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Antimicrobial Agents and Chemotherapy, July 2007, p. 2540-2545, Vol. 51, No. 7
0066-4804/07/$08.00+0     doi:10.1128/AAC.00120-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Efficacy of a Novel Rifamycin Derivative, ABI-0043, against Staphylococcus aureus in an Experimental Model of Foreign-Body Infection{triangledown}

Andrej Trampuz,1,2 Christopher K. Murphy,4 David M. Rothstein,4 Andreas F. Widmer,1 Regine Landmann,1 and Werner Zimmerli3*

Division of Infectious Diseases and Hospital Epidemiology, University Hospital, Basel, Switzerland,1 Infectious Diseases Research Laboratory, Department of Research, University Hospital, Basel, Switzerland,2 Basel University Medical Clinic, Kantonsspital, Liestal, Switzerland,3 ActivBiotics, Inc., Lexington, Massachusetts4

Received 26 January 2007/ Returned for modification 14 March 2007/ Accepted 2 May 2007

We compared the efficacy of a novel rifamycin derivative, ABI-0043, with that of rifampin, alone and in combination with levofloxacin, against methicillin-susceptible Staphylococcus aureus ATCC 29213 in a guinea pig tissue-cage infection model. The MIC, logarithmic-growth-phase minimal bactericidal concentration, and stationary-growth-phase minimal bactericidal concentration of ABI-0043 were 0.001, 0.008, and 0.25 µg/ml, respectively; the corresponding concentrations of rifampin were 0.016, 0.8, and 3.6 µg/ml, respectively. After a single intraperitoneal dose of 12.5 mg/kg of body weight, the peak concentration in cage fluid was 1.13 µg/ml of ABI-0043 and 0.98 µg/ml of rifampin. Five days after completion of treatment, levofloxacin administered alone (5 mg/kg/12 h) resulted in bacterial counts in cage fluid that were similar to those for untreated controls (>8.0 log10 CFU/ml), whereas rifampin and ABI-0043 administered alone (12.5 mg/kg/12 h) decreased the mean titers of bacteria ± standard deviations to 1.43 ± 0.28 log10 and 1.57 ± 0.53 log10 CFU/ml, respectively, in cage fluid. In combination with levofloxacin, both rifamycins cleared bacteria from the cage fluid. The cure rates of cage-associated infections with rifampin and ABI-0043 administered alone were 46% and 58%, respectively, and increased to 88% and 92% in combination with levofloxacin. Emergence of rifamycin resistance was observed in 42% of cages after ABI-0043 therapy and in 38% of cages after rifampin therapy; no emergence of resistance occurred with combination treatment with levofloxacin. In conclusion, ABI-0043 had cure rates comparable to that of rifampin. ABI-0043 in combination with a quinolone has the potential for treatment of implant-associated infections caused by susceptible strains of S. aureus, potentially without drug-drug interactions.

* Corresponding author. Mailing address: Medical University Clinic, Kantonsspital, CH-4410 Liestal, Switzerland. Phone: 41 61 925 21 80. Fax: 41 61 925 28 04. E-mail: werner.zimmerli{at}unibas.ch

{triangledown} Published ahead of print on 14 May 2007.

Antimicrobial Agents and Chemotherapy, July 2007, p. 2540-2545, Vol. 51, No. 7
0066-4804/07/$08.00+0     doi:10.1128/AAC.00120-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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  • John, A.-K., Baldoni, D., Haschke, M., Rentsch, K., Schaerli, P., Zimmerli, W., Trampuz, A. (2009). Efficacy of Daptomycin in Implant-Associated Infection Due to Methicillin-Resistant Staphylococcus aureus: Importance of Combination with Rifampin. Antimicrob. Agents Chemother. 53: 2719-2724 [Abstract] [Full Text]  
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