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Effect of efflux on telithromycin and macrolide susceptibility in Haemophilus influenzae.
Antimicrob Agents Chemother. 2006 Mar; 50(3):893-8.AA

Abstract

This study investigated the presence of telithromycin and azithromycin efflux in 58 clinical strains of Haemophilus influenzae with various susceptibilities to macrolides, azalides, and ketolides. Efflux pumps were studied by measuring accumulation of radioactive [3H]telithromycin and [N-methyl-3H]azithromycin in the presence and absence of carbonyl m-chlorophenylhydrazone (CCCP), a protonophore. In 17 strains for which the telithromycin MICs were 0.06 to 0.5 microg/ml (azithromycin MICs, < or = 0.06 to 0.125 microg/ml; clarithromycin MICs, < or = 0.06 to 2 microg/ml), telithromycin and azithromycin accumulations were high without CCCP and not affected by its addition, which indicates absence of efflux. In 22 strains for which the telithromycin MICs were 0.25 to 4 microg/ml (azithromycin MICs, 0.25 to 1 microg/ml; clarithromycin MICs, 1 to 8 microg/ml), initially low levels of telithromycin accumulation became higher after addition of CCCP, indicating a functioning efflux pump. Nineteen strains for which the telithromycin MICs were > or = 2 microg/ml had efflux as well as various mutations in ribosomal proteins L4, L22, and/or 23S rRNA (domains II and V). Of these 19 strains, the telithromycin MICs (> or = 8 microg/ml) for 17 of them were significantly raised (azithromycin, MICs 4 to >32 microg/ml; clarithromycin MICs, 8 to >32 microg/ml). From these results we conclude that telithromycin efflux with or without additional ribosomal alterations is present in all H. influenzae strains, except for those for which the telithromycin MICs were very low.

Authors+Show Affiliations

Department of Pathology, Hershey Medical Center, P.O. Box 850, Hershey, Pennsylvania 17033, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

16495248

Citation

Bogdanovich, Tatiana, et al. "Effect of Efflux On Telithromycin and Macrolide Susceptibility in Haemophilus Influenzae." Antimicrobial Agents and Chemotherapy, vol. 50, no. 3, 2006, pp. 893-8.
Bogdanovich T, Bozdogan B, Appelbaum PC. Effect of efflux on telithromycin and macrolide susceptibility in Haemophilus influenzae. Antimicrob Agents Chemother. 2006;50(3):893-8.
Bogdanovich, T., Bozdogan, B., & Appelbaum, P. C. (2006). Effect of efflux on telithromycin and macrolide susceptibility in Haemophilus influenzae. Antimicrobial Agents and Chemotherapy, 50(3), 893-8.
Bogdanovich T, Bozdogan B, Appelbaum PC. Effect of Efflux On Telithromycin and Macrolide Susceptibility in Haemophilus Influenzae. Antimicrob Agents Chemother. 2006;50(3):893-8. PubMed PMID: 16495248.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of efflux on telithromycin and macrolide susceptibility in Haemophilus influenzae. AU - Bogdanovich,Tatiana, AU - Bozdogan,Bülent, AU - Appelbaum,Peter C, PY - 2006/2/24/pubmed PY - 2006/4/28/medline PY - 2006/2/24/entrez SP - 893 EP - 8 JF - Antimicrobial agents and chemotherapy JO - Antimicrob Agents Chemother VL - 50 IS - 3 N2 - This study investigated the presence of telithromycin and azithromycin efflux in 58 clinical strains of Haemophilus influenzae with various susceptibilities to macrolides, azalides, and ketolides. Efflux pumps were studied by measuring accumulation of radioactive [3H]telithromycin and [N-methyl-3H]azithromycin in the presence and absence of carbonyl m-chlorophenylhydrazone (CCCP), a protonophore. In 17 strains for which the telithromycin MICs were 0.06 to 0.5 microg/ml (azithromycin MICs, < or = 0.06 to 0.125 microg/ml; clarithromycin MICs, < or = 0.06 to 2 microg/ml), telithromycin and azithromycin accumulations were high without CCCP and not affected by its addition, which indicates absence of efflux. In 22 strains for which the telithromycin MICs were 0.25 to 4 microg/ml (azithromycin MICs, 0.25 to 1 microg/ml; clarithromycin MICs, 1 to 8 microg/ml), initially low levels of telithromycin accumulation became higher after addition of CCCP, indicating a functioning efflux pump. Nineteen strains for which the telithromycin MICs were > or = 2 microg/ml had efflux as well as various mutations in ribosomal proteins L4, L22, and/or 23S rRNA (domains II and V). Of these 19 strains, the telithromycin MICs (> or = 8 microg/ml) for 17 of them were significantly raised (azithromycin, MICs 4 to >32 microg/ml; clarithromycin MICs, 8 to >32 microg/ml). From these results we conclude that telithromycin efflux with or without additional ribosomal alterations is present in all H. influenzae strains, except for those for which the telithromycin MICs were very low. SN - 0066-4804 UR - https://www.unboundmedicine.com/medline/citation/16495248/Effect_of_efflux_on_telithromycin_and_macrolide_susceptibility_in_Haemophilus_influenzae_ L2 - https://journals.asm.org/doi/10.1128/AAC.50.3.893-898.2006?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -