Wafi Siala
Université catholique de Louvain
Belgium
Title: The antifungal caspofungin (CAS) increases moxifloxacin(MXF) activity against Staphylococcus aureusbiofilmsin vitro or in a mice subcutaneous model
Biography
Biography: Wafi Siala
Abstract
Objective: Staphylococcal biofilms are poorly responsive to antibiotics. In a preliminary screening of combinations of moxifloxacin (MXF) with drugs selected based on their amphiphilic character, we observed that the antifungal caspofungin (CAS)was synergistic. Our aim was now to test this combination on biofilms preformed on catheters in vitro and in vivo. Methods: Biofilms were grown inside 1cm polyurethane catheters at 37°C for 24h (initial inoculum: 5.106 cells/ml).In vitro, 7 clinical isolates and the bioluminescent Xen36 strain were used. Biofilms grown on catheters were placed in 24-well plates, incubated with MXF(10mg/L); CAS(80mg/L) or MXF/CAS for 48 h. Catheters were washed, sonicated, and CFUs/catheter were counted.Invivo,5 catheters infected with Xen36 biofilm were implanted subcutaneously in the back of mice. Animals were treated intravenously with MXF(40 mg/kg twice daily), CAS(4 mg/kg/day) or with MXF/CAS combination during 7 days. CFUs/catheter were counted.
Results: In vitro, MXF or CAS alone caused no significant decrease in CFU/catheterfor all tested strains. When combined with CAS, MXF markedly decreased CFU/catheter in all strains, but to different extents (ranging from 2 to 8.2 log CFU decrease). Invivodrugs alone were ineffective as well. The MXF/CAS combination caused a 2.1 log CFU reduction for Xen36 (vs. 3.3 log CFU reduction against the same strain in vitro). Conclusion: CombiningMXF with CASproves highly synergistic in vitro and in vivo against staphylococcal biofilms. This will open perspective to use CAS as adjuvant for the treatment of S.aureus biofilms Log CFU/catheter Strains (origin) In vitro model Untreated MXF CAS MXF-CAS 2011/S027 (cellulitis and bacteremia) 9.08±0.98 8.82±0.24 9.14±0.17 1.43±0.36a 2003/1083 (chirurgical wound) 11.7±0.32 11.5±0.14 12.3±0.21 3.41±0.09a 2005/104 (skin) 6.87±0.32 6.51±0.44 6.99±0.22 3.01±0.32a 2009/S028 (nasal carriage) 6.88±0.22 6.45±0.12 6.78±0.09 2.70±0.15a 2009/S025 (ear) 8.12±0.44 8.16±0.99 8.47±0.45 3.55±0.14a 2005/179 (skin) 6.73±0.65 6.55±0.11 6.77±0.12 2.69±0.06a 2003/651 (respiratory infection) 5.44±0.82 4.19±0.15 5.47±0.08 3.57±0.07 a XEN36 (bioluminescent derived from S.aureus ATCC 49525) 6.26±0.22 6.23±0.32 6.35±0.14 2.91±0.65a In vivo model XEN36 7.31±0.45 6.17±0.13 7.35±0.42 5.15±0.15 b statistical analysis :comparison between MXF treated group and MXF-CAS treated group for each strain ain vitro data; P value ≤0.01 for all strains bin vivo data; P value =0.028