JAC Advance Access published online on November 18, 2002
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkf237
© 2002 by The British Society for Antimicrobial Chemotherapy
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Original Paper
1 Department of Medical Microbiology, Royal Free and University
College Medical School, London NW3 2PF, UK
* Corresponding author. E-mail: j.hamilton-miller{at}rfc.ucl.ac.uk.
Received 17 April 2002
; revised 30 July 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 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.
Activity of ketolide ABT-773 (cethromycin) against
erythromycin-resistant Streptococcus pneumoniae:
correlation with extended MLSK phenotypes
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.
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