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 (microg ml(-1)) were 1/8 for CA-MRSA, 4/32 for HA-MRSA and <or=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 <or=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.
Goldstein
Ellie J C
EJC
UCLA School of Medicine, Los Angeles, CA 90095, USA.|R. M. Alden Research Laboratory, Santa Monica, CA 90404, USA.
Citron
Diane M
DM
R. M. Alden Research Laboratory, Santa Monica, CA 90404, USA.
Warren
Yumi A
YA
R. M. Alden Research Laboratory, Santa Monica, CA 90404, USA.
Tyrrell
Kerin L
KL
R. M. Alden Research Laboratory, Santa Monica, CA 90404, USA.
Rybak
Michael J
MJ
Anti-Infective Research Laboratory, College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA.
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001372:Aza Compounds / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D017714:Community-Acquired Infections / Q000382:microbiology*; D003428:Cross Infection / Q000382:microbiology*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D024841:Fluoroquinolones; D006801:Humans; D008712:Methicillin / Q000494:pharmacology; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D000077266:Moxifloxacin; D011804:Quinolines / Q000494:pharmacology*; D018461:Soft Tissue Infections / Q000382:microbiology; D013203:Staphylococcal Infections / Q000382:microbiology*; D013207:Staphylococcal Skin Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000302:isolation & purification / Q000472:pathogenicity*; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics
D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D001426:Bacterial Proteins; D024841:Fluoroquinolones; D011804:Quinolines; D037521:Virulence Factors; D008712:Methicillin; D000077266:Moxifloxacin