Abstract
Ketolides are a new class of macrolides designed particularly to combat respiratory tract pathogens that have acquired resistance to macrolides. The ketolides are semi-synthetic derivatives of the 14-membered macrolide erythromycin A, and retain the erythromycin macrolactone ring structure as well as the D-desosamine sugar attached at position 5. The defining characteristic of the ketolides is the removal of the neutral sugar, L-cladinose from the 3 position of the ring and the subsequent oxidation of the 3-hydroxyl to a 3-keto functional group. The ketolides presently under development additionally contain an 11, 12 cyclic carbamate linkage in place of the two hydroxyl groups of erythromycin A and an arylalkyl or an arylallyl chain, imparting in vitro activity equal to or better than the newer macrolides.
Telithromycin is the first member of this new class to be approved for clinical use, while ABT-773 is presently in phase III of development. Ketolides have a mechanism of action very similar to erythromycin A from which they have been derived. They potently inhibit protein synthesis by interacting close to the peptidyl transferase site of the bacterial 50S ribosomal subunit. Ketolides bind to ribosomes with higher affinity than macrolides.
The ketolides exhibit good activity against Gram-positive aerobes and some Gram-negative aerobes, and have excellent activity against drug-resistant Streptococcus pneumoniae, including macrolide-resistant (mefA and ermB strains of S. pneumoniae). Ketolides such as telithromycin display excellent pharmacokinetics allowing once daily dose administration and extensive tissue distribution relative to serum. Evidence suggests the ketolides are primarily metabolised in the liver and that elimination is by a combination of biliary, hepatic and urinary excretion. Pharmacodynamically, ketolides display an element of concentration dependent killing unlike macrolides which are considered time dependent killers.
Clinical trial data are only available for telithromycin and have focused on respiratory infections including community-acquired pneumonia, acute exacerbations of chronic bronchitis, sinusitis and streptococcal pharyngitis. Bacteriological and clinical cure rates have been similar to comparators. Limited data suggest very good eradication of macrolide-resistant and penicillin-resistant S. pneumoniae. As a class, the macrolides are well tolerated and can be used safely. Limited clinical trial data suggest that ketolides have similar safety profiles to the newer macrolides. Telithromycin interacts with the cytochrome P450 enzyme system (specifically CYP 3A4) in a reversible fashion and limited clinically significant drug interactions occur.
In summary, clinical trials support the clinical efficacy of the ketolides in upper and lower respiratory tract infections caused by typical and atypical pathogens including strains resistant to penicillins and macrolides. Considerations such as local epidemiology, patterns of resistance and ketolide adverse effects, drug interactions and cost relative to existing agents will define the role of these agents. The addition of the ketolides in the era of antibacterial resistance provides clinicians with more options in the treatment of respiratory infections.
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References
Zhanel GG, Dueck M, Hoban DJ, et al. Review of macrolides and ketolides: focus on respiratory tract infections. Drugs 2001; 61: 443–98
Hoban DJ, Doern GV, Fluit AC, et al. Worldwide Prevalence of Antimicrobial Resistance in Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in the SENTRY Antimicrobial Surveillance Program, 1997–1999. Clin Infect Dis 2001; 32 Suppl. 2: S81–93
Boswell FJ, Andrews JM, Ashby JP, et al. The in-vitro activity of HMR 3647, a new ketolide antimicrobial agent. J Antimicrob Chemother 1998; 42: 703–9
Andrews JM, Weller TM, Ashby JP, et al. The in vitro activity of ABT773, a new ketolide antimicrobial agent. J Antimicrob Chemother 2000; 46: 1017–22
Jamjian C, Biedenbach DJ, Jones RN. In vitro evaluation of a novel ketolide antimicrobial agent, RU-64004. Antimicrob Agents Chemother 1997; 41: 454–9
Felmingham D, Robbins MJ, Mathias I et al. In vitro activity of two ketolides, HMR 3582 and HMR 3787 against clinical bacterial isolates [abstract no. 2154]. 39th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1999 Sep 26–29; San Francisco (CA)
Bryskier A. Novelties in the field of anti-infective compounds in 1999. Clin Infect Dis 2000; 31: 1423–66
Bryskier A. Ketolides-telithromycin, an example of a new class of antibacterial agents. Clin Microbiol Infect 2000; 6: 661–9
Agouridas C, Denis A, Auger JM, et al. Synthesis and antibacterial activity of ketolides (6-O-methyl-3- oxoerythromycin derivatives): a new class of antibacterials highly potent against macrolide-resistant and -susceptible respiratory pathogens. J Med Chem 1998; 41: 4080–100
Champney WS, Tober CL. Structure-activity relationships for six ketolide antibiotics. Curr Microbiol 2001; 42: 203–10
Bonnefoy A, Girard AM, Agouridas C, et al. Ketolides lack inducibility properties of MLS(B) resistance phenotype. J Antimicrob Chemother 1997; 40: 85–90
Rosato A, Vicarini H, Bonnefoy A, et al. A new ketolide, HMR 3004, active against streptococci inducibly resistant to erythromycin. Antimicrob Agents Chemother 1998; 42: 1392–6
Zhong P, Cao Z, Hammond R, et al. Induction of ribosome methylation in MLS-resistant Streptococcus pneumoniae by macrolides and ketolides. Microb Drug Resist 1999; 5: 183–8
Zhong P, Hammond R, Cao Z et al. Molecular basis of ABT-773 activity against erm containing macrolide-resistant S. pneumoniae [abstract no. 2134]. 39th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1999 Sep 26–29; San Francisco (CA)
Douthwaite S, Mauvais P, Champney WS et al. Structure-activity relationship of the ketolide telithromycin (HMR 3647) [abstract no. 02.02]. 5th International Conference on the Macrolides, Azalides, Streptogramins, Ketolides and Oxazolidinones; 2000 Jan 26–28; Seville, Spain
Hansen LH, Mauvais P, Douthwaite S. The macrolide-ketolide antibiotic binding site is formed by structures in domains II and V of 23S ribosomal RNA. Mol Microbiol 1999; 31: 623–31
Champney WS, Tober CL. Superiority of 11,12 carbonate macrolide antibiotics as inhibitors of translation and 50S ribosomal subunit formation in Staphylococcus aureus cells. Curr Microbiol 1999; 38: 342–8
Bertho G, Gharbi-Benarous J, Delaforge M, et al. Conformational analysis of ketolide, conformations of RU 004 in solution and bound to bacterial ribosomes. J Med Chem 1998; 41: 3373–86
Champney WS, Tober CL. Inhibition of translation and 50S ribosomal subunit formation in Staphylococcus aureus cells by 11 different ketolide antibiotics. Curr Microbiol 1998; 37: 418–25
Bryskier A. New research in macrolides and ketolides since 1997. Expert Opin Investig Drugs 1999; 8: 1171–94
Mankin A, Xiong L, Khaitovich P. Interaction of macrolides and ketolides with the ribosome [abstract no. 01.02]. International Conference on the Macrolides, Azalides, Streptogramins, Ketolides and Oxazolidinones; 2000 Jan 26–28; Seville, Spain
Xiong L, Shah S, Mauvais P, et al. A ketolide resistance mutation in domain II of 23S rRNA reveals the proximity of hairpin 35 to the peptidyl transferase centre. Mol Microbiol 1999; 31: 633–9
Ban N, Nissen P, Hansen J, et al. The complete atomic structure of the large ribosomal subunit t 2.4 A resolution. Science 2000; 289: 905–20
Schlunzen F, Zarlvach R, Harms J, et al. Structural basis for the interaction of antibiotics with the peptidyl transferase centre in eubacteria. Nature 2001; 413: 814–21
Ma Z, Clark RF, Brazzale A, et al. Novel erythromycin derivatives with aryl groups tethered to the C-6 position are potent protein synthesis inhibitors and active against multidrug resistant respiratory pathogens. J Med Chem 2001; 44(24): 4137–56
Or YS, Clark RF, Wang S, et al. Design, synthesis, and antimicrobial activity of 6-O-substituted ketolides active against resistant respiratory tract pathogens. J Med Chem 2000; 43: 1045–9
Denis A, Bretin F, Fromentin C, et al. Synthesis and antibacterial activity of 2-halogeno, 2-methyl and 2,3 enol-ether ketolides using beta-keto-ester chemistry. Bioorg Med Chem Lett 2000; 10: 2019–22
Phan LT, Clark RF, Rupp M, et al. Synthesis of 2-fluoro-6-O-propargyl-11,12-carbamate ketolides. A novel class of antibiotics. Org Lett 2000; 2: 2951–4
Kaneko T, McMillen W, Sutcliffe J, et al. Synthesis and in vitro activity of C2-substituted C9-oxime ketolides [abstract 1815]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; y2000 Sep 17–20; Toronto, Canada
Girard D, Mathieu HW, Finegan SM, et al. In vivo antibacterial activity of CP-654, 743, a new C2-fluoro ketolide, against macrolide resistant pneumococci and Haemophilus influenzae [abstract 1816]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Bush K, Arbanat D, Ashley G, et al. In vitro and in vivo SAR of ketolides derived from R13-modified erythromycin A and picromycin core structures [abstract no. 1821]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Yusupov MM, Yusupova GZ, Baucom A, et al. Crystal structure of the ribosome at 5.5 A resolution. Science 2001; 292: 883–96
Capobianco JO, Cao Z, Shortridge VD, et al. Studies of the novel ketolide ABT-773: transport, binding to ribosomes, and inhibition of protein synthesis in Streptococcus pneumoniae. Antimicrob Agents Chemother 2000; 44: 1562–7
Douthwaite S, Hansen LH, Mauvais P. Macrolide-ketolide inhibition of MLS-resistant ribosomes is improved by alternative drug interaction with domain II of 23S rRNA. Mol Microbiol 2000; 36: 183–93
Novotny GW, Andersen NM, Poehlsgaard J, et al. Telithromycin interacts directly with the base of A752 in domain II of 23S ribosomal RNA, in contrast to erythromycin and clarithromycin [abstract no. P480]. 11th European Congress of Clinical Microbiology and Infectious Diseases; 2001 Apr 1–4; Instanbul, Turkey
Bemer-Melchior P, Juvin ME, Tassin S, et al. In vitro activity of the new ketolide telithromycin compared with those of macrolides against Streptococcus pyogenes: influences of resistance mechanisms and methodological factors. Antimicrob Agents Chemother 2000; 44: 2999–3002
Hamilton-Miller JM, Shah S. Patterns of phenotypic resistance to the macrolide-lincosamide-ketolide- streptogramin group of antibiotics in staphylococci. J Antimicrob Chemother 2000; 46: 941–9
Mandell GL, Coleman EJ. Activities of antimicrobial agents against intracellular pneumococci. Antimicrob Agents Chemother 2000; 44: 2561–3
Pascual AA, Ballesta S, Garcia I, et al. Uptake and intracellular activity of ketolide HMR 3647 in human phagocytic and non-phagocytic cells. Clin Microbiol Infect 2001; 7: 65–9
Vazifeh D, Abdelghaffar H, Labro MT. Cellular accumulation of the new ketolide RU 64004 by human neutrophils: comparison with that of azithromycin and roxithromycin. Antimicrob Agents Chemother 1997; 41: 2099–107
Vazifeh D, Preira A, Bryskier A, et al. Interactions between HMR 3647, a new ketolide, and human polymorphonuclear neutrophils. Antimicrob Agents Chemother 1998; 42: 1944–51
Vazifeh D, Bryskier A, Labro MT. Effect of proinflammatory cytokines on the interplay between roxithromycin, HMR 3647, or HMR 3004 and human polymorphonuclear neutrophils. Antimicrob Agents Chemother 2000; 44: 511–21
Labro MT, Vazifeh D, Bryskier A. Uptake of two new fluoroketolides, HMR 3562 and HMR 3787, by human neutrophils (PMN) in vitro [abstractno. 1819]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20, Toronto, Canada
Miossec-Bartoli C, Pilatre L, Peyron P, et al. The new ketolide HMR3647 accumulates in the azurophil granules of human polymorphonuclear cells. Antimicrob Agents Chemother 1999; 43: 2457–62
Mandell GL, Coleman E. Uptake, transport, and delivery of antimicrobial agents by human polymorphonuclear neutrophils. Antimicrob Agents Chemother 2001; 45: 1794–8
Duong M, Simard M, Bergeron Y, et al. Immunomodulating effects of HMR 3004 on pulmonary inflammation caused by heat-killed Streptococcus pneumoniae in mice. Antimicrob Agents Chemother 1998; 42: 3309–12
Duong M, Simard M, Bergeron Y, et al. Kinetic study of the inflammatory response in Streptococcus pneumoniae experimental pneumonia treated with the ketolide HMR 3004. Antimicrob Agents Chemother 2001; 45: 252–62
Jung R, Bearden DT, Danziger LH. Effect of ABT-773 and other antimicrobial agents on the morphology and the release of interleukin-1B and Interleukin-8 against Haemophilus influenzae and Streptococcus pneumoniae in whole blood [abstract no.2141]. 39th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1999 Sep 26–29; San Francisco (CA)
Feldman C, Anderson R, Theron A, et al. The effects of ketolides on bioactive phospholipid-induced injury to human respiratory epithelium in vitro. Eur Respir J 1999; 13: 1022–8
Roberts MC, Sutcliffe J, Courvalin P, et al. Nomenclature for macrolide and macrolide-lincosamide-streptogramin B resistance determinants. Antimicrob Agents Chemother 1999; 43: 2823–30
Tait-Kamradt A, Davies T, Cronan M, et al. Mutations in 23S rRNA and ribosomal protein L4 account for resistance in pneumococcal strains selected in vitro by macrolide passage. Antimicrob Agents Chemother 2000; 44: 2118–25
Vester B and Douthwaite S. Macrolide resistance conferred by base substitutions in 23S rRNA. Antimicrob Agents Chemother 2001; 45: 1–12
Weisblum B. Macrolide resistance. Drug Res Update 1999; 1: 29–41
Giovanetti E, Montanari MP, Mingoia M, et al. Phenotypes and genotypes of erythromycin-resistant Streptococcus pyogenes strains in Italy and heterogeneity of inducibly resistant strains. Antimicrob Agents Chemother 1999; 43: 1935–40
Ono T, Aikawa K, Murakami Y, et al. Susceptibility of Streptococcus mitis and Streptococcus oralis to a new ketolide HMR 3647 [abstract no. 1245]. 39th Interscience Conference of Antimicrobial Agents and Chemotherapy; 1999 Sep 26–29; San Fransisco (CA)
Leclercq R. Resistance to ketolides: role of ribosomal modification and macrolide efflux [abstract no. 1135]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Tait-Kamradt A, Davies T, Appelbaum PC, et al. Two new mechanisms of macrolide resistance in clinical strains of Streptococcus pneumoniae from Eastern Europe and North America. Antimicrob Agents Chemother 2000; 44: 3395–401
Depardieu F, Courvalin P. Mutation in 23S rRNA responsible for resistance to 16-membered macrolides and streptogramins in Streptococcus pneumoniae. Antimicrob Agents Chemother 2001; 45: 319–23
Mauvais P, Bonnefoy A. Lack of in vitro MLSB resistance induction by the ketolide telithromycin (HMR 3647): role of the 3-keto group [abstract no. 02.10]. 5th International Conference on the Macrolides, Azalides, Streptogramins, Ketolides and Oxazolidinones; 2000 Jan 26–28; Seville, Spain
Giovanetti E, Montanari MP, Marchetti F, et al. In vitro activity of ketolides telithromycin and HMR 3004 against Italian isolates of Streptococcus pyogenes and Streptococcus pneumoniae with different erythromycin susceptibility. J Antimicrob Chemother 2000; 46: 905–8
Zhanel GG, Karlowsky JA, Wierzbowski A, et al. ABT-773 demonstrates excellent in vitro activity against macrolide-resistant respiratory isolates of Streptococcus pneumoniae with mefA or ermB genotypes [abstract no. 2169]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Davies TA, Ednie LM, Hoellman DM, et al. Antipneumococcal activity of ABT-773 compared to those of 10 other agents. Antimicrob Agents Chemother 2000; 44: 1894–9
Jalava J, Kataja J, Seppala H, et al. In vitro activities of the novel ketolide telithromycin (HMR 3647) against erythromycin-resistant Streptococcus species. Antimicrob Agents Chemother 2001; 45: 789–93
Agouridas C, Bonnefoy A, Chantot JF. Antibacterial activity of RU 64004 (HMR 3004), a novel ketolide derivative active against respiratory pathogens. Antimicrob Agents Chemother 1997; 41: 2149–58
Davies TA, Dewasse BE, Jacobs MR, et al. In vitro development of resistance to telithromycin (HMR 3647), four macrolides, clindamycin, and pristinamycin in Streptococcus pneumoniae. Antimicrob Agents Chemother 2000; 44: 414–7
Fernandez-Roblas R, Calvo R, Esteban J, et al. The bactericidal activities of HMR 3004, HMR 3647 and erythromycin against gram-positive bacilli and development of resistance. J Antimicrob Chemother 1999; 43: 285–9
Edlund C, Alvan G, Barkholt L, et al. Pharmacokinetics and comparative effects of telithromycin (HMR 3647) and clarithromycin on the oropharyngeal and intestinal microflora. J Antimicrob Chemother 2000; 46: 741–9
Jones RN, Biedenbach DJ. Antimicrobial activity of RU-66647, a new ketolide. Diagn Microbiol Infect Dis 1997; 27: 7–12
Barry AL, Fuchs PC, Brown SD. Comparative in vitro antimicrobial activity of ABT-773 and tentative disk test interpretive criteria [abstractno. 2144]. 39th Interscience Conference on Antimicrobial Agents and Chemotherapy. 1999, San Francisco, USA
Shortridge D, Ramer NC, Beyer J, et al. The in vitro activity of ABT-773 against gram-positive and gram-negative pathogens [abstract no. 2136]. 39th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1999 Sep 26–29; San Francisco (CA)
Nilius AM, Bui MH, Aimer L, et al. Comparative in vitro activity of abt-773, a novel antibacterial ketolide. Antimicrob Agents Chemother 2001; 45: 2163–8
Goldstein EJ, Citron DM, Gerardo SH, et al. Activities of HMR 3004 (RU 64004) and HMR 3647 (RU 66647) compared to those of erythromycin, azithromycin, clarithromycin, roxithromycin, and eight other antimicrobial agents against unusual aerobic and anaerobic human and animal bite pathogens isolated from skin and soft tissue infections in humans. Antimicrob Agents Chemother 1998; 42: 1127–32
Alcaide F, Benitez MA, Carratala J, et al. In vitro activities of the new ketolide HMR 3647 (telithromycin) in comparison with those of eight other antibiotics against viridans group Streptococci isolated from blood of neutropenic patients with cancer. Antimicrob Agents Chemother 2001; 45: 624–6
Hoellman DB, Lin G, Jacobs MR, et al. Activity of HMR 3647 compared to those of six compounds against 235 strains of Enterococcus faecalis. Antimicrob Agents Chemother 1999; 43: 166–8
Martinez-Martinez L, Pascual A, Suarez AI, et al. In vitro activities of ketolide HMR 3647, macrolides, and clindamycin against Coryneform bacteria. Antimicrob Agents Chemother 1998; 42: 3290–2
Torres C, Zarazaga M, Tenorio C, et al. In vitro activity of the new ketolide HMR3647 in comparison with those of macrolides and pristinamycins against Enterococcus spp. Antimicrob Agents Chemother 1998; 42: 3279–81
Soriano F, Fernandez-Roblas R, Calvo R, et al. In vitro susceptibilities of aerobic and facultative non-spore-forming gram-positive bacilli to HMR 3647 (RU 66647) and 14 other antimicrobials. Antimicrob Agents Chemother 1998; 42: 1028–33
Okamoto H, Miyazaki S, Tateda K, et al. Comparative in vitro activity of telithromycin (HMR 3647), three macrolides, amoxicillin, cefdinir and levofloxacin against gram- positive clinical isolates in Japan. J Antimicrob Chemother 2000; 46: 797–802
Pankuch GA, Visalli MA, Jacobs MR, et al. Susceptibilities of penicillin- and erythromycin-susceptible and — resistant pneumococci to HMR 3647 (RU 66647), anew ketolide, compared with susceptibilities to 17 other agents. Antimicrob Agents Chemother 1998; 42: 624–30
Luna VA, Roberts MC. In-vitro activities of 11 antibiotics against 75 strains of Streptococcus pneumoniae with reduced susceptibilities to penicillin isolated from patients in Washington State. J Antimicrob Chemother 1999; 44: 578–80
Schulin T, Wennersten CB, Moellering Jr RC, et al. In-vitro activity of the new ketolide antibiotic HMR 3647 against gram- positive bacteria. J Antimicrob Chemother 1998; 42: 297–301
Hamilton-Miller JM, Shah S. Comparative in-vitro activity of ketolide HMR 3647 and four macrolides against gram-positive cocci of known erythromycin susceptibility status. J Antimicrob Chemother 1998; 41: 649–53
Davies TA, Kelly LM, Jacobs MR, et al. Antipneumococcal activity of telithromycin by agar dilution, microdilution, E test, and disk diffusion methodologies. J Clin Microbiol 2000; 38: 1444–8
Descheemaeker P, Chapelle S, Lammens C, et al. Macrolide resistance and erythromycin resistance determinants among Belgian Streptococcus pyogenes and Streptococcus pneumoniae isolates. J Antimicrob Chemother 2000; 45: 167–73
Felmingham D, Harding I. Telithromycin is highly active against Streptococcus pneumoniae isolates — including resistant strains — collected from France in the PROTEKT study [abstract no. P1260]. 11th European Congress of Clinical Microbiology and Infectious Diseases; 2001 Apr 1–4; Istanbul, Turkey
Felmingham D, Harding I. Telithromycin is highly active against clinical isolates of Streptococcus pneumoniae collected in the PROTEKT study, irrespective of penicillin, macrolide or fluoroquinolone resistance [abstract no. P1253]. 11th European Congress of Clinical Microbiology and Infectious Diseases; 2001 Apr 1–4; Istanbul, Turkey
Linglof T, Olsson-Liljequist B, Naaber P, et al. Activity of telithromycin on S. pyogenes and S. pneumoniae in Russia and Estonia: an epidemiological study [abstract no. P886]. 11th European Congress of Clinical Microbiology and Infectious Diseases; 2001 Apr 1–4; Istanbul, Turkey
Davies TA. In vitro activity of various MLS agents against macrolide-resistant clinical isolates of Streptococcus pneumoniae from Slovakia, Bulgaria, Poland and USA containing ribosomal mutations [abstract no. 513]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Applebaum PC, Hoellman DB, Hryniewicz W, et al. Anti-pneumococcal activity of telithromycin (HMR 3647) against pneumococci from ten central and eastern European countries [abstractno. 2154]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Applebaum PC, Kelly LM, Hryniewicz W, et al. Activity of telithromycin (HMR 3647) against 599 S. pyogenes from ten central and eastern European countries [abstract no. 2153]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Nagai K, Davies TA, Appelbaum PC, et al. Mechanism of macrolide resistance in Streptococcus pneumoniae and Streptococcus pyogenes from central and eastern European countries [abstractno. 0138]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Mazzariol A, Esposito S, Ciammanco A, et al. Genotype analysis of macrolide resistance and activity of the new ketolide telithromycin (HMR 3647) on group A, C and G beta-hemolytic Streptococci [abstract no. 2148]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Mazzariol A, Luzzaro F, Manno G, et al. Multicenter evaluation of telithromycin (HMR 3647) activity on Italian Streptococcus pneumoniae with different genotypes of erythromycin resistance [abstract no. 2147]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Milatovic D, Verhoef J, Fluit AC. Prevalence and genotypes of macrolide-resistant Streptococcus pneumoniae and beta-hemolytic Streptococci in the Netherlands, Denmark and Luxemburg [abstract no. 0140]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Mittermayer H, Jebelean C, Bocksrucker A, et al. Activity of telithromycin (HMR 3647) against erythromycin-susceptible and -resistant isolates of Streptococcus pneumoniae and Streptococcus pyogenes from Austria [abstract no. 2145]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Morosini MI, Conton R, Loza E, et al. Distribution of erythromycin A resistance determinants in Spanish Streptococcus pneumoniae isolates and comparative activity of telithromycin (HMR 3647) [abstract 2157]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Morrissey I, Trezise E, Tsa N, et al. The comparative in vitro activity of telithromycin (HMR 3647) against isolates of Streptococcus pyogenes (Lancefield serogroup A) circulating in Great Britain, Northern Ireland and the Republic of Ireland during late 1999[abstract no. 2149]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Negri MC, Loza E, Canton R, et al. Activity of telithromycin (HMR 3647) against susceptible and well-characterized erythromycin A-resistant isolates of Streptococcus pyogenes [abstractno. 2155]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Verhaegen J, Verbist L. Comparative in vitro activity of telithromycin (HMR 3647) and other antimicrobials against 637 Streptococcus pneumoniae [abstract no. 2156]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Traczewski MM, Brown SD, Barry AL. Susceptibility to telithromycin (HMR 3647) and erythromycin among clinical isolates of gram-positive pathogens and reassessment of disk diffusion test criteria [abstract no. 02.08]. 5th International Conference on the Macrolides, Azalides, Streptogramins, Ketolides and Oxazolidinones; 2000 Jan 26–28; Seville, Spain
Hoban DJ, Zhanel GG, Bellyou T, et al. Telithromycin (HMR 3647) demonstrates excellent in vitro activity against clinical isolates of Streptococcus pyogenes and Streptococcus pneumoniae with M- and MLSB-resistance phenotypes [abstract no. 02.27]. 5th International Conference on the Macrolides, Azalides, Streptogramins, Ketolides and Oxazolidinones; 2000 Jan 26–28; Seville, Spain
Felmingham D, Tesfaslasie YK, Robbins MJ, et al. The in vitro activity of telithromycin (HMR 3647) against 817 isolates of Streptococcus pneumoniae collected from 27 centres throughout Great Britain and Ireland during the 1997–1998 cold season [abstract no. 02.23]. 5th International Conference on the Macrolides, Azalides, Streptogramins, Ketolides and Oxazolidinones; 2000 Jan 26–28; Seville, Spain
Barry AL, Fuchs PC, Brown SD. Antipneumococcal activities of a ketolide (HMR 3647), a streptogramin (quinupristindalfopristin), a macrolide (erythromycin), and a lincosamide (clindamycin). Antimicrob Agents Chemother 1998; 42: 945–6
Reinert RR, Bryskier A, Lutticken R. In vitro activities of the new ketolide antibiotics HMR 3004 and HMR 3647 against Streptococcus pneumoniae in Germany. Antimicrob Agents Chemother 1998; 42: 1509–11
Engler KH, Warner M, George RC. In vitro activity of ketolides HMR 3004 and HMR 3647 and seven other antimicrobial agents against Corynebacterium diphtheriae. J Antimicrob Chemother 2001; 47: 27–31
Malathum K, Coque TM, Singh KV, et al. In vitro activities of two ketolides, HMR 3647 and HMR 3004, against gram-positive bacteria. Antimicrob Agents Chemother 1999; 43: 930–6
Schulin T, Wennersten CB, Moellering Jr RC. Eliopoulos GM. In vitro activity of RU 64004, a new ketolide antibiotic, against gram- positive bacteria. Antimicrob Agents Chemother 1997; 41: 1196–202
Soriano F, Fernandez-Roblas R, Calvo R, et al. In-vitro antimicrobial activity of HMR 3004 (RU 64004) against erythromycin A-sensitive and -resistant Corynebacterium spp. isolated from clinical specimens. J Antimicrob Chemother 1998; 42: 647–9
Ednie LM, Spangler SK, Jacobs MR, et al. Susceptibilities of 228 penicillin- and erythromycin-susceptible and — resistant pneumococci to RU 64004, a new ketolide, compared with susceptibilities to 16 other agents. Antimicrob Agents Chemother 1997; 41: 1033–6
Shortridge D, Ramer N, Darwish A, et al. The in vitro activity of the ketolides ABT-773 and HMR-3004 as measured by broth microdilution against macrolide susceptible and macrolide resistant Streptococci and Staphylococci [abstract no. 02.19]. 5th International Conference on the Macrolides, Azalides, Streptogramins, Ketolides and Oxazolidinones; 2000 Jan 26–28; Seville, Spain
Singh KV, Malathum K, Murray BE. In vitro activities of a new ketolide, ABT-773, against multiresistant gram-positive cocci. Antimicrob Agents Chemother 2001, 3
Shortridge D, Ramer NC, Beyer J, et al. The in vitro activity of ABT-773 against gram-positive respiratory pathogens [abstract no. 02.17]. 5th International Conference on the Macrolides, Azalides, Streptogramins, Ketolides and Oxazolidinones; 2000 Jan 26–28; Seville, Spain
Weiss K, Restieri C, Guilbault C, et al. In vitro activity of ABT-773 against invasive strains of Streptococcus pneumoniae. J Antimicrob Chemother 2001; 48: 407–9
Johnson C, Benjamin W, Gray B, et al. In vitro activities of ABT-773, telithromycin and 8 other antimicrobials against erythromycin-resistant Streptococcus pneumoniae isolates from the respiratory tracts of children. Internal J Antimicrob Chemother 2001; 18(6): 531–5
Willey BM, Trpeski L, Pong-Porter S, et al. The in vitro activities of ABT-773, telithromycin and other macrolides against Canadian Streptococci [abstract no. 2161]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Hoban DJ, Wierzbowski AK, Nichol K, et al. Macrolide-Resistant Streptococcus pneumoniae in Canada during 1998–1999: Prevalence of mef(A) and erm(B) and Susceptibilities to Ketolides. Antimicrob Agents Chemother 2001; 45: 2147–50
Leroy B, Rangaraju M. High in vitro susceptibility of the ketolide telithromycin (HMR 3647) in clinical isolates of key respiratory pathogens [abstract no. 2224]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Barry AL, Fuchs PC, Brown SD. In vitro activities of the ketolide HMR 3647 against recent gram- positive clinical isolates and Haemophilus influenzae. Antimicrob Agents Chemother 1998; 42: 2138–40
Wootton M, Bowker KE, Janowska A, et al. In-vitro activity of HMR 3647 against Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and beta-haemolytic streptococci. J Antimicrob Chemother 1999; 44: 445–53
Hoban DJ, Zhanel GG, Karlowsky JA. In vitro activity of the novel ketolide HMR 3647 and comparative oral antibiotics against Canadian respiratory tract isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Diagn Microbiol Infect Dis 1999; 35: 37–44
Felmingham D, Harding I, Mehl M. Telithromycin has excellent activity against respiratory pathogens collected from Germany in the PROTEKT study [abstract no. P1256]. 11th European Congress of Clinical Microbiology and Infectious Diseases; 2001 Apr 1–4; Istanbul, Turkey
Felmingham D, Harding I. Telithromycin is highly active against respiratory tract isolates collected from Italy in the PROTEKT study [abstract no. P1255]. 11th European Congress of Clinical Microbiology and Infectious Diseases; 2001 Apr 1–4; Istanbul, Turkey
Felmingham D, Harding I, Inoue M. Telithromycin shows excellent activity against bacterial respiratory isolates collected from Japan in the PROTEKT study [abstractno. P1254]. 11th European Congress of Clinical Microbiology and Infectious Diseases; 2001 Apr 1–4; Istanbul, Turkey
Hoban DJ, Palatnick L, Weshnoweski B, et al. Activity of telithromycin and oral comparators against 11 701 Canadian respiratory tract pathogens isolated from 1997–2000 [abstract no. P1259]. 11th European Congress of Clinical Microbiology and Infectious Diseases; 2001 Apr 1–4; Istanbul, Turkey
Dubois J, St-Pierre C. In vitro study of the minimal inhibitory concentrations (MIC) of telithromycin (HMR 3647), macrolides and quinolones against Haemophilus, Streptococcus, Staphylococcus and Moraxella strains obtained from upper and lower respiratory tract infections and from maxillary sinus aspiration [abstract no. 2152]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Bonnefoy A, Denis A, Bretin F, et al. In vitro antibacterial activity of two ketolides, HMR 3562 and HMR 3787, against respiratory pathogens [abstract no. 2155]. 39th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1999Sep 26–29; San Francisco, (CA)
Brueggemann AB, Doern GV, Huynh HK, et al. In vitro activity of ABT-773, a new ketolide, against recent clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Antimicrob Agents Chemother 2000; 44: 447–9
Dubois J, St-Pierre C. In vitro activity of ABT-773 versus macrolides and quinolones against resistant respiratory tract pathogens. Diagn Microbiol Infect Dis 2001; 40: 35–40
Fujikawa T, Miyazaki S, Matsumoto T, et al. In vitro activities of ABT-773, a new ketolide, against major respiratory pathogens [abstract no. 2166]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Prado V, Duran C. Comparative in vitro activity of ABT-773 against respiratory pathogens susceptible and resistant to other antimicrobials [abstract no. 2168]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy Sep 17–20; 2000, Toronto, Canada
Mikamo H, Hua YX, Sato Y, et al. In vitro antibacterial activities of telithromycin, a new ketolide, against bacteria causing infections in obstetric and gynaecological patients. J Antimicrob Chemother 2000; 46: 332–4
Goldstein EJ, Citron DM, Merriam CV, et al. Comparative in vitro activities of ABT-773 against aerobic and anaerobic pathogens isolated from skin and soft-tissue animal and human bite wound infections. Antimicrob Agents Chemother 2000; 44: 2525–9
Pankuch GA, Hoellman DB, Lin G, et al. Activity of HMR 3647 compared to those of five agents against Haemophilus influenzae and Moraxella catarrhalis by MIC determination and time-kill assay. Antimicrob Agents Chemother 1998; 42: 3032–4
Piper KE, Rouse MS, Steckelberg JM, et al. Ketolide treatment of Haemophilus influenzae experimental pneumonia. Antimicrob Agents Chemother 1999; 43: 708–10
Saez-Nieto JA, Vazquez JA. In vitro activities of ketolides HMR 3647 [correction of HRM 3647] and HMR 3004 [correction of HRM 3004], levofloxacin, and other quinolones and macrolides against Neisseria spp. and Moraxella catarrhalis. Antimicrob Agents Chemother 1999; 43: 983–4
Hoppe JE, Bryskier A. In vitro susceptibilities of Bordetella pertussis and Bordetella parapertussis to two ketolides (HMR 3004 and HMR 3647), four macrolides (azithromycin, clarithromycin, erythromycin A, and roxithromycin), and two ansamycins (rifampin and rifapentine). Antimicrob Agents Chemother 1998; 42: 965–6
Biedenbach DJ, Barrett MS, Jones RN. Comparative antimicrobial activity and kill-curve investigations of novel ketolide antimicrobial agents (HMR 3004 and HMR 3647) tested against Haemophilus influenzae and Moraxella catarrhalis strains. Diagn Microbiol Infect Dis 1998; 31: 349–53
Credito KL, Lin G, Pankuch GA, et al. Susceptibilities of Haemophilus influenzae and Moraxella catarrhalis to ABT-773 compared to their susceptibilities to 11 other agents. Antimicrob Agents Chemother 2001; 45: 67–72
Pendland SL, Prause JL, Neuhauser MM, et al. In vitro activities of a new ketolide, ABT-773, alone and in combination with amoxicillin, metronidazole, or tetracycline against Helicobacter pylori. Antimicrob Agents Chemother 2000; 44: 2518–20
Wexler HM, Molitoris E, Molitoris D, et al. In vitro activity of telithromycin (HMR 3647) against 502 strains of anaerobic bacteria. J Antimicrob Chemother 2001; 47: 467–9
Ackermann G, Schaumann R, Pless B, et al. In vitro activity of telithromycin (HMR 3647) and seven other antimicrobial agents against anaerobic bacteria. J Antimicrob Chemother 2000; 46: 115–9
Goldstein EJ, Citron DM, Merriam CV, et al. Activities of telithromycin (HMR 3647, RU 66647) compared to those of erythromycin, azithromycin, clarithromycin, roxithromycin, and other antimicrobial agents against unusual anaerobes. Antimicrob Agents Chemother 1999; 43: 2801–5
Ednie LM, Jacobs MR, Appelbaum PC. Comparative anti-anaerobic activities of the ketolides HMR 3647 (RU 66647) and HMR 3004 (RU 64004). Antimicrob Agents Chemother 1997; 41: 2019–22
Ednie LM, Spangler SK, Jacobs MR, et al. Antianaerobic activity of the ketolide RU 64004 compared to activities of four macrolides, five beta-lactams, clindamycin, and metronidazole. Antimicrob Agents Chemother 1997; 41: 1037–41
Citron DM, Appleman MD. Comparative in vitro activities of ABT-773 against 362 clinical isolates of anaerobic bacteria. Antimicrob Agents Chemother 2001; 45: 345–8
Finegold SM, Summanen P, Molitoris D, et al. In vitro activity of ABT -773 against anaerobic bacteria isolated from bowel flora [abstractno. 02.30]. 5th International Conference on the Macrolides, Azalides, Streptogramins, Ketolides and Oxazolidinones; 2000 Jan 26–28; Seville, Spain
Silierstrom E, Wahlund E, Nord CE. In vitro activity of ABT-773 against anaerobic bacteria. Eur J Clin Microbiol Infect Dis 2000; 19: 635–7
Bebear CM, Renaudin H, Bryskier A, et al. Comparative activities of telithromycin (HMR 3647), levofloxacin, and other antimicrobial agents against human mycoplasmas. Antimicrob Agents Chemother 2000; 44: 1980–2
Yamaguchi T, Hirakata Y, Izumikawa K, et al. In vitro activity of telithromycin (HMR3647), a new ketolide, against clinical isolates of Mycoplasma pneumoniae in Japan. Antimicrob Agents Chemother 2000; 44: 1381–2
Roblin PM, Hammerschlag MR. In vitro activity of a new ketolide antibiotic, HMR 3647, against Chlamydia pneumoniae. Antimicrob Agents Chemother 1998; 42: 1515–6
Gustafsson I, Hjelm E, Cars O. In vitro pharmacodynamics of the new ketolides HMR 3004 and HMR 3647 (Telithromycin) against Chlamydia pneumoniae. Antimicrob Agents Chemother 2000; 44: 1846–9
Bebear CM, Renaudin H, Aydin MD, et al. In-vitro activity of ketolides against mycoplasmas. J Antimicrob Chemother 1997; 39: 669–70
Sens K, Mietzner S, Sagnimeni A, et al. Activity of new quinolones, macrolide, and ketolides against 100 strains of Legionella species using broth dilution and intracellular susceptibility testing methods [abstract no. 2159]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Strigl S, Roblin PM, Reznik T, et al. In vitro activity of ABT 773, a new ketolide antibiotic, against Chlamydia pneumoniae. Antimicrob Agents Chemother 2000; 44: 1112–3
Goldstein EJ, Conrads G, Citron DM, et al. In-vitro activities of ABT-773 a new ketolide against aerobic and anaerobic pathogens isolated from antral sinus puncture specimens and from patients with sinusitis. Antimicrob Agents Chemother 2001; 45: 2363–7
Edelstein PH, Edelstein MA. In vitro activity of the ketolide HMR 3647 (RU 6647) for Legionella spp., its pharmacokinetics in guinea pigs, and use of the drug to treat guinea pigs with Legionella pneumophila pneumonia. Antimicrob Agents Chemother 1999; 43: 90–5
Namour F, Wessels DH, Pascual MH, et al. Pharmacokinetics of the new ketolide telithromycin (HMR 3647) administered in ascending single and multiple doses. Antimicrob Agents Chemother 2001; 45: 170–5
Lenfant B, Sultan E, Wable C, et al. Pharmacokinetics of 800 mg once-daily oral dosing of the ketolide antimicrobial telithromycin (HMR 3647) in healthy young subjects [abstract no. 09.21]. 5th International Conference on the Macrolides, Azalides, Streptogramins, Ketolides and Oxazolidinones; 2000 Jan 26–28; Seville, Spain
Lenfant B, Perret C, Pascual MH. The bioavailability of telithromycin (HMR 3647), a new once-daily ketolide antimicrobial, is unaffected by food [abstract no. 09.24]. The Fifth International Conference on the Macrolides, Azalides, Streptogramins, Ketolides and Oxazolidinones; 2000 Jan 26–28; Seville, Spain
Sultan E, Lenfant B, Wable C, et al. Pharmacokinetic profile of the ketolide telithromycin (HMR 3647) 800 mg once daily in elderly volunteers [abstract no. 09.23]. 5th International Conference on the Macrolides, Azalides, Streptogramins, Ketolides and Oxazolidinones; 2000 Jan 26–28; Seville, Spain
Pluim J, Sultan E, Leroy B. Population pharmacokinetics support the convenient once-daily 800 mg dosage of telithromycin in patients with upper and lower RTIs, including special populations [abstractno. P1263]. 11th European Congress of Clinical Microbiology and Infectious Diseases; 2001 Apr 1–4; Istanbul, Turkey
Pradhan RS, Gustavson LE, Londo DD, et al. Single oral dose pharmacokinetics and safety of ABT-773 in healthy subjects [abstractno. 2135]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Pradhan RS, Gustavson LE, Londo DD, et al. The bioavailability of ABT-773 is unaffected by food [abstract no. 2138]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto
Balfour JA, Figgitt DP. Telithromycin. Drugs 2001; 61: 815–29
Bonnefoy A, Le Priol P. Antibacterial activity of telithromycin (HMR 3647) in relation to in vitro simulated human plasma kinetics. J Antimicrob Chemother 2001; 47: 471–3
Lippert C, Andersen A, Sach S, et al. Telithromycin (HMR 3647) does not require dosage adjustment in patients with renal impairment [abstract no. P893]. 11th European Congress of Clinical Microbiology and Infectious Diseases; 2001 Apr 1–4; Istanbul, Turkey
Ketek (telithromycin) briefing document for the FDA anti-infective drug products advisory committee [executive summary]. Bridgewater (NJ): Aventis Pharma, 2001 Mar
Perret C, Wessels DH. Oral bioavailability of the ketolide telithromycin (HMR 3647) is similar in both elderly and young subjects. Clin Microbiol Infect 2000; 6 Suppl. 1: 203–4
Miyamoto N, Murakami S, Yajin K, et al. Pharmacokinetic study of a new ketolide antimicrobial telithromycin (HMR 3647) in otorhinolaryngology [abstract no. 2144]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Kadota J, Ishimatsu Y, Iwashita T, et al. The ketolide antimicrobial telithromycin (HMR 3647) achieves high and sustained concentrations in alveolar macrophages and bronchoalveolar epithelial lining fluid in healthy Japanese volunteers [abstract no. 2143]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Muller Serieys C, Cantalloube C, Soler P, et al. The ketolide antimicrobial, telithromycin (HMR 3647), achieves high and sustained concentrations in bronchopulmonary tissues [abstract no. 09.26]. 5th International Conference on the Macrolides, Azalides, Streptogramins, Ketolides and Oxazolidinones; 2000 Jan 26–28; Seville, Spain
Gia HP, Roeder V, Namour F, et al. Telithromycin (HMR 3647) achieves high and sustained concentrations in white blood cells in man [abstractno. 09.27]. 5th International Conference on the Macrolides, Azalides, Streptogramins, Ketolides and Oxazolidinones; 2000 Jan 26–28; Seville, Spain
Khair OA, Andrews JM, Honeybourne D, et al. Lung concentrations of telithromycin after oral dosing. J Antimicrob Chemother 2001; 47: 837–40
Watanuki Y, Odagiri S, Ogura T, et al. A new ketolide antimicrobial, telithromycin, achieves high and sustained concentrations in sputum in patients [abstract no. P9.007]. 22nd International Congress of Chemotherapy; 2001 jun 7–9; Amsterdam, The Netherlands
Sultan E, Namour F, Mauriac C, et al. The ketolide antimicrobial, telithromycin (HMR 3647), is metabolized and eliminated predominantly in the faeces in man [abstract no. 09.31]. 5th International Conference on the Macrolides, Azalides, Streptogramins, Ketolides and Oxazolidinones; 2000 Jan 26–28; Seville, Spain
Guan Z, Jayanti V, Johnson M, et al. In vitro and in vivo metabolism of [14C] ABT-773 [abstract no. 09.32]. 5th International Conference on the Macrolides, Azalides, Streptogramins, Ketolides and Oxazolidinones; 2000 Jan 26–28; Seville, Spain
Ledirac N, de Sousa G, Fontaine F, et al. Effects of macrolide antibiotics on CYP3A expression in human and rat hepatocytes: interspecies differences in response to troleandomycin. Drug Metab Dispos 2000; 28: 1391–3
Labbe G, Flor M, Lenfant B. Cytochrome P-450 (CYP-450) activity is not inhibited in vitro by telithromycin (HMR 3647), a new ketolide [abstract no. 09.28]. 5th International Conference on the Macrolides, Azalides, Streptogramins, Ketolides and Oxazolidinones; 2000 Jan 26–28; Seville, Spain
Odenholt I, Lowdin E, Cars O. Pharmacodynamics of telithromycin In vitro against respiratory tract pathogens. Antimicrob Agents Chemother 2001; 45: 23–9
Neuhauser MM, Prause JL, Danziger LH, et al. Postantibiotic effect of ABT-773 and amoxicillin/clavulanate against S.pneumoniae and H.influenzae. Antimicrob Agents Chemother 2001; 45: 3613–5
Dubois J, St-Pierre C. Post-antibiotic effect (PAE) and bactericidal activity of HMR 3647 and other antimicrobial agents against respiratory pathogens [abstract no. 1242]. 39th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1999 Sep 26–29; San Francisco (CA)
Ramer N, McDaniel D, Johnson P, et al. Study of time-kill kinetics and post antibiotic effect of ABT-773 with macrolide susceptible and resistant respiratory pathogens [abstract no. 2137]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Drugeon H, Bryskier A, Bemer-Melchior P, et al. New fluoroketolides — HMR 3562 and HMR 3787: Bactericidal activity against Streptococcus pneumoniae [abstract no. 1818]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Boswell FJ, Andrews JM, Wise R. Pharmacodynamic properties of HMR 3004, a novel ketolide, on respiratory pathogens, enterococci and Bacteroides fragilis demonstrated by studies of time kill kinetics and postantibiotic effect. Clinical Microbiology and Infection 1998; 4: 186–91
Boswell FJ, Andrews JM, Wise R. Pharmacodynamic properties of HMR 3647, a novel ketolide, on respiratory pathogens, enterococci and Bacteroides fragilis demonstrated by studies of time-kill kinetics and postantibiotic effect. J Antimicrob Chemother 1998; 41: 149–53
Gustafsson I, Engstrand L, Cars O. In vitro pharmacodynamic studies of activities of ketolides HMR 3647 (Telithromycin) and HMR 3004 against extracellular or intracellular Helicobacter pylori. Antimicrob Agents Chemother 2001; 45: 353–5
Credito KL, Ednie LM, Jacobs MR, et al. Activity of telithromycin (HMR 3647) against anaerobic bacteria compared to those of eight other agents by time-kill methodology. Antimicrob Agents Chemother 1999; 43: 2027–31
Baltch AL, Smith RP, Ritz WJ, et al. Antibacterial effect of telithromycin (HMR 3647) and comparative antibiotics against intracellular Legionella pneumophila. J Antimicrob Chemother 2000; 46: 51–5
Jung R, Li DH, Pendland SL, et al. Intracellular Activity of ABT-773 and other antimicrobial agents against Legionella pneumophila isolates [abstract no. 2146]. 39th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1999 Sep 26–29; San Francisco (CA)
Dubois J, St-Pierre C. Intracellular activity and post-antibiotic effect of ABT-773 against Legionella [abstract no. 02.33]. 5th International Conference on the Macrolides, Azalides, Streptogramins, Ketolides and Oxazolidinones; 2000 Jan 26–28; Seville, Spain
Munckhof WJ, Borlace G, Turnidge JD. Postantibiotic suppression of growth of erythromycin A-susceptible and — resistant gram-positive bacteria by the ketolides telithromycin (HMR 3647) and HMR 3004. Antimicrob Agents Chemother 2000; 44: 1749–53
Azoulay-Dupuis E, Bedos JP, Isturiz R, et al. Efficacy of ABT-773, a new ketolide, versus erythromycin against penicillin/erythromycin sensitive and macrolide-resistant Streptococcus pneumoniae in a mouse pneumonia model [abstract no. 1018]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Meulbroek J, Mitten M, Mollison KW, et al. Efficacies of ABT-773 and azithromycin against experimental rat lung infections caused by Streptococcus pneumoniae [abstract no. 2151]. 39th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1999 Sep 26–29; San Francisco (CA)
Mitten M, Meulbroek J, Paige L, et al. Efficacies of ABT-773 and HMR-3647 against respiratory pathogens causing acute systemic infections in mice and lung infections in rats [abstract no. 2150]. 39th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1999 Sep 26–29; San Francisco (CA)
Piroth L, Desbiolles N, Mateo-Ponce V, et al. HMR 3647 human-like treatment of experimental pneumonia due to penicillin-resistant and erythromycin-resistant Streptococcus pneumoniae. J Antimicrob Chemother 2001; 47: 33–42
Chuah SK, Iskander L, Qazi S, et al. Experimental Haemophilus influenzae pneumonia: effect of age and telithromycin (HMR 3647) therapy [abstract no. 03.36]. Fifth International Conference on the Macrolides, Azalides, Streptogramins, Ketolides and Oxazolidinones; 2000 Jan 26–28; Seville, Spain
Tormakangas L, Saario E, Bem David D, et al. Experimental mouse model for Chlamydia pneumoniae infection: effect of telithromycin (HMR 3647) treatment on the acute infection in mice [abstract no. P25.007]. 22nd International Congress of Chemotherapy; 2001 Jun 7–9; Amsterdam, The Netherlands
Kim M, Zhou W, Tessier PR, et al. Bactericidal kill of ABT-773 in a murine pneumococcal pneumonia model [abstract no. 1019]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Craig WA, Andes DR. Impact of macrolide resistance on the in vivo activity of ABT-773 on Streptococcus pneumoniae [abstract no. 2140]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Andes DR, Craig WA. In vivo pharmacodynamics of ABT-773, a new ketolide antibiotic [abstract no. 2139]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Bonnefoy A, Guitton M, Delachaume C, et al. In vivo efficacy of the new ketolide telithromycin (hmr 3647) in murine infection models. Antimicrob Agents Chemother 2001; 45: 1688–92
Levasseur P, Vallee E, Bonnefoy A, et al. Activity of ketolides HMR 3562 and HMR 3787 against erythromycin-sensitive (Ery-S) and -resistant (Ery-Rc) pneumococci in murine pneumonia models [abstract no. 2158]. 39th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1999 Sep 26–29; San Francisco (CA)
Edelstein PH, Higa F and Edelstein MA. In vitro activity of ABT-773 against Legionella pneumophila its pharmacokinetics in guinea pigs, and use of the drug to treat guinea pigs with Legionella pneumophila pneumonia. Antimicrob Agents Chemother 2001; 45: 2685–90
Guitton M, Delachaume C, Le Priol P, et al. In vitro and in vivo efficacy of a novel fluoro-ketolide HMR 3562 against enterococci. J Antimicrob Chemother 2001; 48: 131–5
Novelli A, Fallani S, Cassetta MI, et al. In vivo pharmacodynamic evaluation of the new ketolide ABT-773 in comparison to erythromycin [abstract no. P9.016]. 22nd International Congress of Chemotherapy; 2001 Jun 7–9; Amsterdam, The Netherlands
Bermudez LE, Inderlied CB, Wu M, et al. Activities of ABT-773, telithromycin and linezolid against Mycobacterium avium (MAC) in vitro and in vivo [abstract no. 03.16]. Fifth International Conference on the Macrolides, Azalides, Streptogramins, Ketolides and Oxazolidinones; 2000 Jan 26–28; Seville, Spain
Araujo FG, Khan AA, Slifer TL, et al. The ketolide antibiotics HMR 3647 and HMR 3004 are active against Toxoplasma gondii in vitro and in murine models of infection. Antimicrob Agents Chemother 1997; 41: 2137–40
Araujo FG, Khan AA, Bryskier A, et al. Use of ketolides in combination with other drugs to treat experimental toxoplasmosis. J Antimicrob Chemother 1998; 42: 665–7
Singh KV, Zscheck KK, Murray BE. Efficacy of telithromycin (HMR 3647) against enterococci in a mouse peritonitis model. Antimicrob Agents Chemother 2000; 44: 3434–7
Cynamon MH, Carter JL, Shoen CM. Activity of ABT-773 against Mycobacterium avium complex in the beige mouse model. Antimicrob Agents Chemother 2000; 44: 2895–6
Khan AA, Araujo FG, Craft JC, et al. Ketolide ABT-773 is active against Toxoplasma gondii. J Antimicrob Chemother 2000; 46: 489–92
Mitten M, Meulbroek J, Nukkala M, et al. Efficacies of ABT-773 a new ketolide against experimental bacterial infections. Antimicrob Agents Chemother 2001; 45: 2585–93
Aubier M, Aidons PM, Leak A, et al. Efficacy and tolerability of a 5-day course of a new ketolide antimicrobial, telithromycin (HMR 3647), for the treatment of acute exacerbations of chronic bronchitis in patients with COPD [abstract no. 2241]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Carbon C, Moola S, Velancsics I, et al. Efficacy of telithromycin (HMR 3647), a new once-daily antimicrobial, in the treatment of community-acquired pneumonia [abstract no. 2245]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Chang J, Stewart J, Brumpt I, et al. Telithromycin treatment of CAP is associated with lower usage of additional RTI-related antibiotics than high-dose amoxycillin in a randomised, double-blind, comparative trial [abstract no. P418]. 11th European Congress of Clinical Microbiology and Infectious Diseases; 2001 Apr 1–4; Istanbul, Turkey
Chang J, Stewart J, Brumpt I, et al. Telithromycin (HMR 3647) provides more rapid relief from symptoms than penicillin V in patients with GABHS pharyngitis [abstract no. P1262]. 11th European Congress of Clinical Microbiology and Infec- tious Diseases; 2001 2001 Apr 1–4; Istanbul, Turkey
DeAbate CA, Heyder A, Leroy B, et al. Oral telithromycin (HMR 3647) 800 mg once daily for 5 days is well tolerated and as effective as cefuroxime axetil 500 mg twice daily for 10 days in adults with acute exacerbations of chronic bronchitis (AECB) [abstract no. 2228]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Hagberg L, Torres A, Van Rensburg DJ, et al. Efficacy and tolerability of telithromycin (HMR 3647) vs. high-dose amoxicillin in the treatment of community-acquired pneumonia [abstract no. 2244]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Hagberg L, Pullman J, Rangaraju M, et al. Telithromycin is effective in the treatment of pneumococcal bacteremia associated with community-acquired pneumonia [abstract no. 861]. 41th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2001 Sep 22–25; Chicago (IL)
Dunbar L, Hagberg L, Rangaraju M, et al. Seven to 10 day therapy with telithromycin the first ketolide antimicrobial is effective in community-acquired pneumonia caused by atypical and intracellular pathogens [abstract no. 859]. 41th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2001 Sep 22–25; Chicago (IL)
Norrby SR, Rabie W, Bacart P, et al. Efficacy of 5 days’ telithromycin (HMR 3647) vs 10 days’ penicillin V in the treatment of pharyngitis in adults [abstract no. 2242]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Pullman J, Champlin J, Leroy B, et al. Oral telithromycin (HMR 3647) 800 mg once daily for 7–10 days is well tolerated and as effective as oral trovalfloxacin 200 mg once daily for 7–10 days in community-acquired pneumonia [abstract no. 2230]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Quinn J, Ziter P, Leroy B, et al. Oral telithromycin (HMR 3647) 800 mg once daily for 5 days is well tolerated and as effective as oral clarithromycin 250 mg twice daily for 10 days in group A-hemolytic streptococcal (GABHS) pharyngitis/tonsillitis [abstract no. 2229]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Rangaraju M, Leroy B. Clinical and bacteriological efficacy of telithromycin (HMR 3647) in the treatment of community acquired RTIs caused by S. pneumoniae with reduced susceptibility to peniclillins or macrolides [abstract no. P1261]. 11th European Congress of Clinical Microbiology and Infectious Diseases; 2001 Apr 1–4; Istanbul, Turkey
Tellier G, Hassman J, Leroy B, et al. Oral telithromycin (HMR 3647) 800 mg once daily is well tolerated and as effective as oral clarithromycin 500 mg twice daily in community-acquired pneumonia (CAP) in adults [abstract no. 2227]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Tellier G, Lasko B, Leroy B, et al. Oral telithromycin (HMR 3647) 800 mg once daily for 5 days and 10 days is well tolerated and as effective as amoxicillin/clavulanic acid 500/125 mg three-times daily for 10 days in acute maxillary sinusitis (AMS) in adults [abstract no. 2226]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Roos K, Brunswig-Pitschner C, Kostrica R, et al. Efficacy and tolerability of a 5-day course of a new ketolide antimicrobial, telithromycin (HMR-3647), for the treatment of acute sinusitis [abstract no. 2243]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, Canada
Sharma K, Katgely B, Villa R, et al. Safety profile of the first ketolide antimicrobial, telithromycin: a review [abstract no. P17.018]. 22nd International Congress of Chemotherapy; 2001 Jun 7–9; Amsterdam, The Netherlands
Van Rensburg DJ, Matthews PA, Tady D, et al. Efficacy of the first ketolide antibacterial telithromycin in the treatment of adult patients with community acquired pneumonia in S.Africa [abstract no. 858]. 41th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2001 Sep 22–25; Chicago (IL)
Fogarty C, Patel TC, Galbraith H, et al. Efficacy of the first ketolide antibacterial telithromycin in the treatment of adult patients with community acquired pneumonia caused by Streptococcus pneumoniae [abstract no. 857]. 41th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2001 Sep 22–25; Chicago
Buchanan P, McNeil D, Tady D, et al. A 5 day course of telithromycin the first ketolide antibacterial is as effective as 10 days cefuroxime axetil in the treatment of acute maxillary sinusitis [abstract no. 910]. 41th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2001 Sep 22–25; Chicago
Fogarty C, Patel TC, Sidarous EH, et al. Telithromycin is an effective treatment in high-risk patients with community acquired pneumonia [abstract no. 129]. Clin Infect Dis 2001; 33 (7): 1110
Scholtz HE, Sultan E, Wessels D, et al. Telithromycin (HMR 3647), a new ketolide antimicrobial, does not affect the reliability of low-dose, triphasic oral contraceptives [abstract no. 09.29]. 5th International Conference on the Macrolides, Azalides, Streptogramins, Ketolides and Oxazolidinones; 2000 Jan 26–28; Seville, Spain
Scholtz HE, Pretorius SG, Wessels DH, et al. Telithromycin (HMR 3647), a new ketolide antimicrobial, does not affect the pharmacodynamics or pharmacokinetics of warfarin in healthy adult males [abstract no. 09.30]. 5th International Conference on the Macrolides, Azalides, Streptogramins, Ketolides and Oxazolidinones; 2000 Jan 26–28; Seville, Spain
Lippert C, Leese PT, Sultan E. Telithromycin (HMR 3647) does not interact with the CYP 2d6 substrate paroxetine [abstract no. P1268]. 11th European Congress of Clinical Microbiology and Infectious Diseases; 2001 Apr 1–4; Istanbul, Turkey
Lippert C, Leese PT, Sultan E. Effect of gastric pH on the bioavailability of telithromycin (HMR 3647) [abstract no. P1269]. 11th European Congress of Clinical Microbiology and Infectious Diseases; 2001 Apr 1–4; Istanbul, Turkey
Sahm DF, Karlowsky JA, Kelly LJ, et al. Need for Annual Surveillance of Antimicrobial Resistance in Streptococcus pneumoniae in the United States: 2-Year Longitudinal Analysis. Antimicrob Agents Chemother 2001; 45: 1037–42
Diekema DJ, Pfaller MA, Schmitz FJ, et al. Survey of infections due to staphylococcus species: frequency of occurrence and antimicrobial susceptibility of isolates collected in the united states, canada, latin america, europe, and the western pacific region for the sentry antimicrobial surveillance program, 1997–1999. Clin Infect Dis 2001; 32 Suppl. 2: S114–32
Zhanel GG. Influence of Pharmacokinetic and Pharmacodynamic Principles on Antibiotic Selection. Curr Infect Dis Rep 2001; 3: 29–34
Acknowledgements
The authors declare conflicts of interests (financial support for research) from the following macrolide/ketolide manufacturers: G. Zhanel — Pfizer (azithromycin), Abbott (clarithromycin and ABT-773), Aventis (telithromycin); J. Embil — Pfizer (azithromycin), Abbott (clarithromycin); A. Gin — Pfizer (azithromycin), Abbott (clarithromycin); S. Douthwaite — Aventis (telithromycin); D. Hoban — Pfizer (azithromycin), Abbott (clarithromycin and ABT-773), Aventis (telithromycin).
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Zhanel, G.G., Walters, M., Noreddin, A. et al. The Ketolides. Drugs 62, 1771–1804 (2002). https://doi.org/10.2165/00003495-200262120-00006
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DOI: https://doi.org/10.2165/00003495-200262120-00006