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Antimicrobial Agents and Chemotherapy, May 2002, p. 1364-1374, Vol. 46, No. 5
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.5.1364-1374.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Effect of Telithromycin (HMR 3647) on Polymorphonuclear Neutrophil Killing of Staphylococcus aureus in Comparison with Roxithromycin

D. Vazifeh, H. Abdelghaffar,^, and M. T. Labro^*

INSERM U 479, Laboratoire d'Hématologie et Immunologie, CHU Xavier Bichat, 75018 Paris, France

Received 24 April 2001/ Returned for modification 26 October 2001/ Accepted 2 February 2002

HMR 3647 (telithromycin), a new ketolide, is active on intracellular pathogens. It was previously demonstrated that it inhibits superoxide anion production in a time- and concentration-dependent manner, at concentrations which inhibit 50% of the control response of about 55 µg/ml (5 min) to 30 µg/ml (30 min); these values are similar to those obtained with roxithromycin, a classical erythromycin A derivative. Here we investigated whether these drugs modified the bactericidal activity of human polymorphonuclear neutrophils (PMN) on four strains of Staphylococcus aureus with different profiles of susceptibility to macrolides and ketolides. We found that the main factor involved in killing was the antibacterial potency of the drugs, although combinations of antibiotics with PMN were slightly more active than each component used alone against two of the four strains. In addition, high concentrations of the drugs, which impaired the PMN oxidative burst, did not impair PMN bactericidal activity. Likewise, some cytokines which enhance PMN oxidative metabolism did not modify PMN bactericidal activity in the presence or absence of macrolides or ketolides. These data suggest that oxygen-independent mechanisms contribute to the bactericidal activity of PMN on these strains of S. aureus. Both live and/or heat-killed bacteria impaired the uptake of telithromycin and roxithromycin (but not that of levofloxacin, a quinolone) in a concentration-dependent manner, owing to a modulation of PMN transductional systems involved in the activation of the macrolide carrier.

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* Corresponding author. Mailing address: INSERM U 479, CHU Xavier Bichat, 16 rue Henri Huchard, 75018 Paris, France. Phone: 33 1 44 85 62 11. Fax: 33 1 44 85 62 07. E-mail: labro{at}bichat.inserm.fr.

Present address: Laboratoire de Biochimie et Biologie Cellulaire et Moléculaire, Faculté des Sciences I, Ain Chock, BP 5366 Maarif, Casablanca, Morocco.

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Antimicrobial Agents and Chemotherapy, May 2002, p. 1364-1374, Vol. 46, No. 5
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.5.1364-1374.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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