Amphotericin B in the management of COVID-19 associated mucormycosis

Background: Amphotericin B is considered the drug of choice for primary treatment of mucormycosis. During second wave of COVID-19 pandemic there was severe scarcity of liposomal amphotericin B. This study aims to determine role of various formulations of amphotericin and their side effects when used for the treatment of COVID-19 associated mucormycosis. Methods: A retrospective study was conducted between May 2021 and December 2021 at a tertiary care centre. 380 patients with post-COVID rhino-orbito-cerebral mucromycosis (ROCM) were included in the study. Liposomal amphotericin B, conventional amphotericin deoxycholate, lipid complex amphotericin B was used in the treatment. Patients were observed for side effects like fever, chills, rigors, hypokalemia, renal function derangements, thrombophlebitis and respiratory difficulties. Results: Majority of patients received liposomal amphotericin B (331) and 31 patients received conventional amphotericin deoxycholate and 5 patients were given lipid complex amphotericin B injections. The most commonly encountered side effects were of the mild type constituting chills (98% with liposomal and 100% with amphotericin deoxycholate), and fever (94% with liposomal and 74% with amphotericin deoxycholate). Conclusions: Our study highlights the role of various formulations of amphotericin B in the treatment of COVID-19 mucormycosis

COVID-19 associated mucormycosis and COVID-19 vaccination status

Background: Mucormycosis is lethal angio invasive fungal infection affecting mainly the immunocompromised individuals. During second wave of COVID-19 pandemic there was rise in number of rhino-orbito-cerebral (ROCM) cases in both COVID-19 affected patients and patients who recovered from COVID-19 infection. This study was conducted to know the anatomical site and extent of involvement in head and neck region in both COVID-19 vaccinated and unvaccinated individuals. Methods: A retrospective descriptive study was conducted between May 2021 and November 2021 at Bowring and lady Curzon hospital, Shri Atal Bihari Vajpayee medical college and research institute, Bangalore, Karnataka, India. 358 patients with post-covid RTPCR negative rhino-orbital mucormycosis were included in the study. The demographic data, COVID-19 vaccination status and anatomical sites of involvement in the patients was collected and analysed. Results: 4 (1.11%) patients were fully vaccinated with 2 doses of covid vaccine, 18 (5.02%) patients were partially vaccinated, 336 (93.85%) were unvaccinated.  Majority of the patients were in the age group of 41-60 years in all the groups. In unvaccinated group, majority of the patients presented with stage II/III disease (48.51%; 39.88% respectively) and 39 (11.60%) patients with stage IV ROCM. Conclusions: The extent and severity of ROCM was higher in COVID-19 unvaccinated patients as compared to vaccinated group. Further studies are required to determine the role of COVID-19 vaccine in reducing the severity of the of ROCM

Role of Inflammatory Markers as Prognostic Indicators in Treatment of Mucormycosis

Introduction: Mucormycosis is opportunistic fungal infection characterized by extensive inflammation, necrosis and infarction of the involved tissues. It is associated with rise in levels of inflammatory markers [Erythrocyte sedimentation rate (ESR) , C-reactive protein (CRP)]. This study was done to know the role of ESR, CRP as prognostic indicators in the treatment of covid-19 associated mucormycosis (CAM). Materials and Methods: : A retrospective descriptive study was conducted between May 2021 and December 2021 at a tertiary centre. 315 patients with post-covid ROCM (Rhino-orbito-cerebral mucormycosis) were included in study. ESR and CRP were sent for all patients at the time of admission. Postoperatively the same were  repeated on post-op (POD) day 7, day 14, and day 30 during follow-up. Results: 243 (77.14%) patients were male and 72 (22.86%) were female. 6 patients with stage IV ROCM had recurrence of the disease in the postoperative period. Mean  ESR values in these patients at the time of admission, POD-7, 14, 30 were 98.17, 68.17, 44.00, 80.33 respectively. Mean CRP values in these patients at the time of admission, POD-7, 14, 30 were 58.50, 48.17, 26.33,37.83 respectively. Conclusion: Serial measurements of inflammatory markers (ESR, CRP) levels helps in the diagnosis and prognostication of  ROCM along with clinical evaluation and imaging

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline