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In vitro activity of telithromycin against Haemophilus influenzae at epithelial lining fluid concentrations.
BMC Microbiol. 2008 Jan 29; 8:23.BM

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 x, 1/2 x, 1 x, 2 x, 4 x 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 beta-lactams (n = 200), beta-lactamase producer (n = 50) and beta-lactamase negative ampicillin resistant (BLNAR) (n = 10), with MIC from < or =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 x 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 beta-lactamase producers and BLNAR strains, and to azithromycin at ELF concentrations against beta-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.

Authors+Show Affiliations

Laboratory of Clinical Microbiology, Department of Preclinical Sciences LITA Vialba, University of Milan, Via GB Grassi 74, 20159 Milan, Italy. elena.devecchi@unimi.itNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18230154

Citation

De Vecchi, Elena, et al. "In Vitro Activity of Telithromycin Against Haemophilus Influenzae at Epithelial Lining Fluid Concentrations." BMC Microbiology, vol. 8, 2008, p. 23.
De Vecchi E, Nicola L, Larosa M, et al. In vitro activity of telithromycin against Haemophilus influenzae at epithelial lining fluid concentrations. BMC Microbiol. 2008;8:23.
De Vecchi, E., Nicola, L., Larosa, M., & Drago, L. (2008). In vitro activity of telithromycin against Haemophilus influenzae at epithelial lining fluid concentrations. BMC Microbiology, 8, 23. https://doi.org/10.1186/1471-2180-8-23
De Vecchi E, et al. In Vitro Activity of Telithromycin Against Haemophilus Influenzae at Epithelial Lining Fluid Concentrations. BMC Microbiol. 2008 Jan 29;8:23. PubMed PMID: 18230154.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vitro activity of telithromycin against Haemophilus influenzae at epithelial lining fluid concentrations. AU - De Vecchi,Elena, AU - Nicola,Lucia, AU - Larosa,Monica, AU - Drago,Lorenzo, Y1 - 2008/01/29/ PY - 2007/07/13/received PY - 2008/01/29/accepted PY - 2008/1/31/pubmed PY - 2008/5/14/medline PY - 2008/1/31/entrez SP - 23 EP - 23 JF - BMC microbiology JO - BMC Microbiol VL - 8 N2 - 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 x, 1/2 x, 1 x, 2 x, 4 x 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 beta-lactams (n = 200), beta-lactamase producer (n = 50) and beta-lactamase negative ampicillin resistant (BLNAR) (n = 10), with MIC from < or =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 x 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 beta-lactamase producers and BLNAR strains, and to azithromycin at ELF concentrations against beta-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. SN - 1471-2180 UR - https://www.unboundmedicine.com/medline/citation/18230154/In_vitro_activity_of_telithromycin_against_Haemophilus_influenzae_at_epithelial_lining_fluid_concentrations_ L2 - https://bmcmicrobiol.biomedcentral.com/articles/10.1186/1471-2180-8-23 DB - PRIME DP - Unbound Medicine ER -