Abstract
Pharmacodynamic parameters, such as the rate of bactericidal activity with increasing drug concentrations, post-antibiotic effect, sub-MIC effects, post-antibiotic leukocyte enhancement and first-exposure effect, more accurately describe the time course of antimicrobial activity than the MIC and MBC. Aminoglycosides and quinolones exhibit concentration-dependent killing and induce prolonged post-antibiotic effects. The amount of drug rather than the dosing frequency determines the efficacy of these drugs. However, high peak levels can reduce the emergence of resistance, and oncedaily dosing of aminoglycosides can also reduce nephrotoxicity and ototoxicity. On the other hand, beta-lactam antibiotics show time-dependent killing and produce prolonged post-antibiotic effects only with staphylococci. The frequency of drug administration is an important determinant of outcome for these drugs, as the duration of time serum levels exceed the MIC is the major determinant of efficacy.
Similar content being viewed by others
References
Craig WA, Ebert SC: Killing and regrowth of bacteria in vitro: a review. Scandinavian Journal of Infectious Diseases 1991, Supplement 74: 63–70.
Craig WA, Gudmundsson S: Postantibiotic effect. In: Lorian V (ed): Antibiotics in laboratory medicine. Williams & Wilkins, Baltimore, 1991, p. 403–431.
Vogelman B, Gudmundsson S, Turnidge J, Leggett J, Craig WA: In vivo postantibiotic effect in a thigh infection in neutropenic mice. Journal of Infectious Diseases 1988, 157: 287–298.
Odenholt-Tornqvist I, Holm SE, Cars O: Pharmacodynamic effects of subinhibitory antibiotic concentrations. Scandinavian Journal of Infectious Diseases 1991, Supplement 74: 94–101.
McDonald PJ, Wetherall BL, Pruul H: Postantibiotic leukocyte enhancement: increased susceptibility of bacteria pretreated with antibiotics to activity of leukocytes. Reviews of Infectious Diseases 1981, 3: 38–44.
Jackson GG, Diakos GL, Lolans VT: First-exposure effect of netilmicin on bacterial susceptibility as a basis for modifying the dosage regimen of aminoglycoside antibiotics. Journal of Drug Development 1988, 1, Supplement 3: 49–54.
Leggett JE, Fantin B, Ebert SC, Totsuka K, Vogelman B, Craig WA: Comparative antibiotic dose-effect relations at several dosing intervals in murine pneumonitis and thigh-infection models. Journal of Infectious Diseases 1989, 159: 281–292.
Roosendaal R, Bakker-Woudenberg IAJM, van den Berghe-van Raffe M Vink-van den Berg JC, Michel MF: Impact of the dosage schedule on the efficacy of ceftazidime, gentamicin and ciprofloxacin inKlebsiella pneumoniae pneumonia and septicemia in leukopenic rats. European Journal of Clinical Microbiology & Infectious Diseases 1989, 8: 878–887.
Blaser J, Stone BB, Groner MC, Zinner SH: 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. Antimicrobial Agents and Chemotherapy 1987, 31: 1054–1060.
Tulkens PM: Efficacy and safety of aminoglycosides once-a-day: experimental and clinical data. Scandinavian Journal of Infectious Diseases 1991, Supplement 74: 249–257.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Craig, W. Pharmacodynamics of antimicrobial agents as a Basis for Determining Dosage Regimens. Eur. J. Clin. Microbiol. Infect. Dis. 12 (Suppl 1), S6–S8 (1993). https://doi.org/10.1007/BF02389870
Issue Date:
DOI: https://doi.org/10.1007/BF02389870