Intravenous Liposomal Amphotericin Research Articles

A Rare Case of Coronavirus Disease 2019 Encephalitis Mimicking Creutzfeldt-Jacob Disease in an Immunocompromised Patient: A Case Report.

Coronavirus disease 2019 (COVID-19) encephalitis is characterized by viral entry into the brain, resulting in inflammation and a cascade of neuronal damage. Clinical manifestations include headaches, seizures, and movement disorders. A mortality rate of 20% and infrequent presentation make COVID-19 encephalitis a diagnostic challenge. We hereby present the case of a 55-year-old man with a history of diabetes mellitus (potential impact on COVID-19 severity discussed in the supplementary material) presenting with altered sensorium, swelling in the left eye, and involuntary jerky limb movements. Neurological examination revealed neck rigidity, myoclonic jerks, and an extensor plantar response. Brain magnetic resonance imaging (MRI) was performed, which revealed cortical enhancement in the bifrontal, temporal, and occipital lobes. Rapid progression of myoclonus, altered sensorium, and cortical enhancement on MRI suggested Creutzfeldt-Jacob disease. After a thorough workup, the diagnosis was COVID-19 encephalitis with rhino-orbital mucormycosis. The treatment regimen consisted of adequate glycemic control, remdesivir injection, intravenous and retroorbital liposomal amphotericin, and levetiracetam. The patient's condition improved, and he was eventually discharged. This case illustrates the uncommon presentation of COVID-19 with neurological involvement and emphasizes the value of history-taking, neuroimaging, and cerebrospinal fluid analysis. A high index of suspicion is critical for a prompt diagnosis and initiating therapy.

Risk factors and clinical presentation of rhino-orbital mucormycosis: Lesson learnt during Covid pandemic.

To analyze the potential predisposing factors and clinical presentation of mucormycosis in patients with COVID-19. Medical records of 141 patients with COVID-19-associated mucormycosis (CAM) treated at a tertiary care center in Bihar were reviewed. The predisposing factors, clinical features, and imaging findings of mucormycosis were analyzed. The median age was 48 years (IQR, 43-60). A total of 58 patients developed concurrent CAM and 83 post-CAM. The median interval between COVID-19 and onset of CAM symptoms was 15 days (IQR, 9-16). A total of 80 patients received at-home treatment for COVID-19, and 73 had mild-to-moderate disease. While 61 patients received in-hospital treatment, 57 had severe disease. At presentation, 131 patients had hyperglycemia: 64 type 2 diabetes mellitus (DM) and 67 new-onset DM. The history of glucocorticoid use for COVID-19 was present in 125 patients; 47% were administered at home without monitoring plasma glucose. The common presenting features were toothache, periocular or facial pain, and edema. Rhino-orbital mucormycosis was the most common. Imaging revealed rhinosinusitis in all patients, including pansinusitis (68%), pterygopalatine fossa involvement (21%), cavernous sinus thrombosis (38%), brain abscess (8%), and infarct (4%). All patients received intravenous liposomal amphotericin B, and surgical debridement was performed in 113. COVID-19 patients with hyperglycemia are at risk of developing CAM, irrespective of the severity. Timely recognition of symptoms and prompt initiation of therapy by primary healthcare physicians are imperative for enhancing outcomes. Additionally, glucocorticoid overuse should be avoided, and close monitoring for hyperglycemia development is warranted.

Rhino-orbital mucormycosis during COVID-19 pandemic: our clinical experience

Background: The ongoing COVID-19 pandemic declared by the WHO was compounded by the sudden and unexpected increase of Rhino-orbital mucormycosis infections during the year 2021. Mucormycosis a life-threatening infection, with added COVID-19 infection further increases the morbidity and mortality of the disease. Our aim is to shed some light on possible risk factors, treatment options and outcomes when these diseases occur together. Methods: 22 cases diagnosed with rhino-orbital mucormycosis with history of COVID-19 infection were selected. Cases underwent surgical and medical management. Patients were followed up for 3 months and were continued on medical treatment and regular post-operative DNE, CECT PNS and brain and relapses were treated accordingly. Results: Of these 22 patients, 15 were males and 7 were females ranging between 31-60 years. 15 (68.18%) had history of DM, 16 (72.72%) gave history of oxygen therapy and 18 (81.82%) had history of high dose steroid therapy. 15 (68.18%), 4 (18.18%) and 3 (13.64%) respectively underwent Endoscopic debridement, Total maxillectomy and Medial maxillectomy. There were 3 cases of relapse which were managed with additional full course treatment with Intravenous Liposomal Amphotericin B. Conclusion: COIVD-19 and uncontrolled DM to both be probable pre-disposing factors for developing Mucormycosis. Oxygen therapy & high dose of steroids used in the treatment of COIVD-19 may increase incidences of mucormycosis. Early treatment with surgery is necessary to reduce the need for more radical procedures and improving the recovery.

Histopathology of a polyploid laryngeal growth revealing disseminated histoplasmosis

Abstract Any polyploid growth in the laryngeal region may be mistaken for a malignant condition. Histoplasmosis of the larynx rarely causes laryngitis; it often masquerades as malignancy or tuberculosis. The other name of this condition is “Cave’s disease” and is caused by the fungus, Histoplasma capsulatum. Here, we report a 54-year-old diabetic male who presented with a history of progressive hoarseness of voice for 6 months. The patient was a chronic smoker for 15 years. A biopsy of the growth was done, and a histopathological examination of the tissue clinched the diagnosis of laryngeal histoplasmosis. The patient was managed with intravenous liposomal amphotericin B and oral itraconazole with complete resolution of symptoms.

Invasive fungal infections in critically ill children: epidemiology, risk factors and antifungal drugs.

Invasive fungal infections (IFIs) are important infectious complications amongst critically ill children. The most common fungal infections are due to Candida species. Aspergillus, Zygomycetes and Fusarium are also emerging because of the empirical use of antifungal drugs. This updated review discusses the epidemiology of IFIs as well as antifungal drugs, dosing and potential adverse effects in critically ill children. A PubMed search was conducted with Clinical Queries using the key terms "antifungal", "children", "critical care" AND "paediatric intensive care unit" OR "PICU". The search strategy included clinical trials, randomized controlled trials, meta-analyses, observational studies and reviews and was limited to the English literature in paediatrics. Candida and Aspergillus spp. are the most prevalent fungi in paediatric IFIs, causing invasive candidiasis infections (ICIs) and invasive aspergillosis infections (IAIs), respectively. These IFIs are associated with high morbidity, mortality and healthcare costs. Candida albicans is the principal Candida spp. associated with paediatric ICIs. The risks and epidemiology for IFIs vary if considering previously healthy children treated in the paediatric intensive care unit or children with leukaemia, malignancy or a severe haematological disease. The mortality rate for IAIs in children is 2.5-3.5-fold higher than for ICIs. Four major classes of antifungals for critically ill children are azoles, polyenes, antifungal antimetabolites and echinocandins. Antifungal agents are highly efficacious. For successful treatment outcomes, it is crucial to determine the optimal dosage, monitor pharmacokinetics parameters and adverse effects, and individualized therapeutic monitoring. Despite potent antifungal medications, ICIs and IAIs continue to be serious infections with high mortality rates. Pre-emptive therapy has been used for IAIs. Most guidelines recommend voriconazole as initial therapy of invasive aspergillosis in most patients, with consideration of combination therapy with voriconazole plus an echinocandin in selected patients with severe disease. The challenge is to identify critically ill patients at high risks of ICIs for targeted prophylaxis. Intravenous/per os fluconazole is first-line pre-emptive treatment for Candida spp. whereas intravenous micafungin or intravenous liposomal amphotericin B is alternative pre-emptive treatment.This article is part of the Challenges and strategies in the management of invasive fungal infections Special Issue: https://www.drugsincontext.com/special_issues/challenges-and-strategies-in-the-management-of-invasive-fungal-infections.

Surveillance for COVID-19 associated mucormycosis: A coordinated effort in prevention and management of rhino-orbital mucormycosis

Abstract Context: Patients of coronavirus disease 2019 (COVID-19) and factors inducing a diabetogenic state are at increased risk for rhino-orbital mucormycosis (ROM). Efforts to diagnose ROM in its pre-clinical stage would avoid the disease and its consequences. Aim: This study aimed to diagnose ROM in the pre-clinical stage of the disease in high-risk patients and treat patients accordingly. Settings and Design: This is a single-center, prospective study conducted at a tertiary care center in Northern India in collaboration with departments of Otolaryngology, Internal Medicine, and Mycology. Materials and Methods: Fifty-three high-risk patients were enrolled in the study, and all underwent bedside nasal endoscopy with tissue sampling for fungal culture. Patients with suspicious nasal endoscopy findings but negative fungal culture were prescribed oral posaconazole. Those with positive fungal hyphae on nasal endoscopy and culture underwent surgical intervention followed by intravenous amphotericin B, while the remaining patients were kept on follow-up. Statistical Analysis Used: Statistical analysis was performed using the Statistical Package for Social Sciences software. Results: Among the 53 patients, 13 (24.5%) patients had abnormalities on nasal endoscopy, while the remaining 40 (75.5%) patients had normal nasal mucosal cavities. Seven patients (13.2%) underwent surgery and received intravenous liposomal amphotericin B, while another 7 (13.2%) received oral posaconazole. Thirty-five (66.03%) patients were placed under observation, and 4 (7.5%) patients died due to COVID-19-related illness. Conclusions: Nasal endoscopic-guided tissue sampling for fungal culture serves as a valuable surveillance tool for predicting ROM in COVID-19 patients.

Intravenous Liposomal Amphotericin B Efficacy and Safety for Cutaneous and Mucosal Leishmaniasis: A Systematic Review and Meta-analysis.

Tegumentary leishmaniasis is often subject to limited funding, underpowered studies, and a paucity of high-quality interventional studies. Intravenous liposomal amphotericin B (L-AmB) has been increasingly used to treat cutaneous and mucosal leishmaniasis (CL and ML, respectively) despite the lack of well-conducted interventional studies. We conducted a systematic review to consolidate the descriptive evidence on the efficacy and safety of L-AmB in treating CL and ML. Several online databases and the reference lists of included studies were searched to extract data from 132 studies comprising both case reports and case series. The population, intervention, comparison, outcome, and study design strategy and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used. Of 132 studies included, 92 were case reports and 40 were case series. Of the 92 cases, 65 (82.3%) were considered cured after receiving L-AmB as part of their treatment regimen. Twenty-one of the 92 (22.8%) cases reported adverse reactions to L-AmB. A pooled cure rate of 87.0% (95% CI, 79.0%-92.0%) was reported for the 38 case series that reported on treatment efficacy; 40.7% of the cases were associated with an adverse reaction. Observational data on cure rates using L-AmB suggest efficacy between 80% and 90%, similar to rates reported for other antileishmanial drugs. The highest efficacy rates were observed when a single cycle of L-AmB was administered to patients with mild-moderate CL and ML. The limitations of this study include the heterogeneity observed among the included studies and the increased likelihood of publication bias associated with the inclusion of case reports and case series. This systematic review further illustrates the need for high-quality comparative trials of intravenous L-AmB for the treatment of tegumentary leishmaniasis.

P21 Facial papules in an immunocompromised patient

Abstract A 29-year-old man presented with a 6-week history of clustered facial papules. Of note, he had a diagnosis of HIV 5 months previously and was on maintenance antiretroviral treatment. His initial CD4 count was 5, which increased to 38, and his viral load was now no longer detectable. He had also been treated for cytomegalovirus reactivation, pneumocystis pneumonia and suspected mycobacterium infection for the previous 3 months. He had ongoing symptoms of malaise, fevers, weight loss and nausea, along with abnormal liver function tests and a raised C-reactive protein. A bone marrow trephine showed noncaseating discrete small granulomas; Grocott and periodic acid–Schiff (PAS) stains were negative. Prior to his dermatology review, the papules were initially perioral and he had been treated with empiric valaciclovir for suspected herpes simplex virus (HSV) but with no resolution. Testing for HSV DNA and syphilis was negative. On examination, there were clusters of small nontender, well-circumscribed papules (some umbilicated), distributed on the forehead, cheeks, and cutaneous and mucosal lips. A diagnostic punch biopsy was taken of one of the characteristic papules. Histological examination demonstrated a dense dermal infiltrate of histiocytes with focal non-necrotizing granuloma formation. Interspersed neutrophilic microabscesses and occasional eosinophils were present. PAS stain for fungi confirmed the presence of numerous thick-walled spherules, many with a single distinct nucleus, with some showing binucleation, consistent with fungal organisms located within the histiocytes in the dermis. Differential diagnosis included histoplasmosis, cryptococcosis, blastomycosis and coccidiomycosis. He was commenced on intravenous liposomal amphotericin B for disseminated endemic mycosis while awaiting definitive diagnosis. Formal identification by panfungal polymerase chain reaction of skin tissue was positive for Histoplasma capsulatum and itraconazole was added. The diagnosis was consistent with disseminated histoplasmosis with cutaneous involvement. The lesions resolved completely over 4 weeks, with some residual hyperpigmentation remaining. Histoplasma capsulatum is a dimorphic fungus found in soil and the droppings of bats and birds. Infection is through spore inhalation, with most patients being asymptomatic. It is more prevalent in temperate and tropical climates. Disseminated histoplasmosis occurs mostly in immunocompromised individuals and can be fatal if left untreated. Although endemic to specific world regions, disseminated histoplasmosis should be considered in immunocompromised patients presenting with atypical cutaneous findings, even in regions of low prevalence.

Palatal perforation due to disseminated histoplasmosis as the first presentation of HIV-AIDS

Histoplasmosis is a systemic fungal infection caused by H. capsulatum usually in immunocompromised individuals such as those with HIV-AIDS. Though oral manifestations are rare, they could be the only and initial manifestation of HIV-AIDS. We report the case of a 23-year-old female who presented with oral ulcer and palatal perforation and detected to be suffering from disseminated histoplasmosis. She also turned out to be HIV positive. Her CD4+ count was undetectable. She responded well to intravenous liposomal Amphotericin B, oral itraconazole and antiretroviral therapy. To the best of our knowledge, histoplasmosis presenting as palatal perforation as the first manifestation of HIV-AIDS has not been reported from South India previously. A high index of suspicion is needed in such cases of exaggerated oral lesions even in states like Kerala to avoid delay in diagnosis and therapy.

Simplified screening and referral protocol for sinonasal mucormycosis in post COVID-19 patients

BackgroundTo study incidence of sinonasal mucormycosis in active and post COVID-19 patients in a district-level hospital in India and develop a simplified screening and referral protocol for use at peripheral centres to aid rapid diagnosis/treatment.MethodsStudy design: A prospective, interventional cohort study conducted from April 2021 to January 2022. Setting: Secondary level hospital in North India. Inclusion criteria: COVID-19 positive patients with diabetes mellitus as co-morbidity and with at least one of the following: received steroid therapy and/or on high flow oxygen therapy and/or had prolonged hospital stay (> 7 days). Exclusion criteria: Patients already immunocompromised/having malignancy/organ transplant recipients. Clinical workup: History, examination, imaging (CECT/MRI nose and paranasal sinuses if indicated), diagnostic nasal endoscopy + Nasal scrapings for KOH mount to detect fungal elements. STROBE guidelines were followed in the study.ResultsFourteen out of 250 patients tested positive for mucormycosis (incidence 5.6%). Thirteen were symptomatic, one patient was asymptomatic and detected on screening. No significant difference was found in mucormycosis versus non-mucormycosis group with respect to HbA1c status, vaccination status or steroid + oxygen treatment (p > 0.05 in all scenarios). Patients were treated with intravenous liposomal amphotericin B and surgical debridement when indicated. Two succumbed to disease (survival 85.7%). A clinical screening protocol was thus developed which can be used as an effective tool even at far-flung and remote healthcare facilities for diagnosis and timely referral of patients.ConclusionsMucormycosis is a potentially lethal disease which needs rapid diagnosis and timely action to decrease morbidity and mortality.

Treatment of pulmonary mucormycosis with adjunctive nebulized amphotericin B (MUCONAB trial): Results of an open-label randomized controlled trial.

The role of nebulized amphotericin B (NAB) in managing pulmonary mucormycosis (PM) is unknown. In this open-label trial, we randomized PM subjects to receive either intravenous liposomal amphotericin B (control arm, 3-5 mg/kg/day) alone or along with nebulized amphotericin B deoxycholate (NAB, 10 mg twice a day, every alternate day). The primary outcomes were: (1) overall response ('success' [complete or partial response] or 'failure' [stable disease, progressive disease, or death]) at 6 weeks; and (2) the proportion of subjects with adverse events (AE). The key secondary outcome was 90-day mortality. We performed a modified intention-to-treat (mITT) analysis where we included only subjects receiving at least a single dose of NAB. Fifteen and 17 subjects were randomized to the control and NAB arms; two died before the first dose of NAB. Finally, we included 30 subjects (15 in each arm; mean age 49.8 years; 80% men) for the mITT analysis. Diabetes mellitus (n = 27; 16/27 were COVID-19-associated PM) was the most common predisposing factor. The overall treatment success was not significantly different between the control and the NAB arms (71.4% vs. 53.3%; p = .45). Twenty-nine subjects experienced any AE, but none discontinued treatment. The 90-day mortality was not significantly different between the control (28.6%) and NAB arm (53.3%; p = .26). Adjunctive NAB was safe but did not improve overall response at 6 weeks. A different dosing schedule or nebulized liposomal amphotericin B may still need evaluation. More research is needed to explore other treatment options for PM.

Adherence of health workers to guidelines for screening and management of cryptococcal meningitis in Uganda.

Health workers' failure to adhere to guidelines for screening, diagnosis and management of HIV-associated cryptococcal meningitis (CM) remains a significant public health concern. We aimed to assess adherence to the standards of care and management of HIV patients at risk of CM per the MoH guidelines and assess stock management of CM supplies in the period of January to June 2021 at selected public health facilities (HFs) in Uganda. The study employed an observational cross-sectional design to assess the level of adherence of health workers to standards of clinical care and management of HIV positive patients at risk of CM as per the clinical guidelines for Uganda, and stock management of CM supplies in the period of January to June 2021in selected public health facilities. The study team used a survey guide designed by MoH to assess and score the screening, diagnosis and management practices of Health Facilities towards CM. Scoring was categorized as red (< 80%), light green (80%-95%), and dark green (˃95%) in the order from worst to best adherence. The data was transcribed into a spread sheet and analysed using STATA-v15. The study team visited a total of 15 public health facilities including 5 general hospitals, 9 regional referral hospitals (RRHs) and 1 National Referral hospital (NRH). The mean score for adherence to screening and management of CM for all the combined facilities was 15 (64.7%) classified as red. 10 (66.7%) HFs had not performed a baseline CD4 test for eligible patients within 2 weeks of ART initiation. With regards to treatment, 9 (60%) of the HFs were scored as light green on knowledge of the procedure for reconstituting intravenous Liposomal Amphotericin B. None of the HFs visited had potassium chloride tablets in stock. Major MoH guidelines are generally not being adhered to by health workers while managing cryptococcal meningitis. It is vital that government and implementing partners regularly support HFs with training, mentorship, and support supervision on CM management to improve adherence to CM screening and treatment guidelines.

Granulomatous panuveitis in disseminated sporotrichosis: case report and review of the literature

PurposeTo report a case of intraocular sporotrichosis presenting with bilateral granulomatous panuveitis.MethodsObservational case report and literature review.Case presentationA 62-year-old woman with a history of polycythemia vera presented with a non-healing ulcer at the left index finger, generalized erythematous papules, and bilateral granulomatous panuveitis. Cultures of skin and amputated finger identified Sporothrix schenckii. The diagnosis of intraocular sporotrichosis secondary to disseminated sporotrichosis was made. Intravenous liposomal Amphotericin B and intravitreal Amphotericin B were used to control systemic and ocular disease resulting in resolution of the skin lesions and intraocular inflammation.ConclusionsIntraocular sporotrichosis can manifest as bilateral granulomatous panuveitis in the setting of disseminated sporotrichosis. Treatment with intravenous and intravitreal antifungal therapy is useful for controlling intraocular infection.

Histoplasmosis Disguised as Pyrexia of Unknown Origin in Kidney Transplant Recipients: Bone Marrow Biopsy was Key to Diagnosis

Immunocompromised host commonly develops a disseminated form of histoplasmosis and may have diverse manifestations. We present a case of histoplasmosis in a kidney transplant recipient who presented with pyrexia of unknown origin and pancytopenia. Bronchoalveolar lavage fluid analysis and serum antigen were negative for histoplasmosis. Bone marrow biopsy showed periodic acid–Schiff-positive intra and extracellular yeast-like organisms and later confirmed as Histoplasma capsulatum. The patient was successfully treated with intravenous liposomal amphotericin B, followed by oral itraconazole. Thus, bone marrow examination proved as key to diagnosis in our case.

Preclinical Studies of the Nebulized Delivery of Liposomal Amphotericin B.

Background: Intravenous liposomal amphotericin B (L-AMB) has accompanying side effects that may be diminished when administering an inhaled form. Delivery systems for inhaled or aerosolized L-AMB vary, and there has not been a recent comparison of available systems to date. Methods: We compared three differently designed nebulizer delivery systems for the inhaled delivery of L-AMB to determine the best combination of efficient lung dosing and treatment time. Aerosol size was measured using a Malvern Mastersizer, and five separate nebulizers were tested. For drug output measurements, a Harvard Lung was used, and aerosol was collected using HEPA filters. Results: Overall aerosol size characteristics were similar for all devices with volume median diameters in the 4-5 μm range. The highest inhaled dose was delivered by the AeroEclipse. The Aerogen and the AeroEclipse had similar predicted pulmonary doses, and the AeroEclipse had the highest pulmonary delivery rates. Conclusion: The AeroEclipse nebulizer may provide more efficient delivery in a shorter amount of time; however, human studies are warranted to assess the safety, tolerability, and efficacy of inhaled delivery of L-AMB from this system.

INVASIVE PULMONARY FUSARIOSIS WITH SUPERIMPOSED HISTOPLASMOSIS IN AN IMMUNOCOMPETENT HOST

INVASIVE PULMONARY FUSARIOSIS WITH SUPERIMPOSED HISTOPLASMOSIS IN AN IMMUNOCOMPETENT HOST

Brain Abscess with Unusual Organism Staphylococcus hemolyticus in a Renal Transplant Recipient - A Case Report

The immunosuppressive medications in renal transplant recipients are associated with increased risk of infections, leading to significant morbidity and mortality. Here, we report a case of focal brain abscess, presented to us, 8 months after deceased donor renal transplantation with headache and altered mentation. Patient had a history of fungal pneumonia 3 months before presenting illness and received intravenous liposomal amphotericin B, for 6 weeks. On evaluation, he was found to have brain abscess, with mild graft dysfunction. Computerized tomography-guided stereotactic aspiration of the brain abscess was done which grew Staphylococcus hemolyticus. Intravenous catheter placed for 6 weeks for antifungal therapy for the management of previous fungal pneumonia was thought to be cause of staphylococcal infection. He was managed with intravenous clindamycin and levofloxacin for 6 weeks as per antibiogram and immunosuppressive medications were reduced. After 6 months of follow-up, patient was asymptomatic with normal renal function and minimal immunosuppressive medications.

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.

Non-Mucormycetes Causes of Fungal Rhino Sinusitis With Periocular Swelling in COVID-19 With Delta Variant.

Objective: To highlight fungi other than mucormycetes as causative agents of rhinosinusitis with periocular swelling in coronavirus (COVID-19) infection caused by Delta variant of SARS-CoV-2 virus and identify the presenting features, risk factors, intervention, and outcomes.Methods and analysis: A retrospective interventional study of 96 patients with fungal rhinosinusitis and periocular swelling was done in patients with concurrent or recovered COVID-19 infection with the Delta variant (B.1.617.2) of SARS-CoV-2 virus in India. All patients with mucormycetes infection were excluded. Clinical presentation, medical history, blood reports, and imaging were analyzed. Management was by intravenous (IV) liposomal amphotericin B and functional endoscopic sinus surgery (FESS) with paranasal sinus debridement. Limited orbital debridement with or without transcutaneous retrobulbar liposomal amphotericin B (TRAMB) was done in patients with orbital involvement. Postoperative antifungal therapy was decided on the basis of the causative fungi.Results: Four cases of Aspergillus and one each of Fusarium, Curvularia, and Penicillium-associated fungal rhinosinusitis with periocular swelling were seen. Signs of orbital involvement on MRI were present in all four of them. Two of these showed partial third-nerve palsy while one case with aspergillosis suffered cavernous sinus thrombosis. Proptosis was not witnessed in any case. History of diabetes and use of steroids was seen in all patients. All patients had mild to moderate COVID-19 with oxygen supplementation needed in one. No mortality, acute vision loss, or exenteration took place.Conclusion: Aspergillus, Fusarium, Curvularia, and Penicillium were non-mucormycetes causes of fungal rhinosinusitis with periocular swelling in COVID-19 infection with the Delta variant (B.1.617.2) of SARS COV-2 virus. Few cases showed orbital and intracranial involvement.

POS-098 MILKY URINE IN RENAL ALLOGRAFT RECIPIENT - CAN NATIVE KIDNEY BE THE CULPRIT ?

Milky urine can be caused due to both infectious and non-infectious causes. We present a case of 48 years old male, 6 years post kidney transplant who presented as milky urine and was initially managed with diethylcarbamazine (DEC) and intravenous antibiotics. As he was not responding he was evaluated further to be diagnosed as candiduria arising from left native kidney. He had a quick response to left native nephrectomy and liposomal amphotericin. 48 years old male patient, who was 6 years post kidney transplant (Basic disease - diabetic nephropathy), with normal graft function on triple drug immunosupressants ( tacrolimus, mycophenolate and pednisolone) presented with complaint of milky white urine during morning hours only. He was afebrile and had no symptoms of burning or pain during micturition. His urine examination showed few pus cells and was hazy in appearance. Urine cytology for malignant cells showed no evidence of atypical cells. Urine for fat globules was negative though triglycerides were 470 mg/dl and urine was labelled as chylous. His ultrasound was suggestive of mild pelvicalyceal fullness of transplant kidney which was confirmed by CT scan. His leucocyte counts, calcium and phosphorus were within normal range. His early morning smear sample showed no evidence of wuchereria bancrofti microfilariae. He was emperically started on DEC 6mg/kg. After 5 days his urine culture yielded growth of klebsiella species and was treated with injectable ceftriaxone-sulbactum combination as per culture sensitivity report for 2 weeks. He was asymptomatic till the time he was on antibiotics and again developed episodes of milky urine. He also passed some fleshy material in urine was sent for histology. He was posted for cystoscopy which revealed whitish efflux from left native uretric orifice, which was sent for cytology and left uretric catheterization was done. Both the tissue and fluid showed colonies of budding yeast cell and pseudohyphae suggestive of candida species. Considering the non functional status of left native kidney (by imaging and history of anuria pre transplant), left laproscopic native nephrectomy was done and in view of post transplant immunosupressed state, intravenous liposomal amphotericin was given for 2 weeks. He had a quick response to the treatment. In post transplant urinary tract infections, we should also focus on native kidneys especially in diabetic population. There are many case reports of recurrent urinary tract infections post transplant due to native pyelonephritis requiring native nephrectomy.