Schizophyllum commune is a globally distributed basidiomycete fungus that is known as a rare cause of sinusitis, for which no prompt treatment has been established. We describe the first report of S. commune sinusitis following unrelated cord blood transplantation for acute lymphoblastic leukemia. Thirteen days after transplantation, a 23-year-old female developed maxillary and ethmoid sinusitis. The sinusitis was antimicrobial-resistant, and the sinus aspirate culture revealed white wooly mold, which was identified as S. commune by nucleotide sequencing. The patient was successfully treated with intravenous administration of liposomal amphotericin B for 2 months, followed by oral voriconazole. This report suggests the effectiveness of liposomal amphotericin B and voriconazole for S. commune infection in immunocompromised patients. Given the difficulty in distinguishing S. commune infection from aspergillosis by standard culture methods, the incidence of S. commune infection following allogeneic hematopoietic stem cell transplantation may be underestimated. Nucleotide sequencing may be useful in the diagnosis of S. commune infection.

A small hyperpigmented nodule 4 mm in diameter with a smaller satellite lesion was noted on the left hip 5 weeks after spontaneous birth of an otherwise unharmed 490 g female infant at 23 + 5 weeks of gestation. The mother had been treated with antibiotics for a clinically suspected amniotic infection syndrome. Aspergillus fumigatus was identified in both repeated swabs of the lesions and culture of the resected tissue. The infant received liposomal amphotericin B (3 mg/kg/day) for 8 days. No new lesions were noted thereafter. There was no evidence for a primary immunodeficiency.

A 62-year-old woman with acute lymphoblastic leukemia in first complete remission was treated with unrelated cord blood transplantation, but exhibited primary graft failure. She then underwent HLA-haploidentical peripheral blood stem cell transplantation from her daughter. The conditioning regimen consisted of fludarabine 30 mg/m(2)/day for 6 days, intravenous busulfan 3.2 mg/kg/day for 2 days, and thymoglobulin 1 mg/kg/day for 2 days. Voriconazole was administered to prevent fungal infections. The patient achieved prompt hematopoietic recovery. Fever was observed 21 days after the second transplant, followed by sigmoid colon perforation and a liver space occupying lesion (SOL). A filamentous fungus was detected in a percutaneous biopsy of the liver SOL. In spite of changing the antifungal drug from voriconazole to liposomal amphotericin B, the patient died on day 41. The fungus was identified as Mucor indicus, a type of zygomycete. Although Mucor indicus inhabits soil, an infectious disease is extremely rare, and breakthrough infection after voriconazole prophylaxis had not been reported until now. It is mandatory to consider preventive antifungal treatment for drug-resistant fungal infectious diseases in patients after neutrophilic recovery with a strongly immunocompromised state after a HLA-haploidentical transplant.

OBJECTIVE:

To describe a case of successful treatment of severe pulmonary blastomycosis with amphotericin B deoxycholate after failure of liposomal amphotericin B.

CASE SUMMARY:

A 35-year-old male was exposed to damp decomposing wood while cleaning his basement. He subsequently developed a cough, malaise, fever, nausea, vomiting, and diarrhea. He was admitted to the hospital and intubated for worsening pulmonary symptoms. Microscopic examination of his sputum indicated Blastomyces dermatitidis. Liposomal amphotericin B was administered for 6 days, but the patient's temperature reached 39.6 °C and his white blood cell (WBC) count reached 52,300/µL. Extensive consolidation of both lungs fields was observed on chest X-ray. Because of progressive clinical deterioration, the treatment was switched to amphotericin B deoxycholate by continuous infusion. That change resulted in clinical improvement, with abrupt reductions (within 48 hours) in temperature and the WBC count. By day 14 of therapy (day 8 of amphotericin B deoxycholate), the chest X-ray showed improve ment in diffuse airspace filling. After 16 days of amphotericin B treatment, intravenous followed by oral voriconazole was administered for 3 months. Eight months later the patient's strength had improved significantly, but he still had occasional episodes of shortness of breath.

DISCUSSION:

The management of blastomycosis is challenging because of the lack of clinically supporting data. The gold standard for severe pulmonary blastomycosis had been amphotericin B deoxycholate; however, improved safety data with liposomal amphotericin B for other fungal infections has suggested this as an effective alternative. This report describes a patient with severe pulmonary blastomycosis failing 6 days of liposomal amphotericin B, yet he tolerated and clinically responded to continuous infusion of amphotericin B deoxycholate. Based on this case report and a simulated pharmacokinetic/pharmacodynamic analysis, continuous infusion of amphotericin B deoxycholate may be a reasonable option for enhanced efficacy and minimal toxicity in patients with blastomycosis.

CONCLUSIONS:

Ours is the first case report to use continuous infusion of amphotericin B deoxycholate for the management of pulmonary blastomycosis. These results suggest that liposomal amphotericin B may not be adequate in some patients for the management of B. dermatitidis pulmonary infections.

Mucormycosis is a life-threatening invasive fungal infection that arises among immunocompromised patients (haematological malignancies, solid organ transplantation, diabetes mellitus). The most frequent sites of infection are pulmonary, rhinocerebral, cutaneous and disseminated. Reversal of the underlying conditions is mandatory for controlling mucormycosis. Another cornerstone of mucormycosis treatment is prompt and aggressive surgery. It is achieved by extensive surgical debridement of necrotic tissues. Finally an antifungal therapy is needed. The first-line chemotherapy of mucormycosis includes high-dose liposomal amphotericin B (≥ 5 mg/kg/day). The duration of antifungal chemotherapy is not defined but guided by the resolution of all associated symptoms and findings (usually 6-8 weeks). Maintenance therapy/secondary prophylaxis by posaconazole has to be considered in persistently immuno compromised patients.

Cerebral abscess caused by Candida spp. is a rare disease, with a nonspecific presentation, little data on treatment, and generally poor outcomes. We present a case of this type of Candida infection in a 57-year-old man with a history of uncontrolled diabetes mellitus and intravenous drug abuse, and review the literature on this disease. Our patient had a good treatment outcome with liposomal amphotericin B and flucytosine, followed by oral fluconazole. Comorbidities include prior antibiotic use (52%), prior surgery (28%), malignancy (28%), stem cell or solid organ transplant (20%), prior corticosteroid use (16%), central venous catheter (CVC) insertion (10%), and burns (7%). Diagnosis requires a high index of suspicion, as clinical presentations and laboratory data can be nonspecific and difficult to differentiate from bacterial cerebral abscesses. In reviewed cases, 55% of blood cultures and 23% of cerebrospinal fluid (CSF) cultures were positive for Candida spp. and outcomes were poor, as the mortality rate of the non-autopsy cases reviewed was 69%.

Mucormycosis is a life-threatening fungal infection almost uniformly affecting diabetics in ketoacidosis, other form of acidosis, and/or immunocompromised patients. Inhalation of Mucorales spores provides the most common natural route of entry into the host. In this study, we developed an intratracheal instillation model of pulmonary mucormycosis that hematogenously disseminates into other organs using diabetic ketoacidotic (DKA) or cyclophosphamide/cortisone acetate-treated mice. Varying degrees of lethality was achieved for the DKA or cyclophosphamide/cortisone acetate-treated mice when infected with different clinical isolates of Mucorales. In both DKA and cyclophosphamide/cortisone acetate models, liposomal amphotericin B (LAmB) or posaconazole (POS) treatments were effective in improving survival, reducing lungs and brain fungal burdens and histologically resolving the infection when compared with placebo. These models can be used to study mechanisms of infection, develop immunotherapeutic strategies and evaluate drug efficacies against life threatening Mucorales infections.

Abstract

Objective:

The conventional liposomal amphotericin B causes many unwanted side effects like blood disorder, nephrotoxicity, dose-dependent side effects, highly variable oral absorption and formulation-related instability. The objective of the present investigation was to develop cost-effective nanoemulsion as nanocarreir for enhanced and sustained delivery of amphotericin B into the skin. Methods and characterizations: Different oil-in-water nanoemulsions were developed by varying the composition of hydrophilic (Tween® 80) surfactants and co-surfactant by the spontaneous titration method. The developed formulation were characterized, optimized, evaluated and compared for the skin permeation with commercial formulation (fungisome 0.01% w/w). Optimized formulations loaded with amphotericin B were screened using varied concentrations of surfactants and co-surfactants as decided by the ternary phase diagram. Results and discussion: The maximum % transmittance obtained were 96.9 ± 1.0%, 95.9 ± 3.0% and 93.7 ± 1.2% for the optimized formulations F-I, F-III and F-VI, respectively. These optimized nanoemulsions were subjected to thermodynamic stability study to get the most stable nanoemulsions (F-I). The results of the particle size and zeta potential value were found to be 67.32 ± 0.8 nm and -3.7 ± 1.2 mV for the final optimized nanoemulsion F-I supporting transparency and stable nanoemulsion for better skin permeation. The steady state transdermal flux for the formulations was observed between 5.89 ± 2.06 and 18.02 ± 4.3 µg/cm(2)/h whereas the maximum enhancement ratio were found 1.85- and 3.0-fold higher than fungisome and drug solution, respectively, for F-I. The results of the skin deposition study suggests that 231.37 ± 3.6 µg/cm(2) drug deposited from optimized nanoemulsion F-I and 2.11-fold higher enhancement ratio as compared to fungisome. Optimized surfactants and co-surfactant combination-mediated transport of the drug through the skin was also tried and the results were shown to have facilitated drug permeation and skin perturbation (SEM).

Conclusion:

The combined results suggested that amphotericin B nanoemulsion could be a better option for localized topical drug delivery and have greater potential as an effective, efficient and safe approach.

Blastomycosis rarely presents in pregnancy. Pregnancy is a state of partial immunodeficiency that predisposes to blastomyces infection, especially in endemic areas. Blastomycosis in pregnancy has been reported in a few female patients and their offspring. We are reporting a 32-year-old pregnant patient at 34 weeks of gestation who presented with a lung mass. The cytopathological exam of the biopsy taken by fine needle aspiration showed evidence of Blastomyces organisms. She received Liposomal Amphotericin B and was followed closely until delivery. The placenta was examined and did not show evidence of infection in the fetus. Healthcare professionals in endemic areas such as Tennessee should be aware of blastomycosis in pregnancy.

Cutaneous mucormycosis is a rare opportunistic infection caused by zygomycetes that can be rapidly fatal if unrecognized. We describe the clinical, histopathological, fungal and molecular features of a case of gangrenous cutaneous mucormycosis. The patient presented with great necrosis on his right forearm at the site of detained intravenous cannula needle. He had type II diabetes and chronic renal insufficiency. KOH mount of black eschar showed many broad, aseptate fungal hyphae with right-angle branching. PAS staining of the tissue sample revealed similar broad hyphae in the dermis and cutis. Fungal culture and ITS sequence analysis identified this fungus as Rhizopus oryzae. As no organ involvement was detected, the patient was diagnosed with primary cutaneous mucormycosis. Considering the poor state of the patient, complete excision of the infectious tissue was performed without skin graft instead of amputation. At the same time, intravenous liposomal amphotericin B was given, starting from a small dosage and increased to a total dosage amount of 5.45 g. The wound recovered well with granulation. We emphasize that early recognition and prompt therapy including the control of the primary diseases were important. In this article, we also reviewed the features of primary cutaneous mucormycosis reported in China over the last 20 years.