Abstract

Candida-related infections are nowadays a serious Public Health Problem emerging multidrug-resistant strains. Candida biofilm also leads bloodstream infections to invasive systemic infections. The present meta-analysis aimed to analyze Candida biofilm rate, type, and antifungal resistance among hospitalized patients between 1995 and 2020. Web of Science, Scopus, PubMed, and Google Scholar databases were searched for English papers using the following medical subject heading terms (MESH): "invasive candidiasis"; "bloodstream infections"; "biofilm formation"; "biofilm-related infections"; "mortality"; and "prevalence". The major inclusion criteria included reporting the rate of biofilm formation and the prevalence of biofilm-related to Candida species, including observational studies (more exactly, cohort, retrospective, and case-control studies). Furthermore, data regarding the mortality rate, the geographical location of the study set, and the use of anti-fungal agents in clinical isolates were also extracted from the studies. Independent extraction of articles by 2 authors using predefined data fields, including study quality indicators. A total of 31 studies from publicly available databases met our inclusion criteria. The biofilm formation in the data set varied greatly from 16 to 100% in blood samples. Most of the studies belonged to Europe (17/31) and Asia (9/31). Forest plot showed a pooled rate of biofilm formation of 80.0% (CI: 67-90), with high heterogeneity (Q = 2567.45, I2 = 98.83, τ2 = 0.150) in random effects model (p < 0.001). The funnel plot and Egger's linear regression test failed to find publication bias (p = 0.896). The mortality rate in Candida-related bloodstream infections was 37.9% of which 70.0% were from biofilm-associated infections. Furthermore, Candida isolates were also characterized in low, intermediate, or high biofilm formers through their level of biofilm mass (crystal violet staining or XTT assays) after a 24h growth. When comparing between countries, statistical differences were obtained (p = 0.0074), showing the lower and higher biofilm prevalence values in Italy and Spain, respectively. The prevalence of low, intermediate, and high biofilms were 36.2, 18.9, and 35.0% (p < 0.0001), respectively. C. tropicalis was the prevalent species in high biofilm formation (67.5%) showing statistically significant differences when compared to other Candida species, except for C. krusei and C. glabrata. Finally, the rates of antifungal resistance to fluconazole, voriconazole, and caspofungin related to biofilm were 70.5, 67.9 and 72.8% (p < 0.001), respectively. Early detection of biofilms and a better characterization of Candida spp. bloodstream infections should be considered, which eventually will help preserve public health resources and ultimately diminish mortality among patients.

Highlights

  • Invasive candidiasis is a systemic mycosis caused by Candida species, being commonly described as an opportunistic infection

  • Web of Science, Scopus, PubMed, and Google Scholar databases were searched for English papers using the following medical subject heading terms (MESH): “invasive candidiasis”; “bloodstream infections”; “biofilm formation”; “biofilm-related infections”; “mortality”; and “prevalence”

  • All available and relevant data were extracted of each study, more exactly, biofilm rate, biofilm type, underlying disease of the patients, Candida species reported, and antifungal resistance

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Summary

Introduction

Invasive candidiasis is a systemic mycosis caused by Candida species, being commonly described as an opportunistic infection. People that received broad-spectrum antibiotics or with drug habits are susceptible to invasive candidiasis, as well as premature newborns [1]. All these plausible scenarios lead this systemic infection to be nowadays the 4th leading nosocomial infection in the United States, demonstrating mortality of up to 40% [2]. In the Asia-Pacific region, Hsueh and colleagues reported a candidemia incidence in ICUs of 5to 10-fold higher than in the entire hospital and a mortality rate of patients between 35% and 60% [4]. In Latin America, Nucci and colleagues realized a laboratory-based survey between November 2008 and October 2010 among 20 tertiary care hospitals in seven Latin American countries, reporting an overall incidence of 1.18 cases per 1,000 in general admissions [5]. The mortality associated with invasive candidiasis is similar or even higher in other worldwide countries [6]

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