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

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 (mu g 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.