Activity of ketolide ABT-773 (cethromycin) against erythromycin-resistant Streptococcus pneumoniae: correlation with extended MLSK phenotypes.
OBJECTIVE
(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 MLS(B) 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 CO(2) than by the NCCLS method (in broth in air). MBCs were usually < or = 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.
Hamilton-Miller
J M T
JM
Department of Medical Microbiology, Royal Free and University College Medical School, London NW3 2PF, UK. j.hamilton-miller@rfc.ucl.ac.uk
Shah
Saroj
S
D024881:Drug Resistance, Bacterial / Q000235:genetics*; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D048628:Ketolides; D010641:Phenotype; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification
D048628:Ketolides; D004917:Erythromycin; C405499:cethromycin