The role of newer macrolides in the treatment of community-acquired respiratory tract infection. A review of experimental and clinical data

The macrolide class of antibiotics is well established and often recommende d for use in the treatment of community-acquired respiratory tract infectio n (RTI). The newer agents clarithromycin and azithromycin are frequently pr escribed as first- or second-line therapy, and have been considered as supe rior to erythromycin in microbiological activity and clinical efficacy, In-vitro data show that clarithromycin and azithromycin have good activity (MIC less than or equal to 0.5 mu g/ml) against certain RTI pathogens. Howe ver the activity of both compounds is intrinsically low against Haemophilus influenzae whilst several other important RTI pathogens - notably Streptoc occus pneumoniae and Streptococcus pyogenes - exhibit a high prevalence of resistance to them. In many countries, the prevalence of resistance to clar ithromycin and azithromycin is still rising with cross resistance with eryt hromycin, Maximum serum concentrations of clarithromycin and azithromycin are lower t han the MIC(90)s for these agents against H. influenzae and S. pneumoniae, Concentrations in tissues have been reported to be much higher than those i n serum. However, the high concentrations observed in tissues are largely a reflection of high concentrations inside cells. Concentrations of clarithr omycin and azithromycin in extracellular tissue fluids, where Haemophilus a nd streptococci are located, are in equilibrium with concentrations in the serum, and remain low. it has been suggested that phagocytes deliver azithr omycin to infection sites in a targeted fashion, but the evidence in suppor t of this hypothesis is weak. Recent clinical experience with clarithromycin and azithromycin is consiste nt with preclinical results, and suggests that these agents have limited ef ficacy against certain respiratory infections. Clarithromycin and azithromy cin are the first choice treatment of atypical infections caused by intrace llular pathogens. For community-acquired RTIs, where H. influenzae and S. p neumoniae are present, they may no longer be an appropriate choice for firs t-line therapy. Indeed, in areas where levels of drug resistant S. pneumoni ae are high, their use may be questionable as second-line therapy.