The second wave of COVID pandemic was associated with an outbreak of Mucormycosis. The mortality rate of Mucormycosis reaches 50-80% in cases with orbital and intracranial extension (Fadda in Acta Otorhinolaryngol Ital 41:43-50, 2021). In this outbreak we found that few of these patients had bacterial invasive sinusitis mimicking fungal sinusitis. Amphotericin the only effective drug against Mucormycosis is highly toxic and expensive and not indicated in bacterial sinusitis. Our aim was to  determine the exact etiologic agent, predisposing factors and outcome of treatment of COVID associated invasive sinusitis presenting with orbital complications. It is a retrospective observational study done in 33 patients with orbital complications in COVID associated invasive sinusitis. Demographic details of the patients and clinical presentation were documented. Rhinological examination was done and a nasal swab was taken for KOH mount along with Gram`s stain and Culture and Sensitivity. All Patients underwent radiological evaluation by contrast enhanced computed tomography (CECT) or MRI. Liposomal Amphotericin B was started. Surgical debridement done. Amphotericin-B was stopped in cases reported negative for fungal elements and antibiotics administered for two weeks. Outcome of treatment was documented. A total of 33 patients were included in the study. 48.5% patients were found to have bacterial infection and 27.3% patient\'s fungal infections and 24.2% mixed infections.Eschar formation, necrotic tissue, erosion of the lamina papyracea was seen in both Klebsiella (33.3%) and Staphylococcal infections (16.6%) similar to Mucor and mixed infections. Persistent opthalmoplegia and deterioration of vision was associated with Mucor and mixed infections. However improvement in proptosis, ptosis, ophthalmoplegia, and vision was observed in cases associated with bacterial invasive sinusitis. Invasive bacterial sinusitis was under diagnosed during second wave of COVID. Identification of invasive bacterial sinusitis can help in de-escalation of treatment.

BACKGROUND: Focused efforts of the visceral leishmaniasis elimination program have led to a drastic decline in cases, and the present challenge is disease monitoring, which this study aimed to assess.
METHODS: A Leishmania kinetoplastid-targeted qPCR quantified parasite load at disease presentation, and following treatment completion (n=49); an additional 80 cases were monitored after completion of treatment.
RESULTS: The parasite load at disease presentation was 13 461.00 (2560.00-37764.00)/µg gDNA, which upon completion of treatment reduced in 47 of 49 cases to 1(1-1)/µg gDNA, p<0.0001. In 80 cases that presented >2 months post-treatment, their parasite burden similarly decreased to 1(1-1)/µg gDNA except in 6 of 80 cases, which were qPCR positive.
CONCLUSIONS: In 129 cases of visceral leishmaniasis, qPCR by quantification of parasite burden proved effective for monitoring treatment.

COVID-19 disease has been associated with fungal infections such as aspergillosis and mucormycosis, especially in diabetic patients who have suffered from a moderately severe form of COVID-19 infection and are treated with steroids. Though there are multiple case reports describing co-infection with mucormycosis during the second wave of the COVID outbreak, the report of a dual fungal infection along with superadded bacterial infection is rare. Here we report a case where the same patient had a fungal storm with aspergillosis and mucormycosis and superadded Klebsiella. She was treated aggressively with antifungal agents, antibiotics, surgical debridement, and other supportive care. She improved and was discharged from the hospital after a long stay. She is being followed up regularly in the outpatient department and doing well.

The purpose of this systematic review is to provide updated evidence on the preferred induction therapy for the treatment of HIV-associated cryptococcal meningitis considering the most recent evidence available in order to inform the need for updates to WHO guidelines.
We searched Medline via PubMed, EMBASE, the Cochrane Library and clinicaltrials.gov for published or completed randomized clinical trials that evaluated induction treatment of first episode HIV-associated cryptococcal meningitis from 9 July 2018 (date of last search) to 1 September 2021.
One randomized clinical trial of 844 people with HIV-associated cryptococcal meningitis met the inclusion criteria. Participants were randomized to: (1) amphotericin deoxycholate for 7 days, with flucytosine and fluconazole (control); or (2) a single dose of liposomal amphotericin 10 mg/kg with flucytosine and fluconazole (intervention). In the intention-to-treat analysis, 10-week mortality was 24.8% [95% confidence interval (CI): 20.7-29.3%] in the single-dose liposomal amphotericin group compared with 28.7% (95% CI: 24.4-33.4%) in the control group. The absolute difference in 10-week mortality was -3.9% with an upper one-sided 95% CI of 1.2%, within the 10% pre-specified non-inferiority margin. Fewer participants had grade 3 and 4 adverse events in the intervention arm compared with the control arm (50.0% vs. 62.3%, p < 0.001).
In the single study included in this systematic review, single high-dose liposomal amphotericin B with flucytosine and fluconazole was non-inferior to the WHO-recommended standard of care induction therapy for HIV-associated cryptococcal meningitis, with significantly fewer adverse events.

Introduction Fungal rhinosinusitis (FRS) has increased over the past few decades due to the rampant use of antibiotics, steroids, immunosuppressive drugs, increased incidence of HIV and uncontrolled diabetes. The current study reviews the types, clinical presentation, microbiology, histopathology and outcomes related to FRS in a tertiary care center in North India. Methods We retrospectively reviewed the clinical and follow-up records of patients diagnosed with FRS over three years. The data reviewed included clinical workup, ophthalmological profile, comorbidities, immunological status, radiological investigations, intraoperative and histopathological findings, treatment and follow-up records. In addition, we performed a descriptive analysis of the reviewed data. Results The study consisted of 30 FRS patients (16 male, 14 female). In that, 77% of cases were of allergic FRS, while fungal ball, chronic invasive, chronic granulomatous and acute invasive FRS represented 3%, 10%, 3% and 7% cases, respectively. The most common presentation in non-invasive forms was nasal obstruction, nasal discharge, hyposmia and polyposis, while it was facial pain and headache in the invasive varieties. After appropriate medical and surgical management through endoscopic sinus surgery, the recurrence rate in non-invasive and invasive fungal sinusitis was 16.6% and 20.8%, respectively. There was nil mortality at a minimum of one year of follow-up. Conclusion The non-invasive forms of FRS are common and have a relatively mild course. Early medical and surgical intervention and management of the underlying comorbidities are the key factors in managing invasive FRS. Close follow-up after surgery is also necessary for the timely detection and management of recurrences.

BACKGROUND: The risk factors for invasive fungal infection have gradually become evident for pediatric patients with hematological diseases. Here we analyze the efficacy of liposomal amphotericin (L-AMB) for pediatric patients with febrile neutropenia using prophylactic voriconazole (VRCZ).
METHODS: We administered L-AMB (2.5 mg/kg/day) in patients with febrile neutropenia who were receiving prophylactic VRCZ (10 mg/kg/day, orally) and were resistant to second-line antibiotics therapy. Thirteen patients (5 males, 8 females) with 19 febrile neutropenia episodes were targeted in this analysis. The median age of the patients was 14 years (range, 1-19 years). Eighteen out of 19 episodes occurred in patients with acute myeloid leukemia, with the remaining episode occurring in a patient with acute unclassified leukemia.
RESULTS: The median period from start of L-AMB administration to resolution of fever was 4 days (1-27 days). In 15 out of 19 episodes, fever resolved within 5 days from commencement of L-AMB administration. Using criteria proposed by T. J. Walsh et al., the success rate of L-AMB for febrile neutropenia was 89.5% in this study.
CONCLUSIONS: Although the sample size of our study was small, the extremely high efficacy of L-AMB warrants its administration in patients with febrile neutropenia who are receiving VRCZ.

OBJECTIVE: Liposomal amphotericin B (L-AmB) is the cornerstone of many serious invasive fungal infections. Despite lower frequencies of commonly reported adverse events in clinical trials compared to conventional formulations, post-marketing complications continue to mount.
METHODS: We present a case of chest pain following the initial dose of L-AmB for cryptococcal meningitis. Electrocardiogram demonstrated no acute electrocardiogram findings. Upon rechallenge, the chest pain worsened was subsequently accompanied by ST-segment elevation. Emergent coronary angiography found no acute findings.
CONCLUSIONS: Providers should be aware of cardiac complications with L-AmB, including non-occlusive ST-segment elevation.

OBJECTIVE: We describe the use of liposomal amphotericin B and amphotericin B deoxycholate in a critically ill patient with pulmonary blastomycosis receiving both venovenous extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT).
CONCLUSIONS: A 50-year-old African American man presented for dyspnea and cough and was noted to have blastomycosis on bronchoscopy. He developed respiratory failure and acute kidney injury, requiring mechanical ventilation, ECMO, and CRRT. After 4 days of liposomal amphotericin, the transmembrane pressure gradient on the membrane oxygenator increased dramatically without visualization of a clot, requiring a circuit exchange. A trough amphotericin B level taken the day before the exchange was undetectable for amphotericin B. After the circuit exchange, the patient was switched to amphotericin B deoxycholate. A subsequent trough level was 3.8 μg/mL. The patient improved and was able to be decannulated. However, he did require tracheostomy and long-term hemodialysis.
CONCLUSIONS: In our case we believe that liposomal amphotericin B was significantly removed by ECMO and was responsible for the failure of the ECMO circuit. We would suggest amphotericin B deoxycholate be used in such patients preferentially and that serum levels of the drug be assessed when possible.

OBJECTIVE: To evaluate the evidence for use of different formulations of amphotericin B (AmB), minimum effective dose for each formulation and its comparative efficacy against other drugs in achieving definitive cure of visceral leishmaniasis.
METHODS: This systematic review and meta-analysis included following data sources: PubMed, Embase, Scopus, Web of Science and CINAHL. Controlled prospective clinical trials (randomized or nonrandomized, including dose-ranging studies) conducted between 1996 and 2017 with at least one treatment group receiving AmB were included (published data only). The primary outcome was definitive cure at 6 months. Adverse events and mortality were assessed as secondary outcomes. The PROSPERO registration number for this review is CRD42017067488.
RESULTS: Thirty-one studies (26 from India) that enrolled 6903 patients into 84 study groups met the selection criteria. In India, liposomal AmB was not inferior to AmB deoxycholate (relative risk 1.00, 95% confidence interval (CI) 0.96-1.03, two randomized controlled trials (RCTs), 514 participants, high-quality evidence), and a single dose of the earlier formulation as low as 3.75 mg/kg achieved a cure rate of over 89% (95% CI 70.6-97.2). AmB deoxycholate was as effective as miltefosine (relative risk 0.99, 95% CI 0.95-1.03, two trials, 523 participants, high-quality evidence) and may be better than paromomycin (relative risk 1.04, 95% CI 1.02-1.07, one trial, 667 participants, low-quality evidence) in achieving definitive cure.
CONCLUSIONS: AmB is an efficacious drug in the Indian subcontinent. Further evidence is needed from prospective clinical trials in other endemic geographical regions.

Aureobasidium pullulans is a saprophytic fungus that is widely distributed in the environment, and in the right host can be an opportunistic human pathogen.
A 66-year-old man with Crohn\'s disease with a single kidney, and requiring total parenteral nutrition via a Hickman catheter, was admitted with a 10-week history of progressive shortness of breath, fevers and weight loss. Chest imaging demonstrated new multifocal lung parenchymal opacities compatible with septic pulmonary emboli. Blood culture grew a yeast-like organism that transformed into a black mold on subculture, eventually identified as A. pullulans. Due to triazole resistance, the patient was treated with liposomal amphotericin and micafungin. Serum (1,3)-β-d-glucan level was used to monitor therapy, initially measured at >500 pg/mL and decreasing to 66 pg/mL after one year of therapy.
We describe the successful treatment of a case of catheter related fungemia and septic pulmonary emboli due A. pullulans. While initially appearing as an oval yeast on blood culture, subsequent growth as a black mold led to identification of the fungus as A. pullulans. The infection was cured with a combination of antifungal agents, even though the foreign body could not be safely removed. Nephrotoxicity required dosing adjustment of the amphotericin to biweekly during the maintenance phase of treatment. The serum (1,3)-β-d-glucan level proved to be useful in monitoring response to therapy.
We report here successful treatment of a disseminated A. pullulans infection with an induction and maintenance approach to liposomal amphotericin dosing, and monitoring response to therapy with serum (1,3)-β-d-glucan levels.