Optimising Antimicrobial Therapy by using Pharmacokinetic/Pharmacodynamic Parameters

Presented at the Symposium “The need of a Revolution in Respiratory Tract Infection Prescribing”
held during the 11th European Congress of Cllinical Microbiology and Infectious Diseases
(ECCMID, Istanbul, Turkey), on April 2d, 2001, and kindly made available to ISAP by the author

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Table of Contents

Optimising Antimicrobial Therapy by using Pharmacokinetic/Pharmacodynamic Parameters

Predominant Respiratory Tract Pathogens

Outpatient clinical studies in respiratory tract infections

Sample sizes required to detect differences between antibacterial drugs for acute otitis media (AOM) Comparison of bacteriologic versus clinical outcomes in trials of 2 drugs (half the patients would be in each arm of a study)

Numbers of patients required in AECB trials to show differences between antibiotics

Impact of limited clinical data and increasing pathogen resistance on choice of antimicrobial therapy

Evaluating antibiotic efficacy using pharmacokinetics and pharmacodynamics

Patterns of antimicrobial activity

Time above MIC Correlation of serum pharmacokinetics with MIC (susceptibility) of an organism

24-hr AUC/MIC Correlation of serum pharmacokinetics with MIC (susceptibility) of an organism

Patterns of antimicrobial activity

Relationship between Time above MIC and efficacy in animal infection models

Relationship Between T>MIC and Bacterial Eradication with ?-Lactams in Otitis Media (Circles) and Maxillary Sinusitis (Squares)

Susceptibility of Major RTI Pathogens at PK/PD Breakpoints for Current Strains in the USA

Patterns of antimicrobial activity

Pharmacodynamic Predictors of Outcome with Quinolones in Gram-Positive Infections

Relationship between 24 Hr AUC/MIC and mortality for fluoroquinolones against S. pneumoniae in immunocompetent animals

Relationship between 24 Hr AUC/MIC and mortality for fluoroquinolones against Gram-negative bacilli in immunocompromised animals

S.pneumoniae (7 strains) Thigh Infection of Neutropenic and Normal Mice after 24-h Therapy with Levofloxacin - 24-h AUC/MIC Ratios

Distribution of AUC: MIC Ratios of Gatifloxacin and Levofloxacin Against S. pneumoniae: “Monte Carlo” analysis

Levofloxacin pharmacodymanic study

Pharmacokinetics of Quinolones in Humans

Fluoroquinolone AUC/MIC90 ratios for S. pneumoniae

Fuoroquinolone Peak/MIC90 Ratios for S. pneumoniae

AUC/MIC90 Ratios for 75 Canadian fluoroquinolone resistant S. pneumoniae

Peak/ MIC90 Ratios for 75 Canadian fluoroquinolone resistant S. pneumoniae

Clinical Studies of Quinolones in AECB

Correlation between bacterial eradication and clinical efficacy in AECB

Correlation between bacterial eradication and clinical efficacy in AECB

Correlation between bacterial eradication and clinical efficacy in AECB

Use of PK/PD parameters for maximizing efficacy

Author: Michael R. Jacobs

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