Short intravenous amphotericin B followed by oral posaconazole using a simple, stratified treatment approach for diabetes or COVID-19-associated rhino-orbito-cerebral mucormycosis: a prospective cohort study.

OBJECTIVES: To evaluate the efficacy and safety of short-course intravenous amphotericin B followed by sustained release posaconazole tablets for diabetes or COVID-19-associated rhino-orbito-cerebral mucormycosis. METHODS: This prospective, pragmatic study included adults with diabetes or COVID-19-associated rhino-orbito-cerebral mucormycosis. Patients received short (7-14 days) or long (15-28 days) intravenous antifungal therapy (short intravenous antifungal treatment [SHIFT] or long intravenous antifungal treatment [LIFT], respectively) depending on the presence or absence of brain involvement. All patients received step-down posaconazole tablets, debridement, and glycemic control. The primary outcome was the treatment success at week 14, which was determined by assessing survival and the absence of disease progression through clinical evaluation and nasal endoscopy. Log-binomial regression analysis (risk ratio and 95% CI) was performed to assess factors associated with the primary outcome. RESULTS: Intravenous therapy was administered to 251 participants: SHIFT, 205 (median duration, 13 days); LIFT, 46 (median duration, 22 days). Treatment success at 3 months was 88% (217/248; 95% CI, 83-91%): SHIFT group, 93% (189/203; 89-96%); LIFT group, 62% (28/45; 47-76%). All-cause mortality was 12% (30/251): SHIFT group, 6% (13/205); LIFT group, 37% (17/46). Age (aRR [95% CI]: 1.02 [1.00-1.05]; p 0.027), diabetic ketoacidosis at presentation (2.32 [1.20-4.46]; p 0·012), glycated haemoglobin A1c (1.19 [1.03-1.39]; p 0.019), stroke (3.93 [1.94-7.95]; p 0·0001), and brain involvement (5.67 [3.05-10.54]; p < 0.0001) were independently associated with unsuccessful outcomes. DISCUSSION: Short intravenous amphotericin B with step-down posaconazole tablets should be further studied as primary treatment option for diabetes or COVID-19-associated mucormycosis in randomized controlled trials.

Outcomes of transcutaneous retrobulbar Amphotericin B (TRAMB) as an adjuvant therapy for rhino-orbital-cerebral mucormycosis (ROCM) following COVID-19.

PURPOSE: To assess the outcomes of transcutaneous retrobulbar Amphotericin B (TRAMB) for rhino-orbital-cerebral-mucormycosis (ROCM) post-COVID-19, as an adjuvant to standard systemic antifungal therapy. METHODS: In this prospective cohort study involving ROCM patients with clinical/radiological orbital involvement, 44 eyes with ROCM stage ≥ 3B received TRAMB for 7 consecutive days with liposomal Amphotericin-B (3.5 mg/ml) with a minimum clinical and radiological follow-up of 3 months. All patients received standard systemic antifungal therapy also as per institutional protocol. Data pertaining to demography, systemic status, clinical involvement, imaging, surgical/medical management were also recorded. Potential eyes for exenteration were excluded. Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 12 Given name: [Mahendra Kumar ] Last name [Garg]. Also, kindly confirm the details in the metadata are correct.All author names are presented accurately. Details in the metadata are correct. Thank you. RESULTS: Forty-four eyes of 42 patients were included, out of which 30 had diabetes mellitus & 22 had received steroid/oxygen treatment during COVID-19 infection. Forty eyes showed improvement or stable disease on follow-up on radiology. Four eyes which showed progression of the disease in orbit were reaugmented with TRAMB. No patient required exenteration. Subconjunctival haemorrhage occurred in six eyes and temporary blurring of vision in four eyes after TRAMB which resolved spontaneously. CONCLUSION: TRAMB, as an adjuvant to standard systemic antifungal therapy, is associated with a significant reduction or stabilisation of orbital involvement. TRAMB should be considered as an adjuvant therapy for ROCM to reduce disease progression as well as to preserve globe or sight. It has a promising role in preventing potential orbital exenterations.

Hyperglycemia and steroid use increase the risk of rhino-orbito-cerebral mucormycosis regardless of COVID-19 hospitalization: Case-control study, India.

BACKGROUND: In the ongoing COVID-19 pandemic, an increased incidence of ROCM was noted in India among those infected with COVID. We determined risk factors for rhino-orbito-cerebral mucormycosis (ROCM) post Coronavirus disease 2019 (COVID-19) among those never and ever hospitalized for COVID-19 separately through a multicentric, hospital-based, unmatched case-control study across India. METHODS: We defined cases and controls as those with and without post-COVID ROCM, respectively. We compared their socio-demographics, co-morbidities, steroid use, glycaemic status, and practices. We calculated crude and adjusted odds ratio (AOR) with 95% confidence intervals (CI) through logistic regression. The covariates with a p-value for crude OR of less than 0·20 were considered for the regression model. RESULTS: Among hospitalised, we recruited 267 cases and 256 controls and 116 cases and 231 controls among never hospitalised. Risk factors (AOR; 95% CI) for post-COVID ROCM among the hospitalised were age 45-59 years (2·1; 1·4 to 3·1), having diabetes mellitus (4·9; 3·4 to 7·1), elevated plasma glucose (6·4; 2·4 to 17·2), steroid use (3·2; 2 to 5·2) and frequent nasal washing (4·8; 1·4 to 17). Among those never hospitalised, age ≥ 60 years (6·6; 3·3 to 13·3), having diabetes mellitus (6·7; 3·8 to 11·6), elevated plasma glucose (13·7; 2·2 to 84), steroid use (9·8; 5·8 to 16·6), and cloth facemask use (2·6; 1·5 to 4·5) were associated with increased risk of post-COVID ROCM. CONCLUSIONS: Hyperglycemia, irrespective of having diabetes mellitus and steroid use, was associated with an increased risk of ROCM independent of COVID-19 hospitalisation. Rational steroid usage and glucose monitoring may reduce the risk of post-COVID.