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AimInvestigate and characterise acute post-cataract fungal endophthalmitis pooled from the Endophthalmitis Management Study occurring within 6 weeks of primary surgery.MethodsThe fungal infection was confirmed through conventional and molecular microbiology work-ups and antifungal susceptibility testing. Clinical examination included measurement of distant vision and intraocular pressure, anterior segment photo documentation and inflammation score (IS) measurement. Per the microbiology report, the eyes were divided into culture-positive (C+), sequencing-positive (S+) and sequencing-positive-unidentified (U+) fungi. Clinical correlations and statistical comparisons were performed between these three cohorts.ResultsThe study identified 21 patients with fungal endophthalmitis; it was 9.5% (21 of 220) of all acute post-cataract endophthalmitis in this study. Per the microbiology report, C+, S+ and U+ were 6, 9 and 6 patients, respectively. Fusarium and Aspergillus spp were the common fungi. The C+ fungi had higher presenting IS (p=0.023), shorter time to symptoms, worse presenting vision, corneal abscess (p=0.030) and higher probability of repeat intervention (p=0.042) than the other two groups. In the C+ group, the final vision of >20/400 was less (p=0.046) and phthisis bulbi was higher (p=0.010). All culturable fungi were resistant to amphotericin B and voriconazole.ConclusionThere is a 10% probability of acute post-cataract fungal endophthalmitis in India. The eyes presenting with corneal abscesses carry a higher risk. The polymicrobial infections shown in this cohort should be interpreted cautiously since next-generation sequencing detects DNA from all organisms, including residual or low-abundance or non-viable organisms that traditional culture might miss. Despite this, the new molecular microbiology technology is necessary to confirm diagnosis and expedite appropriate treatment. Given multi-antifungal agent resistance, routine susceptibility testing must be considered.

BackgroundFungal infections of the central nervous system (FIs-CNS) have become significantly more common over the past 2 decades. Invasion of the CNS largely depends on the immune status of the host and the virulence of the fungal strain. Infections with fungi cause a significant morbidity in immunocompromised hosts, and the involvement of the CNS may lead to fatal consequences.MethodsOne hundred and thirty-five articles on fungal neuroinfection in PubMed, Google Scholar, and Cochrane databases were selected for review using the following search words: “fungi and CNS mycoses”, CNS fungal infections”, “fungal brain infections”, \" fungal cerebritis”, fungal meningitis”, “diagnostics of fungal infections”, and “treatment of CNS fungal infections”. All were published in English with the majority in the period 2000–2018. This review focuses on the current knowledge of the epidemiology, clinical presentations, diagnosis, and treatment of selected FIs-CNS.ResultsThe FIs-CNS can have various clinical presentations, mainly meningitis, encephalitis, hydrocephalus, cerebral abscesses, and stroke syndromes. The etiologic factors of neuroinfections are yeasts (Cryptococcus neoformans, Candida spp., Trichosporon spp.), moniliaceous moulds (Aspergillus spp., Fusarium spp.), Mucoromycetes (Mucor spp., Rhizopus spp.), dimorphic fungi (Blastomyces dermatitidis, Coccidioides spp., Histoplasma capsulatum), and dematiaceous fungi (Cladophialophora bantiana, Exophiala dermatitidis). Their common route of transmission is inhalation or inoculation from trauma or surgery, with subsequent hematogenous or contiguous spread. As the manifestations of FIs-CNS are often non-specific, their diagnosis is very difficult. A fast identification of the etiological factor of neuroinfection and the application of appropriate therapy are crucial in preventing an often fatal outcome. The choice of effective drug depends on its extent of CNS penetration and spectrum of activity. Pharmaceutical formulations of amphotericin B (AmB) (among others, deoxycholate-AmBd and liposomal L-AmB) have relatively limited distribution in the cerebrospinal fluid (CSF); however, their detectable therapeutic concentrations in the CNS makes them recommended drugs for the treatment of cryptococcal meningoencephalitis (AmBd with flucytosine) and CNS candidiasis (L-AmB) and mucormycosis (L-AmB). Voriconazole, a moderately lipophilic molecule with good CNS penetration, is recommended in the first-line therapy of CNS aspergillosis. Other triazoles, such as posaconazole and itraconazole, with negligible concentrations in the CSF are not considered effective drugs for therapy of CNS fungal neuroinfections. In contrast, clinical data have shown that a novel triazole, isavuconazole, achieved considerable efficacy for the treatment of some fungal neuroinfections. Echinocandins with relatively low or undetectable concentrations in the CSF do not play meaningful role in the treatment of FIs-CNS.ConclusionAlthough the number of fungal species causing CNS mycosis is increasing, only some possess well-defined treatment standards (e.g., cryptococcal meningitis and CNS aspergillosis). The early diagnosis of fungal infection, accompanied by identification of the etiological factor, is needed to allow the selection of effective therapy in patients with FIs-CNS and limit their high mortality.

Fungal keratitis is a severe corneal infection that often results in blindness and eye loss. The disease is most prevalent in tropical and subtropical climates, and infected individuals are frequently young agricultural workers of low socioeconomic status. Early diagnosis and treatment can preserve vision. Here, we discuss the fungal keratitis diagnostic literature and estimate the global burden through a complete systematic literature review from January, 1946 to July, 2019. An adapted GRADE score was used to evaluate incidence papers—116 studies provided the incidence of fungal keratitis as a proportion of microbial keratitis and 18 provided the incidence in a defined population. We calculated a minimum annual incidence estimate of 1 051 787 cases (736 251–1 367 323), with the highest rates in Asia and Africa. If all culture-negative cases are assumed to be fungal, the annual incidence would be 1 480 916 cases (1 036 641–1 925 191). In three case series, 8–11% of patients had to have the eye removed, which represents an annual loss of 84 143–115 697 eyes. As fungal keratitis probably affects over a million people annually, an inexpensive, simple diagnostic method and affordable treatment are needed in every country.

Background. Ocular candidiasis is a major complication of candidemia. The incidence, risk factors, and outcome of eye involvement during candidemia are largely unknown. We prospectively studied the ocular manifestations of candidemia in a large, worldwide, randomized multicenter trial that compared voriconazole with amphotericin B followed by fluconazole for the treatment of candidemia. Methods. Nonneutropenic patients with blood cultures positive for Candida species were assigned treatment with voriconazole or with amphotericin B followed by fluconazole in a randomized 2:1 ratio. Dilated fundoscopy was performed in each patient at baseline, on day 7, at 2 and 6 weeks after the end of treatment (EOT), and, if clinically indicated, at 12 weeks after EOT. Results. Of 370 patients, 49 had findings consistent with the diagnosis of ocular candidiasis at baseline, and an additional 11 patients developed abnormalities during treatment, totaling 60 patients with eye involvement (16%). Of these patients, probable Candida eye infection was diagnosed in 40 patients (6 with endophthalmitis, 34 with chorioretinitis), and possible Candida eye infection in 20 (all with chorioretinitis). The duration of candidemia was significantly longer in patients with ocular candidiasis (median, 4 days; range, 1—18 days) compared with patients without ocular involvement (median, 3 days; range 1—26 days; log rank, P =.026). Therapy with either voriconazole (44 cases) or amphotericin B followed by fluconazole (16 cases) was successful in 65% of patients; outcome was not evaluable in 32% and was unfavorable in 3%. Conclusions. Ocular involvement occurred in 16% of patients with candidemia; however, endophthalmitis was uncommon (1.6%). Treatment with either voriconazole or amphotericin B followed by fluconazole was successful for ocular candidiasis in most cases with follow-up.

Invasive fungal infections remain the leading causes of morbidity and mortality in neonates, especially preterm and very low birth weight infants. Most invasive fungal infections are due to Candida or Aspergillus species, and other fungi are increasingly reported and described. Appropriate identification and treatment are required to augment activity and reduce the toxicity of antifungal drugs. Successful use of antifungals in the vulnerable neonatal population is important for both prevention and treatment of infection. Strategies for prevention, including prophylactic antifungal therapy as well as reducing exposure to modifiable risk factors, like limiting antibiotic exposure, discontinuation of central catheters, and hand hygiene are key techniques to prevent and decrease rates of invasive fungal infections. In conclusion, this is a review of the most common causes, prevention strategies, prophylaxis, and treatment of invasive fungal infections in neonates.

Patients with liver disease in the intensive care unit (ICU) face a unique susceptibility to infection due to the complex immune dysfunction resulting from hepatic failure. Bacterial infections are commonly present in these patients upon arrival to the hospital, often being the primary reason for ICU admission. In contrast, invasive fungal infections (IFIs) afflict a smaller percentage of patients and are usually discovered in the course of the ICU stay. IFI diagnosis in the ICU, particularly in patients with liver disease, is often delayed or overlooked, contributing to the extremely high ICU mortality associated with IFI in these patients despite the availability of effective (and largely safe) antifungal therapy. Thus, to improve outcomes, it is crucial for intensive care clinicians to be vigilant for IFIs in patients with liver disease. This review aims to contribute to the intensive care literature in this regard. We begin with an overview of normal antifungal immunity followed by a summary of how it may become compromised in the setting of hepatic dysfunction. Next, a general discussion of IFIs in liver disease is presented and then the three most relevant fungal pathogens, namely Candida , Aspergillus , and Cryptococcus , are individually examined. This review concludes by highlighting key knowledge and practice gaps that require attention by the scientific and clinical communities in the coming years.

Breakthrough invasive mold infections (IMIs) that occur during posaconazole or voriconazole prophylaxis are rare complications for which epidemiological data are lacking. This retrospective analysis comparing 24 microbiologically documented breakthrough with 66 nonbreakthrough IMIs shows a shift towards non-Aspergillus molds with a significantly increased proportion of rare multidrug-resistant molds.

Ocular fungal infections annually affect more than one million individuals worldwide. The management of these infections is problematic, mainly due to the limited availability of effective antifungal agents. Thus, ocular infections are increasingly recognized as important causes of morbidity and blindness, especially keratitis and endophthalmitis. Thus, this review aims to demonstrate the importance of fungal eye infections through the description of the main related aspects, with emphasis on the treatment of these infections. For this purpose, a search for scientific articles was conducted in databases, such as Medline, published from 2000 onwards, addressing important aspects involving fungal eye infections. In addition, this work highlighted the limited therapeutic arsenal available and the severity associated with these infections. Thus, highlighting the importance of constantly updating knowledge about these pathologies, as it contributes to agility in choosing the available and most appropriate therapeutic alternatives, aiming at positive and minimally harmful results for that particular patient.

Critically ill patients and patients with haematological cancer are HIV-negative populations at high risk of invasive fungal infections. In intensive-care units, candidaemia and intra-abdominal candidiasis predominate, but aspergillosis has emerged as a lethal, under-recognised cause of pneumonia. In patients with haematological malignancies or who have undergone stem-cell transplantations, pulmonary disease due to aspergillus and other mould diseases predominate. In this Series paper, we provide an update on risk assessment, new diagnostic strategies, and therapeutic approaches. New concepts have emerged for use of risk prediction rules and an evidence base now exists for inclusion of biomarkers (eg, galactomannan, 1,3-β-D-glucan, and PCR assays for Aspergillus spp) into early diagnostic and therapeutic strategies. Imaging techniques remain helpful for early diagnosis of pulmonary mould diseases, with PET techniques offering potential improvements in diagnostic specificity and evaluation of clinical response. Echinocandins and triazoles have been validated extensively for prophylaxis, empirical therapy, and targeted therapy, but an increase in intrinsically resistant fungi and emergence of secondary resistance as a result of drug-induced selection pressure are of major concern. Echinocandins remain a major component of treatment of invasive candidiasis and new triazoles are the best alternative for prophylaxis and therapy of invasive aspergillosis.

Invasive fungal infections (IFIs) are life-threatening complications in immunocompromised patients, particularly those with hematologic malignancies or undergoing transplantation. Despite advances in diagnostic methods and antifungal therapy, IFI-related mortality remains unacceptably high. Evidence from Latin America is scarce, limiting the understanding of regional epidemiology and outcomes. Our work aimed to analyze the epidemiological and clinical profiles of pediatric hemato-oncologic patients diagnosed with proven IFIs. We conducted a retrospective, cross-sectional study by reviewing medical records of patients diagnosed with proven IFIs according to the 2020 criteria of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group, at the Hospital Universitario “Dr. José Eleuterio González” in northeast Mexico, between 2018 and 2024. Statistical analysis included descriptive and inferential methods. A p-value < 0.05 was considered statistically significant. Thirty-three patients were included (mean age 6 years; 54.5% male). Most (91%) were classified as high risk for IFIs, and acute lymphoblastic leukemia was the most frequent underlying malignancy (72.7%). Mold infections accounted for 69.7% of cases, mainly Aspergillus spp. and Fusarium spp. , while Candida tropicalis was the most common yeast. The sinonasal region was the predominant site of mold disease. Prophylaxis was administered in 69.7% of patients, most commonly with itraconazole. Amphotericin B was the primary therapeutic agent, alone or in combination with voriconazole, and 42.4% required surgical intervention. Overall mortality was 21.2%, higher in yeast infections (30%) compared with molds (17.4%). Intensive care unit admission was the only independent predictor of death (OR 35.4; p =  0.019). In pediatric hemato-oncologic patients, IFIs were predominantly associated with acute lymphoblastic leukemia, neutropenia, and induction chemotherapy. Mold infections accounted for most cases, and mortality remained high despite prophylaxis. These findings provide novel data from Latin America, where studies on pediatric IFIs are limited, and underscore the need for improved diagnostic and preventive strategies in high-risk populations.