In vitro antibacterial activity and in vivo protective effect of telithromycin The antibacterial activity against clinical isolates and in vivo protective effect

Abstract

The in vitro antibacterial activity of telithromycin (TEL) against clinical isolates in Japan was examined in comparison with those of erythromycin A (EM), clarithromycin (CAM) and azithromycin (AZM)-macrolide antibiotics-, amoxicillin (AMPC)-a penicillin antibiotic-, cefdinir (CFDN) -a cephem antibiotic-and levofloxacin (LVFX) -a new quinolone- The results revealed that TEL demonstrated the most potent antibacterial activity (MIC90 = 0.125 jug/mL) among the tested compounds against not only EM-susceptible Streptococcus pneumoniae (MIC90 = 0.008 jug/mL) but also mefE-carrying (drug-excreting type) EM-resistant strains and ermB -carrying (target-site mutant type) EM-resistant strains. In addition, TEL showed bactericidal activity against EM-susceptible and mefE -carrying EM-resistant strains (MBC90/ MIC90 = 1), but somewhat weaker (MBC90/MIC90 = 4) activity against ermB -carrying EM-resistant strains. TEL also exhibited the most potent antibacterial activity against Streptococcus pyogenes and Streptococcus agalactiae as well as S. pneumoniae. TEL showed the most potent antibacterial activity (MIC90 = 0.125 and 0.25 g/mL) against EM-susceptible and inducible EM-resistant Staphylococcus aureus, but its bactericidal activity was weak (MBC90/MIC90 = 16 and 8). TEL was inactive against constitutive EM-resistant strains and the similar result was also obtained on Staphylococcus epidermidis. TEL exhibited the most potent antibacterial activity against EM-susceptible Enterococcus faecalis (MIC9o0.063 jug/mL), and more than 32 times stronger than EM, CAM and AZM against EM-resistant strains (MIC90 = 4 jug/mL). Furthermore, TEL showed bactericidal activity against the EM-susceptible strains (MBC90/MIC90 = 4), but its bactericidal activity was weak against the EM-resistant strains (MBC90/MIC90 = 32). TEL showed the strongest antibacterial activity against Enterococcus faecium (MIC90 = 2 jug/mL). Antibacterial activity of TEL (MIC.™ = 2 jug/mL, MIC90 = 4//g/mL) was 2 to 4 times stronger than those of EM and CAM and equal to or twice weaker than that of AZM against Haemophilus influenzae. TEL exhibited potent antibacterial activity against Moraxella catarrhalis, Bordetella pertussis, Legionella spp. and Neisseria gonorrhoeae (MIC90 = 0.25, 0.032, 0.063 and 0.125 jug/mL). These effects of TEL were comparable to or more potent than those of EM, CAM and AZM, except for inferiority to that of AZM on M. catarrhalis. However, antibacterial activity of TEL against Klebsiella pneumoniae was weak as well as those of EM, CAM and AZM. TEL showed bactericidal activity against H. influenzae and M. catarrhalis (MBC90/MIC90 = 1). Next, the in vivo protection effect of TEL in a systemic infection model caused by S. aureus Smith in mice was investigated in comparison with CAM, AZM, CFDN and LVFX. The results revealed that TEL and each of the reference compounds provided a protective effect in this model. The ED50 values (mg/kg) were as follows, TEL = 7.3, CAM = 12.1, AZM - 13.2, CFDN = 2.1 and LVFX = 5.7. In conclusion, following results became evident. 1. TEL has very potent antibacterial activity against gram-positive bacteria. 2. It especially was active against even EM-resistant S. pneumoniae. 3. TEL possesses excellent activity against gram-negative causative organisms in common in bacterial community acquired pneumonia. 4. TEL has more potent protective effects than CAM and AZM in a murine model of systemic S. aureus infection. © 2003, Japanese Society of Chemotherapy. All rights reserved.