Differential impact of macrolide compounds in the selection of macrolide nonsusceptibleStreptococcus pneumoniae

Antimicrobial agents are used to treat patients with infectious diseases caused by organisms considered susceptible to the treatment drug. Antimicrobial resistance has reshaped our thinking with regard to the use of antibacterial compounds. In the earlier days of drug-resistant bacteria, the strategy for dealing with the problem was to find new drugs that remained active against the pathogen(s) and not negatively affected by that particular mechanism of resistance. Similar approaches would remain relevant today; however, there clearly appears to be fewer new antimicrobial drugs in development than there was several years ago. How then do we deal with drug-resistant bacteria, given that simply ignoring the problem is not an option? One approach may be to better understand the factors that contribute to resistance and whether the modification of these factors has an impact on slowing, reducing or reversing resistance trends. Such factors may include the propensity of a particular drug class or specific drug to be disproportionately associated with a resistance trend. Such arguments have been previously debated for fluoroquinolones and Streptococcus pneumoniae [1,2], but do similar data exist for the macrolides? It has long been suggested that macrolide use precedes macrolide resistance and the use of longacting macrolides are more likely to correlate with resistance development whereas short-acting compounds were not [3]. When compared with erythromycin, which has a relatively short half-life (2 h), both azithromycin and clarithromycin would be considered longer-acting agents due to their prolonged half-life. However, for azithromycin, the half-life is ten times longer than that of clarithromycin (60–70 vs. 6 h). Is there any evidence to suggest that despite the relatively extended half-lives