Pulmonary mucormycosis is a rare and lethal fungal infection elicited by fungi of the order Mucorales. The disease predominantly affects immunocompromised hosts, like those with diabetes mellitus, hematologic malignancies, or those undergoing immunosuppressive therapy. We, at this moment, report a case of pulmonary mucormycosis in a 55-year-old gentleman, exemplifying the ferocity of clinical disease, diagnostic dilemmas, and rapidity of progression. A diagnosis of pulmonary mucormycosis was based on diagnostic imaging and flexible bronchoscopy. Despite aggressive antifungal and supportive treatment, the patient\'s condition deteriorated further, and unfortunately succumbed to cardiorespiratory arrest. This case reinforces the importance of early recognition of pulmonary mucormycosis and aggressive medical management, especially in immunocompromised patients, in salvaging lives with good outcomes and preventing the fulminant progression of the disease process.

Aim: Currently, we have limited armamentarium of antifungal agents against Mucorales. There is an urgent need to discover novel antifungal agents that are effective, safe and affordable. Materials & methods: In this study, the anti-Mucorale action of native lactoferrin (LF) and its functional fragments CLF, RR6 and LFcin against three common Mucorale species are reported. The synergistic action of LF with antifungal agents like amphotericin B, isavuconazole and posaconazole was analyzed using checkerboard technique. Results: All the three mucor species showed inhibition when treated with fragments. The checkerboard assay confirmed that native LF showed the best synergistic action against Mucorales in combination with Amphotericin B. Conclusion: These results highlight the potential therapeutic value of native LF against Mucorales.
Black fungus, or ‘mucormycosis’, is a dangerous fungal infection. Normally, it affects people with a weakened immune system. It is only treatable when diagnosed early. It spreads by breathing the fungus in, eating contaminated food or direct contact with an infected wound. There are not many medicines that can treat this type of fungus, so it is important to find new ones. In this study, we tested a natural protein called lactoferrin and some of its building blocks, called peptides, to see if they could stop the fungus from growing. Lactoferrin and its peptides could stop the fungus from growing, especially when used with a medicine called amphotericin B. This means that lactoferrin could potentially be a helpful treatment for this fungal infection.

The supramolecular-based macrocyclic amphiphiles have fascinating attention and find extensive utilization in the pharmaceutical industry for efficient drug delivery. In this study, we designed and synthesized a new supramolecular amphiphilic macrocycle to serve as an efficient nanocarrier, achieved by treating 4-hydroxybenzaldehyde with 1-bromotetradecane. The derivatized product was subsequently treated with resorcinol to cyclize, resulting in the formation of a calix(4)-resorcinarene-based supramolecular amphiphilic macrocycle. The synthesized macrocycle and intermediate products were characterized using mass spectrometry, IR, and 1H NMR spectroscopic techniques. The amphotericin-B (Amph-B)-loaded and unloaded amphiphiles were screened for biocompatibility studies, vesicle formation, particle shape, size, surface charge, drug entrapment, in-vitro release profile, and stability through atomic force microscopy (AFM), Zetasizer, HPLC, and FT-IR. Amph-B -loaded macrocycle-based niosomal vesicles were investigated for in-vivo bioavailability in rabbits. The synthesized macrocycle exhibited no cytotoxicity against normal mouse fibroblast cells and was found to be hemocompatible and safe in mice following an acute toxicity study. The drug-loaded macrocycle-based vesicles appeared spherical, nano-sized, and homogeneous in size, with a notable negative surface charge. The vesicles remained stable after 30 days of storage. The results of Amph-B oral bioavailability and pharmacokinetics revealed that the newly tailored niosomal formulation enhanced drug solubility, protected drug degradation at gastric pH, facilitated sustained drug release at the specific target site, and delayed plasma drug clearance. Incorporating such advanced niosomal formulations in the field of drug delivery systems has the potential to revolutionize therapeutic outcomes and improve the quality of patient well-being.

Fixed cutaneous sporotrichosis (FCS) is a rare and chronic infection. Its diagnosis requires a high degree of suspicion. The data on its dermoscopy and follow-up is limited in the literature. We herein report one such case with a follow-up till cure along with its dermoscopy to establish certain specific features that may be used to ascertain the response to treatment for this chronic infection and its prognosis. We found only three such cases following an extensive review of the literature, and this case emphasizes the importance of dermoscopy in recent times as the history, swab cultures, and smears may be misleading at times due to the chronic and long-standing nature of the condition.

New formulations of Amphotericin-B (Am-B), the most popular therapeutic drug for many human infections such as parasitic and fungal pathogens, are safe, economical, and effective in the world. Several newly designed carrier systems for Am-B can also be considered orally with sufficient gastrointestinal permeability and good solubility. However, the clinical application of several new formulations of Am-B with organ cytotoxicity, low bioavailability, high costs, and technical problems have caused some issues. Therefore, more attention and scientific design are required to progress safe and effective drug delivery systems. Currently, the application of nano-based technology and nanomaterials in the advancement of drug delivery systems exhibits promising outcomes to cure many human systemic infections. Designing novel drug delivery systems including solid lipid nanostructured materials, lipo-polymersomes, drug conjugates and microneedles, liposomes, polymer and protein-based nanostructured materials, dendrimers, emulsions, mixed micelles, polymeric micelles, cyclodextrins, nanocapsules, and nanocochleate for Am-B has many advantages to reducing several related issues. The unique properties of nanostructured particles such as proper morphology, small size, surface coatings, and, electrical charge, permit scientists to design new nanocomposite materials against microorganisms for application in various human diseases. These features have made these nanoparticles an ideal candidate for drug delivery systems in clinical approaches to cure a number of human disorders and currently, several therapeutic nanostructured material formulations are under different stages of clinical tests. Hence, this scientific paper mainly discussed the advances in new formulations of Am-B for the treatment of human systemic infections and related clinical tests.

COVID-19-associated pulmonary aspergillosis (CAPA) has emerged as a frequent complication in the intensive care unit (ICU). However, little is known about this life-threatening fungal superinfection in solid organ transplant recipients (SOTRs), including whether targeted anti-mold prophylaxis might be justified in this immunosuppressed population. We performed a multicentric observational retrospective study of all consecutive ICU-admitted COVID-19 SOTRs between August 1, 2020 and December 31, 2021. SOTRs receiving antifungal prophylaxis with nebulized amphotericin-B were compared with those without prophylaxis. CAPA was defined according the ECMM/ISHAM criteria. Sixty-four SOTRs were admitted to ICU for COVID-19 during the study period. One patient received antifungal prophylaxis with isavuconazole and was excluded from the analysis. Of the remaining 63 SOTRs, nineteen (30.2%) received anti-mold prophylaxis with nebulized amphotericin-B. Ten SOTRs who did not receive prophylaxis developed pulmonary mold infections (nine CAPA and one mucormycosis) compared with one who received nebulized amphotericin-B (22.7% vs 5.3%; risk ratio 0.23; 95%CI 0.032-1.68), but with no differences in survival. No severe adverse events related to nebulized amphotericin-B were recorded. SOTRs admitted to ICU with COVID-19 are at high risk for CAPA. However, nebulized amphotericin-B is safe and might reduce the incidence of CAPA in this high-risk population. A randomized clinical trial to confirm these findings is warranted.

BACKGROUND: The COVID-19 pandemic along with its treatment has brought myriad potential complications including the heightened risk of secondary fungal infections like mucormycosis. Mucormycosis is a rare angioinvasive fungal infection that has traditionally been highly fatal despite surgical intervention and antifungal medications.
OBJECTIVE: To re-evaluate the risk factors, epidemiology, and possible COVID-19-associated conditions on a larger sample size than the existing data.
METHODS: We studied the possible risk factors, clinical presentations, treatment, and outcome of 203 patients with mucormycosis in a single-center retrospective-prospective observational study for three months at a tertiary care hospital after obtaining due permission from the institutional ethics committee.
RESULTS: The mean age of patients was 52 ± 11.5 years, and 92.61% had a history of COVID-19 infection. Around 86.7% of patients were suffering from diabetes mellitus with 50% being already known cases whereas the other 50% developed post-COVID-19 infection; 65.02% of patients were administered corticosteroids during their COVID-19 treatment. About 51.72% of patients required hospital admission and among them, 16.25% of patients required ICU support. The mean oxygen saturation (SpO2) levels on admission were 84.61 ± 12.96%, and 38.92% of patients required mechanical respiratory support. The mean duration between COVID-19 infection and the onset of mucormycosis was 18.80 ± 16.61 days. The most common clinical presentations were facial pain and swelling (26.6%) and ophthalmic symptoms including eye swelling, pain, and ptosis (25.12%). Antifungal treatment was given to all the patients and 89.36% of the patients underwent surgical debridement of fungal mass. At the end of three months, 60.59% of the 188 patients survived with improvement, 13.30% had no improvement and/or deterioration of health, and 18.72% succumbed to mucormycosis. Intracranial involvement and leukocytosis were positively associated with mortality whereas surgical intervention was significant for positive outcomes at the end of three months in patients with mucormycosis (p<0.05).
CONCLUSIONS: The sudden rise of mucormycosis during the second wave of COVID-19 can be attributed to uncontrolled blood sugar levels along with high corticosteroid usage as well as various nosocomial factors during the COVID-19 treatment. Early and aggressive treatment with surgical intervention and antifungal drugs can improve disease outcomes.

The most prevalent conditions among ocular surgery and COVID-19 patients are fungal eye infections, which may cause inflammation and dry eye, and may cause ocular morbidity. Amphotericin-B eye drops are commonly used in the treatment of ocular fungal infections. Lactoferrin is an iron-binding glycoprotein with broad-spectrum antimicrobial activity and is used for the treatment of dry eye, conjunctivitis, and ocular inflammation. However, poor aqueous stability and excessive nasolacrimal duct draining impede these agens\' efficiency. The aim of this study was to examine the effect of Amphotericin-B, as an antifungal against Candida albicans, Fusarium, and Aspergillus flavus, and Lactoferrin, as an anti-inflammatory and anti-dry eye, when co-loaded in triblock polymers PLGA-PEG-PEI nanoparticles embedded in P188-P407 ophthalmic thermosensitive gel. The nanoparticles were prepared by a double emulsion solvent evaporation method. The optimized formula showed particle size (177.0 ± 0.3 nm), poly-dispersity index (0.011 ± 0.01), zeta-potential (31.9 ± 0.3 mV), and entrapment% (90.9 ± 0.5) with improved ex-vivo pharmacokinetic parameters and ex-vivo trans-corneal penetrability, compared with drug solution. Confocal laser scanning revealed valuable penetration of fluoro-labeled nanoparticles. Irritation tests (Draize Test), Atomic force microscopy, cell culture and animal tests including histopathological analysis revealed superiority of the nanoparticles in reducing signs of inflammation and eradication of fungal infection in rabbits, without causing any damage to rabbit eyeballs. The nanoparticles exhibited favorable pharmacodynamic features with sustained release profile, and is neither cytotoxic nor irritating in-vitro or in-vivo. The developed formulation might provide a new and safe nanotechnology for treating eye problems, like inflammation and fungal infections.

To study clinicoepidemiology and surgical complications in acute invasive fungal rhinosinusitis. Retrospective observational study carried in GMC Akola from February 2021 to April 2022. Detailed history and clinical examination, nasal endoscopic biopsy or swab for KOH and fungal culture was taken. CECT/MRI PNS + Orbit + Brain was done. All patients underwent surgery and tissue sample send for histopathological examination. Total 146 patients included in study with M:F ratio 1.7:1. Most affected age group was between 40 and 60 years. 107 (78.6%) patients had history of COVID-19.Mucorale is most commonly found fungal species (90.4%) followed by aspergillus (2.7%) & mixed species (6.8%). Diabetes Mellitus is most common comorbidity. Intraoperative complications were bleeding (72.60%), CSF leak (4.1%), orbital hematoma (0.68%), nasolacrimal duct trauma (2.05%), periorbital hematoma (0.68%). Post operative complications like synechiae (56.16%), OAF (45.89%), hypoesthesia (25.34%), decreased vision (16.43%), facial pain (20.54%), facial deformity (20.54%), diplopia (6.8%), headache (30.13%), anosmia (39.72%), dental pain (20.54%), earache (9.58%), hyposmia (45.89%), periorbita ecchymosis (0.68%), residual disease (16.10%), recurrence (2.05%), death (2.05%) was observed. Prompt surgical debridement of devitalized tissue and early adequate dosage of antifungal (inj. Amphotericin-b) treatment are necessary as delay in surgical debridement and treatment can worsen the prognosis of disease. Among all complications faced maximum were manageable with early interventions but few of them were inevitable due to extensive nature of disease.

Rhino orbital cerebral mucormycosis is a medical emergency; though rare it\'s a life threatening infection in patients. It commonly occurs in immunocompromised patients due to various causes. A retrospective study was conducted in tertiary care centre wherein 30 non-covid, diabetic patients were treated for mucormycosis. All underwent intensive debridement and diabetic management along with antifungal- amphotericin. All the cases improved with aggressive therapy: medical and surgical. Early recognition and treatment is needed to prevent morbidity and mortality.