JAC Advance Access originally published online on November 18, 2002
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Journal of Antimicrobial Chemotherapy (2002) 50, 907-913
© 2002 The British Society for Antimicrobial Chemotherapy
Activity of ketolide ABT-773 (cethromycin) against erythromycin-resistant Streptococcus pneumoniae: correlation with extended MLSK phenotypes
Department of Medical Microbiology, Royal Free and University College Medical School, London NW3 2PF, UK
Received 17 April 2002; returned 30 July 2002; revised 30 August 2002; accepted 9 September 2002
Objectives: (i) To determine the inhibitory and bactericidal activities of ABT-773, a novel ketolide, against sensitive and erythromycin-resistant pneumococci; (ii) to subdivide erythromycin-resistant pneumococci into resistance phenotypes, more extensive than the conventional M and MLSB groups, by assessing susceptibilities to, and interactions between, erythromycin (14-membered macrolide), clindamycin (lincosamide), rokitamycin (16-membered macrolide), ABT-773 (ketolide), quinupristin (streptogramin B) and dalfopristin (streptogramin A).
Methods: MICs and MBCs of ABT-773 were determined for 165 strains of pneumococci (113 resistant to erythromycin). Extended phenotypes for the erythromycin-resistant strains were described in terms of intrinsic susceptibility to, and induction of resistance by, the antibiotics listed above.
Results: Erythromycin-resistant strains could be divided into 10 extended phenotypes (designated II–XI), two of which (II and IX) predominated. ABT-773 at 0.12 mg/L inhibited 109 strains (median 0.03 mg/L). MICs for the other four strains (of phenotypes X and XI) were 0.25–1 mg/L. MICs were only slighter higher when measured on agar in CO2 than by the NCCLS method (in broth in air). MBCs were usually 
2 x MIC, but for 10 strains (eight of phenotype X, one each of types IX and XI) MBCs were >1 mg/L, and three of the latter (all type X) were tolerant. Clones of reduced susceptibility (MICs 1–8 mg/L, increased by up to 32-fold) could be isolated from some strains of phenotypes VII, IX and X, but not from those of type II (efflux mechanism) or from erythromycin-sensitive strains.
Conclusions: ABT-773 was active against all 113 erythromycin-resistant pneumococci tested, which belonged to 10 phenotypes. Extended phenotyping of pneumococci revealed interesting and potentially useful subdivisions of the classical phenotypes.
* Corresponding author. Tel: +44-20-7794-0500; Fax: +44-20-7435-9694; E-mail: j.hamilton-miller{at}rfc.ucl.ac.uk
Present address. Department of Pharmaceutics, School of Pharmacy, Brunswick Square, London WC1N 1AX, UK.
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