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.
Highlights
Biofilms are commonly defined as complex systems, comprising consortia of bacteria and/or fungi adhered to biotic or abiotic surfaces and lodged in a three-dimensional extracellular polymeric matrix (EPM) constituted mainly by secreted polysaccharides and proteins (Bandara et al, 2010; Deveau et al, 2018; Ibrahim et al, 2018)
We evaluated the activity of echinocandins and polymyxin B (PMB), alone or in combination, against mixed biofilms of Candida spp. and CR P. aeruginosa
Antimicrobial susceptibility of planktonic bacterial mode of growth revealed that three P. aeruginosa strains (151, 141, and 48-1997A) exhibited a MDR profile (Magiorakos et al, 2012; Supplementary Table S1)
Summary
Biofilms are commonly defined as complex systems, comprising consortia of bacteria and/or fungi adhered to biotic or abiotic surfaces and lodged in a three-dimensional extracellular polymeric matrix (EPM) constituted mainly by secreted polysaccharides and proteins (Bandara et al, 2010; Deveau et al, 2018; Ibrahim et al, 2018). In this regard, most microorganisms are organized into biofilms, instead of living as planktonic cells, since biofilms offer protection against environmental, chemical, and mechanical stresses (Boudarel et al, 2018). Pseudomonas aeruginosa and Candida spp. are among the most commonly found biofilmforming pathogens and their biofilms are considered a risk factor for bacteremia/candidaemia, contributing to increased mortality rate (Ramage et al, 2005; Tumbarello et al, 2007; Vitkauskienė et al, 2010; Li et al, 2018; Lee et al, 2020).
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