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Antimicrobial Agents and Chemotherapy, May 2007, p. 1656-1660, Vol. 51, No. 5
0066-4804/07/$08.00+0     doi:10.1128/AAC.00350-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Comparative Activities of Daptomycin, Linezolid, and Tigecycline against Catheter-Related Methicillin-Resistant Staphylococcus Bacteremic Isolates Embedded in Biofilm{triangledown}

Issam Raad,1 Hend Hanna,1 Ying Jiang,1 Tanya Dvorak,1 Ruth Reitzel,1 Gassan Chaiban,1 Robert Sherertz,2 and Ray Hachem1*

Department of Infectious Diseases, Infection Control and Employee Health, University of Texas M. D. Anderson Cancer Center, Houston, Texas,1 Division of Infectious Diseases, Bowman Gray School of Medicine, Winston-Salem, North Carolina2

Received 22 March 2006/ Returned for modification 31 July 2006/ Accepted 28 February 2007

In the setting of catheter-related bloodstream infections, intraluminal antibiotic lock therapy could be useful for the salvage of vascular catheters. In this in vitro study, we investigated the efficacies of the newer antibiotics daptomycin, linezolid, and tigecycline, in comparison with those of vancomycin, minocycline, and rifampin, against methicillin-resistant Staphylococcus aureus (MRSA) embedded in biofilm. We also assessed the emergence of MRSA strains resistant to these antibiotics, alone or in combination with rifampin, after 4-hour daily use for catheter lock therapy. Minocycline, daptomycin, and tigecycline were more efficacious in inhibiting MRSA in biofilm than linezolid, vancomycin, and the negative control (P < 0.001) after the first day of exposure to these antibiotics, with minocycline being the most active, followed by daptomycin and then tigecycline, and with vancomycin and linezolid lacking activity, similar to the negative control. After 3 days of 4-hour daily exposures, daptomycin was the fastest in eradicating MRSA from biofilm, followed by minocycline and tigecycline, which were faster than linezolid, rifampin, and vancomycin (P < 0.001). When rifampin was used alone, it was the least effective in eradicating MRSA from biofilm after 5 days of 4-hour daily exposures, as it was associated with the emergence of rifampin-resistant MRSA. However, when rifampin was used in combination with other antibiotics, the combination was significantly effective in eliminating MRSA colonization in biofilm more rapidly than each of the antibiotics alone. In summary, daptomycin, minocycline, and tigecycline should be considered further for antibiotic lock therapy, and rifampin should be considered for enhanced antistaphylococcal activity but not as a single agent.

* Corresponding author. Mailing address: The University of Texas M. D. Anderson Cancer Center, Department of Infectious Diseases, Infection Control and Employee Health, Unit 402, 1515 Holcombe Blvd., Houston, TX 77030. Phone: (713) 792-4389. Fax: (713) 792-8233. E-mail: rhachem{at}mdanderson.org

{triangledown} Published ahead of print on 12 March 2007.

Antimicrobial Agents and Chemotherapy, May 2007, p. 1656-1660, Vol. 51, No. 5
0066-4804/07/$08.00+0     doi:10.1128/AAC.00350-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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