Caspofungin and Polymyxin B Reduce the Cell Viability and Total Biomass of Mixed Biofilms of Carbapenem-Resistant Pseudomonas aeruginosa and Candida spp.

Abstract

Pseudomonas aeruginosa and Candida spp. are biofilm-forming pathogens commonly found colonizing medical devices, being mainly associated with pneumonia and bloodstream infections. The coinfection by these pathogens presents higher mortality rates when compared to those caused by a single microbial species. This study aimed to evaluate the antibiofilm activity of echinocandins and polymyxin B (PMB) against polymicrobial biofilms of carbapenem-resistant (CR) Pseudomonas aeruginosa and Candida spp. (C. albicans, C. parapsilosis, C. tropicalis, and C. glabrata). In addition, we tested the antimicrobial effect on their planktonic and monomicrobial biofilm counterparties. Interestingly, beyond inhibition of planktonic [minimum inhibitory concentration (MIC) = 0.5 μg/ml] and biofilm [minimum biofilm inhibitory concentration (MBIC)50 ≤ 2–8 μg/ml] growth of P. aeruginosa, PMB was also effective against planktonic cells of C. tropicalis (MIC = 2 μg/ml), and polymicrobial biofilms of CR P. aeruginosa with C. tropicalis (MBIC50 ≤ 2 μg/ml), C. parapsilosis (MBIC50 = 4–16 μg/ml), C. glabrata (MBIC50 = 8–16 μg/ml), or C. albicans (MBIC50 = 8–64 μg/ml). On the other hand, while micafungin (MFG) showed highest inhibitory activity against planktonic (MIC ≤ 0.008–0.5 μg/ml) and biofilm (MBIC50 ≤ 2–16 μg/ml) growth of Candida spp.; caspofungin (CAS) displays inhibitory activity against planktonic cells (MIC = 0.03–0.25 μg/ml) and monomicrobial biofilms (MBIC50 ≤ 2–64 μg/ml) of Candida spp., and notably on planktonic and monomicrobial biofilms of CR P. aeruginosa (MIC or MBIC50 ≥ 64 μg/ml). Particularly, for mixed biofilms, while CAS reduced significantly viable cell counts of CR P. aeruginosa and Candida spp. at ≥32 and ≥ 2 μg/ml, respectively; PMB was effective in reducing viable cells of CR P. aeruginosa at ≥2 μg/ml and Candida spp. at ≥8 μg/ml. Similar reduction of viable cells was observed for CAS (32–64 μg/ml) combined with PMB (2 μg/ml). These findings highlight the potential of PMB and CAS for the treatment of polymicrobial infections caused by Candida spp. and critical priority CR P. aeruginosa.

Caspofungin Inhibits Mixed Biofilms of Candida albicans and Methicillin-Resistant Staphylococcus aureus and Displays Effectiveness in Coinfected Galleria mellonella Larvae

“…The antibacterial profile of S. aureus strains was determined by diffusion disk test, and the broth microdilution assay was performed to determine the MIC of the antimicrobials against planktonic cells of S. aureus and C. albicans ( 32 , 33 ). The minimum microbicidal concentration was also determined, and it is defined as the lowest concentration that killed 99.9% of microbial cells of the initial inoculum ( 16 ).…”

“…After antimicrobial treatments, the total biomass of bacterial, fungal, and mixed biofilms was quantified using violet crystal staining ( 16 ). The optical density (O.D.)…”

“…× 100)/untreated cells O.D.] for determination of the lowest concentrations that inhibit 50% and 90% of biofilm formation (BIC 50 and BIC 90 , respectively) ( 16 ).…”

Microbial Interkingdom Biofilms and the Quest for Novel Therapeutic Strategies

“…However, voriconazole, a second-generation antifungal drug, was found to inhibit the interaction between C. albicans and Actinomyces viscosus , a Gram-positive bacterium associated with root caries, by inhibiting the ergosterol biosynthesis pathway [ 71 ]. In addition, the antifungal and antibacterial agents caspofungin and polymyxin B were able to reduce both the cell viability and total biomass of mixed biofilms consisting of P. aeruginosa with C. albicans , C. parapsilosis , C. tropicalis or C. glabrata [ 72 ]. The treatment of polymicrobial infections by using a combination of antibacterial and antifungal drugs is generally associated with a poor efficacy; however, combination therapy can also result in desirable outcomes.…”

Potent antifungal agents and use of nanocarriers to improve delivery to the infected site: A systematic review

“…Studies reveal that caspofungin functions as an effective non‐antibiotics, xenobiotic antibacterial [186]. In association with polymyxin B, caspofungin displayed in vitro activity against several polymicrobial biofilms [187]. Total biomass and cell viability reduction have been reported in Candida spp., Pseudomonas aeruginosa , and carbapenem‐resistant strains.…”