Utility of Itraconazole in Combination with Liposomal Amphotericin B in Rhizopus oryzae Associated Mucormycosis-An Exploratory Study.

BACKGROUND: During the COVID-19 pandemic-associated mucor epidemic, acute antifungal drug shortage necessitated the exploration of other antifungals based on culture sensitivity. Itraconazole is a cheap, safe, and effective antifungal in sensitive cases. METHODOLOGY: We enrolled itraconazole-sensitive COVID-19-associated mucormycosis during the mucormycosis pandemic. After the intensive phase course of liposomal amphotericin B, Itraconazole was offered in susceptible cases during the maintenance phase along with standard of care. These patients were clinically and radiologically followed for 6 months. RESULTS: We enrolled 14 patients (Male: Female-11:3) of Rhino-orbito-cerebral mucormycosis (ROCM) which included 12 diabetics. All patients had facial swelling, orbital swelling, visual impairment, and headache. MRI showed involvement of bilateral sinus (10/14), orbital extension (13/14), cavernous sinus (5/14), cerebral part of the internal carotid artery (3/14), and brain infarcts (4/14). All 14 patients showed sensitivity to Itraconazole with 12 having minimum inhibitory concentration (MIC) ≤ 1 µg/ml and 2 having MIC ≤ 2 µg/ml. Follow-up at 6 months showed clinical improvement in the majority (11/14) and radiological improvement in six out of seven scanned patients. CONCLUSION: Our study shows the potential therapeutic role of oral Itraconazole in ROCM.

Severe COVID-19-associated hyperinflammatory syndrome versus classic hemophagocytic lymphohistiocytosis: similarities, differences, and the way forward.

The hyperinflammatory immune response in severe COVID-19 infection shares features with secondary hemophagocytic lymphohistiocytosis (sHLH) in the form of fever, cytopenia, elevated inflammatory markers, and high mortality. There are contrasting opinions regarding utility of HLH 2004 or HScore in the diagnosis of severe COVID-19-related hyperinflammatory syndrome (COVID-HIS). This was a retrospective study of 47 patients of severe COVID-19 infection, suspected to have COVID-HIS and 22 patients of sHLH to other illnesses, to evaluate the diagnostic utility and limitations of HLH 2004 and/or HScore in context to COVID-HIS and to also evaluate the utility of Temple criteria for predicting severity and outcome in COVID-HIS. Clinical findings, hematological, and biochemical parameters along with the predictor of mortality were compared between two groups. Only 6.4% (3/47) of cases fulfilled ≥5/8 HLH 2004 criteria and only 40.52% (19/47) of patients showed HScore >169 in COVID-HIS group. 65.9% (31/47) satisfied the Temple criteria in COVID-HIS as compared with 40.9% (9/22) in the non-COVID group (p = 0.04). Serum ferritin (p = 0.02), lactate dehydrogenase (p = 0.02), direct bilirubin (p = 0.02), and C-reactive protein (p = 0.03) were associated with mortality in COVID-HIS. Both HScore and HLH-2004 criteria perform poorly for identifying COVID-HIS. Presence of bone marrow hemophagocytosis may help to identify about one-third of COVID-HIS missed by the Temple Criteria.

A preliminary experience of plasma exchange in liver failure.

INTRODUCTION: Plasma exchange (PLEX) is one of the experimental modalities of treatment for liver failure. We report our experience of PLEX in patients with acute-(ALF) or acute-on-chronic (ACLF) liver failure. METHODS: Hemodynamically stable adult patients with ALF or ACLF, encephalopathy, model for end-stage liver disease (MELD) score ≥ 15, and clinical worsening/no improvement after 72-h of inpatient care were included. PLEX cycles repeated every 48 h, each of 2.5-4.0 h duration with 1-1.5 times of estimated plasma volume, were given. PLEX cycle was repeated till either of the end-points were achieved (i) MELD < 20 for 48 h or reaches below the baseline, whichever is lower, (ii) completed three PLEX cycles, (iii) hemodynamic instability, (iv) or outcome achieved. Outcome of interest was categorized as favorable (discharged in stable condition) or unfavorable (death or discharge in moribund condition). Data are expressed as median (interquartile range). RESULTS: Sixteen patients (age 35 [27-48] years; male 8; ALF 5, ACLF 11; MELD 33 [27-37]; CLIF-SOFA 10 [8.5-12]) were included. Participants received 2 (1-3) cycles of PLEX during 13 (11-25) days of hospitalization. Overall, serum bilirubin, INR, creatinine, MELD, and CLIF-SOFA scores were significantly improved after PLEX. Five patients (5/16, 31%) had complete resolution of HE. Eight patients (50%) had a favorable outcome. Those with favorable outcome had significant improvement in serum bilirubin, INR, and CLIF-SOFA scores as compared to those with unfavorable outcome. CONCLUSION: PLEX may be effective in patients with ALF or ACLF. More data are needed to establish its role in the management of liver failure.