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Antimicrobial Agents and Chemotherapy, February 2002, p. 321-326, Vol. 46, No. 2
0066-4804/01/$04.00+0     DOI: 10.1128/AAC.46.2.321-326.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

In Vitro Activity of Cephalosporin RWJ-54428 (MC-02479) against Multidrug-Resistant Gram-Positive Cocci

Alan P. Johnson,* Marina Warner, Michael Carter, and David M. Livermore

Antibiotic Resistance Monitoring and Reference Laboratory, Central Public Health Laboratory, Colindale, London NW9 5HT, United Kingdom

Received 16 May 2001/ Returned for modification 11 September 2001/ Accepted 13 October 2001

RWJ-54428 (MC-02479) is a novel cephalosporin that binds to penicillin-binding protein (PBP) PBP 2' (PBP 2a) of methicillin-resistant staphylococci. Its in vitro activity was assessed against 472 gram-positive cocci, largely selected as epidemiologically unrelated isolates with multidrug resistance. The MIC at which 50% of isolates are inhibited (MIC50) and MIC90 of RWJ-54428 for methicillin-resistant Staphylococcus aureus (MRSA) were 1 and 2 µg/ml, respectively, whereas they were 0.5 and 0.5 µg/ml, respectively, for methicillin-susceptible S. aureus. The MIC50 and MIC90 were 1 and 4 µg/ml, respectively, for methicillin-resistant coagulase-negative staphylococci (MRCoNS), whereas they were 0.25 and 1 µg/ml, respectively, for methicillin-susceptible isolates. The highest MICs for MRSA and MRCoNS isolates were 2 and 4 µg/ml, respectively. The MIC50 and MIC90 of RWJ-54428 for Enterococcus faecalis were 0.5 and 1 µg/ml, respectively, but they were 4 and 8 µg/ml, respectively, for Enterococcus faecium. For penicillin-susceptible, -intermediate, and -resistant pneumococci, the MIC90s of RWJ-54428 were 0.03, 0.25, and 0.5 µg/ml, respectively, with the highest MIC for a pneumococcus being 1 µg/ml, recorded for a strain for which penicillin and cefotaxime MICs were 8 and 4 µg/ml. MICs for Lancefield group A, B, C, and G streptococci were <=0.008 µg/ml; those for viridans group streptococci, including isolates not susceptible to penicillin, were from 0.015 to 0.5 µg/ml. RWJ-54428 did not select resistant mutants of MRSA or enterococci in challenge experiments and has the potential to be useful for the treatment of infections caused by gram-positive cocci.

* Corresponding author. Mailing address: Antibiotic Resistance Monitoring and Reference Laboratory, Central Public Health Laboratory, Colindale, London NW9 5HT, United Kingdom. Phone: 44-208-200-4400, ext. 4237. Fax: 44-208-358-3292. E-mail: AJohnson{at}phls.nhs.uk.

Antimicrobial Agents and Chemotherapy, February 2002, p. 321-326, Vol. 46, No. 2
0066-4804/01/$04.00+0     DOI: 10.1128/AAC.46.2.321-326.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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