Antimicrobial pharmacodynamics

Antimicrobials also can be classified as possessing bactericidal or bacteriostatic activity in vitro. Bactericidal antibiotics generally kill at least 99.9% (3 log reduction) of a bacterial population, whereas bacteriostatic antibiotics possess antimicrobial activity but reduce bacterial load by less than 3 logs. Clinically, bactericidal antibiotics may be necessary to achieve success in infections such as endocarditis or meningitis. A full discussion of the application of antimicrobial pharmacodynamics is beyond the scope of this chapter, but excellent sources of information are available.15... 

Craig WA. Pharmacodynamics of antimicrobials. In Nightingale CH, Murakawa T, Ambrose PG, eds. Antimicrobial Pharmacodynamics in Theory and Clinical Practice. 1st ed. New York Marcel Dekker 2002 1-22. 

Zhanel, G.G. (1993) Once daily aminoglycoside dosing the result of research on antimicrobial pharmacodynamics. American Journal of Pharmaceutical Education, 56, 156-167. 

Drusano, G.L. (2004) Antimicrobial pharmacodynamics critical interactions of bug and drug . Nature Reviews. Microbiology, 2 (4), 289—300. 

Antimicrobial pharmacodynamics have become a crucial consideration for the clinician during the selection of both empirical and pathogen-directed therapy in the current era of antimicrobial resistance. 

Optimization of antimicrobial pharmacodynamic param- eters such as the ratio of the peak serum concentration to minimum inhibitory concentration or the time that the serum concentration remains above the minimum inhibitory concentration can improve infection treatment outcomes. 

EVALUATION OF ANTIMICROBIAL ACTIVITY AND DETERMINATION OF ANTIMICROBIAL PHARMACODYNAMICS... 

Salisbury VC, Pfoestl A, Weisinger-Mayr H, Lewis R, Bowker K, MacGowan AP. Use of a clinical Escherichia coli isolate expressing lux genes to study the antimicrobial pharmacodynamics of moxifloxacin. J Antimicrob Chemother 1999 43 829-32. 

JJS, C., The hollow fiber infection model for antimicrobial pharmacodynamics and pharmacokinetics. Adv Pharmacoepidem Drug Saf 2012. SI p. 007. 

Antimicrobial spectrum, pharmacodynamic and phamacokinetic characteristics of rifabutin, a long-acting antituberculosis semisynthetic antibiotic of rifam-icin group 99MI13. 

Drug-specific considerations in antimicrobial selection include the spectrum of activity, effects on nontargeted microbial flora, appropriate dose, pharmacokinetic and pharmacodynamic properties, adverse-effect and drug-interaction profile, and cost. 

Integration of both pharmacokinetic and pharmacodynamic properties of an agent is important when choosing antimicrobial therapy to ensure efficacy and prevent resistance. Antibiotics may demonstrate concentration-dependent (aminoglycosides and fluoroquinolones) or time-depen-dent (/l-1 acta ms) bactericidal effects. 

The most important pharmacodynamic relationship for antimicrobials that display time-depen dent bactericidal effects is the duration that drug concentrations exceed the MIC. 

Dowell JA, Stogniew M, Krause D, Henkel T. (2003) Anidulafungin (ANID) pharmacokinetic (PK)/Pharmacodynamic (PD) correlation Treatment of esophageal candidiasis. 43rd Interscience Conference of Antimicrobial Agents and Chemotherapy Abstract A-1578. 

Scatina J, Abdel-Rahman MS, Gerges SE, et al. 1984. Pharmacodynamics of Alcide, a new antimicrobial compound, in rat and rabbit. Fundam Appl Toxicol 4 479-484. 

Andes, D., Marchillo, K., Stamstad, T. and Conklin, R. (2003) vivo pharmacokinetics and pharmacodynamics of a new triazole, voriconazole, in a murine candidiasis model. Antimicrobial Agents and Chemotherapy, 47, 3165-3169. 

Schentag, J. J. (1999). Antimicrobial action and pharmacokinetics/pharmacodynamics The use of AUIC to improve efficacy and avoid resistance. J. Chemother. 11 426-439. 

Mouton, J., Vinks, A., and Punt, N., Pharmacokinetic-pharmacodynamic modeling of activity of ceftazidime during continuous and intermittent infusion, Antimicrobial Agents and Chemotherapy, Vol. 41, No. 4, 1997, pp. 733-738. 

Lister PD, Sanders CC. Pharmacodynamics of moxifloxacin against Streptococcus pneumoniae in an in vitro pharmacokinetic model. In 38th Interscience Conference on Antimicrobial Agents and Chemotherapy, Abstract A-21. San Diego, CA, 1998. 

Receptor Pharmacology Pharmacogenetics Autonomies Pharmacodynamics Antimicrobials Medicinal Chemistry [ Toxicology... 

Craig, W. (1993) Pharmacodynamics of antimicrobial agents as a basis for determination of dosage regimens. European Journal of Clinical Microbial Infectious Disease, 1, 6-8. 

Response Surface Model A dose-response surface is an extension of dose-response lines (isobols) to three dimensions. In this representation there can be a dose-response surface representing additivity and surfaces above and below suggesting deviation from additivity. Tam et al. [90] studied the combined pharmacodynamic interactions of two antimicrobial agents, meropenem and tobramycin. Total bacterial density data, expressed as CFU (colony forming units), were modeled using a three-dimensional surface. Effect summation was used as the definition of additivity (null interaction hypothesis) and the pharmacodynamic model was assumedi to take the functional form... 

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