Abstract
The in vitro and in vivo antibacterial activities of azithromycin (AZM) were compared with those of erythromycin (EM), clarithromycin (CAM), josamycin (JM), midecamycin acetate (MDM), kitasamycin, rokitamycin, ampicillin, cefaclor (CCL) and ofloxacin (OFLX). In addition, in vitro resistance emergence tests were also conducted.
AZM demonstrated broad-spectrum against gram-positive bacteria and produced a significant improvement in potency against gram-negative organisms as compared with other macrolides. The AZM MIC for 90% of the strains (MIC90) against methicillin-susceptible Staphylococcus aureus was 2-and 4-fold less than that of EM and CAM, respectively. The MIC90 of AZM against Streptococcus pneumoniae was equivalent to that of EM and 2-fold less than that of CAM. AZM was the most active antibiotic against Neisseria gonorrhoeae, Vibrio cholerae and Vibrio parahaemolyticus among the macrolides; with tested MIC90 values of 0.20, 1.56 and 1.56μg/ml, respectively. It was four and eight times more potent than EM and CAM against Haemophilus influenzae (MIC90, 3.13μg/ml). In a killing-kinetics experiment, AZM, at its MIC, showed better bactericidal activity against Staphylococcus aureus than EM and an activity similar to that of CAM. It also showed the best bactericidal effect for S. pneumoniae. In the in vitro emergence of resistance experiment, the increase in the AZM MIC for 80% of the strains (MIC80) was one dilution for S.aureus. Furthermore, the MIC80 of CAM, JM and OFLX for S.aureus increased by two dilutions while the MIC80 of EM and CCL for S.aureus increased by three dilutions. Thus, among the drugs tested the MIC80 increase rate for AZM, namely resistance emergence, was the lowest.
In the therapy of experimental acute systemic infections in mice, AZM exhibited lower activity than CCL and CAM against S.aureus, and demonstrated the lowest ED50 against Streptococcus pyogenes and S.pneumoniae. The number of organisms recovered decreased more significantly following treatment with AZM than with CAM or OFLX in murine models of S. pneumoniae lung infection and H. influenzae lung infection (p<0.01).
Because of its excellent pharmacokinetics, as shown by the serum and lung T1/2 of AZM being 8-and 10-times longer than those of CAM, AZM produces greater in vivo efficacy.
