JAC Advance Access originally published online on September 12, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Journal of Antimicrobial Chemotherapy (2003) 52, 732-733
© 2003 The British Society for Antimicrobial Chemotherapy
Correspondence |
Reply
1 Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Manitoba; Departments of 2 Clinical Microbiology and 3 Medicine, Health Sciences Centre, Winnipeg, Manitoba, Canada
Keywords: antimicrobial resistance, mutant prevention concentration, limitation
Sir,
We thank Drs Livermore and Zhao for their provocative replies.1,2
Firstly, we thank Dr Livermore for his complimentary remarks.1 We agree that mutant prevention concentrations (MPCs) are only relevant for specific antibiotic/organism combinations in which resistance occurs as a result of mutational events. By focusing our discussion on fluoroquinolones,3 we did not mean to underplay the role of the occurrence of mutational resistance in other antibiotic/organism combinations, such as the ß-lactams and aminoglycosides in Pseudomonas aeruginosa.
Dr Livermore raises concerns about the affects of antibiotic therapy on normal flora, such as the flora of the skin, pharynx and colon. We agree that MPCs evaluated for one antibiotic/organism combination cannot be extrapolated to explain resistance development in all organisms affected throughout the course of antibiotic therapy.
Secondly, we will address Dr Zhao’s statements.2 The sole focus of our paper was on the MPC: the antibiotic concentration above which an organism must acquire two resistance mutations for growth.4 The primary concern of our paper3 was that the MPC must only be applied clinically to situations studying the primary mechanism of clinical resistance. Dr Zhao states in his letter that he agrees with our concern.2
However, Dr Zhao introduces additional issues that were not discussed in our original paper, such as the mutant selection window (MSW) concept. This goes beyond the scope of our original paper. We intended simply to discuss the MPC as a potential dosing strategy and our concerns about the situations in which it is applicable. Subsequent to reviewing Dr Zhao’s comments, we still believe that the MPC and MSW pertain to the mutational resistance of a primary pathogen. The best current MPC model examines an organism/antibiotic combination in which a mutational event leads to a new phenotype, such that the organism survives in the presence of an antibiotic concentration that would have killed the organism prior to the mutation. The best documented examples involve the fluoroquinolones and Streptococcus pneumoniae or Mycobacterium tuberculosis.4,5 These are ideal situations for studying the MPC, as resistance develops in sequential mutational events. The current MPC and MSW data have only examined one antibiotic/one organism combinations. There are no data on how MPC measurements are affected in the clinical environment, where multiple organisms are present and the transfer or exchange of genetic material is possible.
We agree that the MSW concept may aid the development of strategies to limit antimicrobial resistance development. We also believe that the MPC has the potential to become another pharmacodynamic parameter for dosing determination in order to limit the selection of resistance. However, it is imperative that the MPC concept and its clinical applicability be carefully considered prior to use (or misuse) in all organism/antibiotic combinations.
Footnotes
* Correspondence address. Clinical Microbiology, Health Sciences Centre, MS673–820 Sherbrook St., Winnipeg, Manitoba R3A 1R9, Canada. Tel: +1-204-787-4684; Fax: +1-204-787-4699; E-mail: smithhj14{at}hotmail.com 
References
1
.
Livermore, D. M. (2003). Overstretching the mutant prevention concentration. Journal of Antimicrobial Chemotherapy 52, 732.
2
.
Zhao, X. (2003). Clarification of MPC and the mutant selection window concept. Journal of Antimicrobial Chemotherapy 52, 731.
3
.
Smith, H. J., Nichol, K. A., Hoban, D. J. et el. (2003). Stretching the mutant prevention concentration (MPC) beyond its limits. Journal of Antimicrobial Chemotherapy 51, 1323–5.
4
.
Blondeau, J. M., Zhao, X., Hansen, G. et al. (2001). Mutant prevention concentrations of fluoroquinolones for clinical isolates of Streptococcus pneumoniae. Antimicrobial Agents and Chemotherapy 45, 433–8.
5. Dong, Y., Zhao, X., Kreiswirth, B. N. et al. (2000). Mutant prevention concentration as a measure of antibiotic potency: studies with clinical Isolates of Mycobacterium tuberculosis. Antimicrobial Agents and Chemotherapy 44, 2581–4.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  H. J. Smith, D. J. Hoban, and G. G. Zhanel Reply J. Antimicrob. Chemother., October 1, 2003; 52(4): 732 - 733. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||