title: Efficacy of linezolid alone and in combination with rifampin in staphylococcal experimental foreign-body infection.
abstract: OBJECTIVE
  The 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.
  
  
  METHODS
  In 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).
  
  
  RESULTS
  After 7-day therapy all groups were significantly better than controls; linezolid (Delta log 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 (Delta log -1.44, no resistance, P<0.05); in contrast, rifampin resulted ineffective (Delta log 0.1) due to the growth of resistant strains (100%).
  
  
  CONCLUSIONS
  Linezolid 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.
authors: Laboratory of Experimental Infection, Infectious Diseases Service, IDIBELL, Hospital Universitari de Bellvitge, Feixa Llarga s/n, 08907 Barcelona, Spain. 32186omr@comb.es
authors: Oscar
authors: O
authors: Murillo
authors: Alejandro
authors: A
authors: Domenech
authors: Gorane
authors: G
authors: Euba
authors: Ricard
authors: R
authors: Verdaguer
authors: Fe
authors: F
authors: Tubau
authors: Javier
authors: J
authors: Cabo
authors: Carmen
authors: C
authors: Cabellos
authors: Francesc
authors: F
authors: Gudiol
authors: Javier
authors: J
authors: Ariza
mesh_terms: D000081:Acetamides / Q000627:therapeutic use*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D015169:Colony Count, Microbial; D024881:Drug Resistance, Bacterial; D004359:Drug Therapy, Combination; D005547:Foreign Bodies / Q000150:complications*; D000069349:Linezolid; D008297:Male; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability; D023303:Oxazolidinones / Q000627:therapeutic use*; D051381:Rats; D012293:Rifampin / Q000627:therapeutic use*; D018461:Soft Tissue Infections / Q000188:drug therapy* / Q000382:microbiology; D013203:Staphylococcal Infections / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D000069349:Linezolid; D012293:Rifampin