1. J Antimicrob Chemother. 2018 Oct 1;73(10):2806-2814. doi: 10.1093/jac/dky246.

Anidulafungin increases the antibacterial activity of tigecycline in
polymicrobial Candida albicans/Staphylococcus aureus biofilms on
intraperitoneally implanted foreign bodies.

Rogiers O(1)(2)(3)(4), Holtappels M(1)(2), Siala W(5)(6), Lamkanfi M(3)(4), Van
Bambeke F(5), Lagrou K(7), Van Dijck P(1)(2), Kucharíková S(1)(2).

Author information: 
(1)VIB-KU Leuven Center for Microbiology, Kasteelpark Arenberg 31, Leuven,
(2)Laboratory of Molecular Cell Biology, Institute of Botany and Microbiology, KU
Leuven, Kasteelpark Arenberg 31, Leuven, Belgium.
(3)Center for Inflammation Research, VIB, Technologiepark 927, Zwijnaarde,
(4)Department of Internal Medicine, Ghent University, Technologiepark 927,
Zwijnaarde, Belgium.
(5)Pharmacologie cellulaire et moléculaire, Louvain Drug Research Institute
Université catholique de Louvain, Avenue Mounier 73/B1.73.05, 1200
Woluwe-Saint-Lambert, Brussels, Belgium.
(6)OneLIFE S.A., Avenue Albert Einstein, 15, Louvain-la-Neuve, Belgium.
(7)KU Leuven, Department of Microbiology and Immunology Laboratory of Clinical
Bacteriology and Mycology, UZ Herestraat 49, Leuven, Belgium.

Objectives: We aimed to establish a novel murine intra-abdominal foreign body
infection model to study the activity of anidulafungin and tigecycline against
dual species Candida albicans/Staphylococcus aureus biofilms.
Methods: In vitro and in vivo single and dual species biofilms were developed
inside serum-coated triple-lumen catheters placed in 24-well plates or implanted 
intraperitoneally in BALB/c mice. The effect of tigecycline and anidulafungin
alone and in combination was tested using clinically relevant concentrations.
Scanning electron microscopy was used to visualize the mature biofilm structure
developed intraperitoneally. Flow cytometry was used to determine the
immunological response upon infection. Immunoblot analysis allowed us to
determine the effect of anidulafungin on poly-β-(1,6)-N-acetylglucosamine in in
vitro-grown S. aureus biofilms.
Results: We determined the MIC, MBC and in vitro susceptibility profile for
anidulafungin and tigecycline against C. albicans and S. aureus in mixed and
single species biofilms. We demonstrated that anidulafungin acts synergistically 
when combined with tigecycline against in vivo intra-abdominal biofilms.
Moreover, we reveal that anidulafungin reduces the abundance of S. aureus
poly-β-(1,6)-N-acetylglucosamine. The influx of neutrophils is much increased
when infected with mixed biofilms compared with single species biofilms.
Conclusions: Currently, treatment of intra-abdominal infections, in particular
polymicrobial catheter-associated peritonitis, is ineffective. To the best of our
knowledge, this is the first study that provides insight into new possible
options for treatment of C. albicans/S. aureus biofilms present in the abdominal 

DOI: 10.1093/jac/dky246 
PMID: 30010876