciprofloxacin alone. These data suggest a highin vivo activity of ciprofloxacin in systemic infection due toK. pneumoniae.
Zusammenfassung
Die therapeutische Aktivität von Ciprofloxacin in Monotherapie und in Kombination mit Ceftazidim oder Gentamicin wurde in einem Modell der experimentellenKlebsiella pneumoniae-Septikämie bei neutropenischen Mäusen untersucht. Zum Vergleich dienten Versuchsgruppen, die mit Ceftazidim oder Gentamicin jeweils allein oder in Kombination behandelt wurden. Die Infektion erfolgte durch i.v. Injektion von zwei verschiedenen Stämmen vonK. pneumoniae. Zur i.m. Therapie wurden 13 Dosen der Antibiotika achtstündlich injiziert. Die Überlebensraten wurden am Ende der Behandlungsperiode und sieben Tage später ermittelt. Die therapeutische Aktivität von Ciprofloxacin entsprach, gemessen an den Überlebensraten, der Kombination aus Ceftazidim und Gentamicin, war jedoch signifikant höher als die Wirksamkeit beider Einzelsubstanzen. Dies wurde auch durch die Ermittlung der Bakterienzahlen in Milz und Blut bestätigt. Mit Ausnahme der Kombination aus Ciprofloxacin und Ceftazidim kam es bei Ciprofloxacin-Kombinationen zu keiner Wirkungssteigerung. Diese Daten weisen auf eine hoheIn vivo-Aktivität von Ciprofloxacin bei systemischenK. pneumoniae-Infektionen hin.
Similar content being viewed by others
Literature
Ljungman, P., Malmborg, A. S., Nyström, B., Tillegard, A. Bacteremia in a Swedish university hospital: a one-year prospective study in 1981 and a comparison with 1975–76. Infection 12 (1984) 243–247.
Maki, D. G. Nosocomial bacteremia. An epidemiologic overview. Am. J. Med. 70 (1981) 719–732.
Weinstein, M. P., Reller, L. B., Murphy, J. R., Lichtenstein, K. A. The significance of positive blood cultures: a comprehensive analysis of 500 episodes of bacteremia and fungemia in adults. I. Laboratory and epidemiologic observations. Rev. Infect. Dis. 5 (1983) 35–53.
Hable, K. A., Matsen, J. M., Wheeler, D. J., Hunt, C. E., Quie, P. G. Klebsiella type 33 septicemia in an infant intensive care unit. J. Pediatr. 80 (1972) 920–924.
Jones, R. J., Roe, E. A., Gupta, J. L. Controlled trial of Pseudomonas immunoglobulin and vaccine in burn patients. Lancet II (1980) 1263–1265.
Umsawasdi, T., Middleman, E. A., Luna, M., Bodey, G. P. Klebsiella bacteremia in cancer patients. Am. J. Med. Sci. 265 (1973) 473–482.
De la Torre, M. G., Romero-Visas, J., Martínez-Beltrán, J., Guerrero, A., Meseguer, M., Bouza, E. Klebsiella bacteremia: an analysis of 100 episodes. Rev. Infect. Dis. 7 (1985) 143–150.
Young, L. S., Stevens, P., Kaijser, B. Gram-negative pathogens in septicaemic infections. Scand. J. Infect. Dis. Suppl. 31 (1982) 78–94.
Chin, N. X., Neu, H. C. Ciprofloxacin, a quinolone carboxylic acid compound active against aerobic and anaerobic bacteria. Antimicrob. Agents Chemother. 25 (1984) 319–326.
Van Caekenberghe, D. L., Pattyn, S. R. In vitro activity of ciprofloxacin compared with those of other new fluorinated piperazinyl-substituted quinolone derivatives. Antimicrob. Agents Chemother. 25 (1984) 518–521.
Chedid, L., Parant, M., Parant, F., Boyer, F. A proposed mechanism for natural immunity to enterobacterial pathogens. J. Immunol. 100 (1968) 292–301.
Cooper, J. McA., Rowley, D. Resistance toKlebsiella pneumoniae and the importance of two bacterial antigens. Aust. J. Exp. Biol. Med. Sci. 60 (1982) 629–641.
Trautmann, M., Müller-Leutloff, Y., Hofstaetter, T., Seiler, F. R., Hahn, H. Experimental Klebsiella septicemia in mice: treatment with specific antibodies from the rabbit alone and in combination with gentamicin. Infection 13 (1985) 29–34.
Trautmann, M., Brückner, O., Marre, R., Hahn, H. Comparative efficacy of different β-lactam antibiotics and gentamicin inKlebsiella pneumoniae septicaemia in neutropenic mice. J. Antimicrob. Chemother. 18 (1986) 387–391.
Haller, I. Comprehensive evaluation of ciprofloxacin-aminoglycoside combinations against Enterobacteriaceae andPseudomonas aeruginosa strains. Antimicrob. Agents Chemother. 28 (1985) 663–666.
Haller, I. Comprehensive evaluation of ciprofloxacin in combination with β-lactam antibiotics against Enterobacteriaceae andPseudomonas aeruginosa. Arzneim.-Forsch./Drug Res. 36 (1986) 226–229.
Bodey, G. P., Chang, H. Y., Rodriguez, V., Stewart, D. Feasibility of administering aminoglycoside antibiotics by continuous infusion. Antimicrob. Agents Chemother. 8 (1975) 328–333.
Brittain, D. C., Scully, B. E., McElrath, J., Steinman, R., Labthavikul, P., Neu, H. C. The pharmacokinetics and serum and urine bactericidal activity of ciprofloxacin. J. Clin. Pharmacol. 25 (1985) 82–88.
Reeves, D. S., Bywater, M. J. Assay of antimicrobial agents. In:de Louvois, J. (ed.): Selected topics in clinical bacteriology. Baillière Tindall, London, 1976, pp 21–74.
Lüthy, R., Blaser, J., Bonetti, A., Simmen, H., Wise, R., Siegenthaler, W. Comparative multiple-dose pharmacokinetics of cefotaxime, moxalactam and ceftazidime. Antimicrob. Agents Chemother. 21 (1981) 567–575.
Wingender, W., Graefe, K. H., Gau, W., Förster, D., Beermann, D., Schacht, P. Pharmacokinetics of ciprofloxacin after oral and intravenous administration in healthy volunteers. Eur. J. Clin. Microbiol. 3 (1984) 355–359.
Wise, R., Andrews, J. R., Edwards, L. J. In vitro activity of Bay 09867, a new quinolone derivative, compared with those of other antimicrobial agents. Antimicrob. Agents Chemother. 23 (1983) 559–564.
Lagast, H., Husson, M., Klastersky, J. Bactericidal activity of ciprofloxacin in serum and urine againstEscherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus andStreptococcus faecalis. J. Antimicrob. Chemother. 16 (1985) 341–347.
Weiss, D., Trautmann, M., Wagner, J., Borner, K., Hahn, H.: Ciprofloxacin: a comparative evaluation of its bactericidal activity in human serum against four enterobacterial species. Drugs Exptl. Clin. Res. (in press).
Strunk, R. W., Gratz, J. C., Maserati, R., Scheld, W. M. Comparison of ciprofloxacin with azlocillin plus tobramycin in the therapy of experimentalPseudomonas aeruginosa endocarditis. Antimicrob. Agents Chemother. 28 (1985) 428–432.
Gordin, F. M., Hackbarth, C. J., Scott, K. G., Sande, M. A. Activities of pefloxacin and ciprofloxacin in experimentally induced Pseudomonas pneumonia in neutropenic guinea pigs. Antimicrob. Agents Chemother. 27 (1985) 452–454.
Kemmerich, B., Small, G. J., Pennington, J. E. Comparative evaluation of ciprofloxacin, enoxacin, and ofloxacin in experimentalPseudomonas aeruginosa pneumonia. Antimicrob. Agents Chemother. 29 (1986) 395–399.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Trautmann, M., Brückner, O., Marre, R. et al. Comparative efficacy of ciprofloxacin, ceftazidime and gentamicin, given alone or in combination, in a model of experimental septicemia due to klebsiella pneumoniae in neutropenic mice. Infection 16, 49–53 (1988). https://doi.org/10.1007/BF01646933
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01646933