Mucormycosis: The hidden and forgotten disease.

Mucormycosis is a rare but serious fungal infection caused by a group of moulds called mucormycetes. More attention has recently been paid to it due to its association with coronavirus disease 2019 (COVID-19). Thus, it is important to review the progress of studies on mucormycosis and highlight the important findings in relation to epidemiology, clinical manifestation, major risk factors, diagnostic strategies and management. An electronic literature search was performed in PubMed using the keywords: Rhizopus, Mucorales, mucormycosis, zygomycosis, zygomycetes, COVID-19, the drugs (azoles, posaconazole, isavuconazole, amphotericin B pharmaceutical preparations and caspofungin), combination therapy, diagnosis and clinical manifestations. Studies written in the English language from January 1960 to 2021 were considered for this review article. All search results were reviewed, and the relevance of each article was determined by the authors independently. The review emphasized the fact that the diagnosis of mucormycosis is difficult, it is necessary to have a high index of suspicion to identify it, surgical debridement should be done prior to the dissemination of infection to improve clinical outcomes and identifying underlying risk factors is important for proper treatment. Moreover, antifungal therapeutic options are few with polyenes and their combinations should be appropriate for empirical therapy while posaconazole and isavuconazole are best reserved for de-escalation, refractory cases or patients intolerant to amphotericin B.

Multiple maxillary periodontal abscesses as a manifestation of post-coronavirus disease 2019 mucormycosis: a case report.

BACKGROUND: Coronavirus disease 2019 makes patients more susceptible to superinfection of fungal disease as a consequence of immunological system impairment. Mucormycosis is a fungal infection that is rare but has a high mortality rate and mostly affects patients with poorly controlled diabetes mellitus or those receiving corticosteroids. CASE PRESENTATION: Here, we present a case of post-coronavirus disease 2019 mucormycosis in a 37-year-old Persian male presenting with multiple periodontal abscess with purulent discharge and necrosis of maxillary bone (without oroantral communication). Surgical debridement following antifungal therapy was the treatment of choice. CONCLUSION: Early diagnosis and immediate referral are the cornerstone of comprehensive treatment.

Decreased mortality in coronavirus disease 2019 associated mucormycosis with aspirin use: a retrospective cohort study.

OBJECTIVE: Rhino-orbito-cerebral mucormycosis is a rapidly progressive disease with high mortality rates of about 60 per cent. The increasing incidence of rhino-orbito-cerebral mucormycosis in coronavirus disease 2019 patients in India and worldwide has become a matter of concern owing to the case fatality rate. This study explored the use of low dose aspirin in decreasing the mortality rate of coronavirus disease 2019 associated mucormycosis. METHOD: This was a retrospective observational study. Patients suffering from post-coronavirus disease 2019 mucormycosis were included in the study. Each patient was treated with surgical debridement and systemic amphotericin B. Low dose aspirin was added, and mortality rates were compared with the patients who did not receive aspirin. RESULTS: The demographic data and rhino-orbito-cerebral mucormycosis staging between the two groups were not significantly different. There was a statistically significant difference in mortality outcomes between the two groups (p = 0.029) and a 1.77 times higher risk of dying for patients not receiving aspirin. Kaplan-Meier survival indicated that patients receiving aspirin had better survival rates (p = 0.04). CONCLUSION: Low dose aspirin improves survival rates in coronavirus disease 2019 associated mucormycosis.

Timing of antibiotic administration, wound debridement, and the stages of reconstructive surgery for open long bone fractures of the upper and lower limbs.

BACKGROUND: Open fractures of the major long bones are complex limb-threatening injuries that are predisposed to deep infection. Treatment includes antibiotics and surgery to debride the wound, stabilise the fracture and reconstruct any soft tissue defect to enable infection-free bone repair. There is a need to assess the effect of timing and duration of antibiotic administration and timing and staging of surgical interventions to optimise outcomes. OBJECTIVES: To assess the effects (risks and benefits) of the timing of antibiotic administration, wound debridement and the stages of surgical interventions in managing people with open long bone fractures of the upper and lower limbs. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and clinical trial registers in February 2021. We also searched conference proceedings and reference lists of included studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs that recruited adults with open fractures of the major long bones, comparing: 1) timings of prophylactic antibiotic treatment, 2) duration of prophylactic antibiotic treatment, 3) timing of wound debridement following injury or 4) timing of the stages of reconstructive surgery. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We aimed to collect data for the following outcomes: limb function, health-related quality of life (HRQoL), deep surgical site infection, delayed or non-union, adverse events (in the short- and long-term course of recovery), and resource-related outcomes. MAIN RESULTS: We included three RCTs of 613 randomised participants with 617 open fractures. Studies were conducted in medical and trauma centres in the USA and Kenya. Where reported, there was a higher proportion of men and a mean age of participants between 30 and 34 years old. Fractures were in the upper and lower limbs in one study, and were tibia fractures in two studies; where reported, these were the result of high-energy trauma such as road traffic accidents. No studies compared the timing of antibiotic treatment or wound debridement. Duration of prophylactic antibiotic treatment (1 study, 77 participants available for analysis) One study compared antibiotic treatment for 24 hours with antibiotic treatment for five days. We are very uncertain about the effects of different durations of antibiotic treatment on superficial infections (risk ratio (RR) 1.19, 95% CI 0.49 to 2.87, favours 5 day treatment; 1 study, 77 participants); this was very low-certainty evidence derived from one small study with unclear and high risks of bias, and with an imprecise effect estimate. This study reported no other review outcomes. Reconstructive surgery: timing of the stages of surgery (2 studies, 458 participants available for analysis) Two studies compared the timing of wound closure, which was completed immediately or delayed. In one study, the mean time of delay was 5.9 days; in the other study, the time of delay was not reported. We are very uncertain about the effects of different timings of wound closure on deep infections (RR 0.82, 95% CI 0.37 to 1.80, favours immediate closure; 2 studies, 458 participants), delayed union or non-union (RR 1.13, 95% CI 0.83 to 1.55, favours delayed closure; 1 study, 387 participants), or superficial infections (RR 6.45, 95% CI 0.35 to 120.43, favours delayed closure; 1 study, 71 participants); this was very low-certainty evidence. We downgraded the certainty of the evidence for very serious risks of bias because both studies had unclear and high risks of bias. We also downgraded for serious imprecision because effect estimates were imprecise, including the possibility of benefits as well as harms, and very serious imprecision when the data were derived from single small study. These studies reported no other review outcomes. AUTHORS' CONCLUSIONS: We could not determine the risks and benefits of different treatment protocols for open long bone fractures because the evidence was very uncertain for the two comparisons and we did not find any studies addressing the other possible comparisons. Well-designed randomised trials with adequate power are needed to guide surgical and antibiotic treatment of open fractures, particularly with regard to timing and duration of antibiotic administration and timing and staging of surgery.

Post-Covid Cerebral Mucormycosis, Varied Presentations and Surgical Strategies of a Newer Epidemic: An Institutional Experience.

Context: During the challenging second wave of the COVID-19 pandemic, we encountered a most dreadful fungal infection in the form of COVID-associated mucormycosis (CAM), with a varied pattern of presentation from previous experience. Patients presented with simple fungal sinusitis or more complicated brain abscesses, and newer manifestations such as skull osteomyelitis. We report our findings and innovative treatment strategies used to manage this morbid condition. Objectives: To study the various presentations and surgical strategies in treating post-COVID rhino-orbito-cerebral mucormycosis (ROCM). Settings and Design: Observational cross-sectional study. Methods and Materials: From May to October 2021, 270 patients with CAM were admitted to Andhra Medical College Department of Neurosurgery, King George Hospital, Visakhapatnam, India. A cohort of 61 cases with intracranial involvement was studied in detail. The varied presentations and different or innovative treatment modalities were analyzed. Results: The death rate was 30/270 in the whole cohort, and three deaths (4.9%) occurred in 61 cases with cranial involvement. Thirty-three (54.1%) of the 61 cases were treated surgically: 17 patients required bone excision (for focal osteomyelitis) and 16 cases required abscess drainage/excision. Conclusions: Post-COVID mucormycosis (especially with intracranial involvement) is a highly challenging entity. A multidisciplinary approach with early and aggressive anti-fungal medication combined with timely surgical interventions offers some hope of overcoming this complex infection in CAM patients. We identified some novel techniques during regular follow-up that have proven helpful in combatting this devastating condition.

A case series of mucormycosis after covid infection in two hospitals.

This paper aims to discuss clinical aspects of mucormycosis. This case series was conducted in two services, comprising six mucormycosis cases during COVID-19 pandemic. About gender, there are 4 (66.7%) males and 2 (33.3%) females with mean age (48.7 ± 9.4) years. All cases presented complaints of pain and swelling in oral cavity and had an aggressive clinical presentation. Five patients had diabetes and one had a nasal non-Hodgkin lymphoma. Histologically, large, branched, hyphae associated with necrotic areas were observed, confirming microscopically such as mucormycosis through PAS and GMS stains. In four cases, treatment consisted in surgical debridement associated with antifungal therapy. All patients were submitted to debridement and received antifungal treatment (amphotericin B). Five patients were followed up without clinical recurrence, but unfortunately one patient died. Diagnosis of mucormycosis should be early because it is related to high mortality. The treatment consists of surgical debridement associated with antifungal therapy.

Localized surgical debridement for the management of orbital mucormycosis.

PURPOSE: To describe the role of localized debridement and instillation of amphotericin B for the management of orbital mucormycosis post COVID-19 infection with a view to avoid exenteration. METHODS: The records of all patients with orbital mucormycosis post COVID-19 infection in the last 6 months from December 2020 to June 2021 were evaluated, and ten patients were identified who were successfully managed with localized debridement, that is, removing the fungal tissue and necrotic material and amphotericin B gel instillation locally. MRI scan was used to identify the area of fungal infiltration and presence of necrotic material. Early surgery in the form of transconjunctival orbitotomy was performed for disease in the infraorbital fissure area, and superior transcutaneous lid crease approach was employed for disease in the superomedial orbit or medial orbit. Most patients had lid edema, ptosis, and proptosis; this resolved with the medication. Systemic antifungals were given and the follow-up ranged from 1 to 5 months. RESULTS: The ptosis, proptosis, and lid edema subsided in all, except in one patient who had residual ptosis and in one who had residual ophthalmoplegia. Vision deficit did not occur in any patient. All patients were successfully discharged on oral antifungal medication. CONCLUSION: Localized clearance of the fungal tissue and the necrotic material is a good option to avoid exenteration in cases of orbital mucormycosis, avoiding disfigurement and mental trauma to the patient.

Temporary obturator using high-density polyurethane foam following maxillectomy during the coronavirus disease 2019 pandemic.

BACKGROUND: Rhino-orbital mucormycosis was seen in epidemic proportions during the second wave of the coronavirus disease 2019 pandemic. Many of these post-coronavirus rhino-orbital mucormycosis patients underwent maxillectomy for disease clearance. Rehabilitating such a large number of patients with surgical obturators as an emergency in a low-income setting was challenging. METHODS: High-density polyurethane foam was used to make a temporary obturator for patients who underwent maxillectomy. These obturators helped alleviate functional problems like dysphagia and nasal regurgitation, improving nutritional outcomes and shortening the hospital stay. CONCLUSION: The coronavirus disease 2019 pandemic gave physicians time-sensitive challenges, for which immediate alternatives to established care were required. A maxillary obturator made of high-density polyurethane foam is an innovative solution to rehabilitate maxillectomy patients in the immediate post-operative period.

Flap coverage for necrotising soft tissue infections: A systematic review.

BACKGROUND: Necrotising soft tissue infections (NSTI) are destructive and often life-threatening infections of the skin and soft tissue, necessitating prompt recognition and aggressive medical and surgical treatment. After debridement, the aim of surgical closure and reconstruction is to minimize disability and optimize appearance. Although skin grafting may fulfil this role, techniques higher on the reconstructive ladder, including local, regional and free flaps, are sometimes undertaken. This systematic review sought to determine the circumstances when this is true, which flaps were most commonly employed, and for which anatomical areas. METHODS: A systematic review of the literature was conducted utilising electronic databases (Medline, Embase, Cochrane Library). Full text studies of flaps used for the management of NSTI's (including Necrotising Fasciitis and Fournier Gangrene) were included. The web-based program 'Covidence' facilitated storage of references and data management. Data obtained in the search included reference details (journal, date and title), the study design, the purpose of the study, the study findings, number of patients with NSTI included, the anatomical areas of NSTI involved, the types of flaps used, and the complication rate. RESULTS: After screening 4555 references, 501 full text manuscripts were assessed for eligibility after duplicates and irrelevant studies were excluded. 230 full text manuscripts discussed the use of 888 flap closures in the context of NSTI in 733 patients; the majority of these were case series published in the last 20 years in a large variety of journals. Reconstruction of the perineum following Fournier's gangrene accounted for the majority of the reported flaps (58.6%). Free flaps were used infrequently (8%), whereas loco-regional muscle flaps (18%) and loco-regional fasciocutaneous flaps (71%) were employed more often. The reported rate of partial or complete flap loss was 3.3%. CONCLUSION: Complex skin and soft tissue defects from NSTIs, not amenable to skin grafting, can be more effectively and durably covered using a spectrum of flaps. This systematic review highlights the important contribution that the plastic surgeon makes as an integral member of multidisciplinary teams managing these patients.

Fungal central skull-base osteomyelitis: atypical presentation and management issues.

Mucormycosis is a very commonly encountered disease in the sinonasal region in patients with diabetes and immunocompromised status specially in the northern part of the Indian continent. Due to its fulminant nature and involvement in the rhino-orbital-cerebral region, prognosis is poor even after extensive debridement and amphotericin-B therapy. We present a case with diagnosis of sarcoidosis being treated with systemic steroids who developed sudden-onset ptosis and left lateral rectus palsy. On radiological evaluation with MRI, a heterogenously peripherally enhancing lesion was seen in the nasopharynx suggestive of nasopharyngeal abscess. The patient was taken up for emergency surgery; a necrotic lesion with destruction of sphenoid bone, pterygoids and clivus was seen originating in the nasopharynx. The lesion on fungal staining came out to be broad aseptate hyphae suggestive of mucormycosis.

Rhino-orbital-cerebral mucormycosis: fungal epidemic in a viral pandemic.

BACKGROUND: Treatment of coronavirus disease 2019 infection can result in immunosuppression. Rhino-orbital-cerebral mucormycosis is a frequent co-infection, even after recovery. METHODS: An ambispective interventional study was conducted of 41 coronavirus patients with rhino-orbital-cerebral mucormycosis at a tertiary care centre from March to May 2021. RESULTS: There were 28 males and 13 females with a mean age of 48.2 years (range, 21-68 years). Twelve had long-standing diabetes mellitus and 28 had been recently diagnosed. Thirty-six had received systemic corticosteroids for coronavirus disease 2019. Nasal signs were present in 95 per cent of patients, ophthalmic symptoms and signs in 87 per cent, palatal necrosis in 46.3 per cent, facial signs in 24.3 per cent, nerve palsies in 60.9 per cent, and intracranial involvement in 21.9 per cent. Treatment with amphotericin B was based on clinical features and co-morbidities. Endonasal debridement was performed in 51.2 per cent of patients, total maxillectomy in 14.6 per cent and orbital exenteration in 9.7 per cent. At the last follow up, 37 patients (90.24 per cent) were on antifungal therapy; 4 (9.75 per cent) did not survive. CONCLUSION: Early detection may improve survival. Follow up of high-risk patients after coronavirus disease 2019 infection is paramount.

Wound bed preparation: an overview.

Wound bed preparation is the management of a wound in order to optimise healing and/or facilitate other therapeutic measures. It is the most pivotal step in healing wounds. Early referral to a specialist wound clinic can markedly improve the wound healing process. This overview will discuss the techniques involved in the preparation of the wound bed that will effectively accelerate the healing process. The process begins with a correct diagnosis of the wound and optimising the patient's medical condition. The TIMERS framework is discussed. Wound dressings, including the use of negative-pressure wound therapy, are discussed, along with debridement techniques and agents. The timing of wound intervention and evaluating progress will also be discussed, and wound bed preparation strategies will be included. There has been an added challenge of wound care in the community as a result of the COVID-19 pandemic. The present article provides an overview of how to prepare a wound bed in the community.

A rare entity to major outbreak: a case report on mucormycosis.

Mucormycosis is relatively uncommon, fulminant, progressive, life threatening fungal disease which is most often seen in debilitating patients with immunocompromised condition. Mucormycosis cases are seen in patients with the use of systemic steroids in the treatment of severely affected COVID-19 cases and also in the patients with uncontrolled diabetes which causes immunosuppression are being reported with mucormycosis. The main symptoms of this disease include pain on the temporal and the orbital region of the affected side which could be throbbing or lancinating type, mobility of the teeth, jaw pain and often swelling is present which could be extraoral and intraoral both or sometimes only intraorally. The diagnostic approach in such cases is done with the help of clinical diagnosis, histopathology and with advanced imaging like cone beam computed tomography, magnetic resonance imaging and computed tomography. We here used cone beam computed tomography imaging that revealed haziness in the sinuses and breach in cortical bone of the affected area which confirmed the diagnosis of mucormycosis. Early treatment planning like administration of antifungal drugs and surgical debridement will be life saving in such a deadly disease.

Rise of the phoenix: Mucormycosis in COVID-19 times.

PURPOSE: Rhino-orbital mucormycosis in times of ongoing COVID-19 pandemic. AIMS: The aim of the study was to document cases of rhino-orbital mucormycosis seen at our Regional Institute of Ophthalmology during COVID-19 (coronavirus disease 2019) times. METHODS: The study is a retrospective, institutional cohort, interventional study. It was carried out at our Regional Institute of Ophthalmology from September 2020 to mid-March 2021. All patients of biopsy-proven mucormycosis were enrolled in the study. The patients were subjected to complete history taking, ophthalmological examination, and imaging studies. The patients were treated via a multidisciplinary approach with intravenous liposomal amphotericin B and debridement of local necrotic tissue. Exenteration was done when indicated. A minimum 75-day follow-up period was accorded to all study patients. Statistical analysis was done using Chi-square test. A P value ≤0.05 was taken as significant. RESULTS: Thirty-one patients were seen, with a mean age of 56.3 years. The major risk factors included uncontrolled diabetes (96.7%) and COVID-19 positivity (61.2%), with concomitant steroid use in 61.2% patients. The most common presentation was diminution of vision (<6/60 in 80.64% patients) and ophthalmoplegia (77.4%). The most common imaging findings were orbital cellulitis (61.29%) and pansinusitis (77.4%). Intravenous liposomal amphotericin B was given to all patients for an average 18.93 days. Exenteration was required in (n = 4) 12.9% of cases. Twenty-eight patients recovered and were alive on follow-up. Mortality was seen in three patients. The presence of cerebral involvement and a HbA1c value of ≥8 were found to be significant in the prediction of survival of patients with mucormycosis. CONCLUSION: We present the largest institutional cohort of rhino-orbital mucormycosis patients during the ongoing COVID-19 pandemic era from our unique perspective.

Invasive Fungal Sinusitis in Post COVID-19 Patients: A New Clinical Entity.

OBJECTIVES: Occurrence of invasive fungal respiratory superinfections in patients with COVID-19 has gained increasing attention in the latest studies. Yet, description of acute invasive fungal sinusitis with its management in those patients is still scarce. This study aims to describe this recently increasing clinical entity in relation to COVID-19 patients. STUDY DESIGN: Longitudinal prospective study. METHODS: Prospective longitudinal study included patients diagnosed with acute invasive fungal rhinosinusitis after a recent COVID-19 infection. Antifungal agents given included amphotericin B, voriconazole, and/or posaconazole. Surgical treatment was restricted to patients with PCR negative results for COVID-19. Endoscopic, open, and combined approaches were utilized to eradicate infection. Follow-up for survived patients was maintained regularly for the first postoperative month. RESULTS: A total of 36 patients with a mean age of 52.92 ± 11.30 years old were included. Most common associated disease was diabetes mellitus (27.8%). Mycological analysis revealed infection with Mucor and Aspergillus species in 77.8% and 30.6% of patients, respectively. Sino-nasal, orbital, cerebral, and palatine involvement was found in 100%, 80.6%, 27.8%, and 33.3% of patients, respectively. The most common reported symptoms and signs are facial pain (75%), facial numbness (66.7%), ophthalmoplegia, and visual loss (63.9%). All patients were treated simultaneously by surgical debridement with antifungal medications except for two patients with PCR-positive swab for COVID-19. These two patients received antifungal therapy alone. Overall survival rate was 63.89% (23/36). CONCLUSION: Clinical suspicion of acute invasive fungal sinusitis among COVID-19 patients and early management with antifungal therapy and surgical debridement is essential for better outcomes and higher survival. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2652-2658, 2021.

Mucormycosis after Coronavirus disease 2019 infection in a heart transplant recipient - Case report and review of literature.

Mucormycosis is an invasive fungal infection (IFI) due to several species of saprophytic fungi, occurring in patients with underlying co-morbidities (including organ transplantation). During the ongoing Coronavirus disease 2019 (COVID-19) pandemic, there have been increasing reports of bacterial and fungal co-infections occurring in COVID-19 patients, including COVID-19 associated pulmonary aspergillosis (CAPA). We describe a case of mucormycosis occurring after COVID-19, in an individual who received a recent heart transplant for severe heart failure. Two months after heart transplant, our patient developed upper respiratory and systemic symptoms and was diagnosed with COVID-19. He was managed with convalescent plasma therapy and supportive care. Approximately three months after COVID-19 diagnosis, he developed cutaneous mucormycosis at an old intravascular device site. He underwent extensive surgical interventions, combined with broad-spectrum antifungal therapy. Despite the aggressive therapeutic measures, he died after a prolonged hospital stay. In this case report, we also review the prior well-reported cases of mucormycosis occurring in COVID-19 patients and discuss potential mechanisms by which COVID-19 may predispose to IFIs. Similar to CAPA, mucormycosis with COVID-19 may need to be evaluated as an emerging disease association. Clinicians should be vigilant to evaluate for invasive fungal infections such as mucormycosis in patients with COVID-19 infection.

Managing breast gangrene during the COVID-19 pandemic.

At the onset of the COVID-19 crisis, a 63-year-old woman with multiple life-limiting comorbidities was referred with a necrotic infected left breast mass on a background of breast cancer treated with conservation surgery and radiotherapy 22 years previously. The clinical diagnosis was locally advanced breast cancer, but four separate biopsies were non-diagnostic. Deteriorating renal function and incipient sepsis and endocarditis resulted in urgent salvage mastectomy during the peak of the COVID19 pandemic. The final diagnosis was infected ischaemic/infarcted breast (wet gangrene) secondary to vascular insufficiency related to diabetes, cardiac revascularisation surgery and breast radiotherapy.