Bacteriological efficacies of three macrolides compared with those of amoxicillin-clavulanate against Streptococcus pneumoniae and Haemophilus influenzae

Comparative antibacterial efficacies of erythromycin, clarithromycin, and a zithromycin were examined against Streptococcus pneumoniae and Haemophilus influenzae, with amoxicillin-clavulanate used as the active control. In vit ro, the macrolides at twice their MICs and at concentrations achieved in hu mans were bacteriostatic or reduced the numbers of viable S. pneumoniae slo wly, whereas amoxicillin-clavulanate showed a rapid antibacterial effect. A gainst H. influenzae, erythromycin, clarithromycin, and clarithromycin plus 14-hydroxy clarithromycin at twice their MICs produced a slow reduction in bacterial numbers, whereas azithromycin was bactericidal. Azithromycin at the concentrations achieved in the serum of humans was bacteriostatic, wher eas erythromycin and clarithromycin were ineffective. In experimental respi ratory tract infections in rats, clarithromycin (equivalent to 250 mg twice daily [b.i.d.]) and amoxicillin-clavulanate (equivalent to 500 plus 125 mg b.i.d., respectively) were highly effective against S. pneumoniae, but azi thromycin (equivalent to 500 and 250 mg once daily) was significantly less effective (P < 0.01). Against H. influenzae, clarithromycin treatment (equi valent to 250 or 500 mg b.i.d.) was similar to no treatment and was signifi cantly less effective than amoxicillin-clavulanate treatment (P < 0.01). Az ithromycin demonstrated significant in vivo activity (P < 0.05) but was sig nificantly less effective than amoxicillin-clavulanate (P < 0.05), Overall, amoxicillin-clavulanate was effective in vitro and in vive. Clarithromycin and erythromycin were ineffective in vitro and in vive against H. influenz ae, and azithromycin (at concentrations achieved in humans) showed unreliab le activity against both pathogens. These results may have clinical implica tions for the utility of macrolides in the empiric therapy of respiratory t ract infections.