To evaluate the efficacy of topical anti-fungal therapy in postoperative cases of COVID Associated Mucormycosis (CAM): A single-blinded randomized control trial.

PURPOSE: To compare the efficacy of 0.1 % w/w Liposomal Amphotericin-B gel with 10 % w/w Povidone-Iodine and saline nasal douching in preventing revision surgery in patients with CAM. STUDY DESIGN: Multi-arm, parallel randomized control trial. STUDY SETTING: The trial was conducted in the Department of ENT, All India Institute of Medical Sciences (AIIMS) Bhubaneswar. METHODS: Participants: Microbiologically and histologically proven cases of mucormycosis who underwent surgical debridement were included in the study. INTERVENTIONS: Postoperatively, patients were randomized into three groups based on the type of topical intervention received, in the form of Lipid-based Amphotericin B gel, povidone­iodine ointment or saline nasal douching. OUTCOME: Requirement of revision surgery in postoperative cases of CAM. RANDOMIZATION: Participants were allotted to one of the three arms by block randomization. BLINDING: Single-blinded trial. RESULTS: Numbers randomized: 15 participants were randomized to each group. Recruitment: Completed recruiting. Numbers analyzed: 15 participants were analyzed in each group. OUTCOMES: Control arm's risk of revision surgery was 4.50 (95 % CI: 1.16-17.44) times than Lipid-based Amphotericin B gel arm and 1.50 (95 % CI: 0.71-3.16) times that of the Povidone- Iodine arm. The difference was statistically significant (p = 0.02) for Amphotericin but not for Povidone-Iodine. CONCLUSIONS: Topical Amphotericin-B gel application in the postoperative cavity can decrease the need for revision surgery and help in early recovery. TRIAL REGISTRATION: CTRI/2021/10/037257. Clinical Trials Registry of India.

Invasive fungal consecutive infections in a patient with acute myeloid leukaemia.

A woman with AML who became febrile and neutropenic after chemotherapy. At the first, Aspergillus was isolated from a sinus biopsy. After 4 weeks, while she was taking voriconazole, another episode of fever combined with dry coughs was detected. Fungal culture and histopathology of sinus biopsy revealed mucormycosis.

New pharmacological opportunities for the treatment of invasive mould diseases.

Recently, several randomized studies have been published that will shape treatment decisions in the prevention and management of invasive mould infections. Liposomal amphotericin B is an option for empirical or targeted treatment of invasive aspergillosis or mucormycosis, but for prophylaxis therapy, the triazole class now predominates. The triazole voriconazole is currently regarded as a drug of choice for the treatment of proven or probable invasive aspergillosis, and has shown significantly higher response rates than amphotericin B deoxycholate in this setting, with fewer severe drug-related adverse events. Isavuconazole, the newest triazole agent, offers the advantages of once-daily dosing, a wider spectrum of antifungal activity than voriconazole, predictable pharmacokinetics and fewer CYP enzyme-mediated drug interactions. A recent large randomized clinical trial showed mortality to be similar under isavuconazole or voriconazole in patients with invasive mould disease, with fewer drug-related adverse events in isavuconazole-treated patients. Another study has indicated that isavuconazole is also effective in mucormycosis infections but patient numbers were small and confirmation is awaited. Experimental studies combining different drug classes with antimould activity have been promising, but the clinical database is limited. A large randomized trial of combination therapy compared voriconazole plus the echinocandin anidulafungin versus voriconazole monotherapy in patients with invasive aspergillosis. Results showed the overall response rate to be similar, but combination therapy improved survival for the subpopulation of patients in whom the diagnosis was confirmed by serum and/or bronchoalveolar lavage fluid galactomannan positivity. This active field of research is likely to continue evolving rapidly in the coming years.

Primary cutaneous mucormycosis caused by Mucor irregularis.

We describe a case of primary cutaneous mucormycosis in a 44-year-old man with an 18-month history of infiltrative erythematous plaques and haemorrhagic crusting on the dorsum of his left hand. The isolate was identified as Mucor irregularis (formerly Rhizomucor variabilis) based on the fungus morphology and DNA sequencing results. Improvement was observed after a 6-month treatment course of itraconazole. No recrudescence was seen during a follow-up of 23 months after treatment.

Rare pediatric rhino-orbital infection caused by Saksenaea vasiformis.

Rhinosinusitis infection due to Saksenaea vasiformis is extremely rare. The present case describes a rhino-orbital infection in a 21-month-old Chadian immunocompetent male child with a 2-month history of excessive tearing from the right eye, followed by swelling of the right upper and lower eye lids, associated with right facial swelling and dark coloration surrounding the lower eye lid. Coronal computed tomography (CT) scan of the paranasal sinuses showed opacification of the right nasal cavities with extension to the orbit. Non-septate fungal hyphae were diagnosed by tissue sections and a Blankophor P fluorescent stain microscopy. The culture grew zygomycetes, S. vasiformis that failed to sporulate on Sabouraud dextrose agar, the organism was sporulated after 1 week on Czapek agar medium, and produced flask-shaped brown pigmented sporangium with lateral rhizoids and hemispherical columella filled with spores. The patient underwent a right functional endoscopic sinus surgery, where debridement of both right maxillary and ethmoid sinuses was done. Treatment with amphotericin B lipid complex was started and continued for 41 days. The patient was clinically doing better with decreased eye and facial swelling, and his erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were decreased to normal values. The patient continued with treatment on posaconazole after his discharge, and his condition resolved without further sequelae. Rhinosinusitis due to mucormycosis should be considered in any patient, even in young children, presenting with progressive rhinosinusitis infection, whether immunocompromised or not. Early diagnosis may lead to a successful treatment and good prognosis.

Pediatric invasive mucormycosis cured with high dose liposomal amphotericin B.

Amphotericin B remains the mainstay medical treatment of pulmonary mucormycosis. Optimal dose is not defined. We described a case of pulmonary mucormycosis, which had been treated with 42.55 g (during to 45 weeks) liposomal amphotericin B. In medical literature this case is one of the highest doses of lyposomal amphotericin B administered to a pediatric patient.

COVID-19-Related Rhino-Orbital-Cerebral Mucormycosis in a Renal Transplant Recipient.

Coronavirus disease 2019 increases transplant recipients' susceptibility to rare opportunistic infections as a consequence of the impairment that COVID-19 can cause in the immune system. Mucormycosis is a rare complication but has a high risk of fatal outcome. A 50-year-old woman who received a kidney transplant 10 years previously was admitted to the hospital with COVID-19. During follow-up by the inpatient service, the patient developed pain, edema, and proptosis in the right eye. She was diagnosed with rhino-orbitalcerebral mucormycosis. This is the first reported case of rhino-orbital-cerebral mucormycosis in a renal transplant recipient with COVID-19 infection.

COVID-19 triggering mucormycosis in a susceptible patient: a new phenomenon in the developing world?

A middle-aged woman with diabetes presented with left-sided facial pain, complete ptosis and fever of short duration. On presentation, she had hyperglycaemia without ketosis. There was total ophthalmoplegia of the left eye with a visual acuity of 6/36. She incidentally tested positive for COVID-19. CT paranasal sinus and MRI brain revealed left-sided pansinusitis with acute infarct in the left parieto-occipital region without angioinvasion. An emergency functional endoscopic sinus procedure was done, which confirmed mucormycosis on histopathological examination. After 1 week of conventional amphotericin B and antibiotics, repeat CT brain showed improvement in mucosal thickening and sinusitis. This case is a rare presentation of mucormycosis associated with rapid progression to orbital apex syndrome with brain infarction in a patient with non-ketotic diabetes and COVID-19. Early diagnosis and treatment are essential to prevent further end-organ damage. It is also interesting that there was no angioinvasion and transient periarterial inflammation was attributed to brain infarction.

Safety and outcomes of open-label deferasirox iron chelation therapy for mucormycosis.

We sought to describe the safety profile of open-label, adjunctive deferasirox iron chelation therapy in eight patients with biopsy-proven mucormycosis. Deferasirox was administered for an average of 14 days (range, 7 to 21) at 5 to 20 mg/kg of body weight/day. The only adverse effects attributable to deferasirox were rashes in two patients. Deferasirox treatment was not associated with changes in renal or liver function, complete blood count, or transplant immunosuppressive levels. Thus, deferasirox appears safe as an adjunctive therapy for mucormycosis.

Mucormycosis in a transplanted kidney.

Mucormycosis of the transplanted kidney has so far been reported in only 9 patients, with a high mortality rate. Here, we report a rare case of isolated mucormycosis of the transplant kidney with successful outcome.

[Primary cutaneous mucormycosis: a case report]. / Mucormycose cutanée primaire: à propos d'un cas.

The authors report the clinical history of a patient having presented a cutaneous mucormycosis at the waning of a traumatic dilapidation post of the left lower limb. Mucormycosis is an opportunistic fungal infection due to fungi of the group of mucorales present in the environment. There are various clinical forms of the disease; it occurs generally in a predisposed environment. The diagnosis is based on the mycologic and pathologic examination. The therapeutic approach must be multidisciplinary; the vital and functional prognosis depends on early diagnosis and treatment.

Successful Treatment of Intestinal Mycosis Caused by a Simultaneous Infection with Lichtheimia ramosa and Aspergillus calidoustus.

A 53-year-old woman was hospitalized due to septic shock after developing pneumococcal pneumonia after undergoing esophageal cancer surgery. Her transverse colon became perforated after receiving antimicrobial chemotherapy; therefore, emergency subtotal colectomy was performed. Fungi detected in both her colon tissue and a drainage sample indicated intestinal mucormycosis. Early intensive treatment with high-dose liposomal amphotericin B was successful, and she was subsequently discharged from the hospital. The fungal isolates were identified to be Lichtheimia ramosa and Aspergillus calidoustus via gene sequencing using panfungal primers as well as species-specific primers against elongation factor 1 and beta-tubulin for detecting Lichtheimia and Aspergillus, respectively.

A Case Report of Mucormycosis with Palatal Ulcer: A Rare Clinical Dilemma.

Mucormycosis represents a group of life-threatening infections caused by fungi of the order mucorales of subphylum mucormycotina (formely known as the class zygomycetes). It is highly invasive and progressive disease resulting in higher rates of morbidity and mortality. Newer therapies have declined the rates of mortality. Early initiation of therapy often before confirmation of the diagnosis is necessary to optimize outcomes. Here, we report a case of mucormycosis with palatal ulcer in a 63-year male patient, which is a rare anatomic site for the occurrence of mucormycosis or is a rare clinical presentation. The patient was successfully treated with surgical debridement and amphotericin B.

Contemporary treatment and outcomes of zygomycosis in a non-oncologic tertiary care center.

BACKGROUND: Zygomycosis is an emerging mycosis of increasing relevance. Limited data exist for outcomes with contemporary therapies. METHODS: A 6-year retrospective chart review was performed in a non-oncological tertiary care center for patients with zygomycosis. RESULTS: Sixteen episodes of proven (EORTC/MSG criteria) zygomycosis were identified. The average age was 49.2 years. Sites of infection were surgical/traumatic wound [5], rhinocerebral [4], disseminated [2], pulmonary [2], peritoneal [2], and localized skin [1]. Associated conditions included diabetes [7], ketoacidosis [2], end-stage renal disease [4], surgery/trauma [4], steroids [3], solid organ transplant [2], neutropenia [1], and intravenous drug use [1]. Twelve patients had surgical debridement. Medical therapy included liposomal amphotericin B, conventional amphotericin B (CAB), and amphotericin B lipid complex. Overall mortality was 4/16 (25%), occurring in a patient each with rhinocerebral, pulmonary, surgical wound infection, and disseminated disease. Mortality with surgical treatment was 2/12 (17%) vs. 2/4 (50%) without surgery. Mortality for patients treated with CAB was 1/3 vs. 3/12 for those treated with any lipid preparation. Serious morbidity occurred in 7/12 survivors. CONCLUSIONS: In this limited study of contemporary therapies, patients with zygomycosis from a non-oncological tertiary care center have lower mortality than classically described. This disease and its treatments are still associated with severe morbidity, disfigurement, and disability.

Salvage Treatment of Mucormycosis Post-Liver Transplant With Posaconazole During Sirolimus Maintenance Immunosuppression.

We describe the first successful case of posaconazole salvage therapy for mucormycosis with concomitant sirolimus (SRL) maintenance immunosuppression following liver transplantation, despite black box drug interaction following intolerance to first-line tacrolimus and amphotericin due to nephrotoxicity and neurotoxicity. This case describes a 55-year-old female who developed rhinocerebral mucormycosis 108 days after liver transplantation. After 3 months of posaconazole therapy, the patient remains free of disease at 3 years posttransplant. This case report illustrates successful resolution of mucormycosis without SRL toxicity to resolve nephrotoxicity of long-term amphotericin on top of already nephrotoxic immunosuppression. With higher bioavailability of recently FDA-approved posaconazole delayed release tablets, this azole may be a therapeutic option for transplant patients who need to remain on CYP3A4-metabolized immunosuppressive agents.

Saksenaea vasiformis infection in an immunocompetent patient in rural Australia.

An 81-year-old man from rural Australia presented with right pretibial cellulitis 7 days after minor trauma against furniture. He failed to improve despite antibiotics and surgical debridement. Subsequent cultures grew the rare fungus Saksenaea vasiformis, which was treated with further surgical debridement, amphotericin B and posaconazole. This was successful and the patient made a full recovery. We present the case and discuss lessons learnt.

Disseminated Infection with Multiple Cold Abscesses Caused by Rhizopus Arrhizusin an Immunocompetent Girl.

Although infections with fungi, such as Rhizopus species,usually occur in diabetics or immunocompromised patients, they can also rarely affect immunocompetent individuals. We present a case of disseminated infection with multiple cold abscesses in a 13-year, otherwise healthy girl caused by Rhizopus arrhizus.

Mucormicosis asociada a COVID-19: revisión de la literatura para odontólogos / COVID-19 associated mucormycosis: a literature review for dentists

La mucormicosis es una infección fúngica rara, con alta morbilidad y mortalidad. Se presenta principalmente en pa- cientes con diabetes mellitus no controlada, inmunocompro- metidos, con tratamiento crónicos con esteroides, entre otros. Actualmente, se cree que la pandemia de COVID-19 y los tratamientos con corticosteroides podrían estar implicados en el aumento de casos de esta micosis. Este hongo invade el sistema vascular, ocluyendo el flujo sanguíneo arterial y generando una rápida trombosis e isque- mia, lo que provoca la necrosis de los tejidos duros y blandos, con invasión rápida a los tejidos circundantes. Hay varias formas clínicas. En la cavidad bucal se presenta la variante rino-orbito-cerebral, que afecta el paladar en forma de lesión eritematosa o grisácea que puede progresar hacia la formación de una masa necrótica o ulceración con muy escaso sangrado de mucosa. Se manifiesta con síntomas típicos de una rinosinusitis con fiebre y dolor en las piezas dentarias superiores. El tratamiento consta de tres pilares fundamentales: el diagnóstico, un manejo adecuado de las comorbilidades y la combinación de las terapias antifúngica y quirúrgica. Desde el año 2020, la mucormicosis asociada a COVID-19 pasó a ser un evento de notificación obligatoria inmediata al Sistema Nacional de Vigilancia de la Salud (SNVS2.0) me- diante el Sistema Integrado de Información Sanitaria Argen- tina (SISA). Es importante destacar que se han reportado casos de mu- cormicosis luego de extracciones dentales; lo que impulsa a afianzar los conocimientos sobre esta enfermedad, extremar las medidas preventivas e incentivar el diagnóstico precoz en la atención odontológica, debido a la rapidez en la evolución de la patología (AU))

Mucormycosis is a rare fungal infection, with high mor- bidity and mortality. It occurs mainly in patients with uncon- trolled diabetes mellitus, immunocompromised, on chronic treatment with steroids, among others. Currently, it is believed that the COVID-19 pandemic and the corticosteroid treatments could be one of the causes of increased cases. This fungus invades the vascular system, occluding arteri- al blood flow and generating rapid thrombosis and ischemia, which causes necrosis of hard and soft tissues, with rapid in- vasion to the surrounding tissues. There are several clinical forms. In the oral cavity, the rhino-orbito-cerebral variant presents itself affecting the pal- ate in the form of an erythematous or grayish lesion that can progress towards the formation of a necrotic mass or ulcera- tion with very little mucosal bleeding. It manifests itself with typical symptoms of rhinosinusitis, with fever and pain in the upper teeth. The treatment consists of three fundamental pillars: diag- nosis, proper management of comorbidities and the combina- tion of antifungal and surgical therapies. Since 2020, COVID-19 associated mucormycosis became an event of mandatory immediate notification to the National Health Surveillance System (SNVS2.0,) through the Argentina Integrated Health Information System (SISA). It is important to emphasize that mucormycosis cases had been reported following tooth extractions, which drives to strengthen knowledge about this disease, extreme preventive measures and encourage early diagnosis in dental care, due to the speed of the evolution of the pathology (AU))

Combined mucormycosis and Aspergillosis of the rhinocerebral region.

BACKGROUND: Opportunistic fungal infections are rare, life-threatening conditions and are a major cause of morbidity and mortality in immunocompromised hosts. Our experience in the management of a case of combined mucormycosis and aspergillosis of the rhinocerebral region is presented. PATIENTS AND METHODS: The infection developed a few weeks after tooth extraction, massively involving facial structures. After diagnosis, the patient underwent prolonged combined systemic antifungal treatment. Once the local and general conditions had stabilized, an extensive surgical debridement was performed, followed by reconstruction with a pedicled myocutaneous flap. RESULTS: This approach was curative with patient survival after 16 months. CONCLUSION: Early diagnosis, early anti-fungal treatment and early stabilization of the patients' general condition are fundamental for patient survival. Surgery is necessary for fungal eradication, but must be performed according to the above conditions. Pedicled muscle flaps are considered the first reconstruction choice because of their excellent blood perfusion and resistance to fungal invasion.