Journal
JOURNAL OF INFECTION
Volume 57, Issue 3, Pages 229-235Publisher
W B SAUNDERS CO LTD
DOI: 10.1016/j.jinf.2008.07.003
Keywords
device infection; linezolid; rifampin; S. aureus; animal models
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Funding
- Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III [FIS 04/005]
- Spanish Network for the Research in Infectious Diseases [REIPI C03/14, REIPI RD06/0008]
- Pfizer (Spain)
- REI PI
- Universidad de Barcelona
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Objectives: 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 atone, but in contrast to rifampin, it increased over time revealing the impact of protection against rifampin resistance and the benefits of rifampin activity. (c) 2008 The British Infection Society. Published by Elsevier Ltd. All rights reserved.
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