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 (AUC(24)) 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 MIC(50/90) (mg/L) and MPC(50/90) (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 AUC(24)/MPC(90) 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 AUC(24)/MPC(90) and/or time above MPC, since previous work indicates that the number of prescriptions per person was similar in the geographical regions examined.
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 (AUC(24)) 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 MIC(50/90) (mg/L) and MPC(50/90) (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 AUC(24)/MPC(90) 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 AUC(24)/MPC(90) and/or time above MPC, since previous work indicates that the number of prescriptions per person was similar in the geographical regions examined.
Authors: Lionel A Mandell; Richard G Wunderink; Antonio Anzueto; John G Bartlett; G Douglas Campbell; Nathan C Dean; Scott F Dowell; Thomas M File; Daniel M Musher; Michael S Niederman; Antonio Torres; Cynthia G Whitney Journal: Clin Infect Dis Date: 2007-03-01 Impact factor: 9.079
Authors: Losee L Ling; Tanja Schneider; Aaron J Peoples; Amy L Spoering; Ina Engels; Brian P Conlon; Anna Mueller; Till F Schäberle; Dallas E Hughes; Slava Epstein; Michael Jones; Linos Lazarides; Victoria A Steadman; Douglas R Cohen; Cintia R Felix; K Ashley Fetterman; William P Millett; Anthony G Nitti; Ashley M Zullo; Chao Chen; Kim Lewis Journal: Nature Date: 2015-01-07 Impact factor: 49.962
Authors: Miguel Octavio Pérez Navarro; Ane Stefano Simionato; Juan Carlos Bedoya Pérez; André Riedi Barazetti; Janaina Emiliano; Erika Tyemi Goya Niekawa; Matheus Felipe de Lima Andreata; Fluvio Modolon; Mickely Liuti Dealis; Eduardo José de Almeida Araújo; Thalita Massi Carlos; Odair José Scarpelim; Denise Brentan da Silva; Andreas Lazaros Chryssafidis; Per Bruheim; Galdino Andrade Journal: Front Microbiol Date: 2019-10-25 Impact factor: 5.640