Invasive pulmonary aspergillosis (IPA) is an important cause of morbidity/mortality in critically ill patients with endstage liver disease. Therefore, aim of this study is to predict the prevalence and outcome of IPA in critically ill patients with underlying liver cirrhosis and evaluation of the necessity Glactomannan (GM) screening in serum and bronchoalveolar lavage (BAL) in this cohort. In total 12 out of 84 patients (14%) had probable IPA. The mean optical density index (ODI) bronchoalveolar lavage (BAL) GM index was 3.6 ± 1.5 (Range: 1.7–5.7). An overall sensitivity of 90% (95% CI 86–96%) and specificity of 85% (95% CI 81–88%) was found for the BAL GM in IPA. Acute Physiology And Chronic Health Evaluation (APACHE II), sequential organ failure assessment (SOFA) as well the model of endstage liver disease (MELD) score were significantly higher in the probable IPA group as compared to the No IPA group (26 versus 21, p < 0.001 and 14 versus 10, p < 0.044). Length of intensive care unit (ICU) stay was significantly longer in probable IPA patients (16 versus 10 days, p < 0.027) and mortality rate was significantly higher in probable IPA patients (100% versus 65%, p < 0.001) as compared to No IPA patients. APACHE II and MELD score were independently associated with higher mortality rate using multivariate logistic regression (p = 0.025 and p = 0.034). In conclusion, IPA has a relevant impact on outcome. Screening for IPA is indicated, easy to perform and a necessity to improve outcome.
Isavuconazole plasma concentrations were measured before and after sustained low-efficiency dialysis (SLED) treatment in 22 critically ill adult patients with probable invasive aspergillosis and underlying hematological malignancies. Isavuconazole levels were significantly lower after SLED treatment (5.73 versus 3.36 μg/ml; P < 0.001). However, even after SLED treatment, isavuconazole concentrations exceeded the in vivo MICs for several relevant Aspergillus species.
Fungal peritonitis is a life-threatening condition which is not only difficult to diagnose, but also to treat. Following recent guidelines, echinocandins and azoles are the recommended antimycotics for the management of intra-abdominal Candida spp. infections, with a favor for echinocandins in critically ill patients. However, the new extended spectrum triazole isavuconazole also has a broad spectrum against Candida spp. Data on its target-site penetration are sparse. Therefore, we assessed isavuconazole concentrations and penetration ratios in ascites fluid of critically ill patients. Obtaining of Isavuconazole plasma and ascites fluid levels as well penetration ratios using paracentesis in critically ill patients. Isavuconazole concentrations were quantified in human plasma and ascites by a liquid chromatography/tandem mass spectrometry (LC-MS/MS) method. Isavuconazole concentrations in plasma and ascites fluid were measured in sixteen critically ill patients. Isavuconazol levels in ascites fluid (1.06 µg/mL) were lower than plasma levels (3.08 µg/mL). Penetration ratio was 36%. In two out of sixteen patients, Candida spp., in detail C. glabrata and C. tropicalis, could be isolated. Cmax/MIC Ratio in plasma of 560 for C. glabrata and 2166 for C. tropicalis could be observed. Following our results, isavuconazole penetrates into ascites. Successful treatment in Candida spp. peritonitis depends on pathogen susceptibility.
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