Previous Article | Next Article 
Antimicrobial Agents and Chemotherapy, August 2009, p. 3205-3210, Vol. 53, No. 8
0066-4804/09/$08.00+0 doi:10.1128/AAC.01628-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Effects of Azithromycin in Combination with Vancomycin, Daptomycin, Fosfomycin, Tigecycline, and Ceftriaxone on Staphylococcus epidermidis Biofilms 
Elisabeth Presterl,1*
Stefan Hajdu,2
Andrea M. Lassnigg,3
Alexander M. Hirschl,4
Johannes Holinka,5 and
Wolfgang Graninger1
Department of Medicine I, Division of Infectious Diseases,1 Department of Trauma and Emergency Surgery,2 Department of Anaesthesia and General Intensive Care Medicine, Division of Cardiothoracic Anaesthesia,3 Department of Clinical Microbiology, Clinical Institute of Hygiene and Medical Microbiology,4 Department of Orthopedic Surgery, Medical University of Vienna, Vienna, Austria5
Received 11 December 2008/ Returned for modification 13 March 2009/ Accepted 12 May 2009
Staphylococcal biofilms on surgical implants are the underlying cause of a lack of response to antimicrobial treatment. We investigated the effects of vancomycin (VAN), daptomycin (DAP), fosfomycin (FOS), tigecycline (TGC), and ceftriaxone (CRX), alone and in combination with azithromycin (AZI), on established biofilms of Staphylococcus epidermidis. Biofilms were studied using the static microtiter plate model with established S. epidermidis biofilms, with an initial inoculum of 106/ml in 96-well polystyrene flat-bottom microtiter plates. Biofilms were inoculated with VAN, DAP, FOS, TGC, or CRX at two concentrations, alone or in combination with AZI (2, 512, or 1,024 mg/liter). To assess the reduction in biomass, the optical density ratio (ODr), calculated as (optical density [OD] of the treated biofilm)/(OD of the untreated biofilm, taken as 1), was used. For antibacterial efficacy, the viable bacterial count was used. Reductions in the biofilm ODr were observed for VAN (15 and 40 mg/liter) and FOS (200 mg/liter) only (ODr [mean ± standard deviation] for VAN at 15 and 40 mg/liter, 0.77 ± 0.32 and 0.8 ± 0.35, respectively; ODr for FOS at 200 mg/liter, 0.78 ± 0.26; P < 0.05), but not for DAP (2 and 5 mg/liter), TGC (0.2 and 2 mg/liter), or CRX (600 and 2,400 mg/liter). The addition of AZI had no further effect on the ODr, but a significant reduction of bacterial growth was achieved with high doses of AZI plus TGC or AZI plus CRX (a 3-log count reduction for AZI at 1,024 mg/liter plus CRX at 600 mg/liter and for AZI at 512 or 1,024 mg/liter plus CRX at 2,400 mg/liter; a 2-log count reduction for AZI at 512 or 1,024 mg/liter plus TGC at 2 mg/liter [P < 0.05]). No significant reduction in bacterial growth was observed for FOS (50 and 200 mg/liter), DAP (2 and 5 mg/liter), or TGC (0.2 mg/liter) in combination with AZI. None of the antibiotics at either concentration reduced the bacterial count of the biofilms when used alone. Thus, the use of a combination of AZI plus TGC, FOS, or CRX at high concentrations has little effect on biofilm density but significantly reduces bacterial growth.
* Corresponding author. Mailing address: Department of Medicine I, Division of Infectious Diseases, Medical University of Vienna, Allgemeines Krankenhaus, Waehringer Guertel 18-20, 1090 Vienna, Austria. Phone: 43 1 40400 5161. Fax: 43 1 40400 5162. E-mail: elisabeth.presterl{at}meduniwien.ac.at
Published ahead of print on 18 May 2009.
Antimicrobial Agents and Chemotherapy, August 2009, p. 3205-3210, Vol. 53, No. 8
0066-4804/09/$08.00+0 doi:10.1128/AAC.01628-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Copyright © 2009 by the American Society for Microbiology. For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»