Research article

In vitro activity of telithromycin against Haemophilus influenzae at epithelial lining fluid concentrations

Elena De Vecchi¹ , Lucia Nicola¹ , Monica Larosa² and Lorenzo Drago¹

¹  Laboratory of Clinical Microbiology, Department of Preclinical Sciences LITA Vialba, University of Milan, Via GB Grassi 74, 20159 Milan, Italy

²  Medical Affairs & Scientific Relations, sanofi-aventis, v.le L. Bodio 37/b – Milano Milan, Italy

author email corresponding author email

BMC Microbiology 2008, 8:23doi:10.1186/1471-2180-8-23

Published:	29 January 2008

Abstract

Background

Haemophilus influenzae is one of the main aetiological agents of community-acquired respiratory tract infections. The primary aim of this study was to evaluate the antibacterial activity of telithromycin against H. influenzae clinical isolates showing different pattern of resistance in comparison with azithromycin and clarithromycin at 1/4 ×, 1/2 ×, 1 ×, 2 ×, 4 × minimum inhibitory concentration (MIC) and to peak concentrations in epithelial lining fluid (ELF). The secondary aim was to determine the influence of CO₂ enriched atmosphere on bacterial susceptibility.

Results

Telithromycin showed high activity against H. influenzae, including strains susceptible to β-lactams (n = 200), β-lactamase producer (n = 50) and β-lactamase negative ampicillin resistant (BLNAR) (n = 10), with MIC from ≤0.03 to 4 mg/L, and MIC₅₀/MIC₉₀ of 1/2 mg/L with susceptibility rate of 100%, and minimum bactericidal concentrations (MBC) from 2 to 4-fold higher than the MIC. Azithromycin was the most active tested macrolide (range: 0.25 – 4 mg/L; MIC₅₀/MIC₉₀: 1/2 mg/L), comparable to telithromycin, while clarithromycin showed the highest MICs and MBCs (range: 0.25 – 8 mg/L; MIC₅₀/MIC₉₀: 2/8 mg/L). In time-kill studies, telithromycin showed a bactericidal activity at the higher concentrations (4 – 2 × MIC and ELF) against all the strains, being complete after 12 – 24 hours from drug exposition. At MIC concentrations, at ambient air, bactericidal activity of telithromycin and azithromycin was quite similar at 12 hours, and better than that of clarithromycin. Besides, telithromycin and clarithromycin at ELF concentrations were bactericidal after 12 hours of incubation for most strains, while 24 hours were needed to azithromycin to be bactericidal. Incubation in CO₂ significantly influenced the MICs and MBCs, and only slightly the in vitro killing curves.

Conclusion

Telithromycin showed an in-vitro potency against H. influenzae comparable to azithromycin, with an in-vitro killing rate more rapid and superior to clarithromycin at 2X-MIC against β-lactamase producers and BLNAR strains, and to azithromycin at ELF concentrations against β-lactamase negative strains. Against all strains, MICs and MBCs were lower in the absence of CO₂ for the tested antibiotics, showing an adverse effect of incubation in a CO₂ environment. The in-vitro potency together with the tissue concentrations of the antimicrobial, should be considered in predicting efficacy.