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Chapter 8 : Pharmacodynamics of Quinolone Antimicrobial Agents

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Pharmacodynamics of Quinolone Antimicrobial Agents, Page 1 of 2

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Abstract:

This chapter focuses on the pharmacodynamic characteristics of the quinolone antimicrobials in in vitro models, in animal infection models, and in humans. It demonstrates that there are many more similarities in results among the various models than there are differences. Numerous in vitro and in vivo studies have demonstrated that the quinolone antimicrobial agents exhibit concentration-dependent killing across a wide range of concentrations. A variety of different parameters have been used to characterize the killing characteristics of the quinolone antimicrobials. There are a variety of in vitro and in vivo persistent effects that have been characterized for the quinolone antimicrobial agents. The first study correlating pharmacokinetic (PK)/pharmacodynamic (PD) parameters of the fluoroquinolones with clinical response in humans was published by Peloquin. In this study, which evaluated intravenous ciprofloxacin in seriously ill patients with lower respiratory tract infections, time above MIC was reported to be the important parameter for eradication of the organism from respiratory secretions. Knowledge of the major PK/PD parameter determining efficacy and the magnitude of that target required for efficacy of specific pathogens has proven to be helpful for developing new quinolone agents, predicting the activity of new quinolone formulations, developing guideline recommendations, and establishing susceptibility and resistance breakpoints for susceptibility testing. Initial studies suggest that pharmacodynamics can also be important in preventing the emergence of resistance. More in vitro, animal and human studies are necessary to fully document the usefulness of pharmacodynamic evaluation in optimizing therapy with the quinolone antimicrobial agents.

Citation: Craig W, Andes D. 2003. Pharmacodynamics of Quinolone Antimicrobial Agents, p 147-155. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch8
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Figures

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Figure 1

Relationship among PK/PD parameters for temafloxacin and logCFU per thigh of after 24 h of therapy in a murine thigh infection model. Reprinted from reference with permission from Elsevier.

Citation: Craig W, Andes D. 2003. Pharmacodynamics of Quinolone Antimicrobial Agents, p 147-155. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch8
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Image of Figure 2
Figure 2

Relationship between the magnitude of the 24-h AUC/MIC for the static doses of the lowly protein-bound sitafloxacin and gatifloxacin and the highly protein-bound gemifloxacin against six strains of in a murine infection model.

Citation: Craig W, Andes D. 2003. Pharmacodynamics of Quinolone Antimicrobial Agents, p 147-155. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch8
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Figure 3

Relationship between mortality at the end of therapy and the 24-h AUC/MIC of fluoroquinolones with multiple pathogens in different animal models. Reprinted from reference with permission from Elsevier.

Citation: Craig W, Andes D. 2003. Pharmacodynamics of Quinolone Antimicrobial Agents, p 147-155. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch8
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Figure 4

Relationship between mortality at the end of therapy and the 24-h AUC/MIC of fluoroquinolones against in nonneutropenic mice. Reprinted from reference with permission from Elsevier.

Citation: Craig W, Andes D. 2003. Pharmacodynamics of Quinolone Antimicrobial Agents, p 147-155. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch8
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Figure 5

Relationship between the 24-h AUC/MIC ratio and mortality for extracellular (open triangles) and intracellular (open circles) pathogens in various experimental infection models in mice, rats, and guinea pigs. Reprinted from reference 13 with permission of Springer-Verlag.

Citation: Craig W, Andes D. 2003. Pharmacodynamics of Quinolone Antimicrobial Agents, p 147-155. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch8
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Image of Figure 6
Figure 6

Relationship between the 24-h AUC/MIC and the microbiologic and clinical efficacy of ciprofloxacin in 64 patients with serious bacterial infections. Reprinted from reference with permission of The University of Chicago Press.

Citation: Craig W, Andes D. 2003. Pharmacodynamics of Quinolone Antimicrobial Agents, p 147-155. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch8
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Figure 7

Relationship between fluoroquinolone free drug 24-h AUC/MIC and microbiologic eradication of in community-acquired respiratory tract infections. Adapted from reference .

Citation: Craig W, Andes D. 2003. Pharmacodynamics of Quinolone Antimicrobial Agents, p 147-155. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch8
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References

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Tables

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Table 1

Relationship of the 24-h AUC/MIC ratio and monotherapy and combination therapy to the emergence of resistant organisms during therapy with ciprofloxacin

Citation: Craig W, Andes D. 2003. Pharmacodynamics of Quinolone Antimicrobial Agents, p 147-155. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch8

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