Telithromycin: An Oral Ketolide for Respiratory Infections

Bearden, David T.; Neuhauser, Melinda M.; Garey, Kevin W.

doi:10.1592/phco.21.15.1204.33902

Cited by 30 publications

(8 citation statements)

References 90 publications

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“…Telithromycin, the first ketolide to undergo clinical development, possesses enhanced activity against penicillin-and macrolide-resistant streptococci [47,48]. In addition, telithromycin displays marked concentration-dependent killing [49] and has an extended half-life that permits once-daily oral administration [50].…”

Section: Clinical Experience With Short-course Therapy For Capmentioning

confidence: 99%

Clinical Efficacy of Newer Agents in Short-Duration Therapy for Community-Acquired Pneumonia

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2004

Clinical Infectious Diseases

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Streptococcus pneumoniae, the most important respiratory tract pathogen implicated in community-acquired pneumonia (CAP), is becoming increasingly resistant in vitro to the beta -lactams and macrolides, and fluoroquinolone resistance has been detected. A growing body of evidence suggests that prolonged antimicrobial use may contribute directly and indirectly to increased antimicrobial resistance among common respiratory pathogens. Long-term exposure to antimicrobial agents, especially less-potent agents, directly increases selection pressure for resistance. Indirectly, poor patient compliance, multiple daily dosing, and the increased risk of adverse events further complicate the resistance issue and diminish the efficacy of long-term antimicrobial use. Controlled clinical trials addressing the appropriate duration of therapy for CAP are lacking. However, available data suggest that with appropriate antibiotic selection, based on appropriate spectrum, potency, and pharmacokinetic/pharmacodynamic profile, lower respiratory tract infections in outpatients can be successfully treated in <7 days rather than the 7-14 days currently recommended.

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Section: Clinical Experience With Short-course Therapy For Capmentioning

confidence: 99%

Clinical Efficacy of Newer Agents in Short-Duration Therapy for Community-Acquired Pneumonia

File

2004

Clinical Infectious Diseases

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“…Telithromycin is a substrate of CYP3A4 (2,16,41), and more recently, we have found that telithromycin significantly inhibits the metabolism of theophylline by reducing the activity and expression of hepatic CYP3A2 and CYP1A2 (Nosaka et al, unpublished). However, to our knowledge, there is no in vivo evidence that telithromycin is a substrate for P glycoprotein and/or Mrp2 and that the hepatobiliary excretion of telithromycin is mediated by P-glycoprotein-and/or Mrp2-mediated transport systems.…”

Section: Discussionmentioning

confidence: 95%

“…On the other hand, it is well known that P-glycoprotein and cytochrome P450 (CYP) 3A4 substances overlap (10,37), and the macrolide antibiotics erythromycin and clarithromycin inhibit not only CYP3A4 but also P glycoprotein (8,20,38,40). Telithromycin is a substrate for CYP3A4 and also inhibits CYP3A4 (2,16,28). On the basis of these findings, it is possible that telithromycin is a substrate for P glycoprotein.…”

mentioning

confidence: 90%

Involvement of the Drug Transporters P Glycoprotein and Multidrug Resistance-Associated Protein Mrp2 in Telithromycin Transport

Yamaguchi

Zhao

Nadai

et al. 2006

Antimicrob Agents Chemother

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The present study aims to investigate the role of P glycoprotein and multidrug resistance-associated protein (Mrp2) in the transport of telithromycin, a newly developed ketolide antibiotic, in vitro and in vivo. The in vitro experiments revealed that the intracellular accumulation of telithromycin in adriamycin-resistant human chronic myelogenous leukemia cells (K562/ADR) overexpressing P glycoprotein was significantly lower than that in human chronic myelogenous leukemia cells (K562/S) not expressing P glycoprotein. Cyclosporine significantly increased the intracellular accumulation of telithromycin in K562/ADR cells. When telithromycin was coadministered intravenously with cyclosporine in Sprague-Dawley (SD) rats, cyclosporine significantly delayed the disappearance of telithromycin from plasma and decreased its systemic clearance to 60% of the corresponding control values. Hepatobiliary excretion experiments revealed that cyclosporine almost completely inhibited the biliary clearance of telithromycin, suggesting that telithromycin is a substrate of P glycoprotein and a potential substrate of Mrp2. Moreover, the biliary clearance of telithromycin was significantly decreased by 80% in Eisai hyperbilirubinemic mutant rats with a hereditary deficiency in Mrp2, indicating that Mrp2, as well as P glycoprotein, plays an important role in the biliary excretion of telithromycin. When the effect of telithromycin on the biliary excretion of doxorubicin, a substrate of P glycoprotein and Mrp2, was examined in SD rats, telithromycin significantly decreased the biliary clearance of doxorubicin by 80%. Results obtained from this study indicate that telithromycin is a substrate of both P glycoprotein and Mrp2, and these transporters are involved in the hepatobiliary transport of telithromycin.

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“…E. faecalis ATCC29213 was used as a control in the MIC determinations. The applied resistance breakpoint of telihromycin was ≥ 4 µg/mL (Bearden et al, 2001).…”

Section: Bacterial Isolates and Susceptibility Testmentioning

confidence: 99%

Alterations in regulatory regions of erm(B) genes from clinical isolates of enterococci resistant to telithromycin

et al. 2011

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We determined rates of resistance to the ketolide telithromycin in 56 Enterococcus faecalis isolates and 44 Enterococcus faecium isolates collected from hospitals in Korea between 2005 and 2006. Twenty nine (51.8%) isolates of E. faecalis and 35 (79.5%) isolates of E. faecium were resistant to telithromycin (minimum inhibitory concentrations, ≥ 4 μg/mL). All of the telithromycin-resistant E. faecalis carried the erm(B) gene only. Of the telithromycin-resistant E. faecium, 29 resistant strains carried erm(B) only, the other six carried erm(A) and erm(B) together. The nucleotide sequence of the erm(B) regulatory regions from 29 E. faecalis and 29 E. faecium isolates with erm(B) only was analyzed. Five types of alterations were detected. The first and second types had point mutations that destabilize the secondary structure of erm(B) mRNA sequestering the translation initiation region of the structural gene. The third type was identical to erm(Bv1), a previously reported variant of erm(B) with different induction specificity. The fourth and fifth types had point mutations within the critical sequence for induction and a point mutation destabilizing the stem-loop of erm(B) mRNA sequestering the translation initiation region of the structural gene.

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Telithromycin: An Oral Ketolide for Respiratory Infections

Cited by 30 publications

References 90 publications

Clinical Efficacy of Newer Agents in Short-Duration Therapy for Community-Acquired Pneumonia

Clinical Efficacy of Newer Agents in Short-Duration Therapy for Community-Acquired Pneumonia

Involvement of the Drug Transporters P Glycoprotein and Multidrug Resistance-Associated Protein Mrp2 in Telithromycin Transport

Alterations in regulatory regions of erm(B) genes from clinical isolates of enterococci resistant to telithromycin

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