The Role of Newer Macrolides in the Treatment of Community-Acquired Respiratory Tract Infections: a Review of Experimental and Clinical Data

Abstract

The macrolide class of antibiotics is well established and often recommended for use in the treatment of community-acquired respiratory tract infections (RTI). The newer agents clarithromycin and azithromycin are frequently prescribed as firstor second-line therapy, and have been considered as superior to erythromycininmicrobiological activity and clinical efficacy. In vitro data show that clarithromycinand azithromycinhave good activity (MIC≤0,5 mg/l) against certain RTI pathogens. However the activity of both compounds is intrinsically low against Haemophilus influenzae whilst several other important RTI pathogens – notably Streptococcus pneu moniae and Streptococcus pyogenes – exhibit a high prevalence of resistance to them. In many countries, the prevalence of resistance to clarithromycinand azithromycinis still rising with crossresistance with erythromycin. Maximum serum concentrations of clarithromycinand azithromycinare lower thanthe MIC90s for these agents against H. influenzae and S. pneumoniae. Concentrations in tissues have beenreported to be much higher thanthose in serum. However, the high concentrations observed in tissues are largely a reflection of high concentrations inside cells. Concentrations of clarithromycin and azithromycininextracellular tissue fluids, where Haemophilus and streptococci are located, are in equilibrium with concentrations in serum, and remainlow. It has beensuggested that phagocytes deliver azithromycinto infectionsites ina targeted fashion, but the evidence in support of this hypothesis is weak. Recent clinical experience with clarithromycin and azithromycin is consistent with preclinical results, and suggests that these agents have limited efficacy against certainRTI. Clarithromycinand azithromycinare the first choice treatment of atypical infections caused by intracellular pathogens. For community-acquired RTIs, where H. influenzae and S. pneumoniae are present, they may no longer be anappropriate choice for first-line therapy. Indeed, in areas where levels of drug resistant S. pneumoniae are high, their use may be questionable as second-line therapy.