Efficacy of linezolid alone and in combination with rifampin in staphylococcal experimental foreign-body infection

SummaryObjectivesThe knowledge about efficacy of linezolid alone or in combination with rifampin in device infections is limited. We test their in vitro and in vivo efficacy in a rat model of foreign-body infection by methicillin-susceptible S. aureus.MethodsIn vitro studies for logarithmic and stationary bacteria were performed. In vivo efficacy (decrease in bacterial counts in tissue cage fluid) was evaluated at: (i) after 7-day therapy (groups: linezolid, cloxacillin, rifampin, linezolid–rifampin and cloxacillin–rifampin); and (ii) after 10-day therapy (groups: rifampin and linezolid–rifampin).ResultsAfter 7-day therapy all groups were significantly better than controls; linezolid (Δlog cfu/ml: −0.59, no resistant strains) and cloxacillin (−0.85) were the least effective therapy; linezolid was significantly less active (P < 0.05) than rifampin (−1.22, resistance 90%), cloxacillin–rifampin (−1.3) and linezolid–rifampin (−1.14). After 10-day therapy linezolid–rifampin was the most effective treatment (Δlog −1.44, no resistance, P < 0.05); in contrast, rifampin resulted ineffective (Δlog 0.1) due to the growth of resistant strains (100%).ConclusionsLinezolid alone showed moderate efficacy, whereas its combination with rifampin prevented the emergence of rifampin resistance. The efficacy of linezolid–rifampin combination was initially similar to that of rifampin alone, but in contrast to rifampin, it increased over time revealing the impact of protection against rifampin resistance and the benefits of rifampin activity.