Abstract
The selection of antibiotic-resistant mutant bacteria is proposed to occur in a drug concentration range (the mutant selection window) that extends from the minimum inhibitory concentration (MIC) of susceptible cells to the MIC of the least susceptible, single-step bacterial mutants (the mutant prevention concentration [MPC]). MPCs were estimated for tobramycin, chloramphenicol, rifampicin, penicillin, vancomycin, and several fluoroquinolones by use of Escherichia coli and Staphylococcus aureus. Comparisons among reported serum drug levels indicate that new fluoroquinolones are the least likely to enrich populations of resistant mutant bacteria during monotherapy. These data partly explain the selective enrichment of populations of resistant mutant bacteria in medical practice. The mutant selection window range (MPC:MIC) was narrowed for fluoroquinolones by structure modification, pointing to a new direction in antibiotic refinement. The mutant selection window and the MPC were determined for combinations of rifampicin and tobramycin, using S. aureus, as a guide for combination therapy with compounds that alone cannot block enrichment of mutant bacterial populations.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 561-565 |
| Number of pages | 5 |
| Journal | Journal of Infectious Diseases |
| Volume | 185 |
| Issue number | 4 |
| DOIs | |
| State | Published - Feb 15 2002 |
| Externally published | Yes |
Fingerprint
All Science Journal Classification (ASJC) codes
- Infectious Diseases
- Immunology and Allergy
Cite this
}
Restricting the selection of antibiotic-resistant mutant bacteria : Measurement and potential use of the mutant selection window. / Zhao, Xilin; Drlica, Karl.
In: Journal of Infectious Diseases, Vol. 185, No. 4, 15.02.2002, p. 561-565.Research output: Contribution to journal › Article
TY - JOUR
T1 - Restricting the selection of antibiotic-resistant mutant bacteria
T2 - Measurement and potential use of the mutant selection window
AU - Zhao, Xilin
AU - Drlica, Karl
PY - 2002/2/15
Y1 - 2002/2/15
N2 - The selection of antibiotic-resistant mutant bacteria is proposed to occur in a drug concentration range (the mutant selection window) that extends from the minimum inhibitory concentration (MIC) of susceptible cells to the MIC of the least susceptible, single-step bacterial mutants (the mutant prevention concentration [MPC]). MPCs were estimated for tobramycin, chloramphenicol, rifampicin, penicillin, vancomycin, and several fluoroquinolones by use of Escherichia coli and Staphylococcus aureus. Comparisons among reported serum drug levels indicate that new fluoroquinolones are the least likely to enrich populations of resistant mutant bacteria during monotherapy. These data partly explain the selective enrichment of populations of resistant mutant bacteria in medical practice. The mutant selection window range (MPC:MIC) was narrowed for fluoroquinolones by structure modification, pointing to a new direction in antibiotic refinement. The mutant selection window and the MPC were determined for combinations of rifampicin and tobramycin, using S. aureus, as a guide for combination therapy with compounds that alone cannot block enrichment of mutant bacterial populations.
AB - The selection of antibiotic-resistant mutant bacteria is proposed to occur in a drug concentration range (the mutant selection window) that extends from the minimum inhibitory concentration (MIC) of susceptible cells to the MIC of the least susceptible, single-step bacterial mutants (the mutant prevention concentration [MPC]). MPCs were estimated for tobramycin, chloramphenicol, rifampicin, penicillin, vancomycin, and several fluoroquinolones by use of Escherichia coli and Staphylococcus aureus. Comparisons among reported serum drug levels indicate that new fluoroquinolones are the least likely to enrich populations of resistant mutant bacteria during monotherapy. These data partly explain the selective enrichment of populations of resistant mutant bacteria in medical practice. The mutant selection window range (MPC:MIC) was narrowed for fluoroquinolones by structure modification, pointing to a new direction in antibiotic refinement. The mutant selection window and the MPC were determined for combinations of rifampicin and tobramycin, using S. aureus, as a guide for combination therapy with compounds that alone cannot block enrichment of mutant bacterial populations.
UR - http://www.scopus.com/inward/record.url?scp=0037083238&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037083238&partnerID=8YFLogxK
U2 - https://doi.org/10.1086/338571
DO - https://doi.org/10.1086/338571
M3 - Article
C2 - 11865411
VL - 185
SP - 561
EP - 565
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
SN - 0022-1899
IS - 4
ER -