744. Non-susceptible Daptomycin Methicillin-Resistant Staphylococcus aureus Isolates Associated with Reduced Susceptibility to Host Defense Cationic Peptides
Session: Poster Abstract Session: Antimicrobials: Resistance Mechanisms
Friday, October 4, 2013
Room: The Moscone Center: Poster Hall C
Background: MRSA produces the carotenoid pigment staphyloxanthin (SX) that helps to stabilize cell membranes (CM). CM fluidity is critical to interactions of membrane-targeting host-defense cationic peptides (HDP). Human cathelicidin LL37 is an HDP with microbicidal activity against Gram+ and Gram- bacteria including antibiotic-resistant microorganisms such as MRSA. Its mechanism of action involves disruption of the CM, similar to that of daptomycin (DAP).

Methods: Clinical isolates from patients with MRSA BSI were characterized by susceptibility to DAP by Microscan® and Etest, (DNS had MIC>1 mg/L), vancomycin (VAN) susceptibility, SX production (OD450nm), and susceptibility to LL37 (mean % survival after 2 hr, 32µM). Differences in the duration of bactremia and the % survival in LL37 were compared by Mann-Whitney U testing.

Results: Twenty four isolates (12 DNS) were evaluated; 1 DNS was from a patient with prior DAP exposure.  83% of the DNS were intermediately-resistant to VAN (MIC>2 mg/L) and produced more SX. DNS showed significantly higher % survival to LL37 compared to DAP susceptible isolates (p=0.01).  DNS was associated with longer bacteremia (12.1d vs. 9.4d p=0.41) and endovascular infection source.

Conclusion: The development of DNS MRSA is heterogenous in nature.  Increasing production of SX leading to greater CM stabilization may result in reduced susceptibility to HDP, resulting in prolonged bacteremia, and consequent prolonged VAN, DAP and further ongoing HDP selection pressure in vivo. This may further complicate therapy by reducing the potency of available antimicrobials and lead to the emergence of DNS. Therefore, prompt eradication of bacteremia is critical, not only to improve patient outcome, but to prevent antimicrobial resistance to VAN and DAP in MRSA BSI.

Michael Virata, MD, Infectious Diseases, Yale-New Haven Hospital-SRC, New Haven, CT; Yale University School of Medicine, New Haven, CT, Nancy L. Havill, MT(ASCP), CIC, Quality Improvement Support Services, Yale-New Haven Hospital, New Haven, CT and George Sakoulas, MD, Sharp Healthcare System, San Deigo, CA

Disclosures:

M. Virata, Cubist Pharmaceuticals: Grant Investigator, Research support

N. L. Havill, None

G. Sakoulas, Cubist Pharmaceuticals: Speaker's Bureau, Speaker honorarium
Forest Pharmaceuticals: Speaker's Bureau, Research grant and Speaker honorarium

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