Efficacy of linezolid alone and in combination with rifampin in staphylococcal experimental foreign-body infection.
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.
Murillo
Oscar
O
Laboratory of Experimental Infection, Infectious Diseases Service, IDIBELL, Hospital Universitari de Bellvitge, Feixa Llarga s/n, 08907 Barcelona, Spain. 32186omr@comb.es
Domenech
Alejandro
A
Euba
Gorane
G
Verdaguer
Ricard
R
Tubau
Fe
F
Cabo
Javier
J
Cabellos
Carmen
C
Gudiol
Francesc
F
Ariza
Javier
J
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
D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D000069349:Linezolid; D012293:Rifampin