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.

Cryptococcosis is a fungal infectious disease that enormously impacts human health worldwide. Cryptococcal meningitis is the most severe disease caused by the fungus Cryptococcus, and can lead to death, if left untreated. Many patients develop resistance and progress to death even after treatment. It requires a prolonged treatment course in people with AIDS. This narrative review provides an evidence-based summary of the current treatment modalities and future trial options, including newer ones, namely, 18B7, T-2307, VT-1598, AR12, manogepix, and miltefosine. This review also evaluated the management and empiric treatment of cryptococcus meningitis. The disease can easily evade diagnosis with subacute presentation. Despite the severity of the disease, treatment options for cryptococcosis remain limited, and more research is needed.

Invasive fungal infections pose significant morbidity and mortality risks, particularly those caused by moulds. Available antifungal classes are limited by toxicities and are increasingly susceptible to resistance, particularly amongst challenging fungal pathogens. The purpose of this case series and literature review was to characterize the use of a high-dose lipid formulation of amphotericin B. A case series is presented including patients who received high-dose lipid formulation amphotericin B (≥7.5 mg/kg/day) between June 2012 and August 2021. Additionally, a systematic literature review was conducted by searching the PubMed database for English-language studies involving individuals who received high-dose amphotericin B therapy (≥7.5 mg/kg) using lipid formulations. Nine patients were included in the case series, receiving an average of 8.9 ± 1.3 mg/kg liposomal amphotericin B over a mean of 11.0 ± 10.8 days predominantly for mould infections including Mucorales, aspergillosis and Fusarium. The patients were primarily cared for in intensive care units, with varying treatment histories and outcomes. A total of 11 studies (n=260 patients) met inclusion criteria for the literature review. Responses to high-dose liposomal amphotericin B ranged from 8% to 100%, often showing favourable outcomes. High doses of liposomal amphotericin B were well tolerated both in the case series and in published literature, with serum creatinine changes being the most commonly reported adverse event. However, multi-patient studies continue to report less than favourable (range 8-62%) response rates. High-dose liposomal amphotericin B, either alone or in combination with other antifungal agents, might be a viable strategy for managing invasive fungal infections when few treatment choices exist. This article is part of the Challenges and strategies in the management of invasive fungal infections Special Issue: https://www.drugsincontext.com/special_issues/challenges-and-strategies-in-the-management-of-invasive-fungal-infections.

Kodamaea ohmeri (K. ohmeri) is an ascosporogenic species of yeast that belongs to the genus Ascosporogenous and the family of Saccharomycetaceae. It has recently been found to cause various types of infections, particularly in critically ill immunocompromised patients. The present study describes a case of hospital-acquired pneumonia caused by K. ohmeri during veno-arterial extracorporeal membrane oxygenation. The fungal culture turned negative after the administration of caspofungin and amphotericin B. Extracorporeal membrane oxygenation (ECMO) is an adjunctive medical technique that provides temporary cardiopulmonary support for patients. Previous observations have suggested that the immune function of patients will typically decline during the use of ECMO, rendering infection to be one of the main complications of ECMO. K. ohmeri is a rare pathogenic fungus, particularly in immunocompromised individuals with vascular catheters, while amphotericin B is the most common antifungal therapy administered to treat K. ohmeri infections. It is important to raise awareness of rare fungal infections and actively treat them.

Although the treatment of aspergillosis has been studied for years, the optimal nonsurgical treatment of chronic cavitary pulmonary aspergillosis (CCPA) remains unsatisfactory, especially in lung cancer. We report two advanced non-small cell lung cancer (NSCLC) patients who recovered from CCPA following instillation of Amphotericin B (AmB) by bronchoscopy combined with systemic voriconazole. The first patient was diagnosed with lung adenocarcinoma after right upper lobe resection and was treated with anaplastic lymphoma kinase-targeted therapy. Chest computed tomography (CT) revealed a right pulmonary cavity containing solid materials. The second patient was diagnosed with squamous cell carcinoma and received immunotherapy following surgery, chemotherapy, and radiotherapy. Chest CT tomography revealed a mass in the right lung cavity. Both patients\' cultures and next-generation sequencing of their bronchoalveolar lavage (BAL) samples revealed presence of Aspergillus fumigatus. In addition, the galactomannan test of both patients BAL samples was positive. Systemic voriconazole was prescribed based on in vitro susceptibility testing. The chest images and clinical symptoms of both patients did not improve after one month of voriconazole therapy within the therapeutic blood concentration. Considering the low local concentrations of antifungals against CCPA, AmB instillation by bronchoscopy combined with systemic voriconazole was utilized. The chest CT images and clinical symptoms of both patients markedly improved in the following third month. Instillation of AmB combined with systemic voriconazole may be a promising treatment option for NSCLC patients with CCPA who fail voriconazole monotherapy.

The emergence of Mucorales infections is an urgent global public health threat rapidly disseminating during the current COVID-19 pandemic. Invasive mucormycosis carries significant morbidity and mortality; this is further compounded by the lack of newer effective antifungals on the horizon. Liposomal Amphotericin (L-AMB) is currently considered the cornerstone of antifungals therapy against mucormycosis; However, two decades later (since the introduction of L-AMB), the outcome remains dismal. Furthermore, adverse events related to therapeutic doses of L-AMB are also a hindrance. There is an imperative need for an alternative therapeutic approach to reduce the high mortality. One such approach is to combine the amphotericin with other agents (e.g., caspofungin, posaconazole, isavuconazole, and iron chelators) that can work synergistically or help in reducing the therapeutic doses of L-AMB. This review aims to highlight the various treatment approaches by gathering the clinical evidence from the literature and considering all potential pharmacological combinations that can provide the direction for future studies.

Rhodotorula mucilaginosa is an emerging fungal infection with the ability of biofilms formation. The identification of R mucilaginosa fungemia should trigger reflexes of prompt central venous line removal and using Amphotericin therapy.

We performed a systematic review of the literature to investigate the efficacy and safety of pentamidine isethionate for the treatment of human tegumentary and visceral leishmaniasis.
A total of 616 papers were evaluated, and 88 studies reporting data on 3108 cases of leishmaniasis (2082 patients with tegumentary leishmaniasis and 1026 with visceral leishmaniasis) were finally included. The majority of available studies were on New World cutaneous leishmaniasis and visceral leishmaniasis caused by Leishmania donovani. At the same time, few data are available for Old World cutaneous leishmaniasis, mucosal leishmaniasis, and visceral leishmaniasis caused by L. infantum. Pooled cure rate for tegumentary leishmaniasis was 78.8% (CI 95%, 76.9-80.6%) and 92.7% (CI 95%, 88.3-97.1%) according to controlled randomized trial and observational studies and case report and case series respectively. Pooled cure rate for visceral leishmaniasis was 84.8% (CI 95%, 82.6-87.1%) and 90.7% (CI 95%, 84.1-97.3%) according to controlled randomized trial and observational studies and case report and case series, respectively. Comparable cure rate was observed in recurrent and refractory cases of visceral leishmaniasis. Concerning the safety profile, among about 2000 treated subjects with some available information, the most relevant side effects were six cases of arrhythmia (including four cases of fatal ventricular fibrillation), 20 cases of irreversible diabetes, 26 cases of muscular aseptic abscess following intramuscular administration.
Pentamidine isethionate is associated with a similar cure rate of the first-line anti-leishmanial drugs. Severe and irreversible adverse effect appear to be rare. The drug may still have a role in the treatment of any form of human leishmaniasis when the first-line option has failed or in patients who cannot tolerate other drugs also in the setting of travel medicine. In difficult cases, the drug can also be considered as a component of a combination treatment regimen.

Cryptococcal meningitis remains a significant contributor to AIDS-related mortality despite widened access to antiretroviral therapy. Cryptococcal antigen (CrAg) can be detected in the blood prior to development of meningitis. Development of highly sensitive and specific rapid diagnostic CrAg tests has helped facilitate the adoption of CrAg screening programs in 19 African countries.
The biological rationale for CrAg screening and the programmatic strategies for its implementation are reviewed. We describe the approach to the investigation of patients with cryptococcal antigenemia and the importance of lumbar puncture to identify individuals who may have cryptococcal meningitis in the absence of symptoms. The limitations of current treatment recommendations and the potential role of newly defined combination antifungal therapies are discussed. A literature review was conducted using a broad database search for cryptococcal antigen screening and related terms in published journal articles dating up to December 2019. Conference abstracts, publicly available guidelines, and project descriptions were also incorporated.
As we learn more about the risks of cryptococcal antigenemia, it has become clear that the current management paradigm is inadequate. More intensive investigation and management are required to prevent the development of cryptococcal meningitis and reduce mortality associated with cryptococcal antigenemia.

Chronic pulmonary aspergillosis (CPA) is a potentially life-threatening debilitating lung disease necessitating long-term oral antifungal treatment. However, development of antifungal-resistant isolates of Aspergillus and major toxicities requiring discontinuation of treatment limits their use. Intravenous (IV) antifungals are an option in this group of patients. We comprehensively evaluate the response rates to IV antifungals in the management of CPA. We searched Medline and Embase databases to select clinical studies providing information about IV amphotericin B or an echinocandin for the treatment of CPA from inception to May 2020. Reviews, single-case reports and case series reporting <10 patients were excluded. We evaluated 12 eligible studies. A total of 380 patients received amphotericin B (n = 143) or an echinocandin (n = 237) and were included in the meta-analysis. In a pooled analysis, overall response to IV antifungals was 61% ((95% confidence interval (CI): 52%-70%; I2  = 73.3%; P < .001), to amphotericin B was 58% (95% CI: 36%-80%; I2  = 86.6%; P < .001) and to echinocandins was 62% (95% CI: 53%-72%; I2  = 63.6%; P < .001). Amphotericin B courses were usually doses at slightly <1 mg/Kg (deoxycholate) or 3 mg/Kg (liposomal) for 2-3 weeks. Micafungin doses varied from 12.5 to 300 mg (frequently, 150 mg) daily for at least 3 weeks, and sometimes much longer. Liposomal amphotericin B was well tolerated, but led to renal function loss in 25% of patients. Adverse events were observed in 5-35.3% of patients receiving echinocandins, none of which was considered major. Intravenous antifungals have a place in the management of CPA. A head-to-head comparison of amphotericin B and echinocandins is lacking, and future studies should look at evaluating short- and longer-term outcomes of these agents.