Polymerase Chain Reaction Versus Blood Culture to Detect Candida Species in High-Risk Patients with Suspected Invasive Candidiasis: The MICAFEM Study

Abstract

Introduction: We evaluated the diagnostic reliability of serum polymerase chain reaction (PCR) versus blood culture, abdominal fluid or both (composite measure) in patients receiving empirical antifungal treatment for suspected invasive candidiasis.

Methods: This observational, prospective, non-interventional, multicentre study in Spain enrolled 176 critically ill patients admitted to the intensive care unit. Separate blood samples for culture and serum PCR were taken before the start of antifungal therapy. Patient assessment was performed according to each site's usual clinical practice. The primary end point was concordance between serum PCR and blood culture. Secondary end points were concordance between serum PCR and a positive abdominal fluid sample or the composite measure. Quality indices included sensitivity, specificity, positive/negative predictive values (PPV/NPV) and kappa indices.

Results: Among 175 evaluable patients, rates of Candida detection were similar for serum PCR (n = 16/175, 9.1%) versus blood culture (n = 14/175, 8.0%). Quality indices for serum PCR relative to blood culture were: sensitivity 21.4%; specificity 91.9%; PPV 18.8%; NPV 93.1%; kappa index 0.125. Thirty-two abdominal fluid samples were positive. Quality indices for serum PCR versus abdominal fluid were: sensitivity 31.3%; specificity 83.0%; PPV 15.6%; NPV 92.3%; kappa index 0.100. Quality indices for serum PCR versus the composite measure were: sensitivity 15.8%; specificity 92.7%; PPV 37.5%; NPV 79.9%; kappa index 0.107.

Conclusion: The sensitivity of serum PCR for Candida detection was low and the rate of concordance was low between serum PCR and the other diagnostic techniques used to identify Candida infections. Hospital-based diagnostic tests need optimising to improve outcomes in patients with suspected invasive candidiasis.

Funding: Astellas Pharma Inc.

Keywords: Abdominal fluid; Blood cultures; Candida; Candida diagnosis; Empirical antifungal treatment; Intensive care unit; Invasive candidiasis; PCR.

Fig. 1

Microbiological analyses. *Patients meeting the following criteria were considered at high risk: those with a Candida score ≥ 3 (based on severe sepsis, 2 points; surgery, 1 point; parenteral nutrition, 1 point; Candida at multiple sites of infection, 1 point); patients with sepsis and ≥ 3 risk factors for invasive candidiasis (from severe acute pancreatitis, extra-renal depuration, broad-spectrum antibiotic treatment for > 7 days, major abdominal surgery, ICU stay of > 15 days, parenteral nutrition, central venous catheterisation, Candida at multiple sites of infection, candiduria and Acute Physiology and Chronic Health Evaluation score > 15); or sepsis in immunocompromised patients with neutropenia, haematological disease, solid organ or bone marrow transplantation, treatment with immunosuppressive drugs, chemotherapy or monoclonal antibodies; or human immunodeficiency virus infection. **Blood sample times were as follows: at baseline (before initiating antifungal treatment) and at follow-up (blood cultures were taken according to the site’s usual clinical practice). Serum PCR was performed at the same time as the blood culture sample. ICU intensive care unit, MALDI-TOF matrix-assisted laser desorption/ionisation time of flight, PCR polymerase chain reaction

Fig. 2

Flow chart of the study population