We report a case of a patient with acute lymphoblastic leukemia (ALL), who developed a disseminated infection by Fusarium verticillioides during chemotherapy-induced neutropenia. He was successfully treated only after combination therapy with voriconazole plus amphotericin B deoxycolate was used, but not when these compounds were used in an isolated form.

Sporotrichosis is a human and animal disease caused by dimorphic pathogenic species of the genus Sporothrix. We report a dramatic presentation of Sporothrix brasiliensis infection, with destruction of the nasal septum, soft palate, and uvula of an HIV-infected woman. She was successfully treated with amphotericin B deoxycholate followed by itraconazole. Sporotrichosis remains a neglected opportunistic infection in patients with AIDS and awareness of this potentially fatal infection is of utmost importance.

Despite the availability of new antifungal compounds, invasive aspergillosis carries high morbidity and mortality in hematopoietic stem cell transplant recipients. In vitro studies and animal models suggest that the adoptive transfer of Natural Killer (NK) cells could be a promising immunotherapeutic option in this setting. As it is unclear whether viability and function of human NK cells are affected by common antifungal agents, we analyzed the interaction of various concentrations of amphotericin B-deoxycholate (AmB-D), liposomal amphotericin B, caspofungin, fluconazole, voriconazole, and posaconazole with human NK cells. When adding NK cells to therapeutic concentrations of antifungal agents, a significant increase of the antifungal effect was seen for caspofungin and voriconazole, whereas NK cells significantly decreased the hyphal damage of escalated doses of AmB-D. In contrast, therapeutic concentrations of all antifungal compounds tested did not have a negative effect on proliferation, viability, and the release of soluble immunomodulatory molecules of NK cells. These data indicate that therapeutic concentrations of the antifungal agents tested do not negatively affect the functional properties of human NK cells, which is a prerequisite for further studies evaluating NK cells as antifungal immunotherapy in immunocompromised patients suffering from invasive aspergillosis.

Amphotericin B deoxycholate (DAmB) is a first-line agent for the initial treatment of talaromycosis. However, little is known about the population pharmacokinetics and pharmacodynamics of DAmB for talaromycosis. Pharmacokinetic data were obtained from 78 patients; among them 55 patients had serial fungal colony forming units counts in blood also available for analysis. A population pharmacokinetics-pharmacodynamics model was fitted to the data. The relationships between area under the concentration time curve (AUC):MIC, and the time to blood culture sterilization and the time to death were investigated. There was only modest pharmacokinetic variability in the average AUC with a mean (standard deviation) of 11.51 (3.39) mg*h/L. The maximal rate of drug induced kill was 0.133 log10CFU/mL/h, and the plasma concentration of the DAmB that induced half-maximal rate of kill was 0.02 mg/L. Fifty percent of patients sterilized their bloodstream by 83.16 hours (range 13-264 hours). A higher initial fungal burden was associated with longer time to sterilization (hazard ratio (HR): 0.51, 95% confidence interval (CI): 0.36-0.70, p<0.001). There was no relationship between AUC:MIC and the time to sterilization (HR: 1.03, 95% CI: 1.00-1.06, p=0.091). Furthermore, there was no relationship between the AUC:MIC and time to death (HR: 0.97, 95% CI: 0.88-1.08, p=0.607); or early fungicidal activity (slope= log(0.501-0.003*AUC:MIC), p=0.319) adjusted for the initial fungal burden. The population pharmacokinetics of DAmB are surprisingly consistent. The time to sterilization of the bloodstream is a useful pharmacodynamic endpoint for future studies.

Most fungal infections found in wounds are secondary or superadded, and are generally benign in their clinical course in healthy individuals, with the exception of mucormycosis. This is a life-threatening infection caused by fungi of the order Mucorales. Primary cutaneous disease may occur following traumatic implantation of spores, or use of contaminated bandages, or as a complication of extensive burns, diabetic acidosis and other specific immunocompromised conditions. The clinical spectrum is highly non-specific and is often triggered by seemingly innocuous trauma. The superficial vesicles or patchy erythema rapidly degrade to haemorrhagic necrosis and rapidly progressive gangrenous lesion. The problem with diagnosing mucormycosis remains, therefore, that the condition has poor clinical indicators and requires reliance on microscopy and fungal culture. Management starts with a clinical suspicion, taking into account the risk factors and lack of response to first-line agents, as well as an aggressive clinical course. Treatment is multimodal, with medical correction of the risk factors and optimisation of limiting factors, such as diabetes, neutropenia and immunosuppressants. Treatment generally involves radical and repetitive surgical debridement, intravenous amphotericin B with monitoring of the nephrotoxicity, along with adjuvant modalities, such as hyperbaric oxygen therapy, colony stimulating factor, interferons gamma and white blood cell transfusion. Successful courses of therapy typically last 4-6 weeks and require cumulative doses that are equivalent to >2g of amphotericin B deoxycholate.

Medication error is a preventable cause of morbidity and death in the inpatient population. We describe a patient with an antifungal overdose treated with therapeutic plasma exchange (TPE). The patient was diagnosed with cryptococcal meningitis and received an acute overdose of amphotericin B deoxycholate instead of the prescribed liposomal amphotericin B. Consequently, the patient developed clinical symptoms including tremors, hypertension, visual hallucinations, vertigo, fever, and acute renal failure. A series of four TPEs was emergently initiated, resulting in complete resolution of most symptoms.