Abstract
An experimentalStreptococcus pneumoniae pneumonia was used to study the influence of continuous versus intermittent administration of penicillin G on therapeutic efficacy in normal rats and in rats whose phagocytic capacities were impaired by decomplementation with cobra venom factor. Response to antibiotic treatment was evaluated with respect to numbers of bacteria in left lung, blood and pleural fluid. Penicillin treatment was started 36 h after bacterial inoculation, and continued for four days. With intermittent intramuscular administration of penicillin normal rats were cured after daily doses of 4 mg/kg at 12 h intervals, whereas decomplemented rats recovered only after daily doses of 100 or 102 mg/kg at 12 h or 8 h intervals, respectively. When penicillin was administered by way of continuous infusion, daily doses of 3.5 mg/kg were required for a cure of infections in both normal rats and in decomplemented rats. This treatment resulted in a constant level of 0.05 μg of penicillin per ml, which was slightly above the minimum bactericidal concentration for the infecting strain. These findings show that maintenance of bactericidal levels of penicillin were particularly important in curing severe infection in rats with impaired defense.
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References
Kunin, C. M.: Dosage schedules of antimicrobial agents: a historical review. Reviews of Infectious Diseases 1981, 3: 4–11.
Neu, H. C.: Current practices in antimicrobial dosing. Reviews of Infectious Diseases 1981, 3: 12–18.
Barza, M.: Principles of tissue penetration of antibiotics. Journal of Antimicrobial Chemotherapy 1981, 8, Supplement C: 7–28.
Peterson, L. R., Gerding, D. N., Fasching, C. E.: Effects of method of antibiotic administration on extravascular penetration: cross-over study of cefazolin given by intermittent injection or constant infusion. Journal of Antimicrobial Chemotherapy 1981, 7: 71–79.
Thys, J. P., Vanderkelen, B., Klastersky, J.: Pharmacological study of cefazolin during intermittent and continuous infusion: a crossover investigation in humans. Antimicrobial Agents and Chemotherapy 1976, 10: 395–398.
Bergeron, M. G., Beauchamps, D., Poirier, A., Bastille, A.: Continuous versus intermittent administration of antimicrobial agents: tissue penetration and efficacy in vivo. Reviews of Infectious Diseases 1981, 3: 84–97.
Sande, M. A., Korzeniowski, O. M., Allegro, G. M., Brennan, R. O., Zak, O., Scheld, W. M.: Intermittent or continuous therapy of experimental meningitis due toStreptococcus pneumoniae in rabbits: preliminary observations on the postantibiotic effect in vivo. Reviews of Infectious Diseases 1981, 3: 98–109.
Bodey, G. P., Ketchel, S. J., Rodriguez, V.: A randomized study of carbenicillin plus cefamandole or tobramycin in the treatment of febrile episodes in cancer patients. American Journal of Medicine 1979, 67: 608–616.
Klastersky, J., Thys, J. P., Mombelli, G.: Comparative studies of intermittent and continuous administration of aminoglycosides in the treatment of bronchopulmonary infections due to gram-negative bacteria. Reviews of Infectious Diseases 1981, 3: 74–83.
Nordbring, F.: Current practice in penicillin dosing. Journal of Antimicrobial Chemotherapy 1981, 8, Supplement C: 1–6.
Bakker-Woudenberg, I. A. J. M., de Jong-Hoenderop, J.Y.T., Michel, M. F.: Efficacy of antimicrobial therapy in experimental rat pneumonia: effects of impaired phagocytosis. Infection and Immunity 1979, 25: 366–375.
Barry, A. L., Sabath, L. D.: Special test: bactericidal activity of antimicrobics in combination. In: Lennette, E. H., Spaulding, E. H., Truant, J. P. (ed.): Manual of clinical microbiology. American Society for Microbiology, Washington, DC, 1974, p. 431–435.
Thonus, I. P., de Lange-Macdaniël, A. V., Otte, C. J., Michel, M. F.: Tissue cage infusion: a technique for the achievement of prolonged steady state in experimental animals. Journal of Pharmacological Methods 1979, 2: 63–69.
Bennet, J. V., Brodie, J. L., Benner, E. J., Kirby, W. M. N.: Simplified, accurate method for antibiotic assay of clinical specimens. Applied Microbiology 1966, 14: 170–177.
Bodey, G. P., Valdivieso, M., Yap, B. S.: The role of schedule in antibiotic therapy of the neutropenic patient. Infection 1980, 8, Supplement 1: 75–81.
Bergan, T.: Kinetics of tissue penetration. Are high plasma peak concentrations or sustained levels preferable for effective antibiotic therapy? Scandinavian Journal of Infectious Diseases 1978, Supplement 14: 36–46.
Barza, M., Brusch, J., Bergeron, M. G., Weinstein, L.: Penetration of antibiotics into fibrin loci in vivo. III. Intermittent versus continuous infusion and the effect of probenecid. Journal of Infectious Diseases 1974, 129: 73–78.
Schmidt, L. H., Walley, A.: The influence of the dosage regimen on the therapeutic effectiveness of penicillin G in experimental lobar pneumonia. Journal of Pharmacology and Experimental Therapeutics 1951, 103: 479–488.
Eagle, H., Fleischmann, R., Musselman, A. D.: Effect of schedule of administration on the therapeutic efficacy of penicillin. Importance of the aggregate time penicillin remains at effectively bactericidal levels. American Journal of Medicine 1950, 9: 280–299.
Eagle, H., Fleischmann, R., Levy, M.: “Continuous” versus “discontinuous” therapy with penicillin. The effect of the interval between injections on therapeutic efficacy. New England Journal of Medicine 1953, 248: 481–488.
Merrikin, D., Rolinson, G. N.: Antibiotic levels in experimentally infected mice in relation to therapeutic effect and antibacterial activity in vitro. Journal of Antimicrobial Chemotherapy 1979, 5: 423–429.
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Bakker-Woudenberg, I.A.J.M., van den Berg, J.C., Fontijne, P. et al. Efficacy of continuous versus intermittent administration of penicillin G inStreptococcus pneumoniae pneumonia in normal and immunodeficient rats. Eur. J, Clin. Microbiol. 3, 131–135 (1984). https://doi.org/10.1007/BF02014330
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DOI: https://doi.org/10.1007/BF02014330