Trends in the activity of macrolide and beta-lactam antibiotics and resistance development. Alexander Project Group

The Alexander Project is an ongoing international multicenter study monitoring trends in the antimicrobial susceptibilities of community-acquired lower respiratory tract (LRT) pathogens. In 1995, 4011 isolates were collected. The incidence of beta-lactamase-positive Haemophilus influenzae was 28.4% in the United States and 15.4% in Europe, and the incidence of beta-lactamase-positive Moraxella catarrhalis has risen to > 90% in Europe and the United States. The incidence of penicillin-resistant Streptococcus pneumoniae is higher in Europe (24.9%) than the Unites States (12.3%). For the majority of centers, there is a marked association between penicillin and macrolide resistance in S. pneumoniae with erythromycin, azithromycin and clarithromycin exhibiting MIC90s of > or = 32 mg/l against penicillin-resistant strains. For Toulouse and Genoa, at least, the high levels of macrolide resistance may be attributable to high macrolide usage. Ceftriaxone and amoxycillin/clavulanate are the most potent agents for empirical therapy, with MIC90s of < or = 2 mg/l against all three principal pathogens. The majority of oral agents studied are active against > 90% H. influenzae and M. catarrhalis and > 80% S. pneumoniae on breakpoint criteria. However, on the basis of the time above MIC criteria for the beta-lactam and macrolide agents tested, only amoxycillin/clavulanate and the parenteral agent ceftriaxone can be recommended for empirical therapy of LRT infections caused by these pathogens.