Should daptomycin-rifampin combinations for MSSA/MRSA isolates be avoided because of antagonism?

There is increasing clinical evidence from observational studies, that combination therapy of daptomycin with rifampin is a valuable treatment option for biofilm-associated difficult to treat Staphylococcus aureus infections such as osteomyelitis, prosthetic joint infection and endocarditis. However, two studies analyzing a limited number of S. aureus isolates reported an antagonism of those two drugs questioning the benefit of this combination. To estimate the frequency of this possible antagonism, we performed in vitro checkerboard assays on 58 consecutive clinical isolates of S. aureus (MSSA n = 9, MRSA n = 49). We determined the fractional inhibitory concentration index (FICI) and the susceptible breakpoint index (SBPI). All isolates were characterized by a microprobe array detecting 336 different genes/alleles to ensure their non-clonal origin. For all isolates, the FICI was between 1.00 and 1.25 indicating additive effects for the daptomycin/rifampin combination. Neither antagonism nor synergism as defined by the FICI was found for any of the isolates. Based on these data, there is no evidence to advise against the daptomycin/rifampin combination therapy.