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Improved β-Lactam Susceptibility Against ica-Dependent Biofilm-Embedded Staphylococcus aureus by 2-Aminothiazole.

BACKGROUND
Due to the emergence of methicillin-resistant Staphylococcus aureus (MRSA) producing biofilm, causing recurrent infections worldwide, new therapeutic combinations need to be discovered to prevent resistance and to make treatment available. It was aimed to improve β-lactam susceptibility against ica-dependent biofilm-embedded Staphylococcus aureus (S. aureus), even in blaZ and mecA carriers, by 2-aminothiazole.


METHODS
Virulence genes in isolates were detected by qRT-PCR. MICs, MBCs of 2-aminothiazole and β-lactams against planktonic and sessile ica-dependent biofilm-producer isolates were investigated. Activities of 2-aminothiazole combined β-lactams against sessile one MRSA ATCC 43300, one MRSA, and two MSSA were investigated by checkerboard-assay.


RESULTS
Activities of 2-aminothiazole combined β-lactams were found synergistic and partially-synergistic against both biofilm-embedded MRSA and MSSA-isolates with FIC-indexes ranging between 0.193 - 0.387 and 0.535 - 0.745 and between 0.358 - 0.415 and 0.707 - 1.0, respectively. MICs of β-lactams against MSSA and MRSA were decreased 2- to 8-fold and 0- to 8-fold by sub-MICs of 2-aminothiazole, respectively.


CONCLUSIONS
Sub-MIC 2-aminothiazole combined Sub-MIC β-lactams can be a choice in varying applications to treat biofilm-associated staphylococcal infections.