Presepsin and (1,3)-β-D-Glucan as a Tool for Predicting Candida Sepsis and Monitoring the Effectiveness of Treatment in Critically Ill Patients

Background: To improve the accuracy in invasive candidiasis diagnostics, a new biomarker panel has been developed and validated on a 165-patient cohort of critically ill adults.Methods: The serum levels of inflammatory biomarkers, C-reactive protein, presepsin (PSEP), procalcitonin (PCT), and of panfungal (1,3)-β-D-glucan (BDG), were correlated with culture-confirmed candidemia or bacteremia in 58 or 107 patients, respectively. The diagnostic effect of the host and pathogen biomarkers was expressed using sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV).Results: For invasive candidiasis, the best performing BDG exhibited 96.6% sensitivity, 97.2% specificity, 94.9% PPV and 98.1% NPV at a cut-off of 200 pg/mL (P ≤ 0.001). PSEP exhibited 100% sensitivity and 100% NPV at a cut-off of 700 pg/mL. Furthermore, PSEP was more accurate for 28-day mortality prediction (AUC = 0.74) than PCT (AUC = 0.31; PCT cut-off 0.5 ng/mL). Finally, PSEP showed a significant serum decrease as early as 14 days after echinocandin therapy initiation (P = 0.0012).Conclusions: At concentrations of BDG > 200 pg/mL and PSEP > 700 pg/mL, the probability of invasive candidiasis in critically ill adults is close to 100% defining a borderline between non-invasive superficial Candida colonization and invasive candidiasis.Trial registration: The study was approved by the University Hospital Ostrava Ethics Committee for Multicenter Clinical Trials (no. 448/2018) and registered in ClinicalTrials.gov (ID: NCT03584594), date of registration June 28,2018.

Candida Contamination in Kidney and Liver Organ Preservation Solution: Does It Matter?

Introduction: Fungal infections remain a major challenge affecting outcomes after kidney (KT) and liver transplantation (LT). Methods: In this retrospective single center study, the incidence of Candida contamination in renal and hepatic graft preservation solution (PS) was evaluated. In addition, Candida associated infections in recipients and related complications were analyzed. Results: Overall, the PS of 1248 hepatic and 1273 renal grafts were evaluated. The incidence of fungal contamination in the PS of hepatic and renal grafts was 1.2% and 0.86%, respectively. Additionally, the hepatic PS of one patient who underwent a combined liver–kidney transplant had Candida contamination. Candida albicans was the most common organism (70.4%) and 65.4% of the patients received antifungal treatment. Candida-associated complications in the recipients was 19%. Complications in LT patients included Candida peritonitis and Candida sepsis. Two KT recipients with contaminated PS developed a mycotic aneurysm at the anastomotic site resulting in severe bleeding. The 1-year mortality in patients with PS contamination for LT and KT recipients was 33% and 18%, respectively. Although the incidence of fungal contamination of PS was low, contaminated PS was associated with a high mortality. Conclusion: The results of the study suggest that PS should be evaluated for fungal growth.

1181. Spectrum and Risk Factors of Early Onset versus Late Onset Neonatal Candidemia from Pakistan

Background Candidemia leads to high morbidity and mortality especially in premature neonates from developing countries. We studied the spectrum and risk factors of candidemia in neonates with early onset disease (EOD) or late onset disease (LOD) which has not been extensively investigated in Pakistan. We also determined whether vaginal delivery is associated with candidemia in neonates with EOD. Methods A case control study was conducted at the Aga Khan University, Karachi, Pakistan. Cases (neonates with EOD) and controls (neonates with LOD) were identified from laboratory database for year 2014-2018, and for 2019 data was collected prospectively from laboratory during routine reporting of cultures at which time clinical information was gathered from the patient’s physician/guardian. Study was conducted after obtaining exemption from the ethical review committee. Results A total of 669 neonates with IC were identified, out of these 162 neonates had EOD while 507 had LOD. Chart 1 shows the year wise distribution and frequency of different C. species. Mean age of neonates with EOD and LOD was 1.7 and 12.2 days respectively. LOD in neonates was more likely to occur in male patients (COR 2.5, 95% CI 0.6-9.9) was and associated with use of carbapenems (COR 5.1, 95% CI 1.4-17.8). However, LOD had no correlation with non-C. albicans Candida sepsis (COR 0.6, 95% CI 0.1-6.3) as causative agent. EOD was more likely in patients delivered via vaginal delivery (COR 11.3, 95% CI 2.6-48.5). Chart 1: Year wise distribution of Candida species in neonates with candidemia from 2014-2019 Conclusion The trends for isolation of C. species in neonates showed a trend with C. tropicalis being more common C. species during the recent years. With the infrequent isolation of C. glabrata and C. krusei among other Candida species in this study, fluconazole may be considered a good empiric choice for neonates with suspected fungal sepsis. Disclosures All Authors: No reported disclosures

Pharmacological serum concentrations of epinephrine and norepinephrine do not affect growth rate, morphogenesis, stress tolerance, and virulence of Candida albicans

Vasopressors are frequently given in hemodynamically unstable patients with severe Candida sepsis. While catecholamines can aggravate sepsis-induced immune dysfunction and modulate bacterial virulence traits, their impact on fungal pathogenicity is poorly understood. Using IncuCyte time-lapse microscopy and a fruit fly candidiasis model, we studied growth rates, morphogenesis, stress tolerance, and virulence of C. albicans cocultured with epinephrine and norepinephrine. We found that pharmacologically attainable catecholamine serum concentrations caused minimal changes to in vitro growth kinetics, filamentation, and fungal resistance to thermal or oxidative stress. Similarly, exposure of C. albicans to catecholamines did not alter the survival of infected flies.