# In Vitro Activity of Antifungals in Combination With Meropenem or Daptomycin Against Dual Candida albicans–Bacterial Biofilms

## TL;DR

This study examines how combining antifungals with antibiotics affects mixed fungal-bacterial biofilms, finding that some combinations are more effective than others.

## Contribution

The study introduces new insights into the synergistic and antagonistic effects of antifungal-antibiotic combinations against dual-species biofilms.

## Key findings

- Meropenem combined with antifungals showed additive effects against Candida albicans–Pseudomonas aeruginosa biofilms.
- Daptomycin combined with anidulafungin or voriconazole had antagonistic effects against Candida albicans–Staphylococcus epidermidis biofilms.
- Dual biofilms had lower biomass compared to single-species Candida biofilms.

## Abstract

The objective was to investigate the effectiveness of anidulafungin (ANI), voriconazole (VOR), and amphotericin (AMB) combined with meropenem against dual biofilms of
Candida albicans
and
Pseudomonas aeruginosa
, as well as with daptomycin against dual biofilms of
C. albicans
–
Staphylococcus epidermidis
. MIC values of antifungals were determined by CLSI M27‐A3 method. The effectiveness of antifungals in combination with antibiotics against biofilms was tested by Checkerboard analysis. Biofilm quantifications were tested by the XTT method. The biofilm images were captured using SEM. The quantity of C. albicans–S. epidermidis and C. albicans–P. aeruginosa was lower (83.2% and 56.3%, respectively) than that of single Candida biofilm. The SMIC50 values for single C. albicans biofilms were 32‐fold higher for AMB and VOR, and 128‐fold higher for ANI when compared to dual Candida biofilms. Daptomycin combined with ANI or VOR showed antagonistic effects against C. albicans–S. epidermidis biofilms, while meropenem in combination with all antifungals was found to be additive against C. albicans–P. aeruginosa biofilms. Antifungals and their combinations resulted in a decrease in blastospore and bacterial density, as observed through SEM. In
C. albicans
–
P. aeruginosa
biofilms, using meropenem alongside antifungals would be beneficial due to its additive effect. Daptomycin combined with ANI or VOR may not be effective in C. albicans–S. epidermidis coinfections.