Risk Factors for Invasive Candida Infection in Critically Ill Patients: A Systematic Review and Meta-analysis

Abstract

Background: Current guidelines recommend empirical antifungal therapy in patients with sepsis with high risk of invasive Candida infection. However, many different risk factors have been derived from multiple studies. These risk factors lack specificity, and broad application would render most ICU patients eligible for empirical antifungal therapy.

Research question: What risk factors for invasive Candida infection can be identified by a systematic review and meta-analysis?

Study design and methods: We searched PubMed, Web of Science, ScienceDirect, Biomed Central, and Cochrane and extracted the raw and adjusted OR for each risk factor associated with invasive Candida infection. We calculated pooled ORs for risk factors present in more than one study.

Results: We included 34 studies in our meta-analysis resulting in the assessment of 29 possible risk factors. Risk factors for invasive Candida infection included demographic factors, comorbid conditions, and medical interventions. Although demographic factors do not play a role for the development of invasive Candida infection, comorbid conditions (eg, HIV, Candida colonization) and medical interventions have a significant impact. The risk factors associated with the highest risk for invasive Candida infection were broad-spectrum antibiotics (OR, 5.6; 95% CI, 3.6-8.8), blood transfusion (OR, 4.9; 95% CI, 1.5-16.3), Candida colonization (OR, 4.7; 95% CI, 1.6-14.3), central venous catheter (OR, 4.7; 95% CI, 2.7-8.1), and total parenteral nutrition (OR, 4.6; 95% CI, 3.3-6.3). However, dependence between the various risk factors is probably high.

Interpretation: Our systematic review and meta-analysis identified patient- and treatment-related factors that were associated with the risk for the development of invasive Candida infection in the ICU. Most of the factors identified were either related to medical interventions during intensive care or to comorbid conditions.

Keywords: Candida; candidiasis, invasive; candidiasis, invasive/epidemiology; critical care; hospital infections; risk factors.

Graphical abstract

Figure 1

Article flow through different stages of the review. BMC = Biomed Central.

Figure 2

Pooled ORs with 95% CIs for each risk factor. ICU length of stay as an extreme outlier was omitted and is presented in the Supplement (e-Fig 7). Meta-analyses for individual risk factors together with heterogeneity and sequential analysis are presented in the Supplement (e-Figs 9-85). APACHE = Acute Physiology And Chronic Health Evaluation.

Figure 3

Pooled ORs with 95% CIs for each risk factor from multivariable analyses. Meta-analyses for individual risk factors from multivariable analyses are presented in the Supplement (e-Figs 92-131).