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J Med Microbiol 57 (2008), 452-456; DOI: 10.1099/jmm.0.47580-0
© 2008 Society for General Microbiology
ISSN 1473-5644

Virulence characteristics of community-associated Staphylococcus aureus and in vitro activities of moxifloxacin alone and in combination against community-associated and healthcare-associated meticillin-resistant and -susceptible S. aureus

Ellie J. C. Goldstein1,2, Diane M. Citron1, Yumi A. Warren1, Kerin L. Tyrrell1 and Michael J. Rybak3

1 R. M. Alden Research Laboratory, Santa Monica, CA 90404, USA

2 UCLA School of Medicine, Los Angeles, CA 90095, USA

3 Anti-Infective Research Laboratory, College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA

Correspondence
Ellie J. C. Goldstein
ejcgmd{at}aol.com

Received 20 August 2007
Accepted 29 November 2007

The increasing prevalence of community-associated meticillin-resistant Staphylococcus aureus (CA-MRSA) poses a challenge for antimicrobial therapy of skin and soft tissue infections (SSTIs). To determine whether another antimicrobial agent might enhance the activity of moxifloxacin against CA-MRSA, this study analysed its activity alone and in chequerboard combination with doxycycline, rifampicin, clindamycin, trimethoprim, sulfamethoxazole/trimethoprim (SXT) and vancomycin against recent SSTI clinical isolates, and also characterized the isolates for Panton–Valentine leukocidin (PVL), agr groups, staphylococcal cassette chromosome mec (SSCmec) types and {delta}-haemolysin production. For comparison, 25 strains of outpatient meticillin-susceptible S. aureus (MSSA), 24 strains of healthcare-associated (HA)-MRSA and six historical strains of vancomycin-intermediate S. aureus (VISA) were included. It was found that 21/25 CA-MRSA strains tested were PVL-positive, SSCmec type 4 and agr type 1, whilst 4/25 were PVL-negative, SSCmec type 2 and agr type 2. Two of the agr type 2 strains were negative for {delta}-haemolysin but all other strains were positive. Moxifloxacin MIC50/90 values (µg ml–1) were 1/8 for CA-MRSA, 4/32 for HA-MRSA and ≤0.03/1 for MSSA and MIC50 of 2 for VISA. The D-test for inducible clindamycin resistance was positive for 3/27 CA-MRSA, 5/14 HA-MRSA and none of the MSSA isolates. In chequerboard studies, fractional inhibitory concentration indices (FICIs) showed that most interactions were additive or indifferent (FICI value >0.5 to ≤2) as follows: rifampicin 43/52 strains, clindamycin 44/44, SXT 44/47, trimethoprim 41/42 and vancomycin 37/43. The FICI values for doxycycline were 3–6 for 32/34 strains, indicating antagonism, suggesting that it should not be used in combination with moxifloxacin.

Abbreviations: CA, community-associated; FICI, fractional inhibitory concentration index; HA, healthcare-associated; MRSA, meticillin-resistant Staphylococcus aureus; MSSA, meticillin-susceptible Staphylococcus aureus; PVL, Panton–Valentine leukocidin; SCCmec, staphylococcal cassette chromosome mec; SSTI, skin and soft tissue infection; SXT, sulfamethoxazole/trimethoprim; VISA, vancomycin-intermediate Staphylococcus aureus.






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