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.
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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