This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Baldoni, D.
Right arrow Articles by Trampuz, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Baldoni, D.
Right arrow Articles by Trampuz, A.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, March 2009, p. 1142-1148, Vol. 53, No. 3
0066-4804/09/$08.00+0     doi:10.1128/AAC.00775-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Linezolid Alone or Combined with Rifampin against Methicillin-Resistant Staphylococcus aureus in Experimental Foreign-Body Infection{triangledown}

Daniela Baldoni,1 Manuel Haschke,2 Zarko Rajacic,1 Werner Zimmerli,3 and Andrej Trampuz1,4*

Infectious Diseases Research Laboratory, Department of Biomedicine, University Hospital Basel, Basel, Switzerland,1 Division of Clinical Pharmacology and Toxicology, University Hospital Basel, Basel, Switzerland,2 Basel University Medical Clinic, Kantonsspital, Liestal, Switzerland,3 Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland4

Received 13 June 2008/ Returned for modification 29 September 2008/ Accepted 3 December 2008

We investigated the activity of linezolid, alone and in combination with rifampin (rifampicin), against a methicillin-resistant Staphylococcus aureus (MRSA) strain in vitro and in a guinea pig model of foreign-body infection. The MIC, minimal bactericidal concentration (MBC) in logarithmic phase, and MBC in stationary growth phase were 2.5, >20, and >20 µg/ml, respectively, for linezolid; 0.01, 0.08, and 2.5 µg/ml, respectively, for rifampin; and 0.16, 0.63, >20 µg/ml, respectively, for levofloxacin. In time-kill studies, bacterial regrowth and the development of rifampin resistance were observed after 24 h with rifampin alone at 1x or 4x the MIC and were prevented by the addition of linezolid. After the administration of single intraperitoneal doses of 25, 50, and 75 mg/kg of body weight, linezolid peak concentrations of 6.8, 12.7, and 18.1 µg/ml, respectively, were achieved in sterile cage fluid at {approx}3 h. The linezolid concentration remained above the MIC of the test organism for 12 h with all doses. Antimicrobial treatments of animals with cage implant infections were given twice daily for 4 days. Linezolid alone at 25, 50, and 75 mg/kg reduced the planktonic bacteria in cage fluid during treatment by 1.2 to 1.7 log10 CFU/ml; only linezolid at 75 mg/kg prevented bacterial regrowth 5 days after the end of treatment. Linezolid used in combination with rifampin (12.5 mg/kg) was more effective than linezolid used as monotherapy, reducing the planktonic bacteria by ≥3 log10 CFU (P < 0.05). Efficacy in the eradication of cage-associated infection was achieved only when linezolid was combined with rifampin, with cure rates being between 50% and 60%, whereas the levofloxacin-rifampin combination demonstrated the highest cure rate (91%) against the strain tested. The linezolid-rifampin combination is a treatment option for implant-associated infections caused by quinolone-resistant MRSA.

* Corresponding author. Mailing address: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Petersgraben 4, Basel CH-4031, Switzerland. Phone: 41 61 328 60 59. Fax: 41 61 265 31 98. E-mail: atrampuz{at}uhbs.ch

{triangledown} Published ahead of print on 15 December 2008.

Antimicrobial Agents and Chemotherapy, March 2009, p. 1142-1148, Vol. 53, No. 3
0066-4804/09/$08.00+0     doi:10.1128/AAC.00775-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • 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]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»