Quantification of 1,3-ß-d-glucan by Wako ß-glucan assay for rapid exclusion of invasive fungal infections in critical patients: A diagnostic test accuracy study.

OBJECTIVES: Rapid and reliable exclusion of invasive fungal infections (IFI) by markers able to avoid unnecessary empirical antifungal treatment is still a critical unmet clinical need. We investigated the diagnostic performance of a newly available ß-d-Glucan (BDG) quantification assay, focusing on the optimisation of the BDG cut-off values for IFI exclusion. METHODS: BDG results by Wako ß-glucan assay (lower limit of detection [LLOD] = 2.16 pg/mL, positivity ≥ 11 pg/mL) on two consecutive serum samples were retrospectively analysed in 170 patients, admitted to haematological wards (N = 42), intensive care units (ICUs; N = 80), or other wards (N = 48), exhibiting clinical signs and/or symptoms suspected for IFI. Only patients with proven IFI (EORTC/MSG criteria) were considered as true positives in the assessment of BDG sensitivity, specificity and predictive values. RESULTS: Patients were diagnosed with no IFI (69.4%), proven IFI (25.3%) or probable IFI (5.3%). Two consecutive BDG values < LLOD performed within a median of 1 (interquartile range: 1-3) day were able to exclude a proven IFI with 100% sensitivity and negative predictive value (primary study goal). Test's specificity improved by using two distinct positivity and negativity cut-offs (7.7 pg/mL and LLOD, respectively), but remained suboptimal in ICU patients (50%), as compared to haematological or other patients (93% and 90%, respectively). CONCLUSIONS: The classification of Wako's results as negative when < LLOD, and positive when > 7.7 pg/mL, could be a promising diagnostic approach to confidently rule out an IFI in both ICU and non-ICU patients. The poor specificity in the ICU setting remains a concern, due to the difficulty to interpret positive results in this fragile population.

Intensive multidisciplinary management in critical care patients affected by severe necrotizing soft tissue infections: a cooperative method to improve the efficacy of treatment.

To illustrate the effectiveness of our intensive multidisciplinary management (IMM) in the treatment of severely ill patients with necrotizing soft tissue infections (NSTIs). A retrospective observational study was conducted in a general ICU. Thirty-two consecutive patients undergoing IMM were carefully compared with 30 consecutive patients receiving a standard management (SM). IMM combined intensive care management, early surgical debridement followed by daily inspection of surgical wounds, close microbiological surveillance, and targeted high-dose antibiotics. IMM was associated with the better decrease of daily SOFA score (p = 0.04). Also, IMM caused + 12% increase in the overall number of surgical procedures (p = 0.022) and a higher number of tissue biopsies/per day (median 0.63 versus 0.32; p = 0.025), leading to a more targeted antimicrobial changes (89.6% vs 51.6%; p < 0.00001). High-dose daptomycin (75% vs 36.7%; p = 0.002) and extended/continuous infusion of beta-lactams (75% vs 43.3%; p = 0.011) were more frequently utilized. A specific efficiency score correlated with the decrease of SOFA score (efficacy) in IMM patients only (p = 0.027). Finally, IMM was associated with a significant lower ICU mortality rate (15.6% vs 40%; p = 0.032). IMM was more effective than SM as it allowed the earlier control of infection and the faster reduction of multiple organ-dysfunction.

Septic shock due to NSTI caused by Actinomyces Turicensis: the role of clinical pharmacology. Case report and review of the literature.

Critical septic patients affected by necrotizing soft tissue infections (NSTI) require an early, aggressive and multidisciplinary treatment. Pharmacokinetic alterations in antibiotic therapy are peculiar in these infections. Clinical pharmacology represents a first step in this setting. We report a case of septic shock due to NSTI in which clinical pharmacology is taken into account.