Pharmacodynamics of MASKO Compounds (Macrolides, Azalides, Streptogramins, Ketolides, and Oxazolidinones)

Table of Contents

Pharmacodynamics of MASKO Compounds (Macrolides, Azalides, Streptogramins, Ketolides, and Oxazolidinones)

Pharmacodynamics

Pattern of Bacterial Killing

Impact of Increasing Doses on Killing of Streptococcus pneumoniae ATCC 10813

Impact of Increasing Doses on Killing of Streptococcus pneumoniae CDC 140

Impact of Increasing Doses on Killing of Streptococcus pneumoniae ATCC 10813

Impact of Increasing Doses of Telithromycin on Killing of Streptococcus pneumoniae in Thighs of Neutropenic Mice

Impact of Increasing Doses of ABT 773 on Killing of Streptococcus pneumoniae in Thighs of Neutropenic Mice

Impact of Increasing Doses of Azithromycin on Killing of Streptococcus pneumoniaein Thighs of Neutropenic Mice

Persistent Effects

Pharmacodynamics of Linezolid

In Vivo PAE of Clarithromycin with Streptococcus pneumoniae ATCC 10813 in Thighs of Neutropenic Mice

In Vivo PAE of Telithromycin withStreptococcus pneumoniae ATCC 10813 in Thighs of Neutropenic Mice

In Vivo PAE for Azithromycin with Streptococcus pneumoniae ATCC 10813 in Thighs of Neutropenic Mice

Pharmacodynamic Characterisitics

Impact of Dosing Frequency on Static Dose for Macrolides and Azalides with Streptococcus pneumoniae ATCC 10813

Impact of Dosing Frequency on Static Dose for Macrolides, Azalides and Ketolides with Streptococcus pneumoniae ATCC 10813

Impact of Dosing Interval on Static Doses for ABT-773 Against S. aureus ATCC 29213

Impact of Dosing Interval on Doseof Synercid (Quinupristin + Dalfopristin) Required for Efficacy in Neutropenic Mice

Impact of Dosing Interval on Dose of Linezolid Required for Efficacy in Neutropenic Mice

Pharmacokinetics of Macrolides, Azalides and Ketolides in Infected Neutropenic Mice at a Dose of 18.8 mgkg

Relationships Between PK/PD Parameters and Efficacy of ABT-773 withStreptococcus pneumoniae ATCC 10813

Relationship Between PK/PD Parameters and Efficacy of Clarithromycin withStreptococcus pneumoniae ATCC 10813

Relationship Between PK/PD Parameters and Log10 CFU/Thigh After 24 Hrs of Therapy withLinezolid at Different Dosing Intervals

Relationship Between PK/PD Parameters and Log10 CFU/Thigh After 24 Hrs of Therapy withLinezolid at Different Dosing Intervals

Relationship Between PK/PD Parameters and Efficacy of AZD2562

PK/PD Parameters and Efficacy

Impact of DosingFrequency on Static Dose for Macrolides, Azalides and Ketolides with Streptococcus pneumoniae ATCC 10813

PK/PD Parameters and Efficacy

24-Hr AUC/MIC with Total and Free Drug for the Static Dose of Different Macrolides with S. pneumoniae ATCC 10813

RESULTS

Change in CFU/Thigh with Strains of CSSP after 24 Hrs of Treatment (48 mg/kg/6 hrs) and in Control Neutropenic Mice

Change in CFU/Thigh with Strains of CRSP (due to Erm) after 24 Hrs of Treatment (48 mg/kg/6 hrs) and in Control Neutropenic Mice

Change in CFU/Thigh with Strains of CRSP (due to Mef) after 24 Hrs of Treatment (48 mg/kg/6 hrs) and in Control Neutropenic Mice

24-Hr AUC/MIC for Free Drug with Susceptible and Resistant Strains of Streptococcus pneumoniae

Static Doses (mg/kg/24 hrs) in Lungs and Thigh with Azithromycin

Static Doses (mg/kg/24 hrs) in Lung and Thigh with Clarithromycin

Impact of Resistance to Quinupristin or Dalfopristin on Activity in Animal Models

Impact of Neutrophils on Activity of Macrolides, Azalides, Ketolides and Oxazolidinones with Strains of Streptococcus pneumoniae

24-Hr AUC/MIC with Total and Free Drug for the Static Dose of Different Macrolides with S. pneumoniae ATCC 10813

Conclusions

Distribution of Antibiotics in the Body Affects Bacteriological Efficacy

Parmacodynamic Breakpoints forNew Macrolides

Clarithromycin and Azithromycin Levels in Plasma and Epithelial Lining Fluid (ELF) of Healthy Adults

Relationship Between Epithelial Lining Fluid/Serum Ratio and Alveolar Macrophage/Serum Ratio

Problems in Evaluating Macrolides in Animal Models

Parmacodynamic Breakpoints forNew Macrolides

Relationship Between Magnitude of PK/PD Parameter and Efficacy in Double Tap Studies in Otitis Media due to S. pneumoniae

Relationship Between Magnitude of PK/PD Parameter and Efficacy in Double Tap Studies in Otitis Media due to H. influenzae

Pneumococcal Breakthrough Bacteremia in Patients Treated with Macrolidesfor Community-Acquired Pneumonia

Resistance and Efficacy in CAP

Increasing Macrolide Resistance in Eight Counties Surrounding Atlanta

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