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.

Primary odontogenic onset invasive mucormycosis-an under recognized clinical entity.

OBJECTIVES: The primary source of facial mucormycosis is through inhalation of fungal sporangiospores, resulting in invasive disease in paranasal sinuses. However, dental onset mucormycosis has not been well documented in literature. The aim of this study was to describe the clinical characteristics and outcomes of patients with odontogenic onset mucormycosis. METHODS: From a large cohort of mucormycosis involving the face between July 2020 and October 2021, we selected patients who had dental symptoms at onset and predominant alveolar involvement with little to no paranasal sinus disease as shown by baseline imaging. All patients had a confirmed diagnosis of mucormycosis through histopathology, with or without the growth of Mucorales in fungal culture. RESULTS: Out of 256 patients with invasive mucormycosis of the face, 8.2% (21 patients) had odontogenic onset. Uncontrolled diabetes was a common risk factor, affecting 71.4% (15/21) of the patients, while recent COVID-19 illness was noted in 80.9% (17/21) of patients. The median duration of symptoms at presentation was 37 days (IQR, 14-80 days). The most common symptoms were dental pain with loose teeth (100%), facial swelling (66.7% [14/21]), pus discharge (28.6% [6/21]), and gingival and palatal abscess (28.6% [6/21]). Extensive osteomyelitis was found in 61.9% (13/21) of the patients, and 28.6% (6/21) had oroantral fistulas. The mortality rate was low, at 9.5% (2/21), with only 9.5% (2/21) of the patients having brain extension and 14.2% (3/21) in the orbit. CONCLUSION: This study suggests that odontogenic onset invasive mucormycosis may be a separate clinical entity with its own distinct clinical features and prognosis.

Persistent bacteremia predicts poor outcomes among neutropenic patients with carbapenem-resistant gram-negative bloodstream infections receiving appropriate therapy.

PURPOSE: Identifying persistent bacteremia early in patients with neutropenia may improve outcome. This study evaluated the role of follow-up blood cultures (FUBC) positivity in predicting outcomes among patients with neutropenia and carbapenem-resistant gram-negative bloodstream infections (CRGNBSI). METHODS: This retrospective cohort study conducted between December 2017 and April 2022 included patients more than 15 years old with neutropenia and CRGNBSI, who survived for ≥ 48 h, receiving appropriate antibiotic therapy and had FUBCs. Patients with polymicrobial bacteremia within 30 days were excluded. The primary outcome was 30 day mortality. Persistent bacteremia, septic shock, recovery from neutropenia, prolonged or profound neutropenia, requirement of intensive care and dialysis, and initiation of appropriate empirical therapy were also studied. RESULTS: In our study cohort of 155 patients, the 30 day mortality rate was 47.7%. Persistent bacteremia was common in our patient cohort (43.8%). Carbapenem resistant isolates identified in the study were K.pneumoniae (80%), E.coli (12.26%), P.aeruginosa (5.16%), A.baumanii (1.94%) and E.cloacae (0.65%). The median time for sending a FUBC was 2 days (IQR, 1-3 days). Patients with persistent bacteremia had higher mortality than those without (56.76% versus 32.1%; p < 0.001). Appropriate initial empirical therapy was given to 70.9%. Recovery from neutropenia occurred in 57.4% while 25.8% had prolonged or profound neutropenia. Sixty-nine percent (107/155) had septic shock and needed intensive care; 12.2% of patients required dialysis. Non-recovery from neutropenia (aHR, 4.28; 95% CI 2.53-7.23), presence of septic shock (aHR, 4.42; 95%CI 1.47-13.28), requirement of intensive care (aHR,3.12;95%CI 1.23-7.93), and persistent bacteremia (aHR,1.74; 95%CI 1.05-2.89) significantly predicted poor outcomes in multivariable analysis. CONCLUSION: FUBC showing persistent bacteremia predicted poor outcomes among neutropenic patients with carbapenem-resistant gram-negative bloodstream infections (CRGNBSI) and should be routinely reported.

Efficacy of Crushed Delayed-Release Posaconazole Tablets in Rhino-Orbito-Cerebral Mucormycosis.

A significant proportion of patients with Rhino-orbito-cerebral mucormycosis (ROCM) develop oroantral fistulas. Due to the unclear efficacy of crushed delayed-release posaconazole tablets (DRPT) via nasogastric tube in this group of patients, clinicians often use inferior alternatives like posaconazole suspension. In this prospective study, we report good plasma concentrations (median, 2,639 ng/mL; interquartile range [IQR], 1,690 to 3,575 ng/mL; and range, 1,004 to 4,835ng/mL) and complete cure and survival at 3 and 6 months in 19 such patients.

Risk factors associated with the mucormycosis epidemic during the COVID-19 pandemic.

This study was performed to assess the risk factors driving the epidemic of coronavirus disease 2019 (COVID-19)-associated mucormycosis (COVID-Mucor) in India that has accompanied the COVID-19 pandemic, particularly during the second wave. Risk factors were analysed among 164 participants: 132 COVID-Mucor (cases) and 32 non-COVID-Mucor (controls). Data from a prospective cohort study of mucormycosis over a period of 1 year were used. Diabetes mellitus remained a significant risk factor in both groups (97%), while uncontrolled diabetes mellitus (odds ratio (OR) 4.6; P = 0.026) and newly detected diabetes (OR 3.3; P = 0.018) were more common among the cases. Most patients with COVID-Mucor had mild COVID-19. Steroid use, often unwarranted, was highly associated with COVID-Mucor after adjusting for other risk factors (OR 28.4; P = 0.001). Serum ferritin was significantly higher (P = 0.041), while C-reactive protein was not, suggesting that alterations in iron metabolism may predispose to COVID-Mucor. Oxygen was used only in a small minority of patients with COVID-Mucor. The in-hospital mortality in both groups was low. In conclusion, the Indian COVID-Mucor epidemic has likely been driven by a convergence of interlinked risk factors: uncontrolled diabetes mellitus, unwarranted steroid use, and perhaps COVID-19 itself. Appropriate steroid use in patients with severe COVID-19 and screening and optimal control of hyperglycaemia can prevent COVID-Mucor.