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Antimicrobial Agents and Chemotherapy, October 2008, p. 3681-3686, Vol. 52, No. 10
0066-4804/08/$08.00+0     doi:10.1128/AAC.00458-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Antagonistic Effect of Rifampin on the Efficacy of High-Dose Levofloxacin in Staphylococcal Experimental Foreign-Body Infection{triangledown}

O. Murillo,1* M. E. Pachón,1 G. Euba,1 R. Verdaguer,2 F. Tubau,2 C. Cabellos,1 J. Cabo,3 F. Gudiol,1 and J. Ariza1

Laboratory of Experimental Infection, Infectious Diseases Service,1 Microbiology Department,2 Orthopaedic Surgery Department, IDIBELL, Hospital Universitari de Bellvitge, Feixa Llarga s/n, Barcelona 08907, Spain3

Received 7 April 2008/ Returned for modification 22 June 2008/ Accepted 24 July 2008

Since levofloxacin at high doses was more active than levofloxacin at conventional doses and was the best therapy alone in a rat model of staphylococcal foreign-body infection, in this study we tested how these differences affect the activities of their respective combinations with rifampin in vitro and in vivo. In vitro studies were performed in the log and stationary phases. By using this model, rifampin at 25 mg/kg of body weight/12 h, levofloxacin at 100 mg/kg/day, levofloxacin at 100 mg/kg/day plus rifampin, levofloxacin at 50 mg/kg/day, levofloxacin at 50 mg/kg/day plus rifampin, or a control treatment was administered for 7 days; and therapy with for levofloxacin at 100 mg/kg/day alone and rifampin alone was prolonged to 14 days. We screened for the appearance of resistant strains. Killing curves in the log phase showed a clear antagonism with levofloxacin at concentrations ≥2x MIC and rifampin and tended to occur in the stationary phase. At the end of 7 days of therapy, levofloxacin at 100 mg/kg/day was the best treatment and decreased the bacterial counts from tissue cage fluid (P < 0.05 compared with the results for groups except those receiving rifampin alone). At the end of 14 days of therapy with levofloxacin at 100 mg/kg/day, levofloxacin at 100 mg/kg/day plus rifampin, and the control treatment, the bacterial counts on the coverslips were 2.24 (P < 0.05 compared with the results with the combined therapy), 3.36, and 5.4 log CFU/ml, respectively. No rifampin or levofloxacin resistance was detected in any group except that receiving rifampin alone. In conclusion, high-dose levofloxacin was the best treatment and no resistant strains appeared; the addition of rifampin showed an antagonistic effect. The efficacy of the rifampin-levofloxacin combination is not significantly improved by the dosage of levofloxacin.

* Corresponding author. Mailing address: Infectious Diseases Service, Hospital Universitari de Bellvitge, Feixa Llarga s/n, 08907 L'Hospitalet de Llobregat, Barcelona 08907, Spain. Phone: 34.93.260.76.25. Fax: 34.93.260.76.37. E-mail: 32186omr{at}comb.es

{triangledown} Published ahead of print on 1 August 2008.

Antimicrobial Agents and Chemotherapy, October 2008, p. 3681-3686, Vol. 52, No. 10
0066-4804/08/$08.00+0     doi:10.1128/AAC.00458-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Murillo, O., Pachon, M. E., Euba, G., Verdaguer, R., Carreras, M., Cabellos, C., Cabo, J., Gudiol, F., Ariza, J. (2009). Intracellular antimicrobial activity appearing as a relevant factor in antibiotic efficacy against an experimental foreign-body infection caused by Staphylococcus aureus. J Antimicrob Chemother 64: 1062-1066 [Abstract] [Full Text]  
  • Murillo, O., Garrigos, C., Pachon, M. E., Euba, G., Verdaguer, R., Cabellos, C., Cabo, J., Gudiol, F., Ariza, J. (2009). Efficacy of High Doses of Daptomycin versus Alternative Therapies against Experimental Foreign-Body Infection by Methicillin-Resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 53: 4252-4257 [Abstract] [Full Text]  
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