Telithromycin (Ketek, HMR 3647, RU 66647) is a semisynthetic antibacterial agent belonging to a class of compounds called ketolides, which are a variation on the existing class of antibiotics known as macrolides like erythromycin, whose structure includes a 14-molecule ring. Telithromycin was developed by the French pharmaceutical company Roussel Uclaf S.A., prior to 1997.
Telithromycin appears to be effective against macrolide-resistant Streptococcus pneumoniae. The defining differentiating characteristic of the ketolides, as opposed to other macrolides, is the removal of the neutral sugar, L-cladinose from the 3-position of the macrolide ring and the subsequent oxidation of the 3-hydroxyl to a 3-keto functional group.
Telithromycin shows activity against Gram-positive and Gram-negative bacteria, as well as mycoplasma. Telithromycin is a bacterial protein synthesis inhibitor that interacts with peptidyl transferase site of the 50S ribosomal subunit. The main binding sites are with domains II and V of the 23S rRNA.
Telithromycin is sparingly soluble in water and has a solubility of approximately 30mg/ml in organic solvents such as DMSO, ethanol, and dimethyl formamide (should be purged with inert gas).
This product is considered a dangerous good. Quantities above 1 g may be subject to additional shipping fees. Please contact us for questions.
| Mechanism of Action | Telithromycin is a very effective inhibitor of the translation function at the level of the 50S ribosomal subunit. It has been shown that 14‐ and 15‐membered ring macrolides are also able to inhibit a second cellular function, the assembly of the nascent 50S ribosomal subunit. Telithromycin, in addition, like many carbamate ketolides, is also able to inhibit the formation of the 30S ribosomal subunit.
23S rRNA is composed of six domains. Domains V and II belong partly to the peptidyl transferase site, and erythromycin A interacts mainly with domain V. Telithromycin, like 14‐ and 15‐membered ring macrolides, interacts with the bacterial 23S rRNA. Interactions are limited to a region of domain V and additionally, for telithromycin, to domain II. The interaction with the 750 loop (position A‐752) of domain II is due to the C11–C12 carbamate chain. |
| Spectrum | Telithromycin shows activity against Gram-positive and Gram-negative bacteria, as well as mycoplasma. More specifically, Telithromycin retains its activity against erm-(MLS(B)) or mef-mediated macrolide-resistant Streptococcus pneumoniae and Streptococcus pyogenes and against Staphylococcus aureus resistant to macrolides through inducible MLS(B) mechanisms. Telithromycin also possesses high activity against the Gram-negative pathogens Haemophilus influenzae and Moraxella catarrhalis, regardless of beta-lactamase production. In vitro, it shows similar activity to azithromycin against H. influenzae, while in vivo its activity against H. influenzae is higher than that of azithromycin. Telithromycin's spectrum of activity also extends to the atypical, intracellular and cell-associated pathogens Legionella pneumophila, Mycoplasma pneumoniae and Chlamydia pneumoniae. |
| Microbiology Applications | Telithromycin is commonly used in clinical in vitro microbiological antimicrobial susceptibility tests (panels, discs, and MIC strips) against gram positive microbial isolates. Medical microbiologists use AST results to recommend antibiotic treatment options. Representative MIC values include:
|
| Molecular Formula | C43H65N5O10 |
| References |
Ackermann G and Rodloff AC (2003) Drugs of the 21st century: telithromycin (HMR 3647) - the first ketolide: J. Antimicrob. Chemother. 51:497 Araujo FG et al (1997) The ketolide antibiotics HMR-3647 and HMR 3004 are active against Toxoplasma gondii in vitro and in murine models of infection: Antimicrob. Agents Chemother. 41:2137 Boswell FJ (1998) The in vitro activity of HMR 3647, a new ketolide antimicrobial agent: J. Antimicrob. Chemother. 42:703 Byoungduck P and Yu M (2015) Hong-inducible expression of erm(B) by the ketolides telithromycin and cethromycin. Int. J. Antimicrob. Agents 46:226 Douthwaite S and Champney WS (2001) Structures of ketolides and macrolides determine their mode of interaction with the ribosomal target site. J. Antimicrob. Chemother. 48 (Topic T1):1-8 Hansen LH, Mauvais, P and Douthwaite S (1999) The macrolide-ketolide antibiotic binding site is formed by structures in domains II and V of 23S ribosomal RNA. Molecular Microbiol 31(2):623-631 Lee JH, et al (2008) Time-dependent effects of Klebsiella pneumonia endotoxin on the Telithromycin pharmacokinetics in rats; Restoration of the parameters in 96-hour KPLPS rats to the control levels: Pulm. Pharmacol. Ther. 21:860 Lonks JR and Goldmann DA (2005) Telithromycin: A ketolide antibiotic for treatment of respiratory tract infections. Clin. Inf. Dis. 40:1657 Lovmar M and Tenson T (2003) The mechanism of action of macrolides, lincosamides and streptogramin B reveals the nascent peptide exit path in the ribosome. J. Molec. Micro. 330(5):1005-1014 Monaghan R and Barrett JF (2008) Benefit-risk assessment of Telithromycin in the treatment of community-acquired pneumonia: S.D. Brown; Drug Safety 31:561 Wellington K and Noble S (2004) Telithromycin Drugs 64:1683 Zeitlinger M et al (2009) Ketolides - the modern relatives of macrolides: The pharmacokinetic perspective. Clin. Pharmacokinet. 48:23 Vimberg V et al (2015) ClpP-independent function of ClpX interferes with Telithromycin resistance conferred by msr(A) in Staphylococcus aureus. Antimicrob. Agents Chemother. 59:3611
|
| MIC | Bacillus spp.| ≤0.12 － >16|| Bacteroides fragilis| 0.03 － 16|| Bacteroides tectum | 0.125 － 0.5|| Bacteroides ureolyticus| 0.125 － 2|| Bilophila wadsworthia| 0.5 － 4|| Borrelia afzelii| ≤0.0002 － 0.0078|| Borrelia bissettii| ≥0.0009|| Borrelia burgdorferi| ≤0.0002 － 0.0078|| Borrelia garinii| ≤0.0002 － 0.0078|| Borrelia valaisiana| ≥0.0004|| Brevibacterium spp.| ≤0.015 － >128|| Campylobacter coli| 0.5 － >64|| Campylobacter jejuni| 0.5 － >64|| Chlamydia pneumonia| 0.015 － 2|| Chlamydophila pneumonia| 0.015 － 2|| Clostridium clostridioforme| 0.06 － 32|| Clostridium difficile| 0.03 － 256|| Clostridium innocuum| 0.06 － >32|| Clostridium ramosum| 0.03 － >32|| Clostridium spp.| 0.03 － 8|| Corynebacterium afermentans| ≤0.015 － >128|| Corynebacterium amycolatum| ≤0.015 － >128|| Corynebacterium jeikeium| ≤0.015 － >128|| Corynebacterium minutissimum| ≤0.015 － >16|| Corynebacterium pseudodiphtheriticum| ≤0.015 － 0.12|| Corynebacterium spp.| ≤0.12 － >16|| Corynebacterium striatum| ≤0.015 － 64|| Corynebacterium urealyticum| ≤0.015 － >64|| Coryneform | ≤0.015 － >128|| Diphtheroids| ≥0.25|| Enterococcus avium| 0.015 － >16|| Enterococcus casseliflavus| 0.015 － >16|| Enterococcus cecorum| ≤0.12 － >16|| Enterococcus durans| 0.015 － >16|| Enterococcus faecalis| 0.008 － >16|| Enterococcus faecium| 0.005 － >16|| Enterococcus gallinarum| 0.015 － >16|| Enterococcus raffinosus| ≤0.12 － >16|| Enterococcus spp.| 0.015 － 8|| Erysipelothrix rhusiopathiae| ≤0.015|| Escherichia coli (250 UC5)| 10|| Fusobacterium gonidiaformans | ≤0.015 － 8|| Fusobacterium mortiferum| 2 － >32|| Fusobacterium naviforme| ≤0.015 － 8|| Fusobacterium necrogenes | 2 － >32|| Fusobacterium necrophorum| ≤0.015 － 8|| Fusobacterium nucleatum| ≤0.015 － 8|| Fusobacterium russii | ≤0.015 － 32|| Fusobacterium ulcerans | 2 － >32|| Fusobacterium varium| 4 － >32|| Gemella spp.| ≤0.12 － >16|| Haemolytic streptococci| 0.001 － 0.25|| Haemophilus influenzae| 0.002 － >32|| Haemophilus spp.| 0.25 － 8|| Lactobacillus spp.| <0.003 － 16|| Legionella adelaidensis| 0.004|| Legionella anisa| ≥0.063|| Legionella birminghamiensis| ≥0.125|| Legionella bozemanii| ≥0.059|| Legionella brunensis| ≥0.063|| Legionella cherrii| ≥0.032|| Legionella cincinnatiensis| ≥0.016|| Legionella dumofii| ≥0.125|| Legionella erythra| ≥0.25|| Legionella fairfieldensis| ≥0.004|| Legionella feeleii| ≥0.016|| Legionella geestiana| ≥0.063|| Legionella gormanii| ≥0.061|| Legionella gratiana| ≥0.063|| Legionella hackeliae| ≥0.063|| Legionella israelensis| ≥0.047|| Legionella jamestowniensis| ≥0.047|| Legionella jordanis| ≥0.25|| Legionella lansingensis| ≥0.032|| Legionella longbeachae| 0.165|| Legionella maceachernii| 0.063|| Legionella micdadei| 0.105|| Legionella moravica| 0.063|| Legionella nautarum| 0.008|| Legionella oakridgensis| 0.063|| Legionella pneumophila| 0.004 － 0.5|| Legionella quateirensis| 0.016|| Legionella quinlivanii| ≥0.063|| Legionella rubrilucens| ≥0.0125|| Legionella sainthelensi| ≥0.0125|| Legionella santicrucis| ≥0.008|| Legionella shakespearei| ≥0.063|| Legionella spiritensis| ≥0.063|| Legionella spp.| ≤0.004 － 0.12|| Legionella steigerwaltii| ≥0.016|| Legionella tucsonensis| ≥0.008|| Legionella wadsworthii| ≥0.032|| Legionella worsleiensis| ≥0.008|| Leuconostoc spp.| 0.03 － >16|| Listeria monocytogenes| 0.06 － >16|| Micrococcus spp.| ≤0.12 － >16|| Moraxella catarrhalis| 0.001 － 4|| Mycobacterium abscessus| 0.12 － >64|| Mycobacterium africanum | ≥40|| Mycobacterium avium| 2.5 － >40|| Mycobacterium bovis| 10 － >40|| Mycobacterium chelonae| ≤0.03 － 32|| Mycobacterium fortuitum| 0.12 － >64|| Mycobacterium marinum| ≥32|| Mycobacterium mucogenicum| ≤0.03 － 2|| Mycobacterium paratuberculosis| 2.5 － >40|| Mycobacterium peregrinum| 0.06 － 1|| Mycobacterium simiae| 20 − ≥40|| Mycobacterium smegmatis| 64 － 128|| Mycobacterium tuberculosis| ≥40|| Mycobacterium ulcerans| 20 － >40|| Mycoplasma fermentans| 0.06 － 0.25|| Mycoplasma genitalium| ≤0.015|| Mycoplasma hominis| 2 － 16|| Mycoplasma penetrans| 0.12|| Mycoplasma pneumonia| 0.00024 － 0.03|| Neisseria cinerea| 0.015 － 1|| Neisseria lactamica| 0.007 － 0.5|| Neisseria meningitidis| <0.008 － 0.5|| Neisseria mucosa| 0.06 － 4|| Neisseria perflava/sicca| 0.06 － 4|| Neisseria polysaccharea| 0.007 － 0.25|| Neisseria spp.| 0.002 － 4|| Oerskovia spp.| ≤0.015 － >128|| Pediococcus spp.| ≤0.12 － >16|| Peptostreptococcus asaccharolyticus| 0.03 － 2|| Peptostreptococcus magnus| 0.06|| Peptostreptococcus micros| ≤0.015 － 0.03|| Peptostreptococcus prevotii| ≤0.015 － 0.5|| Peptostreptococcus spp.| 0.03 － 8|| Pneumococci| 0.004 － 1|| Porphyromonas asaccharolytica| <≤0.015 － >32|| Porphyromonas cangingivalis | ≤0.015 － 0.125|| Porphyromonas canoris | ≤0.015 － 0.125|| Porphyromonas cansulci | ≤0.015 － 0.125|| Porphyromonas circumdentaria | ≤0.015 － 0.125|| Porphyromonas gingivalis| ≤0.015 － 0.06|| Porphyromonas levii | ≤0.015 － 0.125|| Porphyromonas macacae | 0.03 － 0.06|| Prevotella bivia| ≤0.015 － 4|| Prevotella buccae| 0.125 － 8|| Prevotella denticola| 0.06 － 16|| Prevotella heparinolytica | 0.06 － 0.5|| Prevotella intermedia| ≤0.015 － 0.25|| Prevotella loescheii| 0.06 － 16|| Prevotella melaninogenica| 0.06 － 16|| Prevotella oris| 0.125 － 8|| Prevotella spp.| 0.03 － 8|| Rhodococcus equi| ≤0.015 － 0.25|| Rhodococcus spp.| ≤0.12 － >16|| Staphylococcus aureus| 0.008 － >128|| Staphylococcus epidermidis| 0.06 － >16|| Staphylococcus haemolyticus| 0.06 － >16|| Staphylococcus pneumonia| 0.003 － 0.39|| Staphylococcus pyogenes| <0.13 － 8|| Staphylococcus spp.| 0.03 － >16|| Streptococcus agalactiae| 0.004 － 2|| Streptococcus anginosus| ≤0.12 － 4|| Streptococcus bovis| ≤0.12 － 4|| Streptococcus constellatus| ≤0.12 － 4|| Streptococcus intermedius| ≤0.12 － 4|| Streptococcus milleri| ≤0.12 － 4|| Streptococcus mutans| ≤0.12 － 4|| Streptococcus pneumonia| ≤0.0005 － ≥64|| Streptococcus pyogenes| 0.002 － ≥64|| Turicella otitidis| ≤0.015 － >128|| Ureaplasma urealyticum| ≤0.015 － 0.06|| Veillonella spp.| 0.06 － 32|| |