The study tested a human antimicrobial peptide called LL‑37 and some common antifungal drugs against Candida fungi that form tough biofilms. LL‑37 didn’t work against the fungal biofilms, but a drug combo of fluconazole and caspofungin showed a helpful synergistic effect in about 60% of the samples. Other drug combos were mostly ineffective or even counter‑productive.

<b>Introduction.</b> <i>Candida</i> species can form biofilms on tissues and medical devices, making them less susceptible to antifungal agents.<b>Hypothesis/Gap Statement.</b> Antifungal combination may be an effective strategy to fight against <i>Candida</i> biofilm.<b>Aim.</b> In this study, we investigated the <i>in vitro</i> activity of fluconazole, caspofungin and amphotericin B, alone and in combination, against 17 clinical <i>Candida tropicalis</i> and 6 <i>Candida parapsilosis</i> isolates with high biofilm formation. We also tested LL-37 and lysozyme for anti-biofilm activity against a selected <i>C. tropicalis</i> isolate.<b>Methodology.</b> <i>Candida</i> biofilms were prepared using the 96-well plate-based method. The minimum biofilm eradication concentrations were determined for single and combined antifungal drugs. The activity of LL-37 and lysozyme was determined by visual reading for planktonic cells and using the XTT assay for biofilms.<b>Results.</b> Under biofilm conditions, fluconazole plus caspofungin showed synergistic effects against 60.9% (14 of 23) of the tested isolates, including 70.6% of <i>C. tropicalis</i> [fractional inhibitory concentration index (FICI), 0.26-1.03] and 33.3% of <i>C. parapsilosis</i> (FICI, 0.04-2.03) isolates. Using this combination, no antagonism was observed. Amphotericin B plus caspofungin showed no effects against 78.3% (18 of 23) of the tested isolates. Amphotericin B plus fluconazole showed no effects against 65.2% (15 of 23) of the tested isolates and may have led to antagonism against 2 <i>C</i>. <i>tropicalis</i> and 2 <i>C. parapsilosis</i> isolates. LL-37 and lysozyme had no effect on biofilms of the selected <i>C. tropicalis</i> isolate.<b>Conclusions.</b> We found that fluconazole plus caspofungin led to a synergistic effect against <i>C. tropicalis</i> and <i>C. parapsilosis</i> biofilms. The efficacy of the antifungal combination therapies of the proposed schemes against biofilm-associated <i>Candida</i> infections requires careful and constant evaluation.