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Background: Tracheobronchial mucormycosis is a fatal opportunistic infection that mainly causes airway stenosis and is difficult to manage clinically., Case Presentation: We report a case of severe tracheal stenosis caused by tracheobronchial mucormycosis in a 37-year-old female with a history of hyperthyroidism. She developed agranulopenia after oral methimazole administration and subsequently experienced asthma with dyspnea. Bronchoscopy, sputum culture, colony mass spectrometry, and microscopic cotton orchid staining confirmed tracheobronchial mucormycosis. The patient received venous-venous extracorporeal membrane oxygenation (VV-ECMO) and prolonged intratracheal instillation of amphotericin B (AmBD), combined with amphotericin B liposome (L-AmB) and isavuconazole intravenous infusion, ultimately resulting in successful treatment., Conclusion: VV-ECMO combined with prolonged intratracheal instillation of AmBD is an effective method for the treatment of tracheobronchial mucormycosis., Competing Interests: Declarations Ethical approval and consent to participate This study received approval from the Ethics Committee of Drum Tower Hospital affiliated with the Medical School of Nanjing University (ethical code: 2022-261-01).Due to the retrospective nature of the study, the requirement for individual patient informed consent was waived. Consent for publication Written informed consent for publication was obtained from all participants. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Tuberculosis is a highly prevalent disease in India, while Histoplasmosis, an emerging disease, is often underreported due to limited resources in developing countries. Coinfection with both these organisms is rarely documented in immunocompetent host. Due to overlapping symptoms, it can be easily missed and treatment delays are not uncommon., Case Presentation: Here, we report a case of a 62-year-old male with a chronic history of intermittent fever and dry cough, splenomegaly, lymphadenopathy, and persistent pancytopenia. He was diagnosed with tuberculosis with cartridge-based nucleic acid amplification test (CBNAAT) positivity from a paratracheal lymph node biopsy. Simultaneously, a bone marrow biopsy revealed Histoplasmosis and the patient was started on dual treatment (Itraconazole and antitubercular drugs). After an initial response, the patient developed new space-occupying cerebral lesions. CSF histoplasma antigen was also positive. The reason for treatment failure was likely to be drug interaction (suboptimal levels of itraconazole due to rifampicin). The patient received liposomal amphotericin and subsequently put on a modified antitubercular treatment regimen to avoid interaction with itraconazole. At 2-month follow-up, the patient's condition significantly improved with a substantial resolution in CNS lesions., Conclusions: Histoplasmosis and tuberculosis have overlapping symptoms, diagnosing one does not preclude the possibility of other, even in non-HIV patients. Clinicians should also be vigilant about potential drug interactions., Competing Interests: Declarations Ethics approval and consent to participate This study did not require ethical approval. Consent for publication Written informed consent was obtained from the patient included in this report. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Histoplasmosis is endemic in the central/northeast region of Argentina. It is estimated that the incidence of this mycosis is low in solid organ transplant recipients. This work aims to describe the epidemiology, clinical forms, and evolution of kidney transplant recipients diagnosed with histoplasmosis in Santa Fe city, Argentina. A retrospective study was carried out between 2015 and 2020 on kidney transplant patients with symptoms associated with histoplasmosis in Santa Fe. Histoplasmosis diagnosis was performed through histopathology, recovery of Histoplasma spp., by culture, and/or positive nested Polimerase Chain Reaction (PCR) specific for the Histoplasma Hc100 gene. During the study period, 360 kidney transplantations were performed. Of these patients, 12 were diagnosed with histoplasmosis (3.3%). The patients' median age was 51 years, and 75% were male. Eleven patients (92%) presented the disseminated form of the disease. Thirty-three percent were diagnosed with histoplasmosis in their first year post-transplantation (mostly 6-12 months), while 42% received their diagnosis 3 years after transplantation. Laboratory diagnosis was performed by histopathology, culture, and PCR in four cases (33%), by culture and PCR in three cases (25%), and by PCR alone in three cases (25%). Thus, all 12 patients showed positive nested PCR results. All patients received amphotericin B as initial treatment. A good response was observed in 83% of patients. We found a high incidence of histoplasmosis in kidney transplant recipients (up to 10 times higher than reports from other endemic areas). Diagnosis by histopathology/culture showed 75% sensitivity, while nested PCR showed better sensitivity and diagnostic speed., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Background: Visceral leishmaniasis (VL) is a neglected tropical disease primarily affecting Brazil, East Africa, and India, with India accounting for 18% of the global burden. While VL typically presents with systemic symptoms like fever, weight loss, and splenomegaly, it can occasionally manifest atypically, posing significant diagnostic challenges. Neurological presentations of VL are extremely rare, making them difficult to suspect and diagnose. Cases where VL predominantly presents with neurological symptoms are particularly novel, underscoring the need for heightened awareness of such atypical manifestations in endemic regions., Clinical Case: A 38-year-old man with history of recurrent atypical VL presented with diffuse lower back pain, progressive tingling, numbness, weakness in the lower extremities, and double vision for one month. Clinical and radiological evaluations suggested cauda equina syndrome and cranial nerve palsy, accompanied by generalized lymphadenopathy, subcutaneous nodules, and skin papules. The differential diagnosis initially included disseminated tuberculosis, histoplasmosis, and lymphoma. Cerebrospinal fluid (CSF) analysis revealed an inflammatory syndrome. Histopathology of lymph node and bone marrow revealed Leishmania amastigotes and subcutaneous nodule and skin biopsy revealed inflammatory cells with granulomas. Furthermore, the qPCR test on DNA from a subcutaneous nodule, lymph node, and CSF was positive for Leishmania kinetoplast DNA. The species was further confirmed as Leishmania donovani through ITS-based PCR amplification and sequencing. Finally, a diagnosis of relapse of VL with lymph node, cutaneous, and neurological involvement, including abducens nerve palsy and cauda equina syndrome, was established. He was treated with combination of liposomal amphotericin B and miltefosine, along with intrathecal hyaluronidase, resulting in significant improvement., Conclusion: Unlike previously reported cases with both systemic and neurological symptoms, our patient predominantly presented with neurological manifestations, making this a unique and novel presentation of VL. This case highlights diagnostic challenges and management of atypical VL, emphasizing neurological involvement and successful therapeutic strategies., (© 2024. The Author(s).)

Background: Mucormycosis is a severe and fatal fungal infection in patients with coronavirus disease 2019 caused by Mucorales. Here we present a case of a 63-year-old man with coronavirus disease 2019 infection, along with rhinosinusitis mucormycosis caused by Rhizopus delemar., Case Presentation: A 63-year-old Iranian man suffering from a coronavirus disease 2019 infection with symptoms of cough, shortness of breath, and generalized body pain. On the basis of the clinical manifestations, such as headache, a history of black nasal discharge, nasal hypoesthesia, facial swelling, numbness, nasal obstruction, presence of necrotic lesions on the nasal passages on physical examination, and abnormal computed tomography scans of paranasal sinuses, the patient underwent surgical debridement. Direct microscopy of specimens obtained from the paranasal sinuses, and subsequent isolation and identification, revealed a rhinosinusitis mucormycosis caused by R. delemar. Despite therapeutic measures, such as sinus debridement surgery and antifungal therapy with amphotericin B injection (50 mg/day), the patient died after 35 days of hospitalization., Conclusion: In this report, we present the first documented case of human infection with R. delemar in a patient with coronavirus disease 2019 infection, who also exhibited rhinosinusitis mucormycosis. R. delemar appears to be an emerging agent of rhinosinusitis mucormycosis in this region. Furthermore, prompt diagnosis and the exploration of alternative antifungal treatments, beyond amphotericin B, may be crucial for effectively managing patients with R. delemar infections., (© 2024. The Author(s).)

Aim. Melanized fungi were rarely studied for their antifungal resistance (AFR) or clinical outcome, despite rising incidence of melanized fungal ocular infections and AFR in general. We report the antifungal resistance patterns, clinical outcome and clinico-microbiological correlation in two commonly isolated melanized fungi from ocular infections, Curvularia lunata and Lasiodiplodia theobromae , at a tertiary eyecare centre in South India. Gap statement . Despite melanized fungi accounting for a significant proportion of ocular fungal infections in the Indian subcontinent, and despite there being a limited selection of effective antifungal agents available for these infections, the existing data and studies on these issues remain sparse. Therefore, this study aimed to investigate the prevalence of antifungal resistance in two of the most common melanized fungal pathogens in ocular infections, Curvularia lunata and Lasiodiplodia theobromae and correlate it with the treatment given and the clinical outcome in patients. Methodology. Electronic medical records provided the clinical data. Standard broth microdilution was performed for antifungal susceptibility testing (AFST) in 30 isolates (17 C . lunata and 13 L . theobromae ) for amphotericin B and natamycin (polyenes): voriconazole, ketoconazole, posaconazole, itraconazole and fluconazole (azoles) and caspofungin (echinocandin). Multidrug resistance (MDR) was defined as resistance to more than or equal to two classes of antifungals. DNA sequencing was performed for the isolates for species confirmation. The multivariate analysis was done for determining poor prognostic factors. Results. AFST showed highest susceptibility of study isolates for voriconazole (83.3% isolates), followed by natamycin (80%), fluconazole (80%), itraconazole (76.7%), ketoconazole (70%), posaconazole (66.7%), caspofungin (66.7%) and lastly amphotericin B (63.3%). All patients empirically received topical natamycin; additional oral ketoconazole/intraocular voriconazole was administered in select few. MDR was strongly associated with poor clinical outcome (multivariate analysis: P = 0.03, odds ratio = 7.8). All patients had microbial keratitis, one progressed to endophthalmitis. Additionally, therapeutic penetrating keratoplasty was required in 40% of cases. Globe salvage was possible in 80% patients, though good visual outcome was seen in only half of them. Both, anatomical and visual outcomes, were poor in 20% of patients. DNA sequencing showed C. lunata as the highest study species. Conclusion. C. lunata and L. theobromae showed varying in vitro antifungal susceptibility and clinical outcome in ocular infections. Voriconazole had significantly higher activity, while amphotericin B had lower activity in vitro for these melanized fungi. MDR isolates showed poorer clinical outcome.

Patients with orofacial clefts are more likely to develop oral fungal diseases due to anatomo-physiological changes and surgical rehabilitation treatment. This case-series study evaluated the genetic diversity and dynamics of oral colonization and spread of C. albicans and C. tropicalis in four patients with orofacial clefts, from the time of hospital admission, perioperative and outpatient follow-up, with specialized physician. Candida biotypes previously identified by CHROMagar Candida and PCR methods were studied by MALDI-TOF MS assays and clustering analyses. Possible correlations with pathogenicity characteristics were observed, including production of hydrolytic exoenzymes and the antifungal sensitivity profiles. Amphotericin B-sensitive and fluconazole-resistant (low frequency) C. tropicalis and C. albicans, including clinically compatible MIC of nystatin, were found in the oral cavity of these patients. Clusters of isolates revealed phenomena of (i) elimination in the operative phase, (ii) maintenance or (iii) acquisition of oral C. tropicalis in the perioperative period and specialized outpatient and medical follow-up. For C. albicans, these phenomena included (i) elimination in the operative phase, (ii) acquisition in the operative phase and propagation from the hospital environment, and (iii) maintenance during hospitalization and operative phase. Amphotericin B and nystatin were shown to be effective in cases of clinical treatment and/or prophylaxis, especially considering the pre-existence of fluconazole-resistant strains. This study confirmed the phenomena of septic maintenance, septic neocolonization and septic elimination involving the opportunistic pathogens. MALDI-TOF MS associated with clustering analysis may assist the monitoring of clinical isolates or groups of epidemiologically important microbial strains in the hospital setting., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background/aim: This experimental study aimed to examine the effectiveness of transdermal antimicrobial photodynamic therapy (APDT) with and without antimicrobial lock therapy (ALT), on catheter biofilms., Methods: S. epidermidis and C. orthopsilosis biofilms were formed within peripheral venous catheters positioned in the marginal ear veins of New Zealand white rabbits. Biofilm formation was confirmed with scanning electron microscopy in two catheters. 24 catheters with staphylococcal biofilms and 24 with fungal biofilms were treated with APDT, ALT or "APDT plus ALT" for five days. Six catheters were separated as controls. APDT was applied with a red colored LED lamp and methylene blue as the photosensitizer. Vancomycin lock solutions were used as ALT for staphylococcal biofilms and amphotericin B for fungal biofilms. The effect of treatment procedures was evaluated by intraluminal biofilm viability testing based on spectrophotometric evaluation, and a quantitative (OD) value was obtained for each catheter., Results: The mean OD values obtained by 600 nm spectrophotometric reading at 24 h (biofilm viability) after "ALT", "APDT" and "ALT plus APDT" procedures were 0.363, 0.151 and 0.128 for S. epidermidis and 0.092, 0.104 and 0.227 for C. orthopsilosis, respectively. All these OD values obtained after treatment procedures were lower than controls for both S. epidermidis (OD: 0,802) and C. orthopsilosis (OD: 0,315), although there were large fluctuations in our results., Conclusions: Our results suggest that transdermal APDT may be an effective method for treating staphylococcal and candida biofilms formed within intravenous catheters in our rabbit ear model. The combined use of APDT and ALT might be beneficial in these staphylococcal biofilms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Visceral Leishmaniasis (VL) is the most severe and fatal disease if left untreated. In people living with HIV/AIDS (PLHA), VL is considered an emerging opportunistic infection. The aim of this manuscript was to report a first case in Tunisia of a concomitant presentation of visceral and oral leishmaniasis in a patient LHA. A systematic review of the literature was performed according to PRISMA guidelines, as well., Case Presentation: The patient, a 43-year-old heterosexual man, treated for HIV/AIDS was referred for macrocheilitis of the upper and lower lips. A noticeable nodular and painless swelling extending to the cheeks' mucosa was noted. The patient's poor oral hygiene was evident due to the presence of multiple dental caries. Histological analysis of the biopsied lower lip sample revealed the presence of numerous Leishmania amastigotes. The diagnosis of VL was clinically confirmed by the presence of a mild splenomegaly and pancytopenia and biologically by the identification of the parasite using PCR Lei and the species L. infantum involved using RFLP-PCR and culture. The treatment consisted of an intravenous administration of liposomal Amphotericin B (Ambisome®, 40 mg/kg/weight) for a period of 6 weeks. A favorable outcome was noted after one year with the resolution of clinical symptoms and a negative Leishmania blood PCR test. After 2 years, the patient remained asymptomatic but showed a positive Leishmania blood PCR test. Dolutegravir® was introduced in the patient's ART regimen., Conclusions: To the best of our knowledge, this is the first case report in Tunisia of atypical VL diagnosed through an uncommon oral location in an HIV/AIDS co-infected patient . Since VL is a severe and potentially fatal disease, it is essential for dentists to perform a thorough clinical examination and adopt a multidisciplinary approach in order to ensure an early diagnosis and an effective treatment outcome., (© 2024. The Author(s).)

Cryptococcal meningitis causes an estimated 112,000 global deaths per annum. Genomic and phenotypic features of the infecting strain of Cryptococcus spp. have been associated with outcomes from cryptococcal meningitis. Additionally, population-level pharmacokinetic variability is well documented in these patient cohorts. The relative contribution of these factors to clinical outcomes is unknown. Based in Malawi, we conducted a sub-study of the phase 3 Ambition-CM trial (ISRCTN72509687), collecting plasma and cerebrospinal fluid at serial time points during the first 14 days of antifungal therapy. We explored the relative contribution of pathogen genotype, drug resistance phenotype, and pharmacokinetics on clinical outcomes including lumbar opening pressure, pharmacodynamic effect, and mortality. We report remarkable genomic homogeneity among infecting strains of Cryptococcus spp., within and between patients. There was no evidence of acquisition of antifungal resistance in our isolates. Genotypic features of the infecting strain were not consistently associated with adverse or favorable clinical outcomes. However, baseline fungal burden and early fungicidal activity (EFA) were associated with mortality. The strongest predictor of EFA was the level of exposure to amphotericin B. Our analysis suggests the most effective means of improving clinical outcomes from HIV-associated cryptococcal meningitis is to optimize exposure to potent antifungal therapy., Importance: HIV-associated cryptococcal meningitis is associated with a high burden of mortality. Research into the different strain types causing this disease has yielded inconsistent findings in terms of which strains are associated with worse clinical outcomes. Our study suggests that the exposure of patients to potent anti-cryptococcal drugs has a more significant impact on clinical outcomes than the strain type of the infecting organism. Future research should focus on optimizing drug exposure, particularly in the context of novel anticryptococcal drugs coming into clinical use., Competing Interests: The authors declare no conflict of interest.

Tropicoporus tropicalis (formerly Phellinus tropicalis) is a saprophytic basidiomycete that has been implicated in refractory mycoses in humans, particularly in patients with chronic granulomatous disease. Despite its clinical significance, T. tropicalis is an under-recognised cause of eumycetoma, with no prior reports available. We present a case of white grain eumycetoma with associated osteomyelitis of the left foot, caused by T. tropicalis, confirmed through 18S-ITS1-5.8S-ITS2-28S rRNA gene amplification and sequencing. The patient was treated with itraconazole 200 mg daily, leading to gradual improvement. A review of the literature on T. tropicalis infections in humans reveals its characteristic manifestations, which include osteomyelitis, soft tissue abscesses, pulmonary nodules and keratitis. These infections are locally destructive but have the potential to disseminate. Diagnosis is often delayed and relies on molecular techniques. Amphotericin B combined with an azole appears to be the most effective treatment, often necessitating concurrent surgical drainage. In conclusion, T. tropicalis is a newly recognised pathogen associated with eumycetoma and poses an increased risk of osteomyelitis. Molecular identification, such as sequencing the internal transcribed spacer (ITS) region from cultures or tissue specimens, is crucial for accurate identification of this pathogen., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Leishmaniasis is a parasitic disease spread by the bite of an infected sandfly and caused by protozoan parasites of the genus Leishmania. Currently, there is no vaccine available for leishmaniasis in humans, and the existing chemotherapy methods face various clinical challenges. The majority of drugs are limited to a few toxic compounds, with some parasite strains developing resistance. Therefore, the discovery and development of a new anti-leishmanial compound is crucial. One promising strategy involves the use of nanoparticle delivery systems to accelerate the effectiveness of existing treatments. In this study, Amphotericin B (AmB) was incorporated into functionalized carbon nanotube (f-CNT) and evaluated for its efficacy against Leishmania major in vitro and in a BALB/c mice model. The increase in footpad thickness was measured, and real-time PCR was used to quantify the parasite load post-infection. Levels of nitric oxide and cytokines IL-4 and IFN-γ were also determined. We found that f-CNT-AmB significantly reduced the levels of promastigotes and amastigotes of the Leishmania parasite. The nanoparticle showed strong anti-leishmanial activity with an IC 50 of 0.00494 ± 0.00095 mg/mL for promastigotes and EC 50 of 0.00294 ± 0.00065 mg/mL for amastigotes at 72 h post-infection, without causing harm to mice macrophages. Treatment of infected BALB/c mice with f-CNT-AmB resulted in a significant decrease in cutaneous leishmania (CL) lesion size in the foot pad, as well as reduced Leishmania burden in both lymph nodes and spleen. The levels of nitric oxide and IFN-γ significantly increased in the f-CNT-AmB treated groups. Also, our results showed that the level of IL-4 significantly decreased after f-CNT-AmB treatment in comparison to other groups. In conclusion, our results demonstrate that AmB loaded into f-CNT is significantly more effective than AmB alone in inhibiting parasite propagation and promoting a shift towards a Th1 response., (© 2024 John Wiley & Sons Ltd.)

Introduction: Many countries from South-East Asia reported an epidemic of sino-orbital mucormycosis (SOM), otherwise a rare disease, during the coronavirus disease 2019 pandemic. SOM, a potentially fatal disease, is typically treated with orbital exenteration and systemic antifungals after metabolic stabilization. There is no clear evidence of survival benefit of exenteration in the literature, and thus, there have been attempts at globe conserving treatments like orbital infusion after limited debridement and intraorbital injections with Amphotericin B (IOAB)., Methods: We conducted a prospective comparative interventional study at a tertiary eye care hospital to evaluate treatment outcomes with the use of adjunctive IOAB in cases of SOM with mild to moderate orbital disease., Results: Thirty-six patients of SOM with mild to moderate orbital disease were recruited in the study. In the intervention group, 23/26 (885%) eyes had stable orbital disease at the end of treatment (4-6 weeks). No deterioration in visual acuity was noted as a result of treatment. In 8/26 (30.77%) patients, inflammation was noted as a side effect of IOAB requiring temporary discontinuation of injections. The mean follow-up for cases was 14.2 months (range 12-15 months). 1/23 (4.35%) patients had relapse of orbital disease at 3 months. Twenty-one patients are alive on last follow-up. Of the patients who refused treatment (controls), 2/9 (22.22%) patients relapsed. One of these patients with relapse underwent exenteration, while the other was managed with IOAB. At a follow-up of 14 months (range 12-15 months), eight patients are alive. On evaluating the ocular parameters in salvaged eyes, improvement in extraocular movements was noted in 75-80% cases. The degree of proptosis and resistance to retropulsion did not change significantly., Conclusion: In the current study, an improvement in the globe salvage rates was noted in cases of SOM with mild to moderate orbital disease treated with adjunctive IOAB as compared to controls at a mean follow-up of 14 months, although it did not achieve statistical significance. The study supports the inclusion of IOAB in routine management of mild to moderate orbital disease., (Copyright © 2024 Copyright: © 2024 Indian Journal of Ophthalmology.)

A 57-year old man with uncontrolled diabetes presented with features suggestive of chronic meningitis. Cerebrospinal fluid (CSF) analysis revealed a polymorphonuclear pleocytosis with low glucose and high protein levels in the CSF. Bacterial and fungal cultures and tests for M. tuberculosis were negative. MRI spine showed leptomeningeal enhancement. On ruling out other causes, fungal meningitis was considered. The patient developed paraparesis in the hospital. MRI showed peripherally enhancing subdural lesion with dorsal cord involvement at the level of D4 and D5 vertebrae. On laminectomy and exploration, an intradural extramedullary abscess and a granuloma were noticed at T4--T5 spinal levels causing compression of the cord below. Histopathological examination of the lesions revealed acute on chronic inflammatory infiltrates interspersed by broad, aseptate, ribbon-like fungal elements highlighted by PAS stain, diagnostic of mucormycosis. Intravenous amphotericin B and oral posaconazole were administered for more than 8 weeks. On follow-up, he had complete neurological recovery without sequelae., Competing Interests: Patient consentBefore manuscript preparation, written informed consent was granted by the patient for the publication of his clinical data and the figures. Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose of Review: The number of cases of visceral leishmaniasis associated with transplant-associated immunosuppression has increased in recent years. Reviewing and updating the latest developments in its diagnostic management, treatment, and follow-up is necessary and relevant., Recent Findings: Visceral leishmaniasis cases associated with non-HIV immunosuppression are a growing cause of the parasitic infections, and the transplant patients are included in this context. These have been described especially in kidney transplantation. Liposomal amphotericin B is the first-line treatment. Due to immunosuppression, these patients often suffer from recurrent infections. The use of markers that indicate whether the patient has developed an adequate cellular response against Leishmania after treatment seems to be good biomarkers of cure and useful for monitoring and guiding secondary prophylaxis., Summary: There is a lack of consensus regarding the need for leishmaniasis screening in donors and recipients and the indications for secondary prophylaxis. The study of new biomarkers of cure may be useful in all three contexts., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Progressive disseminated histoplasmosis is a significant issue in Latin America, particularly in Brazil, contributing to high mortality rates., Objectives: Our objectives were to comprehensively describe histoplasmosis treatment with various amphotericin B (AmB) formulations, including mortality rates, adverse effects and risk factors for mortality., Methods: This multicentre retrospective cohort study (January 2014-December 2019) evaluated medical records of patients with proven or probable histoplasmosis treated with at least two doses of AmB in seven tertiary medical centres in Brazil. We assessed risk factors associated with death during hospitalization using univariate and multivariate analyses., Results: The study included 215 patients, mostly male (n = 158, 73%) with HIV infection (n = 187, 87%), and a median age of 40 years. Only 11 (5%) patients initiated treatment with liposomal amphotericin B (L-AmB). Amphotericin B deoxycholate (D-AmB) was administered to 159 (74%) patients without changes in the treatment. The overall mortality during hospitalization was 23% (50/215). Variables independently associated with mortality were use of D-AmB (OR 4.93) and hospitalization in ICU (OR 9.46). There was a high incidence of anaemia (n = 19, 90%), acute kidney injury (n = 96, 59%), hypokalaemia (n = 73, 55%) and infusion reactions (n = 44, 20%) during treatment., Conclusions: We found that D-AmB was the main formulation, which was also associated with a higher mortality rate. Lipid formulations of AmB have become more readily available in the public health system in Brazil. Further studies to evaluate the effectiveness of L-AmB will likely show improvements in the treatment outcomes for patients with disseminated histoplasmosis., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

We share a case of a 54-year-old Caucasian immune-competent male with a suspected long latent visceral leishmaniasis presenting primarily with parasitic colitis, splenomegaly, and pancytopenia. Due to histopathologically and endoscopically mimicking ulcerative colitis, the patient was initially treated for UC, until the parasites were identified and eradicated with liposomal Amphotericin B., Competing Interests: Declarations of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The scintillating association between Leishmania and HIV has contributed exceptionally towards expansion of Visceral Leishmaniasis (VL) with Acquired Immunodeficiency Syndrome (AIDS). The co-infection poses a grievous threat to elimination of VL and containment of Human Immunodeficiency Virus (HIV). When coinfected, Leishmania and HIV complement each other's proliferation and survival by inducing immunesenescence, T cell fatigue and exhaustion. Antigen presentation is lost, co-stimulatory molecules are diminished whereas co-inhibitory molecules such as CTLA-4, TIGIT, LAG-3 etc. are upregulated to ensure a Th2-baised immune environment. As a consequence, Leishmania-HIV coinfection causes poor outcomes, inflates the spread of Leishmania parasites, enhances the severity of side-effects to drugs, as well as escalate the probability of treatment failure and mortality. What makes control extremely strenuous is that there are frequent episodes of VL relapse with no prognostic markers, no standard immunophenotype(s) and appearance of atypical clinical symptoms. Thus, a standard therapeutic regimen has been difficult to develop and treatment is majorly dependent upon a combination of liposomal Amphotericin B and Miltefosine, a therapy that is expensive and capable of causing drastic side-effects in recipients. As World Health Organization is committed to eliminate both VL and HIV in due course of future, the existing therapeutic interventions require advancements to grapple and overcome this hazardous co-infection. In this context, an overview of HIV-VL co-infection, immunopathology of HIV and Leishmania co-inhabitance, available therapeutic options and their limitations in the treatment of co-infection are discussed in-depth., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Central nervous system (CNS) aspergillosis is an opportunistic infection with an increasing incidence and a high mortality rate. It is seen in immunocompromised patients as well as in immunocompetent patients. Here, we present disseminated aspergillosis in a child with nephrotic syndrome treated with long-term and aggressive systemic antifungal treatment and intraventricular (IVent) liposomal amphotericin B (L-AmB) as well as surgical excision and drainage due to difficulty in management., Case Report: A 10-year-old boy with nephrotic syndrome on steroid therapy was admitted with limping and weakness. The cranial magnetic resonance imaging showed multiple intraparenchymal scattered abscesses. The largest one was excised and drained. Abscess culture revealed Aspergillus fumigatus and histopathological examination revealed septate hyphae compatible with Aspergillosis. Intravenous (IV) voriconazole was started, and IV L-AmB was added. The size of lesions and perilesional edema continued to increase, and then IVent L-AmB was added. With IVent and systemic antifungal treatment, regression of the lesions was observed. He was followed up with oral voriconazole and weekly IVent L-AmB. After 2 and a half months, he was re-operated because of increased lesion size, number and perilesional edema, and IV voriconazole and other salvage antifungal therapies were started. Since the lesions had decreased and remained stable, IV voriconazole was switched to oral therapy, and he was followed up as an outpatient. Immunodeficiency diseases were excluded by immunological and genetic tests., Conclusion: Management of central nervous system aspergillosis can be challenging despite long-term and aggressive systemic and IVent antifungal treatment as well as surgical excision and drainage., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

We conducted a retrospective, observational study among acquired immune deficiency syndrome (AIDS) patients with cryptococcal meningitis or talaromycosis to assess AmB formulations-related adverse events (AEs). Total 205 eligible patients were enrolled. Of them, 139 received AmB therapy, 51 received liposomal AmB (L-AmB) therapy, and 15 received AmB cholesteryl sulfate complex (ABCD) therapy. The incidences of total AEs between the AmB, L-AmB and ABCD group had no significant differences. The ABCD group had significantly higher incidences of hepatotoxicity and hematological toxicity than the AmB and L-AmB groups. The incidence of grade 3-4 hematological toxicity in the ABCD group was significantly higher than that in the AmB and L-AmB groups. Multinomial logistic regression models showed that compared with AmB, ABCD had a higher risk for the occurrence of grade 3-4 hematological toxicity (aOR = 43.924, 95%CI 6.296-306.418; p < 0.001). We demonstrated that ABCD was more prone to hepatotoxicity and hematological toxicity than AmB and L-AmB among AIDS patients, which is worth noting., (© 2024. The Author(s).)

Leishmaniasis is caused by an obligate intracellular protozoa of the genus Leishmania. Its clinical manifestations include cutaneous, mucocutaneous, and visceral forms. Sporotrichoid cutaneous leishmaniasis (SCL) is an atypical and rare form of cutaneous leishmaniasis (CL) reported mainly in the Old World. This case report describes SCL in a Japanese man infected with Leishmania (Viannia) peruviana in Peru. His lesions occurred on both feet, with the left foot lesion being a simple CL that resolved spontaneously. However, the lesion on the right foot did not cure by itself; instead, it progressed centrally along the lymph nodes, eventually forming an SCL. Amastigotes were detected in both feet and genetically identified as L. (V.) peruviana. The lesions gradually resolved after treatment with intravenous liposomal amphotericin B. Here, we report the first case of SCL caused by L. (V.) peruviana.

Introduction: Hemophagocytic lymphohistiocytosis characterized by hemophagocytosis leading to uncontrolled inflammation; the most common etiology in secondary cases of hemophagocytic lymphohistiocytosis is viral infections, especially Epstein-Barr virus. Visceral leishmaniasis is a vectorborne protozoal disease caused by Leishmania donovani complex. It is common in tropical and subtropical regions, with 50,000-90,000 new cases annually., Case Presentation: A 15-month-old Arab female was admitted to our hospital with 15 days of fever and decreased weight. On clinical examination, she had a markedly enlarged liver and spleen that were palpable 4 cm and 6 cm below the costal margin, respectively. The peripheral blood smear showed hypochromic microcytic anemia, poikilocytosis, reactive lymphocytosis, and mild thrombocytopenia. Bone marrow aspiration did not show malignancy or any other pathological findings. The patient was put on antibiotic therapy without improvement. Repeated bone marrow aspiration showed erythrophagocytosis; intracellular small round organisms looked like the amastigote form of Leishmania (Donovan bodies) with no evidence of malignancies. Her lab values showed ferritin greater than 500 ug/L, pancytopenia, and hypertriglyceridemia. The patient was diagnosed with hemophagocytic lymphohistiocytosis secondary to visceral leishmaniasis., Conclusion: Hemophagocytic lymphohistiocytosis secondary to visceral leishmaniasis is an extensively rare phenomenon in the medical literature that causes challenges in diagnosis and management. Steroids should be used wisely to not cover the symptoms of infections or malignancy, and amphotericin B resistance should be kept in mind in unresponsive Leishmania cases., (© 2024. The Author(s).)

Background: Reports of pulmonary aspergillosis and mucormycosis co-infections are rare; thus, limited guidance is available on early diagnosis and treatment. We present a case of mixed pulmonary Aspergillus and Mucor infection and review the literature regarding this co-infection. The diagnosis and treatment methods are summarized to improve clinicians' understanding of the disease and to facilitate early diagnosis and treatment., Case Presentation: A 60-year-old male farmer with poorly controlled diabetes mellitus was admitted to hospital with a fever of unknown origin that had been present for 15 days and pulmonary aspergillosis complicated by Mucor spp., Infection: Because multiple lobes were involved, the infection worsened despite surgical resection and antifungal therapy. Finally, we treated this patient with a bronchoscopic infusion of amphotericin B. After four courses of bronchoscopic amphotericin B infusion, we observed rapid clinical improvement and subsequent resolution of pulmonary infiltrates., Conclusion: Our case highlights the use of bronchoscopy in the successful clinical treatment of invasive fungal diseases of the lung., (© 2024. The Author(s).)

We present a novel case of acute invasive fungal rhinosinusitis (AIFRS) following a maxillary molar root canal in a 69-year-old diabetic female, who subsequently developed unilateral vision loss. The patient reported a 1-week history of progressive left facial pain, trismus, and numbness following the procedure. Initial evaluation was unremarkable, but her condition rapidly deteriorated, culminating in complete vision loss in the left eye. Imaging studies revealed opacification of the left-sided sinuses and a rim-enhancing collection in the left pterygopalatine fossa. Surgical debridement confirmed mucormycosis. The therapeutic approach included systemic and retrobulbar amphotericin B administration, along with multiple sinonasal debridements. The patient's poorly controlled diabetes mellitus significantly contributed to the rapid progression of the infection. Retrobulbar amphotericin B injections were effective in managing orbital involvement, thus avoiding the need for exenteration. Early diagnosis and aggressive treatment are paramount in improving outcomes for patients with AIFRS., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Visceral leishmaniasis (VL) is caused by an intracellular parasite that is transmitted to humans by sandfly bites. It is prevalent throughout Asia, Africa, the Americas, and the Mediterranean area, where 147 million people are at risk of contracting the illness. The manifestation of heterotrophic illness relies on both Leishmania implicated and the host's immunological response, ranging from asymptomatic to severe leishmaniasis with potentially lethal effects., Method: We reviewed the literature (published till 31st December 2023) on the worldwide situation of leishmaniasis, standard and novel detection techniques, and traditional and modern treatment strategies and endeavors to eliminate VL. Moreover, epidemiological data was collected from the World Health Organization's publicly available databases. GraphPad Prism Version 8 was used to analyze and produce figures based on the epidemiological data., Results: Diagnosis of parasites in tissues or serology is commonly employed. Diagnosis by identifying parasite DNA using molecular techniques is becoming more popular. Despite recent findings of L. donovani resistance to pentavalent antimoniate medications, it continues to be the cornerstone in the medical management of VL. Amphotericin B and its lipid formulations, injectable paromomycin, and oral miltefosine are among the new therapy options being researched. The number of reported VL cases has reduced remarkably over the last decade due to human interventions made to eliminate VL. Particularly countries from the South East Asian region have experienced momentous progress in reducing VL cases and eliminating this disease from this region. Owing to the robust elimination programs, countries such as Bangladesh has eliminated VL as a public health concern. India and Nepal are on the verge of its elimination., Conclusion: Rapid diagnosis, effective and inexpensive treatment, simple access to newly discovered medications, appropriate vector control, and a well-designed vaccine are all required for the elimination of this disease burden in impoverished areas of the globe., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Materials and Methods: Patients diagnosed with COVID-19 associated mucormycosis were followed up for 6 months to study the clinical profile, readmissions, long-term treatment outcome and the mortality rate., Results: Among 37 patients with COVID-19 associated mucormycosis, the mortality rate was 33.3 %, 42.9% and 100 % among patients with mild, moderate and severe COVID-19 infection. One month after discharge, among the 20 patients who survived, 10 (50 %) patients had worsening symptoms and required readmission. Nine patients required readmission for amphotericin and 1 patient was admitted for surgical intervention. On follow-up at 1 month, 30 % (6/20) patients became asymptomatic. However, at 3 months, 45 % (9/20) of the patients were asymptomatic. At 6 months of follow-up, 80 % (16/20) were asymptomatic. At 6 months, one each had residual abnormalities like visual loss in one eye, visual field deficit, change in voice and residual weakness of the limbs along with cranial nerve paresis., Conclusion: The follow-up study revealed that a significant number of patients required readmission within the first month, but most of the patients became asymptomatic by 6 months. The readmission rate was higher in patients who received a shorter duration of amphotericin., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare that are relevant to the content of this article., (Copyright © 2024 SFMM. Published by Elsevier Masson SAS. All rights reserved.)

The ascomycete filamentous fungus Neurospora intermedia is commonly used in the food industry and considered nonpathogenic to humans. This study characterizes four N. intermedia isolates recovered from three patients. The first patient had a mediastinal germ cell tumor with multiple metastases. N. intermedia was recovered from his endotracheal aspirate and from the endobronchial mass obtained by bronchoscopic forceps biopsy. Histopathology of the biopsy tissue revealed necrotic tissue mixed with septate fungal hyphae with right-angle branching. An endobronchial mass caused by N. intermedia was thus diagnosed. Another two N. intermedia isolates were recovered from the endotracheal aspirates of two critically ill patients. In vitro, N. intermedia grows rapidly and forms orange, conidiating colonies composed of septate hyphae. Two isolates from the first patient belong to mating type a; the other two isolates belong to mating type A. Coculture of isolates of opposite mating types yielded dark ascomata containing ascospores, supporting that N. intermedia is a heterothallic fungus. N. intermedia isolates cross-reacted with the Aspergillus galactomannan antigen assay and were susceptible to amphotericin B and voriconazole. In conclusion, this report describes the first human infection (endobronchial mass) caused by N. intermedia, highlighting its potential to invade the human respiratory tract., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Orbital involvement of invasive fungal sinusitis (IFS) is an ominous prognostic marker that should prompt rapid intervention. Transcutaneous retrobulbar administration of amphotericin B (TRAMB) is an off-label adjunctive treatment that can increase drug penetrance into diseased orbital tissue. To date, there is a lack of consensus regarding the use of TRAMB for treatment of IFS with orbital involvement., Objective: This systematic review aims to synthesize the indications, efficacy, and potential complications of TRAMB., Methods: PubMed, EMBASE, and Web of Science databases were probed for systematic review. Article search was conducted through June 2023 using the keywords "invasive fungal sinusitis," "invasive fungal rhinosinusitis," "rhino-orbital mucormycosis," "rhinosinusitis," "orbital," "retrobulbar," and "amphotericin.", Results: In suitable cases as determined by radiologic and clinical evaluation, TRAMB administration has the potential to improve orbital salvage rates and improve versus stabilize visual acuity. Treatment complications are more likely with deoxycholate than with liposomal amphotericin formulations. The existing literature describing use of TRAMB is limited due to its retrospective nature, but the increase in IFS cases since 2020 due to the COVID pandemic has broadened the literature., Conclusions: TRAMB is an effective adjunctive treatment in IFS with mild-to-moderate orbital involvement when used in combination with standard of care debridement, systemic antifungal therapy, and immunosuppression reversal. Prospective longitudinal studies and multi-institutional randomized trials are necessary to determine the definitive utility of TRAMB.

Background: The host cellular immune response associated with two treatments for post-kala-azar dermal leishmaniasis (PKDL) - paromomycin plus miltefosine (Arm 1), and liposomal amphotericin B plus miltefosine (Arm 2) - was examined in Sudanese patients before treatment (D0), at the end of treatment (D42), and during the post-treatment period (D180)., Methods: Whole blood samples were stimulated with soluble Leishmania antigen for 24 h (whole blood assay [WBA]) and the concentrations of Th1/Th2/Th17-associated cytokines, IP-10, PDL-1 and granzyme B were determined., Results: The Arm 1 treatment (98.2% cure rate) induced a Th1/Th2/Th17 response, while the Arm 2 treatment (80% cure rate) induced a Th1/Th2 response. Five Arm 2 patients relapsed and showed lower IFN-γ, TNF and IL-1β concentrations at D0 than non-relapsers in this Arm. In patients with low-IFN-γ-production at D0, Arm 1 treatment led to a better host immune response and clinical outcome than Arm 2 treatment., Conclusions: A Th1/Th2/Th17 response was associated with a higher cure rate. Patients with low IFN-γ, TNF and IL-1β before treatment are more likely to relapse if they undergo Arm 2-type treatment. Determining IFN-γ, TNF and IL-10 levels prior to treatment could help predict patients at higher risk of relapse/recovery from PKDL., Trial Registration: ClinicalTrials.gov NCT03399955, Registered 17 January 2018, https://clinicaltrials.gov/study/ NCT03399955., (© 2024. The Author(s).)

Cutaneous leishmaniasis (CL), a parasitic infection caused by Leishmania protozoa and transmitted by sandfly bites, can be classified into Old World and New World subtypes. We report a case of a 2-year-old female who developed complex CL after travel to Panama. Ultimately, successful treatment required two rounds of liposomal amphotericin B. We report this case for its challenging clinical course and management., (© 2024 Wiley Periodicals LLC.)

Introduction: The present study investigated the impact of immune recovery and the duration of antifungal adherence in the consolidation phase of disseminated histoplasmosis (DH) in acquired immune deficiency syndrome (AIDS) patients living in a hyperendemic area in northeastern Brazil., Material and Methods: Sixty-nine patients with DH/AIDS, admitted to the São José Hospital between 2010 and 2015, who continued histoplasmosis consolidation therapy at the outpatient clinic were studied. The follow-up duration was at least 24 months., Results: Sixty-eight patients used itraconazole 200-400 mg/day or amphotericin B deoxycholate weekly during the consolidation phase, and six patients relapsed during follow-up. The overall median duration of consolidation antifungal use was 250 days [IQR 101 - 372]. Antifungal withdrawal by medical decision occurred in 41 patients (70.7 %) after a median of 293 days [IQR 128 - 372] of use; 16 patients discontinued by their own decision, with a median of 106 days [IQR 37 - 244] of therapy; three patients had no information available, and nine continued on AF therapy. The median CD4+ T-cell count in the group without relapse was 248 cells/µL [IQR 115-355] within 6 months after admission; conversely, in the relapse group, the median cell count remained below 100 cells/µL. Irregular adherence to highly active antiretroviral therapy (HAART) was the leading risk factor associated with relapse and death (p< 0.01)., Discussion: The regular use of HAART, combined with immune recovery, proved to be highly effective in preventing relapses in DH/AIDS patients, suggesting that long-term antifungal therapy may not be necessary., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 SFMM. Published by Elsevier Masson SAS. All rights reserved.)

Substantial gains have been achieved in the control of visceral leishmaniasis (VL) in the four endemic states of India; however, cases are sporadically reported from other nonendemic regions of India such as the sub-Himalayan region, which can be a hurdle to VL elimination. We analyzed VL reports published from the sub-Himalayan regions of India over seven decades (1967-2023) in this systematic review. Medline, Embase, Scopus, and Web of Science were searched for VL cases from sub-Himalayan regions of India. The demographic data, clinical presentation, diagnostic modality, treatment, outcomes of the cases, and overall year-wise and geographical distribution of the cases were analyzed; studies on the sand fly vector were also included. From 535 articles, 33 studies were included in the analysis. Overall, 228 patients were diagnosed with VL in the sub-Himalayan region of India from 1967 to 2023. These cases were reported from Uttarakhand (n = 178), Himachal Pradesh (n = 39), and Jammu and Kashmir (n = 11). Most patients (88.4%) did not have a history of travel outside their native places. Three pediatric cases were reported from Jammu and Kashmir. The DNA of Leishmania donovani was detected in four of the 52 (7.7%) sand flies collected from Himachal Pradesh. The published literature points toward the existence of local transmission of VL in the sub-Himalayan region of India, strongly substantiated by the emergence of pediatric VL in some places. Thus, these difficult-to-reach hilly states of India will require focused surveillance for VL to successfully achieve elimination goals.

Background: To evaluate the demographic, clinical, and prognostic characteristics of patients diagnosed with COVID-19-associated mucormycosis (CAM) in Iranian patients., Methods: This prospective observational study was conducted in 8 tertiary referral ophthalmology centers in different provinces of Iran during the fifth wave of the COVID-19 pandemic. All patients were subjected to complete history taking and comprehensive ophthalmological examination and underwent standard accepted treatment strategy based on the disease stage., Results: Two hundred seventy-four CAM patients (most were males (150, 54.7%)) with a mean age of 56.8 ± 12.44 years were enrolled. Patients with a history of cigarette smoking (Adjusted Odds Ratio (AOR) = 4.36), Intensive Care Unit admission (ICU) (AOR = 16.26), higher stage of CAM (AOR = 2.72), and receiving endoscopic debridement and transcutaneous retrobulbar amphotericin B (AOR = 3.30) had higher odds of mortality. History of taking systemic corticosteroids during COVID-19 was significantly associated with reduced odds of mortality (AOR = 0.16). Generalized Estimating Equations analysis showed that the visual acuity of deceased patients (LogMAR: 3.71, 95% CI: 3.04-4.38) was worse than that of patients who were discharged from the hospital (LogMAR: 2.42, 95% CI: 2.16-2.68) (P < 0.001)., Conclusions: This study highlights significant risk factors for mortality in patients with CAM, such as cigarette smoking, ICU admission, advanced CAM stages, receiving transcutaneous retrobulbar amphotericin B and worser visual acuity. Conversely, a history of systemic corticosteroid use during COVID-19 was linked to reduced mortality. These findings underscore the critical need for early identification and targeted interventions for high-risk CAM patients to improve clinical outcomes., (© 2024. The Author(s).)

This study aimed to estimate the cost-effectiveness of four therapeutic approaches available for mucosal leishmaniasis in Brazil: miltefosine, meglumine antimoniate, combined with and without pentoxifylline, and liposomal amphotericin B. The perspective adopted was that of the Brazilian Unified National Health System (SUS). The outcome of interest was "cured patient", which was analyzed using a decision tree model. Estimates of direct costs and effectiveness were obtained from the scientific literature. Meglumine antimoniate alone was the base comparator strategy; liposomal amphotericin B showed an incremental cost-effectiveness ratio (ICER) of USD 7,409.13 per cured patient, and the combination of meglumine antimoniate with pentoxifylline presented an ICER of USD 85.13. Miltefosine was absolutely dominated, with higher cost and similar effectiveness when compared to meglumine antimoniate. Sensitivity analyses, varying the cost by ±25%, did not change the results. However, when the cost of miltefosine was estimated at less than USD 171.23, this strategy was dominant over meglumine antimoniate alone. The results confirm that treatment with liposomal amphotericin B remains the option with the highest ICER among the approaches analyzed. Miltefosine may be cost-effective based on the variation in the acquisition price, which deserves attention because it is the only available oral option. The non-accounting of other aspects prevent the use of these results immediately to support decision-making, but they point out the need to negotiate the prices of drugs available for mucosal leishmaniasis and indicates the need of encouraging technology transfer or other actions aimed at expanding the performance of the Brazilian national industrial complex.

Background: Mycotic keratitis (MK) represents a corneal infection, with Fusarium species identified as the leading cause. Fusarium is a genus of filamentous fungi commonly found in soil and plants. While many Fusarium species are harmless, some can cause serious infections in humans and animals, particularly Fusarium keratitis, that can lead to severe ocular infections, prevalent cause of monocular blindness in tropical and subtropical regions of the world. Due to its incidence and importance in ophthalmology, we conducted a systematic analysis of clinical cases to increase our understanding of Fusarium keratitis by gathering clinical and demographic data., Methods: To conduct an analysis of Fusarium keratitis, we looked through the literature from the databases PubMed, Embase, Lilacs, and Google Scholar and found 99 papers that, between March 1969 and September 2023, corresponded to 163 cases of Fusarium keratitis., Results: Our analysis revealed the Fusarium solani species complex as the predominant isolate, with females disproportionately affected by Fusarium keratitis. Notably, contact lens usage emerged as a significant risk factor, implicated in nearly half of cases. Diagnosis primarily relied on culture, while treatment predominantly involved topical natamycin, amphotericin B, and/or voriconazole. Surprisingly, our findings demonstrated a prevalence of cases originating from the United States, suggesting potential underreporting and underestimation of this mycosis in tropical regions. This shows the imperative for heightened vigilance, particularly in underdeveloped regions with substantial agricultural activity, where Fusarium infections may be more prevalent than currently reported., Conclusion: Our study sheds light on the clinical complexities of Fusarium keratitis and emphasizes the need for further research and surveillance to effectively tackle this vision-threatening condition. Furthermore, a timely identification and early initiation of antifungal treatment appear to be as important as the choice of initial treatment itself., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Histoplasmosis capsulatum is a dimorphic fungus, recognised for its endemic presence in multiple global regions. It may cause severe opportunistic disseminated infection in immunocompromised individuals. This is a case report of a 33-year-old man from Thailand who was admitted at a Danish hospital with fever, weight loss, cough, nosebleeds, and newly diagnosed HIV. The clinical condition rapidly deteriorated with lung and kidney failure. The patient was diagnosed with H. capsulatum fungaemia first detected on blood smear. He was treated with intravenous amphotericin B followed by oral itraconazole as well as antiretroviral therapy., (Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/.)

Rationale: Renal artery rupture due to allograft infection, especially by fungi, is a serious clinical complication that can occur after kidney transplantation, and may lead to graft loss and death., Patient Concerns: Two kidney recipients from China who developed renal artery rupture at our hospital on 5 days (47-year-old female) and 45 days (39-year-old male) after surgery., Diagnoses: The male had immunoglobulin A nephropathy as a primary disease, and experienced a postoperative attack of vascular rejection and mixed infection by Mucor and bacteria. The female had chronic glomerulonephritis as a primary disease, and experienced renal artery rupture near the anastomosis site with infection by fungi and other pathogens., Interventions: The male received resection of the implanted kidney and antibiotic therapy with intravenous vancomycin (0.5 g, 2 days) and amphotericin B (530 mg in 33 days). The female received replacing the segment of renal arterial and internal iliac artery by saphenous vein, as well as antibiotic therapy with amphotericin B (320 mg in 8 days)., Outcomes: The male was recovered and received a second transplantation, while the female was discharged on postoperative day 19., Lessons: In both patients, prompt surgery and aggressive treatment with an antifungal drug (amphotericin B) and antidrugs led to successful rescue., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

We present a case of a 56-year-old female with rheumatoid arthritis (RA) who has been on methotrexate for 9 years and has been complaining of high-grade fever for the past 1 month with no localizing signs and symptoms. She was thoroughly evaluated before being labeled as pyrexia of unknown origin. Histoplasmosis was suspected after bone marrow aspiration smear examination. The presence of histoplasma antigen in the urine confirmed our diagnosis. Fever responded after 2 weeks of liposomal amphotericin B and patient discharged in stable condition on tablet itraconazole., (© Journal of the Association of Physicians of India 2024.)

Cryptococcus is an encapsulated yeast that is found in both yeast and hyphal forms. Cryptococcus neoformans and C. gattii are the most medically important species, causing disease in both immunocompromised and immunocompetent individuals. A large, friable, sublingual mass was surgically resected from the oral cavity of a pink-tongued skink (Cyclodomorphus gerarrdii). Histopathology, fungal culture and PCR testing with Sanger sequencing confirmed granulomatous inflammation containing large numbers of yeasts identified as Cryptococcus neoformans var. grubii. Surgical excision and treatment with oral amphotericin B and terbinafine was unsuccessful in managing the infection. On Day 67 after surgery, Cryptococcus DNA was detected by PCR in the blood but not oral, cloacal or skin swabs. The skink was euthanised 72 days after surgery due to anorexia, weight loss and progressive neurological signs of disease. Necropsy results showed disseminated cryptococcosis, including meningoencephalitis and ventriculitis. Two in-contact pink-tongued skinks remained asymptomatic and PCR-negative during 198 days of observation. This case suggests Cryptococcus infections should be considered for oral masses presenting with or without neurological signs in skinks. Further investigation is required to determine the best treatment options for disseminated cryptococcosis in reptiles. This report describes the third reported case of Cryptococcus in a reptile and the first case of cryptococcosis in a pink-tongued skink. It is also the first report of Cryptococcus in a reptile identified to the variety level using PCR, including in whole blood samples., (© 2024 The Authors. Australian Veterinary Journal published by John Wiley & Sons Australia, Ltd on behalf of Australian Veterinary Association.)

Introduction: Fungal infection after lung transplantation can lead to poor clinical outcome, for which lung transplant recipients require prophylaxis. One of the antifungal agents used after lung transplantation is nebulized amphotericin B (AMB). Nebulized AMB causes adverse events such as dyspnea and airway irritation, and long-term use leads to high economic costs. So far, prophylactic regimens employing AMB deoxycholate (AMB-d) and liposomal AMB (L-AMB) have been developed. This study compared the efficacy, safety, and cost of AMB-d and L-AMB., Patients and Methods: Patients who underwent lung transplantation at Kyoto University Hospital from January 2021 to May 2023 were included in this study. Thirty-three patients received nebulized AMB-d, whereas 29 received nebulized L-AMB., Results: Both regimens maintained comparable prophylactic efficacy regarding the development of fungal infection in the AMB-d and L-AMB groups (3.0% vs. 3.4%, P = 0.877). Patients treated with nebulized L-AMB experienced fewer respiratory-related adverse reactions than those treated with nebulized AMB-d (6.9% vs. 30.3%, P < 0.05), leading to a longer treatment duration with L-AMB than with AMB-d. Additionally, the daily cost of administering L-AMB was lower than that of administering AMB-d (3609 Japanese yen vs. 1792.3 Japanese yen, P < 0.05)., Discussion: These results suggest that nebulized L-AMB is safer and more cost-effective than nebulized AMB-d, with comparable efficacy., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Blastomycoses dermatitidis is a dimorphic fungus that can cause disseminated blastomycosis with varying clinical manifestations and multiorgan involvement. While blastomycosis commonly causes pulmonary disease, extrapulmonary spread can result in skin, bone, and central nervous system involvement. Cutaneous blastomycosis can present as pustular lesions that evolve into ulcerative or verrucous plaques. We present a case of disseminated blastomycosis in an immunocompetent patient with both pulmonary and cutaneous features. The patient developed hypoxic respiratory failure and was subsequently diagnosed with disseminated blastomycosis after undergoing bronchoscopy with bronchial washing. He was found to have ulcerative nasal lesions as part of his disseminated disease. He was successfully treated with amphotericin B and ultimately discharged from the hospital., (© 2024. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Introduction. Sporotrichosis is a subcutaneous infection caused by dimorphic Sporothrix species embedded in the clinical clade. Fungi have virulence factors, such as biofilm and melanin production, which contribute to their survival and are related to the increase in the number of cases of therapeutic failure, making it necessary to search for new options. Gap statement. Proton pump inhibitors (PPIs) have already been shown to inhibit the growth and melanogenesis of other fungi. Aim. Therefore, this study aimed to evaluate the effect of the PPIs omeprazole (OMP), rabeprazole (RBP), esomeprazole, pantoprazole and lansoprazole on the susceptibility and melanogenesis of Sporothrix species, and their interactions with itraconazole, terbinafine and amphotericin B. Methodology. The antifungal activity of PPIs was evaluated using the microdilution method, and the combination of PPIs with itraconazole, terbinafine and amphotericin B was assessed using the checkerboard method. The assessment of melanogenesis inhibition was assessed using grey scale. Results. The OMP and RBP showed significant MIC results ranging from 32 to 256 µg ml -1 and 32 to 128 µg ml -1 , respectively. Biofilms were sensitive, with a significant reduction ( P <0.05) in metabolic activity of 52% for OMP and 50% for RBP at a concentration of 512 µg ml -1 and of biomass by 53% for OMP and 51% for RBP at concentrations of 512 µg ml -1 . As for the inhibition of melanogenesis, only OMP showed inhibition, with a 54% reduction. Conclusion. It concludes that the PPIs OMP and RBP have antifungal activity in vitro against planktonic cells and biofilms of Sporothrix species and that, in addition, OMP can inhibit the melanization process in Sporothrix species.

Cryptococcosis is a fungal infection that is becoming increasingly prevalent worldwide, particularly among individuals with compromised immune systems, such as HIV patients. Amphotericin B (AmB) is the first-line treatment mainly combined with flucytosine. The scarcity and the prohibitive cost of this regimen urge the use of fluconazole as an alternative, leading to increased rates of treatment failure and relapses. Therefore, there is a critical need for efficient and cost-effective therapy to enhance the efficacy of AmB. In this study, we evaluated the efficacy of the HIV protease inhibitors (PIs) to synergize the activity of AmB in the treatment of cryptococcosis. Five PIs (ritonavir, atazanavir, saquinavir, lopinavir, and nelfinavir) were found to synergistically potentiate the killing activity of AmB against Cryptococcus strains with ƩFICI ranging between 0.09 and 0.5 against 20 clinical isolates. This synergistic activity was further confirmed in a time-kill assay, where different AmB/PIs combinations exhibited fungicidal activity within 24 hrs. Additionally, PIs in combination with AmB exhibited an extended post-antifungal effect on treated cryptococcal cells for approximately 10 hrs compared to 4 hours with AmB alone. This promising activity against cryptococcal cells did not exhibit increased cytotoxicity towards treated kidney cells, ruling out the risk of drug combination-induced nephrotoxicity. Finally, we evaluated the efficacy of AmB/PIs combinations in the Caenorhabditis elegans model of cryptococcosis, where these combinations significantly reduced the fungal burden of the treated nematodes by approximately 2.44 Log10 CFU (92.4%) compared to the untreated worms and 1.40 Log10 ((39.4%) compared to AmB alone. The cost-effectiveness and accessibility of PIs in resource-limited geographical areas compared to other antifungal agents, such as flucytosine, make them an appealing choice for combination therapy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Alkashef, Seleem. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Although the level of medical care has been improved in recent years, the probability of patients contracting pathogens has increased greatly, with a rising incidence of invasive fungal infections. Deep-seated fungi have become common pathogens of nosocomial infections., Objective: This study aims to systematically assess the effectiveness, mortality, survival rate, and adverse reactions (ARs) of high-dose (HD) liposomal amphotericin B (L-AMB) for human diseases., Methods: Ten articles (1661 patients) of randomized controlled trials (RCTs; whether randomized, single-blind, or double-blind) from January 1, 1960, to December 31, 2020, of HD-L-AMB treatment of diseases were retrieved from the PubMed, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials databases. The primary outcome measure was the overall therapeutic effect, and the secondary outcome measures were mortality, ≥10-week survival, and ARs. Data were meta-analyzed using RevMan 5.3., Results: Ten RCTs involving 1661 patients were included. HD-L-AMB did not show a significant therapeutic advantage in anti-infection treatment. In addition, HD-L-AMB treatment of invasive Aspergillus infection led to high mortality and low survival (≥10 weeks, OR = 0.57, 95%CI 0.34-0.94, P = .03). According to subgroup analysis, the incidence of ARs and the incidence of renal dysfunction associated with invasive fungal infection treatment were higher with HD-L-AMB than with regular-dose L-AMB., Conclusion: HD-L-AMB had no obvious advantage for the treatment of diseases and was accompanied by increased mortality, reduced long-term survival, and increased ARs (including renal insufficiency). Therefore, the use of HD-L-AMB to control infections is recommended with caution only when the preferred treatment is contraindicated.

Purpose: COVID-19 associated pulmonary aspergillosis (CAPA) is common and linked with high fatality rates. To assess the impact on the incidence and outcome of CAPA of an antifungal prophylaxis (AFP) we compared two cohorts of COVID-19 patients admitted to intensive care units (ICU) in Brescia, Italy, from January to August 2021., Methods: The study cohort included all mechanically ventilated patients observed between April 2021 and August 2021 with SARS-CoV-2-pneumonia, who received AFP with oral posaconazole (200 mg every 6 h) and nebulized liposomal amphotericin B (50 mg every 2 weeks) from ICU admission to 7 days after discharge or, if applicable, until tracheostomy removal. The control cohort included COVID-19 patients admitted to the same ICU between January and March 2021 who did not receive any AFP. Subjects with CAPA at ICU admission were excluded., Results: We included 270 patients, of whom 64 (23.7%) received AFP. In patients in the study group, CAPA-related mortality was significantly reduced (29% vs. 48% p = 0.04), as well as the incidence of CAPA (3.1% vs 12.1%, p = 0.03). Patients who developed CAPA were older (mean of 70-y-old vs 63-y-old, p < 0.001). One subject discontinued posaconazole due to an adverse reaction. Among the 46 patients who received it, only one patient reached an effective plasma concentration of posaconazole., Conclusion: AFP was associated with reduced incidence and mortality from CAPA and was well tolerated in patients with severe COVID-19. Posaconazole concentrations below the efficacy threshold in almost all patients may be attributable to drug interactions and prompt further studies to define its clinical significance., (© 2024. The Author(s).)

Chronic wounds of significant severity and acute injuries are highly vulnerable to fungal infections, drastically impeding the expected wound healing trajectory. The clinical use of antifungal therapeutic drug is hampered by poor solubility, high toxicity and adverse reactions, thereby necessitating the urgent development of novel antifungal therapy strategy. Herein, this study proposes a new strategy to enhance the bioactivity of small-molecule antifungal drugs based on multifunctional metal nanozyme engineering, using amphotericin B (AmB) as an example. AmB-decorated gold nanoparticles (AmB@AuNPs) are synthesized by a facile one-pot reaction strategy, and the AmB@AuNPs exhibit superior peroxidase (POD)-like enzyme activity, with maximal reaction rates (V max ) 3.4 times higher than that of AuNPs for the catalytic reaction of H 2 O 2 . Importantly, the enzyme-like activity of AuNPs significantly enhanced the antifungal properties of AmB, and the minimum inhibitory concentrations of AmB@AuNPs against Candida albicans (C. albicans) and Saccharomyces cerevisiae (S. cerevisiae) W303 are reduced by 1.6-fold and 50-fold, respectively, as compared with AmB alone. Concurrent in vivo studies conducted on fungal-infected wounds in mice underscored the fundamentally superior antifungal ability and biosafety of AmB@AuNPs. The proposed strategy of engineering antifungal drugs with nanozymes has great potential for enhanced therapy of fungal infections and related diseases., (© 2024 Wiley‐VCH GmbH.)

Introduction: New diagnostic methods and antifungal strategies may improve prognosis of mucormycosis. We describe the diagnostic value of metagenomic next⁃generation sequencing (mNGS) and identify the prognostic factors of mucormycosis., Methods: We conducted a retrospective study of hematologic patients suffered from mucormycosis and treated with monotherapy [amphotericin B (AmB) or posaconazole] or combination therapy (AmB and posaconazole). The primary outcome was 84-day all-cause mortality after diagnosis., Results: Ninety-five patients were included, with "proven" (n = 27), "probable" (n = 16) mucormycosis confirmed by traditional diagnostic methods, and "possible" (n = 52) mucormycosis with positive mNGS results. The mortality rate at 84 days was 44.2%. Possible + mNGS patients and probable patients had similar diagnosis processes, overall survival rates (44.2% vs 50.0%, p = 0.685) and overall response rates to effective drugs (44.0% vs 37.5%, p = 0.647). Furthermore, the median diagnostic time was shorter in possible + mNGS patients than proven and probable patients (14 vs 26 days, p < 0.001). Combination therapy was associated with better survival compared to monotherapy at six weeks after treatment (78.8% vs 53.1%, p = 0.0075). Multivariate analysis showed that combination therapy was the protective factor (HR = 0.338, 95% CI: 0.162-0.703, p = 0.004), though diabetes (HR = 3.864, 95% CI: 1.897-7.874, p < 0.001) and hypoxemia (HR = 3.536, 95% CI: 1.874-6.673, p < 0.001) were risk factors for mortality., Conclusions: Mucormycosis is a life-threatening infection. Early management of diabetes and hypoxemia may improve the prognosis. Exploring effective diagnostic and treatment methods is important, and combination antifungal therapy seems to hold potential benefits., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Vulvovaginal candidiasis is a common fungal infection that affects the female lower genital tract. This study determined the major risk factors associated with vulvovaginal infection (VVI) in the Ashanti region of Ghana and also determined the antifungal resistance patterns of Candida albicans isolates to some antifungals., Methods: Three hundred and fifty (350) high vaginal swab (HVS) samples were collected from women who presented with signs and symptoms of VVI. A structured questionnaire was administered to one hundred and seventy-two (172) of the women. HVS samples were cultured on Sabouraud dextrose agar with 2% chloramphenicol. The polymerase chain reaction was employed to confirm C. albicans. Antifungal susceptibility testing was performed and the susceptibility of C. albicans isolates to fluconazole, clotrimazole, amphotericin B, nystatin, miconazole and 5-flurocytosine were assessed., Results: Vaginal infection was most prevalent amongst females in their reproductive age (21 to 30 years; 63.0%). The study found a significant association between vaginal infections and some risk factors such as sexual practices (p < 0.001), antibiotic misuse (p < 0.05), poor personal hygiene (p < 0.005) and birth control methods (p < 0.049). Out of the 350 HVS samples collected, 112 yielded yeast cells with 65 (58%) identified as C. albicans. The C. albicans isolates were resistant to 5' flucytosine (100%), fluconazole (70%), voriconazole (69.2%), miconazole (58.5%) and nystatin (49.2%). C. albicans isolates were more susceptible to amphotericin B (53.8%) and clotrimazole (45.1%), although an appreciable number of isolates showed resistance (46.1% and 52.3%, respectively)., Conclusion: There should be nationwide education on all associated risk factors of VVI. Also, use of the various antifungal agents in vaginal candidiasis should proceed after antifungal susceptibility testing to ensure efficacious use of these agents., (© 2024. The Author(s).)

Background: American Cutaneous Leishmaniasis (ACL) shows variable response to therapy, but data on species-specific treatment efficacy is scarce. We describe the clinical characteristics and outcome of patients with ACL imported to a tertiary centre in Germany and determine whether species-specific therapy according to the 2014 "LeishMan" group recommendations is associated with cure., Methods: A retrospective chart review was conducted at the Charité Institute of International Health in Berlin. We analysed data on PCR-confirmed ACL cases collected between 2000 and 2023. Systemic therapy included liposomal amphotericin B, miltefosine, pentavalent antimony, ketoconazole or itraconazole. Localized therapy included perilesional pentavalent antimony or paromomycin ointment. Cure was defined as re-epithelialization of ulcers or disappearance of papular-nodular lesions after 3 months of treatment. Logistic regression models were used to quantify the effect of species-specific systemic therapy on the outcome., Results: 75 cases were analysed. Most patients were male (62%), median age was 35 years, no patient had a history of immunosuppression. The most common reason for travel was tourism (60%), the most common destination was Costa Rica (28%), the median duration of illness was 8 weeks, and most patients presented with ulcers (87%). Lesions were complex in 43%. The most common Leishmania (L.) species was L. braziliensis (28%), followed by L. panamensis (21%). 51/73 (70%) patients were cured after initial therapy and 17/21 (81%) after secondary therapy. Cure after systemic therapy was more frequent when species-specific treatment recommendations were followed (33/45; 73%), compared to when not followed, (6/17; 35%, P = 0.008). This association was independent of age, sex, previous therapy, complex lesions, and Leishmania species (adjusted OR, 5.06; 95% CI, 1.22-24.16)., Conclusions: ACL is a rare, imported disease in Germany. Complex lesions were common, challenging successful therapy. This study highlights the importance of identifying the parasite species and suggests that a species-specific approach to treatment leads to better outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lindner et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)