Judicious use of antibiotics to minimize emerging resistance: the macrolide clarithromycin as a case study

Author(s): Joseph Blondeau, Charles K Chan, Ross Davidson

Infections remain a major cause of death worldwide and antimicrobial

resistance is increasing. With fewer new antimicrobial agents in development it is imperative

for available antibiotics to last by observing key points: judicious use, appropriate doses

and optimizing regimen compliance in order to reduce the risk of increasing resistance.

This review discusses these issues, using treatment of the respiratory tract pathogen

Streptococcus pneumoniae with the macrolide clarithromycin as a case study. Clarithromycin

is active against common respiratory pathogens achieving high tissue, fluid and serum levels,

and has a relatively short half-life. These characteristics influence the risk of developing

resistance when compared with erythromycin or azithromycin. High local drug concentrations

further reduce the risk of therapeutic failure. Long half-lives associated with a long tail in the

curve of minimum inhibitory concentration (MIC) over time may increase the risk of emerging

was found to be statistically more likely than clarithromycin or erythromycin to select for

organisms with higher MIC values. Poor adherence to antibiotic regimens may accelerate

the development of resistance. Compliance is enhanced by convenient dosing regimens,

for example with extended-release formulations. The ideal antibiotic regimen should achieve

maximal-eradication MIC while minimizing the total time with sub-MICs present in the treated

population, and have mutant prevention concentration values within clinically achievable and

sustainable drug concentrations.

Clinical Practice