Antimicrobial Resistance and Biofilms Underlying Catheter-Related Bloodstream Coinfection by Enterobacter cloacae Complex and Candida parapsilosis

Abstract

Biofilm-associated infections are a public health concern especially in the context of healthcare-associated infections such as catheter-related bloodstream infections (CRBSIs). We evaluated the biofilm formation and antimicrobials resistance (AMR) of Enterobacter cloacae complex and Candida parapsilosis co-isolated from a CRBSI patient. Antimicrobial susceptibility of central venous catheters (CVCs) and hemoculture (HC) isolates was evaluated, including whole genome sequencing (WGS) resistome analysis and evaluation of gene expression to obtain insight into their AMR determinants. Crystal violet assay was used to assess dual biofilm biomass and microscopy was used to elucidate a microorganism’s distribution within biofilms assembled on different materials. Bacteria were multidrug-resistant including resistance to colistin and beta-lactams, likely linked to the mcr-9-like phosphoethanolamine transferase and to an ACT family cephalosporin-hydrolyzing class C beta-lactamase, respectively. The R398I and Y132F mutations in the ERG11 gene and its differential expression might account for C. parapsilosis resistance to fluconazole. The phenotype of dual biofilms assembled on glass, polystyrene and polyurethane depends on the material and how biofilms were initiated by one or both pathogens. Biofilms assembled on polyurethane were denser and richer in the extracellular polymeric matrix, and microorganisms were differently distributed on the inner/outer surface of the CVC.

Invasive Candida parapsilosis Bloodstream Infections in Children: The Antifungal Susceptibility, Clinical Characteristics and Impacts on Outcomes

“…The proportion of C. parapsilosis candidemia ranged between 14% and 34% of all Candida BSIs in both children and adults [ 11 , 12 , 13 , 14 , 18 , 26 ]. In recent years, non- albicans candidemia has outnumbered C. albicans candidemia, especially among critically ill patients, neonates with long-term CVC placement, those on TPN and those with antifungal prophylaxis [ 1 , 4 , 5 , 26 , 27 ].…”

“…C. parapsilosis is known to exhibit a strong biofilm forming capability on the surfaces of a CVC or other artificial devices, which accounts for its higher prevalence among neonates with low birth weight, ICU patients with long term use of CVC and those who are immunocompromised [ 11 , 12 , 13 , 14 , 34 ]. Therefore, the most effective control strategy to avoid persistent candidemia is early catheter removal [ 7 , 16 , 34 ], although sometimes it is not applicable.…”

“…Most studies found that patients with C. parapsilosis BSIs have comparable outcomes when compared with those with C. albicans BSIs or other non- parapsilosis candidemia [ 14 , 28 , 29 , 34 ], while others even found that the mortality rate was lower than that of C. albicans BSIs [ 37 , 38 ]. Overall, the different therapeutic strategies, study cohorts and different underlying demographics may account for the controversial results [ 11 , 12 , 13 , 14 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ]. The candidemia-attributable mortality rate in our cohort was relatively higher than that of previous studies [ 4 , 5 , 30 , 31 , 32 , 33 , 34 ], especially in extremely preterm neonates.…”

“…Candida parapsilosis is an important non- albicans Candida species and accounts for 18–46% of all Candida BSIs [ 11 , 12 ]. Candida parapsilosis is well known to develop biofilm on the surfaces of artificial devices, the hands and the vulvovaginal mucosa, which results in the high likelihood of indwelling catheter-associated BSIs caused by C. parapsilosis [ 11 , 12 , 13 , 14 ]. Extremely preterm neonates need long-term central venous catheter (CVC) placement, and implanted Port-A-Cath catheters are common in pediatric hematology/oncology patients, which puts them at a higher risk of having C. parapsilosis -associated BSIs [ 15 , 16 ].…”

Comparative Analysis of Two Candida parapsilosis Isolates Originating from the Same Patient Harbouring the Y132F and R398I Mutations in the ERG11 Gene

“…The resistance to fluconazole (FLC), the most widely used antifungal drug among azole derivatives, can be caused by (i) up-regulation of the ERG11 gene, (ii) up-regulation of the efflux transporter genes CDR1 and MDR1 , and (iii) point mutations in the ERG11 and ERG3 genes [ 12 , 13 , 14 , 15 , 16 , 17 , 18 ].…”