Hostname: page-component-586b7cd67f-dsjbd Total loading time: 0 Render date: 2024-11-25T22:46:59.476Z Has data issue: false hasContentIssue false

Pharmacodynamic Properties of Antibiotics: Application to Drug Monitoring and Dosage Regimen Design

Published online by Cambridge University Press:  21 June 2016

Steven C. Ebert
Affiliation:
University of Wisconsin, Madison, Wisconsin
William A. Craig*
Affiliation:
Department of Medicine, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin
*
Associate Chief of Staff for Education, William S. Middleton Memorial Veterans Hospital, 2500 Overlook Terrace, Madison, WI 53705

Extract

The goal of antimicrobial chemotherapy is to effectively eradicate pathogenic organisms while minimizing the likelihood of drug-related adverse effects. In this era of cost containment, consideration should also be given to performing this task with the smallest total dose of drug and the shortest duration of therapy. Determination of the appropriate dose and dosing interval of an antimicrobial requires knowledge and integration of both its pharmacokinetic and pharmacodynamic properties.

Type
Special Sections
Copyright
Copyright © The Society for Healthcare Epidemiology of America 1990

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Craig, WA, Vogelman, B. Changing concepts and new applications of antibiotic pharmacokinetics. Am J Med. 1984;77(suppl):2428.CrossRefGoogle ScholarPubMed
2. Bundtzen, RW, Gerber, AU, Cohn, D, Craig, WA. Postantibiotic suppression of bacterial growth. Reu Infect Dis. 1981;3:2837.CrossRefGoogle ScholarPubMed
3. Vogelman, B, Craig, WA. Postantibiotic effects. J Antimicrob Chemother. 1985;15(suppl A):3746.CrossRefGoogle ScholarPubMed
4. Vogelman, B, Gudmundsson, S. Turnidge, J, Leggett, J, Craig, WA. In vivo postantibiotic effect in a thigh infection in neutropenic mice. J Infect Dis. 1988;157:287298.CrossRefGoogle Scholar
5. Craig, WA, Vogelman, B. The postantibiotic effect. Ann Intern Med. 1987;106:900902.CrossRefGoogle ScholarPubMed
6. Vogelmain, B, Craig, WA. Kinetics of antimicrobial activity. J Pediatr, 1986;108:835840.CrossRefGoogle Scholar
7. McCormack, JP, Schentag, JJ. Potential impact of quantitative susceptibility tests on the design of aminoglycoside dosing regimens. Drug Intell Clin Pharm. 1987;21:187191.Google ScholarPubMed
8. Schumacher, GE. Comparison of antibiotic dosage regimens using pharmacokinetic and microbiologic factors. Clin Pharm. 1987;6:5968.Google ScholarPubMed
9. Drusano, GL, Ryan, PA, Standiford, HC. Moody, MR, Schimpff, A. Integration of selected pharmacologic and microbiologic properties of three new ß-lactam antibiotics: a hypothesis for rational comparison. Rev Infect Dis. 1984;3:357363.CrossRefGoogle Scholar
10. Barriere, SL, Ely, E, Kapusnik, JE. et al. Analysis of a new method of assessing activity of combinations of antimicrobials: area under the bactericidal curve. J Antimicrob Chemother. 1985;16:4959.CrossRefGoogle ScholarPubMed
11. Weinstein, MP, Stratton, CW, Ackley, A, et al. Multicenter collaborative evaluation of a standardized serum bactericidal test as a prognostic indicator in infective endocarditis. Am J Med. 1985;78:262269.CrossRefGoogle ScholarPubMed
12. Weinstein, MP, Stratton, CW, Hawley, HB. Ackley, A, Relier, LB. Multicenter collaborative evaluation of a standardized serum bactericidal test as a predictor of therapeutic efficacy in acute and chronic osteomyelitis. Am J Med, 1987;83:218222.CrossRefGoogle ScholarPubMed
13. Klastersky, J, Daneau, D, Swings, G, et al. Antibacterial activity in serum and urine as a therapeutic guide in bacterial infections. J Infect Dis. l974;129:187193.CrossRefGoogle Scholar
14. Sculien, JP, Klastersky, J. Significance of serum bactericidal activity in gram-negative bacillary bacteremia in patients with and without granulocytopenia. Am J Med. 1984;76:429435.CrossRefGoogle Scholar
15. Moore, RD, Smith, CR, Lietman, PS. The association of aminoglycoside plasma levels with mortality in gram-negative bacteremia. J Infect Dis. 1984;149:443448.CrossRefGoogle ScholarPubMed
16. Moore, RD, Smith, CR, Lietman, PS. Association of aminoglycoside plasma levels with therapeutic outcome in gram-negative pneumo-ma. Am J Med. 1984;77:657662.CrossRefGoogle Scholar
17. Moore, RD, Lietman, PS, Smith, CR. Clinical response to aminogly co-side therapy: importance of the ratio of peak concentration to minimal inhibitory concentration. J Infect Dis. 1987;155:9399.CrossRefGoogle Scholar
18. Parker, RF, Luse, S. The action of penicillin on staphylococcus: further observations on the effect of a short exposure. J Bacterid, 1948;56:7584.CrossRefGoogle ScholarPubMed
19. Gudmundsson, S, Vogelman, B, Craig, WA. The in vivo postantibiotic effect of imipenem and other new antimicrobials. J Antimicrob Chemother. 1986;18(suppl E):6773.CrossRefGoogle ScholarPubMed
20. Bustamante, CI, Drusano, GL, Tatem, BA, et al. Postantibiotic effect of imipenem on Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1984;26:678682.CrossRefGoogle ScholarPubMed
21. Bergan, T, Carlsen, IB. Bacterial kill rates of amoxycillin and ampicillin at exponentially diminishing concentrations simulating in vivo conditions. Infection. 1980;8:S103S108.CrossRefGoogle Scholar
22. Shah, PM, Ghahremani, M, Gorres, F-J. et al. Bactericidal activity of antimicrobials in the dynamic kill-curve model. Journal of Drug Development. 1988;l(suppl 3):3547.Google Scholar
23. Garrett, ER. Kinetics of antimicrobial action. Scand J Infect Dis. 1978;14:5485.Google Scholar
24. Navashm, SM. Fomina, IP, Firsov, AA, Chernykh, VM, Kuznetsoua, SM. A dynamic model for in vitro evaluation of antimicrobial action by simulation of the pharmacokinetic profiles of antibiotics. J Antimicrob Chemother. 1989;23:389399.CrossRefGoogle Scholar
25. Briceland, LL, Pasko, MT, Mylotte, JM. Serum bactericidal rate as a measure of antibiotic interactions. Antimicrob Agents Chemother. 1987;31:679685.CrossRefGoogle ScholarPubMed
26. Tisdale, JE, Pasko, MT, Mylotte, JM. Antipseudomonal activity of simulated infusions of gentamicin alone or with piperacillin assessed by serum bactericidal rate and area under the killing curve. Antimicrob Agents Chemother. 1989;33:15001505.CrossRefGoogle ScholarPubMed
27. Giuliano, RA, Verpooten, GA, Verbist, L, Wedeen, RR, De Broe, ME. In uptake kinetics of aminoglycosides in the kidney cortex of rats. J Pharmacol Exp Ther. 1986;236:470475.Google ScholarPubMed
28. Verpooten, GA, Giuliano, RA, Verbist, L, Ester-mans, G, De Broe, ME. Once-daily dosing decreases renal accumulation of gentamicin and netilmicin. Clin Pharmacol Ther, 1989;45:2227.CrossRefGoogle ScholarPubMed
29. Mattie, H, Craig, WA, Pechere, JC. Determinants of efficacy and toxicity of aminoglycosides. J Antimicrob Chemother. 1989;24:281293.CrossRefGoogle ScholarPubMed
30. Grasso, S, Menardi, G, De Carneri, I, et al. New in vitro model to study the effect of antibiotic concentration and rate of elimination on antibacterial activity. Antimicrob Agents Chemother. 1978;13:570576.CrossRefGoogle Scholar
31. Ibothaker, RD, Welling, PG, Craig, WA. An in vitro model for the study of antibacterial dosage regimen design. J Pharm Sci. 1982;71:861864.Google Scholar
32. Zinner, SH, Hussori, M, Klastersky, J. An artificial capillary in vitro kinetic model of antibiotic bactericidal activity. J Infect Dis. 1981;144:583587.CrossRefGoogle ScholarPubMed
33. White, CA, Toothaker, RD. Influence of ampicillin elimination halflife on in vitro bactericidal effect. J Antimicrob Chemother. 1985;15(suppl A):257260.CrossRefGoogle ScholarPubMed
34. Klaus, U, Henninger, W, Jacobi, P, Wiedemann, B. Bacterial elimination and therapeutic effectiveness under different schedules of amoxicillin administration. Chemotherapy. 1981;27:200208.CrossRefGoogle ScholarPubMed
35. Zinner, SH, Dudley, MN, Gilbert, D, Bassignam, M. Effect of dose and schedule on cefoperazone pharmacodynamics in an in vitro model of infection in a neutropenic host. Am J Med. 1988;85(suppl lA):5658.CrossRefGoogle Scholar
36. Eagle, H, Fleischman, R, Musselman, AD. Effect of schedule of administration on the therapeutic efficacy of penicillin. Am J Med. 1950;9:280299.CrossRefGoogle ScholarPubMed
37. Eagle, H, Fleischman, R, Musselman, AD. The effective concentrations of penicillin in vitro and in vivo for streptococci, pneumococci, and treponema pallidum. J BacterioL 1950;59:625643.CrossRefGoogle ScholarPubMed
38. Vogelman, B, Gudmundsson, S, Leggett, J, et al. Correlation of antimicrobial pharmacokinetic parameters with therapeutic efficacy m an animal model. J Infect Dis. l988;158:831847.CrossRefGoogle Scholar
39. Frimodt-Moller, N, Bentzon, MW, Thomsen, VF. Experimental infection with Streptococcus pneumoniae in mice: correlation of in vitro activity and pharmacokinetic parameters with in vivo effect for 14 cephalosporins. J Infect Dis. 1986;154:511517.CrossRefGoogle ScholarPubMed
40. Frimodt-Moller, NM, Bentzon, MW, Thomsen, VF. Experimental pneumococcus infection in mice: comparative in vitro and in vivo effects of cefuroxime, cefotaxime, and ceftriaxone. Acta Path Microbiol Immunol Scand, 1987;95:261267.Google ScholarPubMed
41. Gerber, AU, Craig, WA, Brugger, HP, Feller, C, Vastda, AP, Brandel, J. Impact of dosing intervals on activity of gentamicin and ticarcillin against Pseudomonas aeruginosa in granulocytopenic mice. J Infect Dis. 1983;147:910917.CrossRefGoogle ScholarPubMed
42. Leggett, JE, Fantin, B, Ebert, S, et al. Comparative antibiotic dose-effect relationships at several dosing intervals in murine pneumonitis and thigh-mfection models. J Infect Dis. 1989;159:281292.CrossRefGoogle Scholar
43. Bakker-Woudenberg, IAJM, van den Berg, JC, Fontijne, P, et al. Efficacy of continuous versus intermittent administration of penicillin G in Streptococcus pneumoniae pneumonia in normal and immu-nodeficient rats. Kur J Clin Microbiol Infect Dis. 1984;3:131135.Google ScholarPubMed
44. Roosendaal, R, Bakker-Woudenberg, IAJM, van den Berghe, JC, Michel, MF. Therapeutic efficacy of continuous versus intermittent administration of ceftazidime in an experimental Klebsiella pneumoniae pneumonia in rats. J Infect Dis. 1985;152:373378.CrossRefGoogle Scholar
45. Roosendaal, R, Bakker-Woudenberg, IAJM, van den Berghe-van Raffe, M, et al. Impact of the dosage schedule on the efficacy of ceftazidime, gentamicin, and ciprofloxacin in Klebsiella pneumoniae pneumonia and septicemia in mice. Eur J Clin Microbiol Infect Dis. 1989;8:878887.CrossRefGoogle Scholar
46. Ingerman, MJ, Pitsakis, PG, Rosenberg, AF, Levison, ME. The importance of pharmacodynamics in determining dosing interval in therapy for experimental Pseudomonas endocarditis in the rat. J Infect Dis. 1986;153:707714.CrossRefGoogle ScholarPubMed
47. Mordenti, JJ, Quintiliani, R, Nightingale, CH. Combination antibiotic therapy: comparison of constant infusion and intermittent bolus-dosing in an experimental animal model. J Antimicrob Chemother. 1985;15(supp 1A):313321.CrossRefGoogle Scholar
48. Thauvm, C, Eliopoulos, GM, Willey, S, Wennersten, C, Moellermg, RC. Continuous-infusion ampicillin therapy of enterococcal endocarditis in rats. Antimicrob Agents Chemother. 1987;31:139143.CrossRefGoogle Scholar
49. Schentag, JJ, Smith, IL, Swanson, DJ, et al. Role of dual individualization with cefmenoxime. Am J Med. 1984;77(suppl 6A):4350 CrossRefGoogle ScholarPubMed
50. Bodey, GP, Ketchel, SJ, Rodriguez, V. A randomized study of carbeni-cillin plus cefamandole or tobramycin in the treatment of febrile episodes in cancer patients. Am J Med, 1979;67:608616.CrossRefGoogle ScholarPubMed
51. Bodey, G, Valdivieso, M, Yap, BS. The role of schedule in antibiotic therapy of the neutropenic patient. Infection. 1980;8(suppl 1):S75S81.CrossRefGoogle Scholar
52. Feld, R, Valdivieso, M, Bodey, GP, et al. A comparative trial of sisomicin therapy by intermittent versus continuous infusion. Am J Med Sci 1977;274:179188.CrossRefGoogle ScholarPubMed
53. Daenen, S, De Vries-Hosper, H. Cure of Pseudomonas aeruginosa infection in neutropenic patients by continuous infusion of ceftazidime. Lancet. 1988;1:937.CrossRefGoogle ScholarPubMed
54. Gerber, AU, Wiprachtiger, P, Stettier-Spichiger, U, Lebek, G. Constant infusions vs. intermittent doses of gentamicin against Pseudomonas aeruginosa in vitro. J Infect Dis. 1982;145:554560.CrossRefGoogle ScholarPubMed
55. Blaser, J, Stone, BB, Groner, MC, et al. Comparative study with 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;31:10541060.CrossRefGoogle Scholar
56. Blaser, J, Stone, BB, Zinner, SH. Efficacy of intermittent versus continuous administration of netilmicin in a two-compartment in vitro model. Antimicrob Agents Chemother. 1985;27:343349.CrossRefGoogle Scholar
57. Kapusmk, JE, Hackbarth, CJ, Chambers, HF, Carpenter, T, Sande, MA. Single, large daily dosing vs intermittent dosing of tobramycin for treating experimental pseudomonas pneumonia. J Infect Dis. 1988;158:712.CrossRefGoogle Scholar
58. Pechere, M, Letarte, R, Pechere, JC. Efficacy of different dosing schedules of tobramycin for treating a murine Klebsiella pneumoniae bronchopneumonia. J Antimicrob Chemother. 1987;19:487491.CrossRefGoogle ScholarPubMed
59. Powell, SH, Thompson, WL, Luthe, MA, et al. Once-daily vs continuous aminoglycoside dosing: efficacy and toxicity in animal and clinical studies of gentamicin, netilmicin and tobramycin. J Infect Dis. 1983;147:918932.CrossRefGoogle ScholarPubMed
60. Queiroz, MLS, Bathirunathan, N, Mawer, GE. Influence of dosage interval on the therapeutic response to gentamicin in mice infected with Klebsiella pneumoniae. Chemotherapy. 1987;33:6876.CrossRefGoogle ScholarPubMed
61. Wood, CA, Norton, DR, Kohlhepp, SJ, et al. The influence of tobramycin dosage regimens on neohrotoxicity., ototoxicity., and antibacterial efficacy in a rat model of subcutaneous abscess. J infect Dis. 1988;158:1322.CrossRefGoogle Scholar
62. Deziel-Evans, LM, Murphy, JE. Job, ML. Correlation of pharmacokinetic indices with therapeutic outcome in patients receiving aminoglycosides. Clin Pharm. l986;5:319324.Google Scholar
63. Peloquin, CA, Cumbo, TJ, Nix, DE, et al. Evaluation of intravenous ciprofloxacin in patients with nosocomial lower respiratory tract infections: impact of plasma concentrations, organism, minimum inhibitory concentration, and clinical condition on bacterial eradication. Arch Intern Med. 1989;149:22692273.CrossRefGoogle ScholarPubMed
64. DeVries, PJ, Leguit, P, Verkooyen, RP, et al. Toxicity of once daily netilmicin in patients with intraabdominal infections. Abstract 608. Program and Abstracts, 27th Interscience Conference for Antimicrobial Agents and Chemotherapy. New York, NY: American Society for Microbiology; 1987.Google Scholar
65. Fan, ST, Lau, WY, Teah-Chan, et al. Once daily administration of netilmicin compared with thrice daily, both in combination with metronidazole, in gangrenous and perforated appendicitis. J Antimicrob Chemother. 1988;22:6974.CrossRefGoogle ScholarPubMed
66. Maller, R, Isaksson, B, Nilsson, L, et al. A study of amikacin given once versus twice daily in serious infections. J Antimacrob Chemother. 1988;22:7579.CrossRefGoogle ScholarPubMed
67. Hollender, LF, Bahnini, J, DeManzini, N, et al. A multicentric study of netilmicin once daily versus thrice daily in patients with appendicitis and other intraabdominal infections. J Antimicrob Chemother. 1989;23:773783.CrossRefGoogle Scholar
68. Sturm, AW. Netilmicin in the treatment of Gram-negative bacteremia: single daily versus multiple daily dosage. J Infect Dis. 1989;159:931937.CrossRefGoogle ScholarPubMed
69. lulkens, PM, Clerckx-Braun, F, Donnez, J, et al. Safety and efficacy of aminoglycosides once-a-day: experimental data and randomized, controlled evaluation in patients suffering from pelvic inflammatory disease. Journal of Drug Development. 1988;1(suppl 3):7182.Google Scholar
70. Pizzo, PA, Eddy, J, Falloon, J, et al. Effect of continuous infusion of zidovudine (AZT) in children with symptomatic HIV infection. N Engl J Med. 1988;319:889896.CrossRefGoogle ScholarPubMed
71. Fletcher, CV, Englund, JA, Bean, B, et al. Continuous high-dose acyclovir for serious herpesvirus infections. Antimicrob Agents Chemother. 1989;33:13751378.CrossRefGoogle ScholarPubMed