Persisters are implicated in chronic recurrent infections and in biofilms because the antibiotic treatment may leave a small subset of persisters which may later repopulate and cause infections (Lewis 2007). This small subpopulation is considered to be the nucleus for chronic infections. However, the significance of these in vitro survivors is questionable as they may not affect the outcome of treatment.
If 100% killing is necessary, how can one justify the determination of dosage regimen of an antibiotic using the kinetic parameters based on MIC? After all, MIC only indicates that bacteria are inhibited from growth. The important PK/PD parameters such as the percentage of time above the MIC (t > MIC), ratio of peak concentration to MIC (Cmax/MIC) and the ratio of the area under the curve to MIC (AUC/MIC) are based on MIC. If 100% in vitro killing is a necessity, will it be more appropriate to use MBC values? Even MBC may not be ideal as, by definition, it kills only 99.9% of bacteria. Should we consider MBC100 as the single most important parameter that determine the in vivo antibiotic efficacy?
Lewis, K. (2007). Persister cells, dormancy and infectious diseases. Nat Rev Microbiol. 5(1): 48-56.
No comments:
Post a Comment