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| Content Provider | PubMed Central |
|---|---|
| Author | Chin, Judy N. Rybak, Michael J. Cheung, Chrissy M. Savage, Paul B. |
| Copyright Year | 2007 |
| Abstract | The rise in the rates of glycopeptide resistance among Staphylococcus aureus isolates is concerning and underscores the need for the development of novel potent compounds. Ceragenins CSA-8 and CSA-13, cationic steroid molecules that mimic endogenous antimicrobial peptides, have previously been demonstrated to possess broad-spectrum activities against multidrug-resistant bacteria. We examined the activities of CSA-8 and CSA-13 against clinical isolates of vancomycin-intermediate S. aureus (VISA), heterogeneous vancomycin-intermediate S. aureus (hVISA), as well as vancomycin-resistant S. aureus (VRSA) and compared them to those of daptomycin, linezolid, and vancomycin by susceptibility testing and killing curve analysis. We also examined CSA-13 for its concentration-dependent activity, inoculum effect, postantibiotic effect (PAE), and synergy in combination with various antimicrobials. Overall, the MICs and minimal bactericidal concentrations of CSA-13 were fourfold lower than those of CSA-8. Time-kill curve analysis of the VRSA, VISA, and hVISA clinical isolates demonstrated concentration-dependent bactericidal killing. An inoculum effect was also observed when a higher starting bacterial density was used, with the time required to achieve 99.9% killing reaching 1 h with a 6-log10-CFU/ml starting inoculum, whereas it was ≥24 h with a 8- to 9-log10-CFU/ml starting inoculum with 10× the MIC (P ≤ 0.001). A concentration-dependent PAE was demonstrated with CSA-13, nearly doubling from 2× to 4× the MIC (P = 0.03). With respect to the CSA-13 antimicrobial combinations, time-kill curve analysis showed no difference in the log10 CFU/ml at 24 h for the majority of the organisms tested. However, early synergy at 4 to 8 h was detected against the VRSA Pennsylvania strain (2002) when CSA-13 was tested in combination with gentamicin, while early additivity was demonstrated against all of the other organisms. |
| Related Links | http://dx.doi.org/10.1128/aac.01325-06 |
| Ending Page | 1273 |
| Page Count | 6 |
| Starting Page | 1268 |
| File Format | |
| ISSN | 00664804 |
| e-ISSN | 10986596 |
| Journal | Antimicrobial Agents and Chemotherapy |
| Issue Number | 4 |
| Volume Number | 51 |
| Language | English |
| Publisher | American Society for Microbiology |
| Publisher Date | 2007-04-01 |
| Access Restriction | Open |
| Rights Holder | American Society for Microbiology |
| Subject Keyword | Pharmacology (medical) Pharmacology Infectious Diseases Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Infectious Diseases Pharmacology Pharmacology (medical) |
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