Mucormycosis in Liver Allograft Following Transplant for Secondary Biliary Cirrhosis.

Mucormycosis, a group of opportunistic mycoses caused by Mucorales, present a significant threat to immunocompromised patients. In this report, we present the case of a 57-year-old male patient who underwent liver transplant for secondary biliary cirrhosis following inadvertent bile duct injury. Despite initial satisfactory postoperative evolution, the patient developed fever, and imaging revealed a suspicious lesion. Preliminary culture growth suggested a filamentous fungus, leading to initiation of liposomal amphotericin B. However, the lesion progressed, and a surgical debridement was necessary. During surgery, involvement of the liver dome and diaphragm was observed, and a nonanatomical hepatectomy was performed. Despite efforts, the patient's condition deteriorated, ultimately resulting in multiple organ failure and mortality. This case emphasizes the challenging nature of mucormycosis in livertransplant recipients.

Visceral Leishmaniasis Masquerading as Drug-Induced Pancytopenia in Lung Cancer Patients.

Maintenance chemotherapy is a standard treatment in patients with non-progressive advance staged IV non-squamous non-small cell lung cancer after induction therapy. Here, we report the case of a 53-year-old man undergoing a maintenance monotherapy with pemetrexed who presented prolonged pancytopenia despite filgrastim injections. A bone marrow aspiration revealed a macrophage activation syndrome with Leishmania amastigotes. A Polymerase Chest Reaction testing confirmed the diagnosis of visceral leishmaniasis. Treatment with liposomal amphotericin B was started. Oncologists should bear in mind that visceral leishmaniasis in endemic areas can potentially induce severe and prolonged pancytopenia in immunosuppressed patients, during chemotherapy in particular.

Successful treatment of recurrent visceral leishmaniasis relapse in an immunocompetent adult female with functional hypopituitarism in Bangladesh.

BACKGROUND: Currently available treatment options are mostly effective in achieving long-term cure in visceral leishmaniasis (VL) patients. However, there have been reports of recurrence of this illness in both immunosuppressed and immunocompetent patients. CASE PRESENTATION: We report the first case of recurrent VL relapse in a 19-year-old immunocompetent female with functional hypopituitarism (hypogonadotropic hypogonadism with central hypothyroidism) from Bangladesh, who has been treated three times previously with optimal dosage and duration- liposomal amphotericin B (LAmB) alone and in combination with miltefosine. We treated the patient successfully with a modified treatment regimen of 10 mg/kg body weight LAmB for two consecutive days along with oral miltefosine for seven days as loading dose. For secondary prophylaxis, the patient received 3 mg/kg body weight LAmB along with oral miltefosine for seven days monthly for five doses followed by hormonal replacement. The patient remained relapse free after 12 months of her treatment completion. CONCLUSION: In the absence of protective vaccines against Leishmania species and standard treatment regimen, this modified treatment regimen could help the management of recurrent relapse cases.

A link between circulating immune complexes and acute kidney injury in human visceral leishmaniasis.

Visceral leishmaniasis (VL) is an infectious disease caused by Leishmania infantum. Clinically, VL evolves with systemic impairment, immunosuppression and hyperactivation with hypergammaglobulinemia. Although renal involvement has been recognized, a dearth of understanding about the underlying mechanisms driving acute kidney injury (AKI) in VL remains. We aimed to evaluate the involvement of immunoglobulins (Igs) and immune complexes (CIC) in the occurrence of AKI in VL patients. Fourteen VL patients were evaluated between early treatment and 12 months post-treatment (mpt). Anti-Leishmania Igs, CIC, cystatin C, C3a and C5a were assessed and correlated with AKI markers. Interestingly, high levels of CIC were observed in VL patients up to 6 mpt. Concomitantly, twelve patients met the criteria for AKI, while high levels of cystatin C were observed up to 6 mpt. Plasmatic cystatin C was positively correlated with CIC and Igs. Moreover, C5a was correlated with cystatin C, CIC and Igs. We did not identify any correlation between amphotericin B use and kidney function markers in VL patients, although this association needs to be further explored in subsequent studies. Our data reinforce the presence of an important renal function impairment during VL, suggesting the involvement of Igs, CIC, and C5a in this clinical condition.

HIV-associated disseminated cryptococcosis-An unusual clinical and diagnostic picture with successful cure by single dose liposomal amphotericin B treatment.

BACKGROUND: Cryptococcosis is an invasive, opportunistic fungal infection seen especially in human immunodeficiency virus (HIV) infected patients. Cryptococcal meningitis (CM) is the second leading cause of mortality in HIV patients. We report a case of disseminated cryptococcosis presenting with altered mental status in a newly diagnosed HIV infection. METHODS AND RESULTS: A 50-year-old with a short history of altered mental sensorium and a history of low-grade fever and weight loss for few months presented at a tertiary care hospital in North India. He was detected positive for HIV-1. Cryptococcal antigen (CRAG) was positive in Cerebrospinal fluid (CSF), and negative in serum. The fungal culture in CSF was sterile while the fungal blood culture grew Cryptococcus neoformans. The patient was treated with single high-dose Liposomal Amphotericin B (LAmB) therapy followed by Fluconazole and Flucytosine for the next two weeks followed by fluconazole daily for consolidation and maintenance therapy. Antiretroviral therapy (ART) was started 4 weeks after induction therapy. After 6 months, the patient is doing fine. CONCLUSION: Single dose LAmB along with the backbone of fluconazole and flucytosine appears promising in disseminated cryptococcal infection in HIV-infected individuals.

Airway necrosis and granulation tissue formation caused by Rhizopus oryzae leading to severe upper airway obstruction: a case report.

Pulmonary Mucormycosis is a fatal infectious disease with high mortality rate. The occurrence of Mucormycosis is commonly related to the fungal virulence and the host's immunological defenses against pathogens. Mucormycosis infection and granulation tissue formation occurred in the upper airway was rarely reported. This patient was a 60-year-old male with diabetes mellitus, who was admitted to hospital due to progressive cough, sputum and dyspnea. High-resolution computed tomography (HRCT) and bronchoscopy revealed extensive tracheal mucosal necrosis, granulation tissue proliferation, and severe airway stenosis. The mucosal necrotic tissue was induced by the infection of Rhizopus Oryzae, confirmed by metagenomic next-generation sequencing (mNGS) in tissue biopsy. This patient was treated with the placement of a covered stent and local instillation of amphotericin B via bronchoscope. The tracheal mucosal necrosis was markedly alleviated, the symptoms of cough, shortness of breath, as well as exercise tolerance were significantly improved. The placement of airway stent and transbronchial microtube drip of amphotericin B could conduce to rapidly relieve the severe airway obstruction due to Mucormycosis infection.

Case Report: Disseminated Paracoccidioidomycosis and Strongyloides Hyperinfection in a Patient with Human T-Lymphotropic Virus Type 1/2 Infection.

Co-occurrence of paracoccidioidomycosis and strongyloidiasis in immunosuppressed patients, particularly those infected with human T-lymphotropic virus type 1/2, is infrequent. We describe the case of a Peruvian farmer from the central jungle with human T-lymphotropic virus type 1/2 infection, with 2 months of illness characterized by respiratory and gastrointestinal symptoms associated with fever, weight loss, and enlarged lymph nodes. Strongyloides stercoralis and Paracoccidioides brasiliensis were isolated in sputum and bronchoalveolar lavage samples, respectively. The clinical evolution was favorable after the patient received ivermectin and amphotericin B. We hypothesize that autoinfestation by S. stercoralis in human T-lymphotropic virus type 1/2-infected patients may contribute to the disseminated presentation of Paracoccidioides spp. Understanding epidemiological context is crucial for suspecting opportunistic regional infections, particularly those that may coexist in immunosuppressed patients.

Invasive pulmonary and central nervous system aspergillosis in a child: A case report and literature review.

RATIONALE: Children with haematological malignancies have a higher risk of developing aggressive pulmonary aspergillosis and a higher mortality rate. The most common site of extrapulmonary aspergillosis in children is the central nervous system (CNS), and the death rate is higher when CNS is affected. Therefore, early diagnosis and treatment of invasive aspergillosis are essential for reducing mortality. PATIENT CONCERNS: We report a case of an 8-year-old girl with acute lymphoblastic leukaemia who developed invasive pulmonary aspergillosis complicated by CNS aspergillosis. Aspergillus was confirmed by metagenomic sequencing of pathogenic microorganisms. DIAGNOSES: Invasive pulmonary and central nervous system aspergillosis. INTERVENTIONS: The patient was treated with combined systemic antifungal agents (voriconazole and liposomal amphotericin B) and intrathecal injection of amphotericin B. OUTCOMES: The treatment was well tolerated and resulted in remarkable clinical and radiological head improvements. LESSONS: Invasive aspergillosis has a high mortality rate and requires early diagnosis and treatment. Pathogenic microbial metagenomic sequencing is a convenient method to assist in the early diagnosis of aspergillosis. Voriconazole is the drug of choice for the treatment of invasive aspergillosis. When CNS aspergillosis occurs, it can be combined with other systemic antifungal drugs and intrathecal injection of amphotericin B.

Brain glucose induces tolerance of Cryptococcus neoformans to amphotericin B during meningitis.

Antibiotic tolerance is the ability of a susceptible population to survive high doses of cidal drugs and has been shown to compromise therapeutic outcomes in bacterial infections. In comparison, whether fungicide tolerance can be induced by host-derived factors during fungal diseases remains largely unknown. Here, through a systematic evaluation of metabolite-drug-fungal interactions in the leading fungal meningitis pathogen, Cryptococcus neoformans, we found that brain glucose induces fungal tolerance to amphotericin B (AmB) in mouse brain tissue and patient cerebrospinal fluid via the fungal glucose repression activator Mig1. Mig1-mediated tolerance limits treatment efficacy for cryptococcal meningitis in mice via inhibiting the synthesis of ergosterol, the target of AmB, and promoting the production of inositolphosphorylceramide, which competes with AmB for ergosterol. Furthermore, AmB combined with an inhibitor of fungal-specific inositolphosphorylceramide synthase, aureobasidin A, shows better efficacy against cryptococcal meningitis in mice than do clinically recommended therapies.

Debulking corneal biopsy with tectonic amniotic membrane transplantation in refractory clinically presumed fungal keratitis.

The treatment of fungal keratitis (FK) is challenging due to the subacute indolent course, and initial misdiagnosis. In this retrospective case series, we highlight both the diagnostic and therapeutic roles of corneal biopsy together with amniotic membrane transplantation (AMT) in patients with refractory clinically presumed FK. Debulking biopsy and tectonic AMT were performed during the initial presentation. Biopsy specimens were sent for KOH smears and cultures. After KOH smears confirmed the presence of fungal elements, topical voriconazole 1% was prescribed for the first 72 h then tailored according to the clinical response and the culture results. The outcome measures were complete resolution of infection and restoration of corneal integrity. Cases associated with culture proven bacterial keratitis were excluded. Twelve cases were included in the study. KOH smears confirmed the presence of fungal growth in all specimens. Cultures grew Aspergillus in 6/12 cases, sensitive to voriconazole (5/6) and amphotericin (3/6); Fusarium (4/12), sensitive to both voriconazole and amphotericin; and no growth in 2/12 cases. Amphotericin 0.15% eye drops were added to the 7 cases with proven sensitivity and to the remaining 2 culture negative cases. Gradual resolution of infection was seen in all cases after 35.6 ± 7.8 days. In FK, a debulking biopsy simultaneously with AMT help decrease the microbial load, suppress the inflammatory process, support the corneal integrity, confirm the presence of fungal pathogen.

Transcutaneous retrobulbar amphotericin B for rhino-orbital-cerebral mucormycosis: a multi-center retrospective comparative study.

PURPOSE: To assess whether transcutaneous retrobulbar amphotericin B injections (TRAMB) reduce exenteration rate without increasing mortality in rhino-orbital-cerebral mucormycosis (ROCM). METHODS: In this retrospective case-control study, 46 patients (51 eyes) with biopsy-proven ROCM were evaluated at 9 tertiary care institutions from 1998 to 2021. Patients were stratified by radiographic evidence of local orbital versus extensive involvement at presentation. Extensive involvement was defined by MRI or CT evidence of abnormal or loss of contrast enhancement of the orbital apex with or without cavernous sinus, bilateral orbital, or intracranial extension. Cases (+TRAMB) received TRAMB as adjunctive therapy while controls (-TRAMB) did not. Patient survival, globe survival, and vision/motility loss were compared between +TRAMB and -TRAMB groups. A generalized linear mixed effects model including demographic and clinical covariates was used to evaluate the impact of TRAMB on orbital exenteration and disease-specific mortality. RESULTS: Among eyes with local orbital involvement, exenteration was significantly lower in the +TRAMB group (1/8) versus -TRAMB (8/14) (p = 0.04). No significant difference in mortality was observed between the ±TRAMB groups. Among eyes with extensive involvement, there was no significant difference in exenteration or mortality rates between the ±TRAMB groups. Across all eyes, the number of TRAMB injections correlated with a statistically significant decreased rate of exenteration (p = 0.048); there was no correlation with mortality. CONCLUSIONS: Patients with ROCM with local orbital involvement treated with adjunctive TRAMB demonstrated a lower exenteration rate and no increased risk of mortality. For extensive involvement, adjunctive TRAMB does not improve or worsen these outcomes.

[Expert consensus on diagnosis and treatment of severe COVID-19 associated pulmonary aspergillosis and mucormycosis].

The incidence and mortality of COVID-19 associated pulmonary aspergillosis (CAPA) are high in critically ill patients. Although COVID-19 associated mucormycosis (CAPM) is relatively rare, its severity and often a delayed diagnosis or misdiagnosis lead to its high mortality. The diagnosis and treatment of CAPA and CAPM in critically ill patients are challenging. Early diagnosis and a standardized therapy are the two most important factors for a good outcome. Therefore, a working group of experts from Chinese Thoracic Society and Chinese Association of Chest Physicians Critical Care Group was organized to develop this consensus based on the current medical evidence and clinical practice, in order to improve the ability of clinical treatment for critically ill patients with CAPA and CAPM. The working group drafted a preliminary text based on the literature and clinical practice experience. Following two rounds of discussion, 16 final recommendations were made, with the recommendation strength divided into recommend, suggest and not recommend.-Utilization of chest images and bronchoscopy1. Chest CT, rather than chest X-ray, is recommended for possible CAPA or CAPM patients to provide diagnostic evidence and localization for bronchoscopy to obtain microbiological specimens. A diagnosis of CAPA could not be made on the basis of positive signs on chest CT alone. Chest contrast CT or pulmonary artery CT (CTPA) is recommended in patients with probable CAPM.2. In the case of possible CAPA or CAPM, it is recommended that bronchoscopy and BALF collection for microbiological examinations be pereformed as soon as possible.-The selection strategies of microbiological examinations3. Microscopic examination, culture, GM testing and PCR for aspergillus Spp. of BALF are recommended in patients with probable CAPA. Fungal staining and culture of BALF are suggested for possible CAPM. Selected appropriate specimens for molecular biological detection are suggested in critically ill patients and possible CAPM.-Diagnostic critieria4. The revised ECMM/ISHAM consensus statement is recommended as the diagnostic criteria for CAPA and the Delphi consensus statement is recommended as the diagnostic criteria for CAPM.-Appropriate time for antifungal therapy5. Prophylactic therapy of CAPA with amphotericin B or its liposomes is suggested for patients with severe COVID-19, especially those with risk factors for CAPA.6. It is recommended to start the empirical anti-Aspergillus therapy as soon as possible for possible CAPA, and obtain the microbiological evidence for aspergillosis at the same time.7. Prophylactic therapy for CAPM is not recommended for severe COVID-19 patients.8. Early initiation of empirical therapy for possible CAPM is recommended, and microbiological evidence should be obtained at the same time.-Clinical applications for antifungal agents9.Voriconazole or isavuconazole are recommended as initial treatment for CAPA. Amphotericin B liposomes are suggested as the initial treatment for CAPM. Isavuconazole or posaconazole may be an option in patients with renal insufficiency or amphotericin B liposome intolerance/unavailability.10. In CAPA patients with tracheobronchitis, antifungal drug inhalation is recommended in addition to systemic antifungal medication.11. Combination therapy is not recommended as initial therapy for CAPA, but may be used as a salvage therapy strategy. Triazole or amphotericin B in combination with caspofungin or micafungin is recommended; whereas amphotericin B in combination with triazole is not recommended. For CAPM patients with extensive lesions, rapid progression or poor general condition, a combination of amphotericin B liposome with isavuconazole or posaconazole is suggested.-Response assessment and treatment duration12. It is recommended that treatment response be assessed comprehensively according to the clinical symptoms/signs, imaging and microbiological examination of patients. CAPA can be evaluated in combination with the dynamic change in serum GM.13. The recommended treatment duration of CAPA is at least 6-12 weeks. A total course of at least 3-6 months is suggested for CAPM, and the sequential treatment should be considered according to the response to 4-6 weeks of intravenous therapy.-How to adjust the anti-inflammatory therapy14. In patients with severe COVID-19 combined with possible or probable filamentous fungal infection, it is suggested that of anti-inflammatory therapy be stopped or reduced appropriately, taking into account of the severity of the infection and inflammation of the disease course. The combination of baritinib and/or tozzizumab based on glucocorticoids is not suggested in these patients.-How to treat the underlying diseases15. In patients with diabetes, strict glycaemic control is suggested. In patients with long-term use of glucocorticoids and/or immunosuppressants, it is suggested to reduce the intensity of immunosuppression. Granulocyte colony-stimulating factor is suggested to use to improve the circulating granulocyte levels in patients with granulocyte deficiency due to various causes.-When an operation should be considered16. In patients with CAPA, surgery is not recommended unless large blood vessels, pericardium, or chest wall are involved, or the patient has recurrent or massive hemoptysis. For CAPM patients, early surgical removal of lesions after diagnosis is recommended. Surgery is a high-risk procedure in patients with severe COVID-19, and a multidisciplinary team discuss is suggested.

[Local administration of amphotericin B by VAC instillation: Therapeutic aid in the treatment of mucormycosis]. / Application locale d'amphotéricine B par VAC instillation : aide thérapeutique dans le traitement de la mucormycose.

Mucormycosis is a rare and serious fungal infection, occurring mainly in immunocompromised, diabetic, polytrauma or burn patients. Current standard treatments include iterative carcinological surgical trimming, systemic treatment with liposomal amphotericin B and second-line Posaconazole or Isavuconazole. We report the case of a 37-year-old female patient with no previous medical history who developed a disseminated mucormycosis, with an estimated 25 % loss of skin substance and major decay of the chest wall. In addition to standard treatment, local instillations of amphotericin B using the VAC Veraflow® system were performed. We believe that local instillations of amphotericin B by VAC could improve the functional prognosis of patients with skin involvement.

A case report on para-kala-azar dermal leishmaniasis: an unresolved mystery.

BACKGROUND: Post-kala-azar dermal leishmaniasis (PKDL) is a dermatosis that occurs 2-3 years after an apparently successful treatment of visceral leishmaniasis (VL). In rare cases, PKDL occurs concurrently with VL and is characterized by fever, splenomegaly, hepatomegaly or lymphadenopathy, and poor nutritional status and is known as Para-kala-azar dermal leishmaniasis (Para-KDL). Co-association of active VL in PKDL patients is documented in Africa, but very few case reports are found in South Asia. We present a case of Para-kala-azar Dermal Leishmaniasis (Para-KDL) in a 50-year-old male patient with a history of one primary Visceral Leishmaniasis (VL) and 2 times relapse of Visceral Leishmaniasis (VL). The patient presented with fever, skin lesions, and hepatosplenomegaly. Laboratory tests revealed LD bodies in the slit skin smear and splenic biopsy. The patient was treated with two cycles of Amphotericin B with Miltefosine in between cycles for 12 weeks to obtain full recovery. CONCLUSION: This case report serves as a reminder that Para-kala-azar dermal leishmaniasis can develop as a consequence of prior visceral leishmaniasis episodes, even after apparently effective therapy. Since para-kala-azar is a source of infectious spread, endemics cannot be avoided unless it is effectively recognized and treated.

Clinical characteristics of tracheobronchial Talaromyces marneffei infection in non-HIV-infected patients in South China.

OBJECTIVES: Tracheobronchial Talaromyces marneffei (T. marneffei) infections among non-HIV-infected patients are rare. To improve understanding, we analysed the clinical features, immune mechanisms, treatment, and prognosis. METHODS: Data on hospitalized patients with tracheobronchial T. marneffei infections from September 2013 to May 2022 were collected. The clinical and imaging features were analysed. RESULTS: Nineteen patients were enrolled, with a median age of 52 years (45-62 years). The most common symptoms were cough, expectoration, fever, weight loss, and anaemia. The total white blood cell and neutrophil counts, erythrocyte sedimentation rate, C-reactive protein, procalcitonin and globulin were increased, and the serum albumin levels were decreased. Chest CT manifestations included patchy shadows, masses, obstructive atelectasis, cavities, pleural effusion, and hilar and mediastinal lymphadenopathy. The fibreoptic bronchoscopy findings included masses, polyps or nodules with mucosal oedema, hypertrophic bulges, lumen stenosis or obstruction, and purulent secretions. T. marneffei infection was confirmed in 10 patients by positive culture, in five by both culture and metagenomic next-generation sequencing (mNGS), in two by mNGS, in one by culture and pathology and in 1 by histopathology. BALF (15/19, 78.9%) had the highest culture positive rate, followed by sputum (3/19), bronchial mucosa (1/1), lung biopsy (1/2); 36.8% of the patients were coinfected with other pathogens. For induction therapy, 7, 6, 2, and 4 patients received voriconazole, amphotericin B, voriconazole combined with amphotericin B, and fluconazole therapy, respectively, and 26.3% received treatment combined with nebulization and/or administration of amphotericin B under fibreoptic bronchoscopy. Four patients were treated for underlying diseases or coinfection, 31.6% were cured, 42.1% improved, and 26.3% died. CONCLUSIONS: T. marneffei infection is common in the tracheobronchial airway tissue or secretions, and bronchoscopy has important diagnostic and treatment value. Antifungal therapy, including systemic therapy, involves triazoles and amphotericin administration, and aerosol inhalation and administration of amphotericin B under bronchoscopy are important.

T. marneffei infection involving the tracheobronchial region in airway tissue or secretions is high, and bronchoscopy has important value in diagnosing and treating these patientsThe use of triazoles and amphotericin and the aerosol inhalation and instillation of amphotericin B under bronchoscopy are essential to antifungal therapy.

Fusariosis in Mexico: A 10-year retrospective series.

Fusarium species represent an opportunistic fungal pathogen. The data in Mexico about Fusarium infections in humans are scarce. Here, we present a retrospective series of patients with a confirmed diagnosis of fusariosis in eight different hospitals in Mexico from January 2010 to December 2019. The diagnosis of proven fusariosis was made according to the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORT/MSG) criteria. A total of 49 cases were identified in our series. Most patients had burn injuries (49%), and 37% had hematological malignancies. Most patients had fire injuries (40%), followed by electric injuries (8%), febrile neutropenia (10%), and pancytopenia (6%). Patients had skin and soft tissue involvement in 49%, followed by blood culture isolation and biopsies from different sites of the body (lung, sinuses, bone tissue, and eyes). Febrile neutropenia (10%) and fungemia (8%) were the most common clinical syndromes in immunosuppressed patients. Most patients received monotherapy (67%), where voriconazole was used in 30% of the cases, followed by conventional amphotericin B (16%), and lipidic formulations of amphotericin B in 10% (either liposomal amphotericin B or amphotericin B lipid complex). Combination therapy was used in 20% of the cases, and the most common combination therapy was triazole plus any lipidic formulation of amphotericin B (10%). Mortality related to Fusarium infection occurred in 22% of patients. Fusariosis is a serious threat. Burn injuries and hematologic malignancies represent the most common causes of infection in this small series from Mexico.

This study describes the epidemiological characteristics of patients with fusariosis from a multicenter cohort in Mexico. These findings provide information from this invasive fungal disease that threatens different countries in Latin America.

Cryptococcal meningitis.

Cryptococcus neoformans and Cryptococcus gattii species complexes cause meningoencephalitis with high fatality rates and considerable morbidity, particularly in persons with deficient T cell-mediated immunity, most commonly affecting people living with HIV. Whereas the global incidence of HIV-associated cryptococcal meningitis (HIV-CM) has decreased over the past decade, cryptococcosis still accounts for one in five AIDS-related deaths globally due to the persistent burden of advanced HIV disease. Moreover, mortality remains high (~50%) in low-resource settings. The armamentarium to decrease cryptococcosis-associated mortality is expanding: cryptococcal antigen screening in the serum and pre-emptive azole therapy for cryptococcal antigenaemia are well established, whereas enhanced pre-emptive combination treatment regimens to improve survival of persons with cryptococcal antigenaemia are in clinical trials. Short courses (≤7 days) of amphotericin-based therapy combined with flucytosine are currently the preferred options for induction therapy of cryptococcal meningitis. Whether short-course induction regimens improve long-term morbidity such as depression, reduced neurocognitive performance and physical disability among survivors is the subject of further study. Here, we discuss underlying immunology, changing epidemiology, and updates on the management of cryptococcal meningitis with emphasis on HIV-associated disease.

Diagnosis and management of cryptococcal meningitis in HIV-infected adults.

Cryptococcal meningitis is a leading cause of morbidity and mortality globally, especially in people with advanced HIV disease. Cryptococcal meningitis is responsible for nearly 20% of all deaths related to advanced HIV disease, with the burden of disease predominantly experienced by people in resource-limited countries. Major advancements in diagnostics have introduced low-cost, easy-to-use antigen tests with remarkably high sensitivity and specificity. These tests have led to improved diagnostic accuracy and are essential for screening campaigns to reduce the burden of cryptococcosis. In the last 5 years, several high-quality, multisite clinical trials have led to innovations in therapeutics that have allowed for simplified regimens, which are better tolerated and result in less intensive monitoring and management of medication adverse effects. One trial found that a shorter, 7-day course of deoxycholate amphotericin B is as effective as the longer 14-day course and that flucytosine is an essential partner drug for reducing mortality in the acute phase of disease. Single-dose liposomal amphotericin B has also been found to be as effective as a 7-day course of deoxycholate amphotericin B. These findings have allowed for simpler and safer treatment regimens that also reduce the burden on the healthcare system. This review provides a detailed discussion of the latest evidence guiding the clinical management and special circumstances that make cryptococcal meningitis uniquely difficult to treat.

Virulence traits and novel drug delivery strategies for mucormycosis post-COVID-19: a comprehensive review.

The outbreak of a fatal black fungus infection after the resurgence of the cadaverous COVID-19 has exhorted scientists worldwide to develop a nutshell by repurposing or designing new formulations to address the crisis. Patients expressing COVID-19 are more susceptible to Mucormycosis (MCR) and thus fall easy prey to decease accounting for this global threat. Their mortality rates range around 32-70% depending on the organs affected and grow even higher despite the treatment. The many contemporary recommendations strongly advise using liposomal amphotericin B and surgery as first-line therapy whenever practicable. MCR is a dangerous infection that requires an antifungal drug administration on appropriate prescription, typically one of the following: Amphotericin B, Posaconazole, or Isavuconazole since the fungi that cause MCR are resistant to other medications like fluconazole, voriconazole, and echinocandins. Amphotericin B and Posaconazole are administered through veins (intravenously), and isavuconazole by mouth (orally). From last several years so many compounds are developed against invasive fungal disease but only few of them are able to induce effective treatment against the micorals. Adjuvant medicines, more particularly, are difficult to assess without prospective randomized controlled investigations, which are challenging to conduct given the lower incidence and higher mortality from Mucormycosis. The present analysis provides insight into pathogenesis, epidemiology, clinical manifestations, underlying fungal virulence, and growth mechanisms. In addition, current therapy for MCR in Post Covid-19 individuals includes conventional and novel nano-based advanced management systems for procuring against deadly fungal infection. The study urges involving nanomedicine to prevent fungal growth at the commencement of infection, delay the progression, and mitigate fatality risk.

Palmitoylethanolamide shows limited efficacy in controlling cerebral cryptococcosis in vivo.

Cryptococcus neoformans (Cn) is an encapsulated neurotropic fungal pathogen and the causative agent of cryptococcal meningoencephalitis (CME) in humans. Recommended treatment for CME is Amphotericin B (AmpB) and 5-fluorocytosine (5-FC). Though effective, AmpB has displayed numerous adverse side effects due to its potency and nephrotoxicity, prompting investigation into alternative treatments. Palmitoylethanolamide (PEA) is an immunomodulatory compound capable of promoting neuroprotection and reducing inflammation. To investigate the efficacy of PEA as a therapeutic alternative for CME, we intracerebrally infected mice with Cn and treated them with PEA or AmpB alone or in combination. Our results demonstrate that PEA alone does not significantly prolong survival nor reduce fungal burden, but when combined with AmpB, PEA exerts an additive effect and promotes both survivability and fungal clearance. However, we compared this combination to traditional AmpB and 5-FC treatment in a survivability study and observed lower efficacy. Overall, our study revealed that PEA alone is not effective as an antifungal agent in the treatment of CME. Importantly, we describe the therapeutic capability of PEA in the context of Cn infection and show that its immunomodulatory properties may confer limited protection when combined with an effective fungicidal agent.