Oral Posaconazole Research Articles

ENDOBRONCHIAL MUCORMYCOSIS: A RARE PRESENTATION OF PULMONARY MUCORMYCOSIS DIAGNOSED BY ENDOBRONCHIAL CRYOBIOPSY

ENDOBRONCHIAL MUCORMYCOSIS: A RARE PRESENTATION OF PULMONARY MUCORMYCOSIS DIAGNOSED BY ENDOBRONCHIAL CRYOBIOPSY

P147 Fungal osteomyelitis in patients with chronic granulomatous disease: a case series from a tertiary care medical centre.

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PM ObjectivesTo present details of a case series of fungal osteomyelitis initially misdiagnosed as disseminated tuberculosis, in pediatric patients with chronic granulomatous disease.MethodInformed consent was obtained from the parents of three children (known cases of chronic granulomatous disease) with clinical features suggestive of chronic osteomyelitis. Clinical history was collected by interview and chart review. Samples were sent to the mycology laboratory for direct microscopy and fungal culture. Following a diagnosis of fungal osteomyelitis, antifungal therapy was administered and patients were monitored till discharge.ResultsFirst case:The first patient presented with fever, cough and progressive painful swelling over the left lower chest, and a past history of recurrent pneumonia and cervical lymphadenopathy, which were previously empirically treated with anti-tubercular therapy (ATT) and broad-spectrum antibiotics. Imaging revealed a soft tissue abscess with underlying rib osteomyelitis and pulmonary consolidation. Pus samples showed hyaline septate hyphae in direct microscopy and growth of Aspergillus nidulans in culture. The patient was successfully treated with intravenous voriconazole, which was switched to oral formulation on discharge.Second case:The second patient presented with fever and post-auricular swelling with multiple discharging sinuses, and a past history of fever and hilar lymphadenopathy, which were previously empirically treated with ATT and broad-spectrum antibiotics. Imaging revealed osteomyelitis involving mandible, temporal bone and skull base, with underlying sigmoid sinus thrombosis. Pus and tissue samples showed hyaline septate hyphae in direct microscopy and growth of Aspergillus fumigatus in culture. The patient was successfully treated with a combination of intravenous voriconazole and liposomal amphotericin B, and discharged on oral posaconazole.Third case:The third patient presented with progressive painful swelling over the right upper chest, and a past history of pneumonia, hemoptysis, and mediastinal lymphadenopathy, which were previously empirically treated with ATT and broad-spectrum antibiotics. During a previous hospitalization, imaging showed features suggestive of fungal pneumonia; BAL showed hyaline septate hyphae in direct microscopy and growth of Aspergillus fumigatus and Aspergillus flavus in culture, providing a diagnosis of fungal pneumonia which was treated with voriconazole and liposomal amphotericin B. During the present admission, imaging of the chest lesion revealed pus collection with underlying rib osteomyelitis, communicating with a cavity in the middle lobe of the right lung. FNAC from the lesion showed hyaline septate hyphae in direct microscopy but no growth in culture (probably due to previous antifungal therapy). The patient was successfully treated with a combination of intravenous voriconazole and liposomal amphotericin B, and discharged on oral posaconazole.ConclusionsFungal pneumonia and fungal osteomyelitis are often misdiagnosed as tuberculosis or bacterial infections, leading to unnecessary and ineffective ATT or broad-spectrum antibiotics. A high index of suspicion for fungal osteomyelitis is required in pediatric patients with a history of recurrent/chronic soft tissue infections, preceded by febrile episodes and/or pneumonia, especially if a diagnosis of chronic granulomatous disease (CGD) has already been established; if not, this characteristic clinical picture should in fact warrant evaluation for CGD.

P303 An unusual case of isolated gluteal abscess

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMBackgroundMucormycosis is an invasive infection caused by fungi belonging to the order Mucorales. The angioinvasive disease caused by these fungi can prove to be fatal despite appropriate treatment. We report an unusual case of a gluteal abscess caused by a probable mucormycosis in an apparently immunocompetent individual.Case DescriptionA 68-year-old gentleman hailing from a rural area of Bihar, India presented with a painful swelling over the left buttock region for 4 weeks. He was a known hypertensive and had ischemic heart disease. He denied any history of fever. The lump had gradually increased in size. He was a retired school teacher with a farmland and reared livestock at home. He was a non-vegetarian and denied any addictions. He had a history of intermittent lower backache for which he used to take occasional intramuscular analgesic injections over his buttocks from a local medical practitioner.On examination, the swelling was about 4 cm X 4 cm in size, fluctuant, with ill-defined margins over the lateral region of the left buttock. The swelling was tender, warm, and not fixed to underlying structures. Systemic examination was unremarkable. Ultrasound examination revealed an ∼7.2 × 4.2 × 7.8 cm cystic lesion with a volume of 126cC. It was located predominantly in subcutaneous fat extending into muscular plane with septa and solid components in the left gluteal region (Fig. 1). It had thick walls and fine internal echoes within. Other investigations were unremarkable except for glycosylated Hb, which was 6.2%. Incision and drainage were done.During the procedure, it was seen as a cyst with a thick wall that was removed in toto. The contents were explored after removal and were found to be yellowish black with mucoid consistency. Histopathological examination revealed numerous broad, ribbon-like, aseptate fungal hyphae with right-angled branching infiltrating the inflamed tissue (Fig.2). There were numerous epithelioid granulomas surrounding the fungal elements in the soft tissue of the wall. The findings were consistent with a fungal abscess caused by mucormycosis. Culture of the fluid/pus was negative. Thus, a diagnosis of mucormycotic gluteal abscess was made and patient was commenced on 50 mg of amphotericin B deoxycholate in view of financial restraints. High resolution computed tomography of chest was done which was unremarkable.He developed an acute kidney injury after 2 doses of amphotericin B deoxycholate which was then stopped. Oral posaconazole was started. He has developed bilateral leg swelling post-oral posaconazole and is commenced on oral spironolactone for the same. The postoperative wound has healed well and there is no new swelling or tenderness over the area. He is planned for further follow-up.ConclusionsIsolated gluteal abscess caused by mucormycosis is rare in an apparently immunocompetent host.We assume that repeated intramuscular injections might have caused traumatic inoculation of fungus into the host which led to this outcome.

P317 Phaeohyphomycosis caused by Phialophora verrucosa in a patient with CARD9 mutations

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMObjectivesTo study an intractable case of phaeohyphomycosis caused by Phialophora verrucosa and the underlying genetic and immunological mechanisms.MethodsClinical and laboratory findings of the patient were studied. The patient's DNA was sequenced for CARD9. Innate and adaptive immunological responses of patient-derived PBMCs were evaluated with ELISA and flow cytometry.ResultsA 29-year-old Chinese male, born to nonconsanguineous parents, developed an enlarging plaque on his right anterior tibia at 25 years and underwent a 15-month treatment of oral itraconazole at the local hospital. Upon discontinuation of the medication, the plaque spread over his face, upper limbs, and back. Physical examination indicated dark brown verrucous plaques and nodules with surface ulcers and scabs on his right leg, upper limbs, and face. Skin biopsy revealed pigmented yeast cells with budding and yeast cell chain in the dermis. Based on tissue culture, we identified P. verrucosa as the causative pathogen, which was further validated by ITS, BT, and TEF gene sequencing. Thus, subcutaneous phaeohyphomycosis was diagnosed, and itraconazole combined with amphotericin B was prescribed. The lesions improved only marginally. We, therefore, gave him oral posaconazole instead, based on in vitro antifungal susceptibility results. After 1 month of posaconazole treatment, the serum BG assay value decreased and the lesions improved markedly.Based on previous reports linking CARD9 deficiency to phaeohyphomycosis, as well as early onset and recalcitrance characters, Sanger sequencing was performed in this patient and identified two compound heterozygous mutations in exon 6 (R373P) and exon 8 (D274GfsX60) of CARD9. We then evaluated the functional effect of the CARD9 mutations by assessing the stimuli-dependent release of proinflammatory cytokines and helper T cell differentiation. Cytokine production was markedly impaired in PBMCs post 24 h of stimulation with LPS, curdlan, TDB, mannan, MDP, β‐glucan, and various fungal ligands. Moreover, the patient showed a significant absence in Th22 and Th17 cell proportions, as well as lower IL-17A and IL-22 production after six days of co-incubation with the stimuli mentioned above.ConclusionOur report highlighted that otherwise healthy patients diagnosed with early-onset, unexplained, and recalcitrant phaeohyphomycosis should be analyzed for CARD9 mutations and immune deficiency. Furthermore, posaconazole may be an alternative worth trying after the failure of other antifungals due to its ideal results achieved in our case.

P299 A clinicomycological study of suspected mucormycosis in post-COVID patients attending a tertiary care hospital

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PM ObjectiveTo study the fungal etiology, clinical, and epidemiological profile of suspected mucormycosis in post-COVID patients.MethodsA prospective observational study was undertaken over a period of 10 months from March to December 2021. A total of 175 biopsy samples were collected from 150 suspected cases of post-COVID mucormycosis patients in sterile normal saline at the ENT department and received in the department of microbiology. MRI of brain, orbital, and paranasal sinus was done in all patients.Tissue specimens were examined by direct KOH mount and cultures were inoculated on SDA with chloramphenicol and incubated at 22°C and 37°C for a minimum of 3-5 days and up to 4 weeks before declaring negative. The cultures were identified based on standard mycological protocols.ResultsThe prevalence of mucormycosis laboratory confirmed was found to be 42.66%. Out of 150 patients, 47 were KOH positive while 33 were culture positive. The most common isolate was Rhizopus arrhizus (84.85%) followed by R.microsporus var. rhizopodiformis (9.09%), Rhizomucor pusillus (3.03%), and Saksenaea vasiformis (3.03%).Rhino-orbital-cerebral mycormycosis was the most common clinical form (33 cases). Diabetes mellitus was the most common predisposing factor n = 112 (74.66%). Many patients had multiple symptoms like periorbital swelling (52%), headache (44.7%), fever (41.3%), loss of vision (16%), facial swelling (27.3%), and nasal pain (8.7%). Invasive fungal sinusitis was seen in MRI in 116 (77.33%) cases.Tissue debridement was done in all positive patients along with treatment with liposomal amphotericin B (1.5-5.0 mg/kg/d) and then switched over to oral posaconazole 300 mg BD on the first day then 300 mg OD for several weeks. Inspite of rigorous treatment in 4.6% cases the prognosis was not good resulting in mortality. Also, in 40% of the patients who recovered, long-term morbidity related to vision was observed.ConclusionPresent study determined the fungal etiology of post covid mucormycosis with R. arrhizus being the most common cause in our region compared to other studies from India. The identification of risk factors, clinical features, and laboratory findings helped in early diagnosis, leading to prompt treatment, and favorable outcomes. With diabetes mellitus being the most common predisposing factor seen, it is suggested that a holistic approach to prevent, revert and treat this condition needs to be strengthened.

Single-Stage Reconstruction of Maxillectomy and Midfacial Defects in Cases of Covid Associated Mucormycosis.

ObjectiveTo advocate a single stage reconstruction in cases of maxillectomy and midfacial defects operated for covid associated mucormycosis to enable a favorable overall outcome within a shorter duration in terms of survival, quality of life, speech, deglutition and aesthetics.MethodIn our series of six patients with signs and symptoms suggestive of covid associated mucormycosis with diabetes as a predisposing factor had undergone Contrast enhanced CT and MRI with biopsy confirming the diagnosis, were then subsequently posted for resection and reconstruction depending upon extent of disease and defect left behind. Out of six, three were revision cases and the other three were primary cases. All had undergone single stage reconstruction using free flap (5/6) and pedicle (1/6) after intra-operative margins and distal most part of recipient vessels was found negative for mucormycosis on histopathology. Post-operative Liposomal Amphotericin B with Oral Posaconazole along with antibiotics and supportive treatment were given and were then followed up.ResultsAll the cases have complete flap survival after a mean follow-up of 90 days with no recurrence of mucormycosis. We had a survival rate of 100% with patients having good quality of life, speech, deglutition and acceptable aesthetical outcome.ConclusionStepping up on the reconstruction ladder to provide a single stage management in patients of covid associated mucormycosis by adequate surgical debridement, intraoperative negative margins on histopathology and subsequent reconstruction using autologous flaps is the need of the hour to provide within a shorter duration, favourable overall outcome in terms of survival, quality of life, speech, deglutition and aesthetics.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12070-022-03121-1.

Factors associated with subtherapeutic levels of oral posaconazole tablet: a detailed analysis from a tertiary care center in India

ObjectivesPosaconazole is a broad-spectrum triazole antifungal, with activity against various clinically important fungi. The delayed release (DR) tablet of posaconazole has been shown to have a superior pharmacokinetic profile in comparison with the oral suspension. MethodsWe retrospectively analyzed the factors associated with posaconazole levels <1.25 μg/ml in 164 patients receiving the DR tablet for therapeutic purposes. ResultsOf the 164 patients, 53 (32.3%) showed subtherapeutic trough levels of posaconazole. The use of proton pump inhibitors (95% CI 1.41-3.91; P-value = 0.028) and the presence of diarrhea (95% CI 1.95-6.93; P-value = 0.001) were significantly associated with subtherapeutic levels. A total of 13 of the 21 patients receiving posaconazole tablets through a nasogastric tube had therapeutic levels. ConclusionThis is the largest study from India that analyzed factors associated with subtherapeutic levels of the DR tablet of posaconazole. These findings reinforce the importance of therapeutic drug monitoring. Unlike in previous studies, obesity and hypoalbuminemia were not found to be significant factors in our settings. The use of proton pump inhibitors and diarrhea remained significant factors, as found in previous studies. Administering the DR tablet of posaconazole through a nasogastric tube may be a viable option.

Rhino-Orbital Mucormycosis in a COVID-19 Patient: A Dreadful Challenge

Coronavirus disease 2019 (COVID-19) is a pandemic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). COVID-19 infections may be associated with a wide range of bacterial and fungal co-infections. Recent studies are reporting invasive fungal infection associated with severe COVID-19. Herein, we report a case of COVID-19 rhino-orbital mucormycosis infection caused by Rhizopus sps in a 32 year old diabetic patient who was successfully managed with early aggressive debridement of infected tissue endoscopically with extended ethmoidectomy by modified Denker’s approach along with orbital decompression and antifungal therapy with Liposomal Amphotericin B and Posaconazole. Serial diagnostic nasal endoscopy showed no evidence of progression of the infection. The patient was discharged on 21st day of hospitalization still on oral Posaconazole for a total of 3 months.

Fungal Endophthalmitis in a Case of Rhino-Orbito-Cerebral Mucormycosis: Successfully Treated With Amphotericin B Colloidal Dispersion.

BackgroundRhino-orbito-cerebral mucormycosis (ROCM) is an acute, fulminant, opportunistic fungal infection that usually occurs in diabetes or immunocompromised patients. Amphotericin B combined with surgical debridement remains the standard treatment, although it is controversial due to its lager nephrotoxicity. Thus far, no studies have reported the treatment for ROCM-associated fungal endophthalmitis because the exact pathogenesis and transmission routes in ROCM remain unclear. Here, we reported a case of ROCM complicated with fungal endophthalmitis treated favorably with amphotericin B colloidal dispersion (ABCD) in combination with other antifungals and surgical debridement.Case PresentationA 34-year-old woman with diabetes was admitted to our hospital owing to right-sided headache for 8 days, blindness with swelling in the right eye for 5 days, and blindness in the left eye for 1 day. MRI showed that the patient had sphenoid sinus, sinuses, frontal lobe lesions, and proptosis of the right eye. Metagenomic sequencing revealed that the patient had Rhizopus oryzae infection. During hospitalization, the patient received intravenous ABCD, oral posaconazole, and topical amphotericin B and underwent surgical debridement. After 67 days of treatment, the patient’s condition was significantly improved, and limb muscle strength showed grade V. Rhizopus oryzae showed negative results, and conjunctival swelling decreased. Additionally, no nephrotoxicity occurred during treatment. After discharge, the patient’s treatment was transitioned to oral posaconazole and she was free of complaints during the 30-day follow-up without any additional treatment for ROCM.ConclusionTreatment with ABCD combined with other antifungal drugs and surgical debridement for ROCM complicated with fungal endophthalmitis showed remarkable efficacy and good safety. Hence, this regimen is a promising treatment strategy for this fatal disease.

A study on clinico-radiological profile, risk factors, and management of mucormycosis during COVID pandemic in Rewa, (M.P.)

Background: Second wave of coronavirus disease 2019 (Covid-19) pandemic has been particularly devastating in India. COVID-19 and mucormycosis (also known as black fungus) are causing comorbid conditions to worsen the extent of infection and mortality rates especially in India. Mucormycosis can involve nose, sinuses, orbit, central nervous system, lung (pulmonary), gastrointestinal tract any many other organs, but rhino orbital cerebral mucormycosis is the most common variety seen. Rapidity of dissemination of mucormycosis is an extraordinary phenomenon and a delay in the diagnosis could be fatal. Aims and Objectives: The objective of this study is to document the clinical features, radiological extent, risk factors, management,and outcome of mucormycosis. Materials and Methods: The study was retrospective observational study. Eighty-two mucormycosis patients admitted in SGMH Rewa were selected as study subjects. Data regarding clinical features, radiological extent, associated risk factors, comorbidities, management during hospital stay, and outcome of mucormycosis patients were collected on excel sheet and analyzed using appropriate statistical tests. Results: In our study, majority of the patients were unvaccinated (88%). Most common presenting complaint was nasal congestion with or without discharge in 78% patients followed by Facial swelling, visual disturbances, facial weakness, dental pain, etc. On CT or magnetic resonance imaging examination, all cases of mucormycosis had maxillary sinus (100%) involvement, followed by ethmoid (82%) and sphenoid (78%) sinuses. Diabetes mellitus was most common comorbidity seen in 52% cases. About 83% cases had history of receiving high dose steroid intravenously during management of COVID illness. Among study cases 72% patients have taken oxygen supplementation for more than 72 h, for COVID-19 pneumonia before hospitalization for mucormycosis. Therapy of Liposomal Amphotericin B and Oral Triazole (predominantly oral Posaconazole) was the most common medical treatment offered to all patients with COVID associated mucorpatient. Functional endoscopic sinus surgery was done on 93% cases followed by Modified Denker’s procedure was done in 12% cases. Conclusion: In our study, mucormycosis appears to be associated with COVID-19, diabetes, and use of corticosteroids. Full vaccination with COVID-19 vaccines, judicious use of corticosteroids in patients with COVID-19 and strict control of blood glucose level along with timely and proper management is highly recommended to reduce the incidence of fatal mucormycosis.

Breakthrough Penile Mucormycosis in a Patient With Acute Myelogenous Leukemia on Posaconazole Prophylaxis

Abstract In patients with acute myelogenous leukemia, posaconazole prophylaxis has been shown to prevent deep invasive fungal infections, including mucormycosis. In the present case, posaconazole prophylaxis was initiated in a 58-year-old man undergoing induction chemotherapy for acute myelogenous leukemia. Three weeks after initiating chemotherapy, he developed a tender violaceous macule on the shaft of his penis. The initial differential included fixed drug eruption versus pyoderma gangrenosum. However, punch biopsy ultimately showed mucormycosis, and cultures grew Rhizopus species, despite therapeutic posaconazole trough. He was treated with intravenous amphotericin B and required right orchiectomy, penectomy, and hyperbaric oxygen therapy. Oral posaconazole was reinstituted after completion of amphotericin B course, and at 4 months follow-up, his penectomy site was fully healed. As demonstrated by the present case, not all mucormycoses are prevented by posaconazole prophylaxis. A high index of suspicion and early biopsy for prompt diagnosis are of critical importance in improving outcomes.

Epidemiology, clinical presentation and management of COVID-19 associated mucormycosis: A single centre experience from Pune, Western India.

BackgroundThe second COVID‐19 wave in India has been associated with an unprecedented increase in cases of COVID‐19 associated mucormycosis (CAM), mainly Rhino‐orbito‐cerebral mucormycosis (ROCM).MethodsThis retrospective cohort study was conducted at Noble hospital and Research Centre (NHRC), Pune, India, between 1 April, 2020, and 1 August, 2021, to identify CAM patients and assess their management outcomes. The primary endpoint was incidence of all‐cause mortality due to CAM.Results59 patients were diagnosed with CAM. Median duration from the first positive COVID‐19 RT PCR test to diagnosis of CAM was 17 (IQR: 12,22) days. 90% patients were diabetic with 89% having uncontrolled sugar level (HbA1c >7%). All patients were prescribed steroids during treatment for COVID‐19. 56% patients were prescribed steroids for non‐hypoxemic, mild COVID‐19 (irrational steroid therapy), while in 9%, steroids were prescribed in inappropriately high dose. Patients were treated with a combination of surgical debridement (94%), intravenous liposomal Amphotericin B (91%) and concomitant oral Posaconazole (95.4%). 74.6% patients were discharged after clinical and radiologic recovery while 25.4% died. On relative risk analysis, COVID‐19 CT severity index ≥18 (p = .017), presence of orbital symptoms (p = .002), presence of diabetic ketoacidosis (p = .011) and cerebral involvement (p = .0004) were associated with increased risk of death.ConclusionsCAM is a rapidly progressive, angio‐invasive, opportunistic fungal infection, which is fatal if left untreated. Combination of surgical debridement and antifungal therapy leads to clinical and radiologic improvement in majority of cases.

Posaconazole bioavailability of the solid oral tablet is reduced during severe intestinal mucositis

ObjectivesThis study aimed to describe the absolute oral bioavailability of the solid oral formulation of posaconazole and the impact of severe intestinal mucositis in haematology patients. This study also aimed to describe posaconazole protein binding in haematology patients. MethodsA pharmacokinetic study was performed of patients receiving induction chemotherapy or a haematopoietic cell transplantation who were randomized to receive 7 days of intravenous posaconazole therapy followed by 9 days of oral therapy, or vice versa. Patients received a posaconazole licensed dose until day 12, after which a reduced once-daily dose of 200 mg was given. At days 7, 12, and 16, blood samples were obtained for pharmacokinetic curves, and trough samples were collected on all other days. Total and unbound posaconazole pharmacokinetics were analyzed by population pharmacokinetic modelling. The presence of severe intestinal mucositis was assessed by plasma citrulline levels and analyzed as a binary covariate using 10 μmol/L as the cut-off. Monte Carlo simulations were performed to simulate posaconazole exposure at a steady state. ResultsTwenty-three patients were included for analysis, with 581 total posaconazole concentrations and 91 paired unbound concentrations. Absolute bioavailability in the final model was estimated at 51.4% (percentage relative standard error (%RSE): 56.5) and 67.6% (%RSE: 75.0) in patients with and without severe intestinal mucositis, respectively. Posaconazole unbound fraction was estimated at 2.7% (%RSE: 3.9). DiscussionPosaconazole bioavailability is reduced in haematological patients with severe intestinal mucositis, requiring an increase in oral posaconazole dose to 400 mg twice daily on day 1, followed by 400 mg once daily or a switch to intravenous therapy.

Post-COVID, neurosurgical interventions in rhinocerebral mucormycosis, an institutional experience

Objective: Mucormycosis is an opportunistic, fungal infection, often lethal fungal infection which occurs in immunocompromised patients. However, in this second phase of COVID-19, we faced many post-COVID mucormycosis cases at our institution, IGIMS, Patna. We present our experience in eight patients with this condition who underwent neurosurgical interventions.Patients and Methods: A prospective study for eight patients underwent neurosurgical interventions for rhinocerebral mucormycosis. All cases were operated by same surgeons from ENT and Neurosurgery.Results: Total 42 patients referred for neurosurgical opinion, out of that eight patients taken for neurosurgical interventions. Out of 8, seven patients had COVID reverse transcription-polymerase chain reaction (RT-PCR) positive and treated with steroid and oxygen inhalation and one patient had fever but COVID RT-PCR was negative and treated at home with oxygen cylinder. All of them were treated with either liposomal amphotericin B/amphotericin B or oral posaconazole. Sinus surgery was performed in all eight patients by ENT surgeons, two underwent orbital exenteration by eye surgeon, five patients underwent open craniotomy for cerebral infection while in two patients, cerebral exploration done endoscopically. Six patients survived, while two patients died.Conclusion: Patients with rhino-cerebral mucormycosis spreading outside the sinonasal cavity to the base of brain can be treated successfully to some extent by neurosurgical interventions.

Mucormycosis in the setting of the Covid-19 pandemic in patients without exposure to steroids and oxygen: A case series from a tertiary care center in North India

Background: Sudden surge of mucormycosis cases in India needs an urgent attention as multiple factors have been implicated. However, diabetes mellitus remains to be one of the most important and modifiable factors. Methodology: We prospectively followed 11 patients with mucormycosis in May 2021 and June 2021, admitted to our hospital to study the possible etiologies. Results: Out of the 11 patients, six were males and five were females, with an average age of 52.45 years. Type 2 diabetes mellitus was the ubiquitous comorbidity, and every patient presented with uncontrolled hyperglycemia (six out of them were in diabetic ketoacidosis). Glycated hemoglobin levels ranged from 10.2% to 15.1%. Out of 11 patients, four patients were non-COVID, whereas five patients had a history of COVID-19 infection. All these five post COVID-19 patients presented approximately 20 days after recovery, out of which one patient had severe infection who was hospitalized. The remaining two patients were COVID-19-positive. Out of 11 patients, 10 patients had rhino-orbital mucormycosis at presentation, among which four patients had cerebral involvement, and one out of them later developed invasive disease. However, one patient had only pulmonary mucormycosis at presentation. Serum ferritin was raised in all the patients, and six had serum zinc levels below the reference range. Serum flow cytometry showed leukopenia with normal CD4:CD8 ratio in seven patients. In the clinical outcome, six patients expired, whereas five patients responded to the treatment and were discharged on oral posaconazole therapy. Conclusion: From our study, it is quite evident that uncontrolled diabetes and its complications such as diabetic ketoacidosis were an important risk factor for the occurrence of mucormycosis in COVID-19 patients as well as non-COVID-19 patients, even without exposure to steroids or oxygen. Thus, blood glucose levels should be kept at optimum level during the management of COVID-19 patients.

COVID-19 Induced Immunosuppression resulting in Pulmonary Mucormycosis : A Long COVID sequalae

With increasing incidence of Severe Acute Respiratory Distress Virus 2(SARS -CoV -2) in India, there has been growing reports of super infections in post covid 19 period. Long COVID refers to persistence of COVID19 symptoms for weeks to months. While most common manifestation of long COVID is fatigue and ill health, it may lead to development of life-threatening complications like Pulmonary Mucormycosis. We report a case of 54 year young, non-diabetic previously healthy male who had moderate COVID19 treated with low dose steroids and recovered completely, only to present with hemoptysis 3 months later on High Resolution Computed Tomography Scan of the Chest and Rhizopus fungi on bronchoalveolar lavage confirming Post Covid Pulmonary Mucormycosis in non-immunocompromised host. Patient was managed with dual antifungal therapy intravenous Liposomal Amphotericin B and Posaconazole for 3 weeks, followed by oral Posaconazole. J MEDICINE 2021; 22: 150-154

POSACONAZOLE INDUCED PSEUDOHYPERALDOSTERONISM WITH CONCURRENT ACUTE PRIMARY ADRENAL INSUFFICIENCY-A CASE REPORT

In this covid 19 pandemic,there were increased incidence of Mucormycosis and thereby increase in usage of antifungals especially oral posaconazole which is more recently available in tablet form.There are already enough case reports of the incidence of new onset hypertension and hypokalemia with supressed renin and aldosterone which is termed as “Posaconazole induced pseudohyperaldosteronism”.We describe here about a similar case that presented with hypertensive urgency as Acute pulmonary edema with an associated primary adrenal insufciency.The potential mechanism include inhibition of 11 β HSD which degrades cortisol to cortisone,thereby increasing the levels of cortisol that stimulates Mineralocorticoid receptor.Also there is inhibition of steroidogenesis at the level of adrenal which in our patient presented with features of Acute adrenal insufciency.

Comprehensive study on manifestation, management and outcome of post COVID rhino orbito cerebral mucormycosis in our institution

&lt;p class="abstract"&gt;Rhino orbital mucor mycosis in covid infected patients presented a challenge in management. We tried analysing comprehensively the manifestations and management and prognosis of post COVID rhino orbito cerebral mucormycosis (ROCM) patients in our institution. Patients with symptoms of ROCM were managed according to the guidelines issued by the directorate of medical education, Tamil Nadu, India. 30 possible ROCM patients were treated so far from May 2021. Patients underwent radiological, microbiological and pathological investigation. In stage 1, nasal cavity alone was involved in 11 patients. In stage 2, paranasal sinus extension was seen in 8 patients. In stage 3, orbital extension was seen in 10 patients. In stage 4, intra cranial extension was seen in 1 patient. 10 patients were probable ROCM without microbiological or pathological evidence. 20 patients had proven ROCM. They were treated with endoscopic debridement. Out of them 10 patients had to undergo orbital decompression and 5 of them had improvement in vision. All proven ROCM patients were treated with 3 weeks of injection liposomal amphotericin B along with oral posaconazole 300 mg for 3-6 weeks. Post-operative histopathology noted fungal invasion of blood vessels in 19 cases and thrombus in 10 cases of orbital involvement. No mortality was reported in the study group. COVID variant associated thrombosis may be the reason for increased incidence of mucor mycosis in post COVID patients. Team work, appropriate guidelines and adequate supply of medications helped in achieving desired outcome.&lt;/p&gt;

CHRONIC CAVITARY PULMONARY ASPERGILLOSIS IN A PATIENT WITH IDIOPATHIC PULMONARY FIBROSIS

TOPIC: Diffuse Lung Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Chronic cavitary pulmonary aspergillosis (CCPA) is a rare form of aspergillosis involving patients with structural lung diseases. Here we will describe a case of CCPA in a patient with idiopathic pulmonary fibrosis (IPF), which is rarely reported. CASE PRESENTATION: The patient was a 78-year-old male with a medical history significant for IPF diagnosed 13 years prior, on oral pirfenidone and long-term oxygen therapy, who presented to the hospital for worsening shortness of breath, productive cough, and fatigue of two months duration. The patient was initially hospitalized in another facility for the above symptoms where he received two courses of antibiotics without significant improvement. Chest examination showed bilateral fine inspiratory crackles, worse on the right side. The results of routine blood tests were normal. The nasal swab for the respiratory viral panel was negative. Chest X-ray showed fibrotic lung disease with a superimposed alveolar and interstitial process involving the lung bases and right upper lobe. Computed Tomography (CT) scan of the chest was suggestive of a thick-walled cavitary lesion in the right apex measuring 4.8 x 3.3 cm, enlarged mediastinal and right hilar lymph nodes along with other chronic changes. Three sets of sputum acid-fast bacilli (AFB) smears along with serum Quantiferon TB gold plus test were negative. The patient was empirically started on intravenous (IV) ceftriaxone and azithromycin. Later, blood and sputum cultures were reported negative for bacteriological growth. Interestingly, the sputum cultures were positive for Aspergillus species along with positive serum Aspergillus immunoglobulin (Ig)G level. The patient was diagnosed with CCPA based on the serology, culture results, and radiological findings. IV antibiotics were discontinued and the patient was started on oral posaconazole 300 mg daily resulting in clinical improvement. Currently, the patient is on a 6-month posaconazole regimen. DISCUSSION: Pulmonary aspergillosis is a common opportunistic infection that can present as aspergilloma, allergic bronchopulmonary aspergillosis, CCPA, and invasive pulmonary aspergillosis based on lung changes. Mycobacterium infection and obstructive lung diseases are the most frequent underlying pulmonary diseases that are associated with CCPA. However, IPF with CCPA is rare, and its clinical features and radiological findings lack specificity leading to delays in diagnosis and treatment. Once confirmed, the treatment is straightforward with long-term triazole antifungals. CONCLUSIONS: In a patient with IPF, presenting with rapidly progressing radiologic findings suggestive of pulmonary cavitation, CCPA should be considered in the differential diagnosis. REFERENCE #1: Liu C, Yang J, Lu Z. Idiopathic pulmonary fibrosis with chronic necrotizing pulmonary aspergillosis: a case report. Int J Clin Exp Pathol. 2019 Jul 1;12(7):2653-2656. PMID: 31934094; PMCID:PMC6949565 REFERENCE #2: Graham KG, Nasir A. Chronic Cavitary Pulmonary Aspergillosis: A Case Report and Review of the Literature. Am J Case Rep. 2019 Aug 18;20:1220-1224 doi: 10.12659/AJCR.915893. PMID: 31422416; PMCID: PMC6711266. REFERENCE #3: Sehgal IS, Dhooria S, Muthu V, Prasad KT, Agarwal R. An overview of the available treatments for chronic cavitary pulmonary aspergillosis. Expert Rev Respir Med. 2020 Jul;14(7):715-727. doi: 10.1080/17476348.2020.1750956. Epub 2020 Apr 20. PMID: 32249630. DISCLOSURES: No relevant relationships by Rabab Elmezayen, source=Web Response No relevant relationships by Syed yousaf Shah, source=Web Response

High-Dose Oral Posaconazole for the Treatment of Recalcitrant Fungal Keratitis.

To report the successful treatment of 3 cases of recalcitrant fungal keratitis (FK) with high-dose oral posaconazole. This is a series of 3 patients from a single academic center with a culture-positive FK who were treated with oral posaconazole after failing to respond to conventional treatments. All 3 patients had a history of contact lens wear. Two of the 3 cases were culture positive for Fusarium and the other for Paecilomyces . The infections of all 3 failed to respond to conventional antifungal therapies including varying combinations of topical, systemic, and intraocular antifungal therapies. All 3 cases rapidly responded to high-dose oral posaconazole ranging from 500 to 600 mg once daily. In 1 case, multiple courses of high-dose therapy were required to treat delayed recurrences of a latent infection. There were no significant adverse effects with the elevated dose, and treatment was administered with the guidance of an infectious disease specialist. In cases of recalcitrant FK failing to respond to conventional therapies, high-dose posaconazole, in the delayed-release tablet formulation, can be an effective treatment option.