Invasive fungal infections amongst patients with acute‐on‐chronic liver failure at high risk for fungal infections

Abstract

Aims To study the prevalence, risk factors, role of serum biomarkers for diagnosis and impact of invasive fungal infections (IFIs) in patients with acute‐on‐chronic liver failure (ACLF). Methods An analysis of IFI in patients with ACLF (EASL criteria) was conducted retrospectively. The diagnosis of IFI in clinically suspected patients was based on EORTC/MSG criteria. The demographical, clinical, laboratory details and outcomes were analysed. Results Out of 264 patients with ACLF, 54 (20.4%) patients with suspicion of IFI were evaluated and IFI was diagnosed in 39 (14.7%). Invasive candidiasis was documented in 25 (64.1%) and invasive aspergillosis in 14 (35.8%). The most common source of infection was respiratory (n = 13) followed by renal (n = 7) and spontaneous fungal peritonitis (n = 6). On univariate analysis, diabetes mellitus, hemodialysis, prior antibiotic use, cerebral and respiratory organ failures, Chronic Liver Failure Consortium (CLIF‐OF and CLIF‐C ACLF) scores were predictors for development of IFI (P < 0.05). On multivariate analysis, hemodialysis and prior antibiotics use predicted the development of IFI (P < 0.05). Non‐survivors were more likely to have IFI (P = 0.029), high CLIF‐OF and CLIF‐C ACLF scores (P < 0.001; for both) and higher 1,3‐β D Glucan (BDG) levels (P = 0.009). The sensitivity, specificity, and AUROC of BDG (80 pg/mL) and Galactomannan index (GMI [0.5]) for diagnosing IFI were 97.4%, 60%, 0.770% and 43.6%, 100%, 0.745 respectively. Conclusions Invasive fungal infections constitutes an important cause of mortality in ACLF patients. BDG and GMI can be useful markers to guide antifungal therapy in patients at high risk for IFI.

Identifying factors affecting the pharmacokinetics of voriconazole in patients with liver dysfunction: A population pharmacokinetic approach

“…Patients with liver dysfunction are at increased risk of fungal infections, resulting in increased morbidity and significant mortality . Risk factors such as impaired immune system, multiple organ failure, long‐term use of broad‐spectrum antibiotics, invasive procedures and multiple hospitalizations are associated with fungal infections in patients with liver dysfunction …”

Pharmacokinetics Modeling and Simulation of Voriconazole Dosing and Safety in Patients with Liver Cirrhosis

“…We reviewed the laboratory information system from May 2014 to May 2018 at two tertiary hospitals. Patients who treated by voriconazole and therapeutic drug monitoring (TDM) had been performed during antifungal therapy were identified and then screened by applying inclusion criteria of (1) presence of liver cirrhosis, including CP-A, CP-B and CP-C patients and (2) age >18 years, and exclusion criteria of (1) the initial TDM after dose adjustment and (2) missing the values of key covariates. This study was approved by all participating institutional review boards.…”

“…Finally, we retrospectively collected 120 cirrhotic patients into the analysis. Among these patients, four initial dosage regimens were administered: (1) patients received the recommended dosage regimen based on package insert or a fixed dose of 200 mg twice daily orally or intravenously; (2) patients received the loading dose of 200 mg twice daily on day 1, following by 100 mg twice daily orally or intravenously or a fixed dose of 100 mg twice daily orally or intravenously; (3) patients received loading dose of 200 mg twice daily on day 1, following by 200 mg daily orally or intravenously or a fixed dose of 200 mg daily orally or intravenously; (4) patients received a fixed dose of 100 mg daily orally or intravenously.…”

“…Liver cirrhosis is a late stage of hepatic fibrosis and is a leading cause of death worldwide (1). Due to the immunocompromised state of cirrhotic patients and their requirement for use of steroids and broad-spectrum antimicrobial agents, as well as invasive procedures, invasive fungal disease (IFD) constitutes an important cause of morbidity in patients with liver cirrhosis (2-4). Voriconazole is a triazole antifungal agent with activity against a broad spectrum of clinically significant fungal pathogens, and it is used to treat and prevent IFD in clinical practice (5, 6).…”

“…The present study aimed (1) to describe the pharmacokinetics characteristics and safety of voriconazole, and identify the factors influencing pharmacokinetics variability; and (2) to establish the optimal intravenous and oral voriconazole doses with an appropriate efficacy and safety profile in patients with liver cirrhosis.…”