1845. Beta-Lactam Specific Antibiogram of Daptomycin Susceptible (DSSA) and Non-Susceptible Staphylococcus aureus (DNSA) Isolates
Session: Poster Abstract Session: Treatment of HAIs/Antimicrobial Resistant Infections
Saturday, October 10, 2015
Room: Poster Hall
Background: With growing reports of vancomycin failure and the emergence of DNSA invasive infections, clinicians have sought alternative antibiotic therapies to treat multi-drug resistant (MDR) S. aureus infections. Recently, investigators have observed a see-saw effect with anti-staphylococcal beta-lactams (ASBL) and DAP, by which ASBL efficacy increased parallel to a decreased DAP activity; this effect has translated in a successful clinical antibiotic combination. The purpose of the study is to investigate differences in DSSA and DNSA isolates and possible alterations in beta-lactam (BL) susceptibility. 

Methods:  DAP MICs of all 12 paired S. aureus isolates (parent and DNSA progeny) were determined by broth microdilution in Mueller-Hinton broth with 50mg/L calcium and Trek Sensititre®. MIC Susceptibility of 17 different BLs was determined using Trek Sensititre® MIC plates.  Resultant MICs were recorded at 18-24 hours and analyzed according to CLSI susceptibility breakpoints. Additional phenotypic testing performed on the paired isolates included a polystyrene adherence assay, congo red assay, and autolysis assay. 

Results: Penicillins (Pcn, Amp, Pip-Tazo, Oxa, Ticar-Clav) exhibited a >2 fold MIC decrease in 41% DNSA isolates. Cefazolin and Cephalothin exhibited a >2 fold MIC decrease in 25% DNSAs. Cefuroxime and Cefoxitin exhibited a >2 fold MIC change in 23% DNSAs.  Ceftriaxone and Ceftazidime showed a >2 fold MIC decrease in 17% DNSAs.  Cefepime showed a >2 fold MIC decrease in 33% DNSAs.  Ceftaroline showed a >2 fold MIC decrease in 10% of DNSAs.  Carbapenems (Doripenem, Ertapenem, Meropenem) exhibited a >2 fold MIC decrease in 39% DNSAs. A transition from oxacillin, cefazolin, cefepime, ertapenem/ doripenem, and meropenem S. aureus resistance to sensitivity occurred in 25%, 25%, 8%, 16%, and 8% of DNSA strains, respectively. Additionally, biofilm development differences were observed in 8 of 12 pairs (5 DNSA exhibited a biofilm enhancement).    

Conclusion: Our study is consistent with previous findings that showed enhanced ASBL activity and trends in phenotypic alterations among DNSA. Additionally, a similar enhanced activity trend was noticed in non-ASBL agents for DNSA isolates. This study provides additional information and supports further evaluation on possible novel BL agents to combine with daptomycin in combating MDR-S. aureus.

Christopher Wilming, Pharm.D. candidate, Mena Raouf, Pharm.D. candidate, Karina Petrovets, Pharm.D. candidate, John Tremblay, BS, Steven Lane, MS and Anthony M. Nicasio, PharmD, Albany College of Pharmacy & Health Sciences, Albany, NY

Disclosures:

C. Wilming, None

M. Raouf, None

K. Petrovets, None

J. Tremblay, None

S. Lane, None

A. M. Nicasio, Merck: Investigator , Research support
Medicines Company: Speaker's Bureau , Speaker honorarium

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