Minimal inhibitory and mutant prevention concentrations of azithromycin, clarithromycin and erythromycin for clinical isolates of streptococcus pneumoniae

Kelli Metzler, Karl Drlica, Joseph M. Blondeau

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22 Citations (Scopus)

Abstract

Background: Previous work showed a higher prevalence of macrolide/azalide resistance in provinces of Canada where azithromycin was the major treatment for Streptococcus pneumoniae as compared with regions where clarithromycin was the dominant treatment. These data provided a way to test the mutant selection window hypothesis, which predicts that the serum drug concentration (AUC24) relative to the mutant prevention concentration (MPC) would be higher for clarithromycin than for azithromycin. Methods: The MIC and MPC were determined for 191 penicillin/macrolide-susceptible clinical isolates of S. pneumoniae with azithromycin, clarithromycin and erythromycin using agar plate assays. Results: The MIC50/90 (mg/L) and MPC50/90 (mg/L), respectively, were as follows: azithromycin 0.13/0.25 and 1/4; clarithromycin 0.031/0.063 and 0.13/0.5; erythromycin 0.063/0.13 and 0.25/2. We calculated from published pharmacokinetic values that the AUC24/MPC90 for azithromycin was 0.85; for clarithromycin it was 96, and for erythromycin base and estolate it was 4 and 10, respectively. Thus the AUC. 24/MPC. 90 was about 50 times higher for clarithromycin than for azithromycin. Conclusions: The elevated prevalence of azithromycin resistance may derive in part from a low value of AUC24/MPC90 and/or time above MPC, since previous work indicates that the number of prescriptions per person was similar in the geographical regions examined.

Original languageEnglish (US)
Pages (from-to)631-635
Number of pages5
JournalJournal of Antimicrobial Chemotherapy
Volume68
Issue number3
DOIs
StatePublished - Mar 1 2013

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Azithromycin
Clarithromycin
Erythromycin
Streptococcus pneumoniae
Macrolides
Erythromycin Estolate
Penicillins
Agar
Area Under Curve
Canada
Prescriptions
Pharmacokinetics
Serum
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Microbiology (medical)
  • Pharmacology (medical)
  • Infectious Diseases

Keywords

  • Azalide
  • MPC
  • Macrolide
  • Pneumococcus

Cite this

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title = "Minimal inhibitory and mutant prevention concentrations of azithromycin, clarithromycin and erythromycin for clinical isolates of streptococcus pneumoniae",
abstract = "Background: Previous work showed a higher prevalence of macrolide/azalide resistance in provinces of Canada where azithromycin was the major treatment for Streptococcus pneumoniae as compared with regions where clarithromycin was the dominant treatment. These data provided a way to test the mutant selection window hypothesis, which predicts that the serum drug concentration (AUC24) relative to the mutant prevention concentration (MPC) would be higher for clarithromycin than for azithromycin. Methods: The MIC and MPC were determined for 191 penicillin/macrolide-susceptible clinical isolates of S. pneumoniae with azithromycin, clarithromycin and erythromycin using agar plate assays. Results: The MIC50/90 (mg/L) and MPC50/90 (mg/L), respectively, were as follows: azithromycin 0.13/0.25 and 1/4; clarithromycin 0.031/0.063 and 0.13/0.5; erythromycin 0.063/0.13 and 0.25/2. We calculated from published pharmacokinetic values that the AUC24/MPC90 for azithromycin was 0.85; for clarithromycin it was 96, and for erythromycin base and estolate it was 4 and 10, respectively. Thus the AUC. 24/MPC. 90 was about 50 times higher for clarithromycin than for azithromycin. Conclusions: The elevated prevalence of azithromycin resistance may derive in part from a low value of AUC24/MPC90 and/or time above MPC, since previous work indicates that the number of prescriptions per person was similar in the geographical regions examined.",
keywords = "Azalide, MPC, Macrolide, Pneumococcus",
author = "Kelli Metzler and Karl Drlica and Blondeau, {Joseph M.}",
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TY - JOUR

T1 - Minimal inhibitory and mutant prevention concentrations of azithromycin, clarithromycin and erythromycin for clinical isolates of streptococcus pneumoniae

AU - Metzler, Kelli

AU - Drlica, Karl

AU - Blondeau, Joseph M.

PY - 2013/3/1

Y1 - 2013/3/1

N2 - Background: Previous work showed a higher prevalence of macrolide/azalide resistance in provinces of Canada where azithromycin was the major treatment for Streptococcus pneumoniae as compared with regions where clarithromycin was the dominant treatment. These data provided a way to test the mutant selection window hypothesis, which predicts that the serum drug concentration (AUC24) relative to the mutant prevention concentration (MPC) would be higher for clarithromycin than for azithromycin. Methods: The MIC and MPC were determined for 191 penicillin/macrolide-susceptible clinical isolates of S. pneumoniae with azithromycin, clarithromycin and erythromycin using agar plate assays. Results: The MIC50/90 (mg/L) and MPC50/90 (mg/L), respectively, were as follows: azithromycin 0.13/0.25 and 1/4; clarithromycin 0.031/0.063 and 0.13/0.5; erythromycin 0.063/0.13 and 0.25/2. We calculated from published pharmacokinetic values that the AUC24/MPC90 for azithromycin was 0.85; for clarithromycin it was 96, and for erythromycin base and estolate it was 4 and 10, respectively. Thus the AUC. 24/MPC. 90 was about 50 times higher for clarithromycin than for azithromycin. Conclusions: The elevated prevalence of azithromycin resistance may derive in part from a low value of AUC24/MPC90 and/or time above MPC, since previous work indicates that the number of prescriptions per person was similar in the geographical regions examined.

AB - Background: Previous work showed a higher prevalence of macrolide/azalide resistance in provinces of Canada where azithromycin was the major treatment for Streptococcus pneumoniae as compared with regions where clarithromycin was the dominant treatment. These data provided a way to test the mutant selection window hypothesis, which predicts that the serum drug concentration (AUC24) relative to the mutant prevention concentration (MPC) would be higher for clarithromycin than for azithromycin. Methods: The MIC and MPC were determined for 191 penicillin/macrolide-susceptible clinical isolates of S. pneumoniae with azithromycin, clarithromycin and erythromycin using agar plate assays. Results: The MIC50/90 (mg/L) and MPC50/90 (mg/L), respectively, were as follows: azithromycin 0.13/0.25 and 1/4; clarithromycin 0.031/0.063 and 0.13/0.5; erythromycin 0.063/0.13 and 0.25/2. We calculated from published pharmacokinetic values that the AUC24/MPC90 for azithromycin was 0.85; for clarithromycin it was 96, and for erythromycin base and estolate it was 4 and 10, respectively. Thus the AUC. 24/MPC. 90 was about 50 times higher for clarithromycin than for azithromycin. Conclusions: The elevated prevalence of azithromycin resistance may derive in part from a low value of AUC24/MPC90 and/or time above MPC, since previous work indicates that the number of prescriptions per person was similar in the geographical regions examined.

KW - Azalide

KW - MPC

KW - Macrolide

KW - Pneumococcus

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DO - 10.1093/jac/dks461

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