Telithromycin: a new ketolide antimicrobial for treatment of respiratory tract infections

Yassin, Hossam M; Dever, Lisa L.

doi:10.1517/13543784.10.2.353

Cited by 40 publications

(18 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Given the MICs at which 90% of isolates are inhibited (MIC 90 s) for pathogens that frequently cause STIs (3, 10), the AUC 0-24 /MIC 90 ratios indicate that telithromycin will be sufficient to eradicate highly susceptible bacteria such as Streptococcus pyogenes from tissues and plasma (5,22). However, the AUC 0-24 /MIC 90 ratios for telithromycin appeared to be too low for the treatment of infections caused by Staphylococcus aureus or bite pathogens, such as Prevotella canis.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Telithromycin in Plasma and Soft Tissues after Single-Dose Administration to Healthy Volunteers

Gattringer

Urbauer²,

Traunmüller³

et al. 2004

Antimicrob Agents Chemother

View full text Add to dashboard Cite

By use of microdialysis we assessed the concentrations of telithromycin in muscle and adipose tissue to test its ability to penetrate soft tissues. The ratios of the area under the concentration-versus-time curve from 0 to 24 h to the MIC indicated that free concentrations of telithromycin in tissue and plasma might be effective against Streptococcus pyogenes but not against staphylococci and human and animal bite pathogens.

show abstract

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Telithromycin in Plasma and Soft Tissues after Single-Dose Administration to Healthy Volunteers

Gattringer

Urbauer²,

Traunmüller³

et al. 2004

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…1A to C) and by electron microscopy. Moreover, maximum concentrations of ketolides in plasma after regular oral dosage (1,6,27) are 90 to 270 times higher than the MIC 90 s against borreliae in our study, and tissue concentrations exceed by 10-fold the maximum plasma concentrations of both drugs in controls (1,6,27). Therefore, the potential role of ketolides in the treatment of LD merits further evaluation.…”

mentioning

confidence: 46%

Comparison of In Vitro Activities of Ketolides, Macrolides, and an Azalide against the SpirocheteBorrelia burgdorferi

Hunfeld

Wichelhaus

Rödel

et al. 2004

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Two ketolides, three macrolides, and one azalide were tested in vitro against 17 isolates of the B. burgdorferi s.l. complex. As measured in micrograms per milliliter, activity was highest for cethromycin (MIC at which 90% of the tested isolates were inhibited [MIC 90 ], 0.0019 g/ml) and telithromycin (MIC 90 , 0.0078 g/ml). Electron-microscope analysis and time-kill studies also supported enhanced effectiveness of both ketolides.Borrelia burgdorferi is susceptible to macrolides in vitro (5,8,9,18,20), and important clinical indications for macrolides in the therapy of acute Lyme diseases (LD) include pregnancy, ␤-lactam allergy, and treatment of children Ͻ14 years of age (17,23,24,26). Recently new clarithromycin derivatives, the ketolides, proved highly active in vitro against atypical microorganisms, such as Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella species (1,3,6,22). If effective in vitro and in vivo against borreliae, ketolides should be considered for treatment of LD as well. Here, we investigated under standardized conditions the in vitro activities of ketolides in comparison to those of macrolides and one azalide against 17 isolates of the B. burgdorferi complex, including all three genospecies pathogenic for humans, in addition to one Borrelia valaisiana and one Borrelia bissettii tick isolate.The clinical, geographic, and genotypic characteristics of the strains tested (Table 1) have been published elsewhere (8,10,12). Except for reference strain B31 (ATCC 35210), low-passage isolates (10 to 20 passages) were tested using microtiter trays carrying lyophilized antimicrobial agents (Merlin-Diagnostika GmbH, Bornheim-Hersel, Germany). The test ranges appear in Table 1. Ceftriaxone and apramycin served as controls with known high activity and no activity, respectively, against borreliae (12, 13). MICs were determined after 72 h using a colorimetric assay, as recently described in detail (9, 13). Minimal borreliacidal concentrations (MBCs) were determined under stringent conditions (100% killing in liquid medium) at 72 h. Aliquots (20 l) from all vials without detectable growth were diluted (1:1,000) below the MIC in BarbourStoenner-Kelly medium (BSK) and inspected for regrowth after 3 weeks of subculture (9, 10, 12). For each isolate and substance, independent experiments were performed on different days, with MICs and MBCs reported as the median of all three experiments. Moreover, time-kill studies with B. burgdorferi strain PKa-1 and Borrelia afzelii strain FEM1 exposed to telithromycin, cethromycin, and erythromycin for 120 h and electron-microscope analysis of B. garinii PSth cultures in the log phase of growth treated with 0.0312 g of cethromycin/ml for 72 h were performed as described elsewhere (10,13,19). To detect possible differences in MIC and MBC data for the borrelial genospecies, the Kruskall-Wallis test was applied using BIAS, version 5.03 (Epsilon Verlag, Hochheim, Germany), for statistical calculation. Finally, possible antibiotic-medium interactions were investigated af...

show abstract

“…In a fortunate circumstance of timing, the specter of pan-microbial resistance was rising and desperate calls for new antibiotics were becoming increasingly frequent, which publicized the need and urgency for developing new antibiotics such as the ketolides (56)(57)(58). The profile exhibited by the ketolides positioned them to become once/day orally administered therapy for treating a variety of community-acquired respiratory infections (50,(59)(60)(61)(62).…”

Section: Ketolides: Third-generation Derivatives Of Erythromycinmentioning

confidence: 99%

Macrolide Antibiotics

Kirst

2015

Kirk-Othmer Encyclopedia of Chemical Technology

View full text Add to dashboard Cite

Macrolide antibiotics are one of the larger classes of fermentation‐derived natural products. In addition, many semisynthetic derivatives have been synthesized. They treat infections caused by most Gram‐positive bacteria, some susceptible Gram‐negative bacteria, and atypical bacteria such as Mycoplasma pneumoniae and Legionella pneumophila . They are orally bioavailable and accumulate in tissues and organs. They are regarded as one of the safest groups of antibiotics. Erythromycin is a 14‐membered ring macrolide and foremost member of the class. First‐generation derivatives focused on deficiencies such as compound instability in acidic environments, bitter taste, low water solubility, low oral bioavailability, and gastrointestinal and cardiac side effects. Many of these problems were at least partly solved by first‐generation derivatives such as esters and salts that made the active entities less prone to degradation. Second‐generation derivatives chemically changed substituents on the aglycone to stabilize it from intramolecular decomposition. This group includes clarithromycin and azithromycin that have become the most important macrolides to date. The problem of bacterial resistance to antibiotics was elegantly addressed by the ketolides. Telithromycin (Ketek®) was the first ketolide (third generation of erythromycin derivatives) to be approved and marketed, but postmarketing surveillance uncovered side effects and its use has been restricted. Macrolides are also important veterinary antibiotics and three new agents have been developed. Studies have continued to search for new agents using combinatorial biosynthesis, but the generation of large numbers of novel polyketides remains unfulfilled at this time.

show abstract

Telithromycin: a new ketolide antimicrobial for treatment of respiratory tract infections

Cited by 40 publications

References 32 publications

Pharmacokinetics of Telithromycin in Plasma and Soft Tissues after Single-Dose Administration to Healthy Volunteers

Pharmacokinetics of Telithromycin in Plasma and Soft Tissues after Single-Dose Administration to Healthy Volunteers

Comparison of In Vitro Activities of Ketolides, Macrolides, and an Azalide against the SpirocheteBorrelia burgdorferi

Macrolide Antibiotics

Contact Info

Product

Resources

About