Guidelines from 3 clinical societies and peer-reviewed publications have been reviewed for recent changes in the management of opportunistic infections. Trimethoprim and sulfamethoxazol administered intravenously is an option to treat cerebral toxoplasmosis if oral therapy is not feasible. CD4 T cell cut-off for starting prophylaxis with trimethoprim and sulfamethoxazole is now 200/µl. For prophylaxis and treatment of Pneumocystis pneumonia trimethoprim and sulfamethoxazole still are recommended. Liposomal amphotericin B + fluconazole is a new treatment option for cryptococcosis. Addition of steroids can be considered in the treatment of tuberculosis to avoid immune reconstitution inflammatory syndrome. A new syndrome associated with HHV8 has been described: Kaposi Sarcoma Inflammatory Cytokine Syndrome (KICS). Localization and dissemination of herpes zoster have to be considered for treatment determination.

AmBisome® is a liposomal formulation of amphotericin B (Amp B), a complex parenteral antifungal product with no US FDA approved generic version available to date. For generic Amp B liposomal product development, examination of the drug release profile is important for product quality control and analytical comparability evaluation with the reference listed drug. Yet, there is no standardized in vitro drug release (IVR) assay currently available for Amp B liposomes. In this study, we describe the development of a USP-4 apparatus-based IVR assay capable of discriminating liposomal Amp B formulations based on the drug release profile. The goal of the IVR assay development was to identify release media compositions and assay temperatures capable of facilitating 70-100% of drug release from AmBisome® in 24 hours without Amp B precipitation or disruption of liposome structure. We found that an addition of 5% w/v of γ-cyclodextrin to the release media of 5% sucrose, 10 mM HEPES, and 0.01% NaN3 (pH = 7.4) prevented Amp B precipitation and facilitated drug release. Increased IVR assay temperature led to increased drug release rate, and 55°C was selected as the highest temperature that induced drug release close to our target without causing product precipitation. The developed IVR assay was used to discriminate between drug release rates from AmBisome® and micellar Amp B products like Fungizone® and Fungcosome. The IVR assay was also capable of discriminating between Amp B liposomes with the same composition as AmBisome® but prepared by either extrusion or homogenization processes, both of which resulted in measurable liposomal particle size heterogeneity and Amp B concentration differences. Finally, the USP-4 IVR assay was used to compare Amp B release profiles between AmBisome® and two generic products approved in India, Amphonex® (Bharat Serums and Vaccines Ltd.) (f2 = 66.3) and Phosome® (Cipla Ltd.) (f2 = 55.4). Taken together, the developed USP-4 IVR assay can be a useful tool for drug release profile characterization in generic liposomal Amp B formulation development.

Infections due to zygomycetes, caused by mucorales and entomophthorales, are characterized by angioinvasion and invasion of neighboring organs or structures. Mucorales most commonly cause rhinocerebral, pulmonary, cutaneous or disseminated infection and its spread is favored by several diseases (such as diabetes or chronic kidney disease) and risk factors (neutropenia, immunosuppression, iron overload). They have a high mortality rate, and the key to success in their treatment are early diagnosis, prompt administration of antifungal treatment, and extensive surgical debridement. Currently, isavuconazole constitutes an option for the treatment of those mucormycosis refractory to liposomal amphotericin B. Due to its pharmacokinetic and pharmacodynamic characteristics and its low toxicity, it is also the best choice for maintenance therapy.

Invasive fungal infections are a leading cause of morbidity and mortality in the immunocompromised patients. We report a case of Triadelphia pulvinata, a rare dematiaceous fungi causing invasive fungal infection in a 68 year old diabetic Iraqi female. The diagnosis was made by combining the phenotypic findings and genome sequencing. There are only 4 case reports in literature and this is probably the first from India which was treated by Liposomal Amphotericin B.

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.