We report a case of mucormycosis induced by Cunninghamella spp. infection in a ten-year-old girl with acute lymphoblastic leukemia, who developed fever and respiratory symptoms after chemotherapy and was diagnosed with invasive fungal disease. Peripheral blood DNA sequences were analyzed using metagenomic next-generation sequencing (mNGS), and by comparison with the Pathogens Metagenomics Database (PMDB), we identified Cunninghamella spp. with sequence number 514 as the pathogen. The patient was treated with amphotericin B combined with posaconazole and showed a favorable response. We searched Pubmed, Embase, CNKI, and Wanfang database for reports of cases of Cunninghamella spp. infection in children and retrieved 22 reported cases (including 12 males) with a median age of 13.5 (3-18) years. In these 22 cases, hematological malignancy was the most common underlying condition (19/22), and most of patients experienced an acute onset and rapid progression with respiratory symptoms (14/20) and fever (16/20) as the most common symptoms. CT imaging often showed unilateral lesions with varying imaging findings, including pulmonary nodules or masses, infiltrative changes, and pleural effusion. Definite diagnoses were established in 18 of the cases, and 4 had probable diagnoses; the lungs and skin were the most frequent organs compromised by the infection. A definite diagnosis of Cunninghamella spp. infection still relied on histopathological examination and fungal culture, but the molecular techniques including PCR and mNGS had shown potentials in the diagnosis. Almost all the cases received antifungal treatment after diagnosis (21/22), and 13 patients also underwent surgeries. Death occurred in 9 (42%) of the cases at a median of 19 (4-54) days after onset of the signs or symptoms. The patients receiving antifungal therapy combined with surgery had a high survival rate (9/13, 69%) than those with antifungal therapy alone (3/8, 37%). Invasive fungal disease is a common complication in immunoco-mpromised patients, but Cunninghamella spp. infection is rare and has a high mortality rate. In cases highly suspected of this disease, active diagnosis and early treatment are critical to improve the survival outcomes of the patients.
Adolescent ; Amphotericin B/therapeutic use* ; Antifungal Agents/therapeutic use* ; Child ; Cunninghamella ; Female ; Humans ; Male ; Mucormycosis/etiology*

Currently, the first-line drugs for invasive fungal infections (IFI), such as amphotericin B, fluconazole and itraconazole, have drawbacks including poor water solubility, low bioavailability, and severe side effects. Using drug delivery systems is a promising strategy to improve the efficacy and safety of traditional antifungal therapy. Synthetic and biomimetic carriers have greatly facilitated the development of targeted delivery systems for antifungal drugs. Synthetic carrier drug delivery systems, such as liposomes, nanoparticles, polymer micelles, and microspheres, can improve the physicochemical properties of antifungal drugs, prolong their circulation time, enhance targeting capabilities, and reduce toxic side effects. Cell membrane biomimetic drug delivery systems, such as macrophage or red blood cell membrane-coated drug delivery systems, retain the membrane structure of somatic cells and confer various biological functions and specific targeting abilities to the loaded antifungal drugs, exhibiting better biocompatibility and lower toxicity. This article reviews the development of antifungal drug delivery systems and their application in the treatment of IFI, and also discusses the prospects of novel biomimetic carriers in antifungal drug delivery.
Antifungal Agents/therapeutic use* ; Drug Delivery Systems ; Amphotericin B/therapeutic use* ; Liposomes/chemistry* ; Nanoparticles ; Drug Carriers

<b>BACKGROUNDb>Nowadays, there are published trials in regards to the comparison of caspofungin with liposomal amphotericin B (L-AmB). However, these studies have a modest sample size and convey inconclusive results. The aim of this study was to review the efficacy and safety of caspofungin for the treatment of invasive fungal infections (IFIs), compared with L-AmB.

<b>METHODSb>Electronic databases (up to July 31, 2013) PubMed and Embase databases, the Cochrane Library, and Google Scholar were searched to identify relevant trials of caspofungin and L-AmB. Analyses of efficacy and adverse outcomes were performed by relative risks (RRs) and 95% confidence intervals (CIs). Heterogeneity was assessed by χ(2)-test and the I(2)-statistic.

<b>RESULTSb>Three trials were included in this meta-analysis with 1249 modified intention-to-treat (MITT) patients. The results showed that caspofungin produced equal efficacy in favorable overall response (RR = 1.02, 95% CI 0.88-1.18; P = 0.81) and mortality rate (RR = 1.53, 95% CI 0.38-6.27, P = 0.55), safer in clinical adverse events (RR = 0.20, 95% CI 0.08-0.54; P = 0.001), laboratory adverse events (RR = 0.69, 95% CI 0. 57-0.84; P = 0.0002), and discontinuation rate (RR = 0.26, 95% CI 0.08-0.83, P = 0.02), compared with L-AmB in the treatment of patients with IFIs.

<b>CONCLUSIONb>Based on the results of this meta-analysis, it would appear that caspofungin was measured to have equal efficacy in clinical outcomes and safer in terms of adverse events.

Amphotericin B ; therapeutic use ; Antifungal Agents ; therapeutic use ; Echinocandins ; therapeutic use ; Febrile Neutropenia ; drug therapy ; Humans ; Lipopeptides ; Mycoses ; drug therapy

Disseminated coccidioidomycosis is a systemic fungal infection that is occurring more commonly and causes high mortality in patients with compromised host defense or debilitated. It is endemic in certain areas of North, Central, and South America. Increasingly, cases are being recognized outside the endemic area, due to travelers who have visited an endemic area. We experienced a case of disseminated coccidioidomycosis, as a reactivation of infection acquired earlier in a patient, who was a former resident of an endemic area.
Amphotericin B/therapeutic use ; Case Report ; Coccidioidomycosis/diagnosis/drug therapy/*pathology ; Female ; Human ; Middle Age

Trichosporonosis is a potentially life-threatening infection with Trichosporon beigelii, the causative agent of white piedra. The systemic infection by this fungus has been most frequently described in immunocompromised hosts with neutropenia. Here, we report the first patient with disseminated infection by T. beigelii in Korea, acquired during a period of severe neutropenia after chemo-therapy for myelodysplastic syndrome. The patient recovered from the infection after an early-intensified treatment with amphotericin B and a rapid neutrophil recovery. The disseminated infection by T. beigelii is still rare, however, is an emerging fatal mycosis in immunocompromised patients with severe neutropenia.
Adult ; Amphotericin B/therapeutic use ; Human ; Male ; Mycoses/drug therapy/*etiology ; Myelodysplastic Syndromes/*complications/drug therapy

Hansenula anomala (H. anomaly) is part of the normal flora in the alimentary tract and throat. It has been reported to be an organism causing opportunistic infections in immunocompromised patients. However, cases of fungal arthritis caused by H. anomala are rare. We encountered a case of H. anomala arthritis in a 70-year-old man who was treated with an empirical antibiotic treatment and surgery under the impression of septic arthritis. However, the patient did not improve after antibiotic therapy and surgery. Consequently, knee joint aspiration was performed again, which identified fungal arthritis caused by H. anomala. It was treated successfully with amphotericin B and fluconazole. When treating arthritis patients with diabetes, it is important to consider the possibility of septic arthritis by H. anomala and provide the appropriate treatment.
Aged ; Amphotericin B/therapeutic use ; Antifungal Agents/therapeutic use ; Arthritis, Infectious/*diagnosis/drug therapy/microbiology ; Fluconazole/therapeutic use ; Humans ; *Knee Joint ; Male ; Mycoses/*diagnosis/drug therapy ; *Pichia

Isolated fungal soft-tissue infections are uncommon, but may cause severe morbidity or mortality. Aspergillosis infection is rare, but the frequency in increasing over the last two decades. Here, we present a patient with utaneous aspergillosis of his right elbow with unusual clinical and radiological features suggestive of a malignant disease, which remained undiagnosed for an extended period of time. The patient presented with necrotic, black-colored skin ulcerations. We completely removed the skin ulcer with the surrounding erythematous skin lesion, and then we reconstructed the area with thoracodorsal perforator free flap. The biopsy specimen contained septate hyphae with dichotomous branching, which is morphologically consistent with a finding of Aspergillus. After surgery, we initiated antifungal medication therapy with amphotericin B and itraconazole. At the time of follow-up, the elbow with the reconstructed flap had fully healed, and no recurrent disease was found.
Amphotericin B/therapeutic use ; Antifungal Agents/therapeutic use ; Aspergillosis/*therapy ; Biopsy ; Humans ; Itraconazole/therapeutic use ; Male ; Middle Aged ; Skin Diseases/*surgery ; *Surgical Flaps ; Treatment Outcome

Objective:b> To investigate the clinical manifestations, treatments, and prognosis of pediatric patients with Talaromyces marneffei infection. Methods:b> In this retrospective study, 7 children diagnosed with Talaromyces marneffei infection in Shenzhen Children's Hospital from July 2017 to October 2021 were recruited. The clinical features, radiology, pathogen detection, immunological evaluation, treatments, and prognosis were analyzed. Results:b> In 7 cases, 5 were male, 2 were females. The age was from 0.75 to 8.75 years. The main clinical manifestations were fever in 7 cases, cough in 6 cases, malnutrition in 4 cases, papules in 2 cases and medical history of recurrent infection in 3 cases. Physical examination showed that all 7 patients had hepatosplenomegaly, 4 had superficial lymphadenopathy. Laboratory examination showed that 6 cases had decreased hemoglobin and 3 cases had decreased platelet. Chest CT showed that 4 cases had patchy shadows, pleural effusion, mediastinal or axillary lymph node enlargement, 3 had nodular shadows and 2 had cavities. The positive ratio of Talaromyces marneffei culture was 2/2 with tissue samples, 4/5 with bone marrow. The positive ratio was 3/4 by metagenomic next generation sequencing. The fungus was detected in 3 cases by smear microscopy of bone marrow and (or) peripheral blood. All patients were negative for human immunodeficiency virus by the immune function assay. However, 5 cases were confirmed as primary immunodeficiency disease, including 2 cases with high IgM syndrome, 2 with STAT1 gene variation, and the last with severe combined immunodeficiency (IL2RG gene variation). Exclude 1 case which gave up treatment due to acute intracranial infection, and the other patients received effective treatments along with amphotericin B, voriconazole, and itraconazole alone or in combination. Two cases relapsed after medication withdrawal, but 1 case got complete rehabilitation after hematopoietic stem cell transplantation. Conclusions:b> The clinical manifestations involve multisystem, the common charateristics are fever and cough. The chest CT imaging manifestations are diverse, it should be considered in differentiating tuberculosis. The amphotericin B, voriconazole and itraconazole are effective, but it will easily relapse when withdrawing those antifungal agents.
Amphotericin B/therapeutic use* ; Antifungal Agents/therapeutic use* ; Child ; Child, Preschool ; Cough ; Female ; Fever ; Humans ; Infant ; Itraconazole/therapeutic use* ; Male ; Mycoses ; Retrospective Studies ; Talaromyces ; Voriconazole

<b>BACKGROUNDb>In our clinical practice we have been attracted by a group of patients with airway aspergillosis who have airway obstruction; we termed the condition as pseudomembranous necrotizing tracheobronchial aspergillosis (PNTA). In this study we analyzed the clinical data from patients with PNTA, so as to guide the diagnosis and treatment of the disease.

<b>METHODSb>A total of 16 PNTA patients were treated in Changhai Hospital from January 2000 to January 2009. Their clinical data, including the demographic information, clinical symptoms, imaging findings, bronchoscopy findings, treatment strategies and efficacy, and prognosis, were retrospectively analyzed.

<b>RESULTSb>All 16 patients were found to have primary systemic immunodeficiency diseases and/or damage of the focal airways. Nine patients (9/16, 56.3%) had pulmonary and tracheobronchial tumors, 5/16 (31.3%) had tracheobronchial involvement secondary to non-pulmonary tumors, and 2/16 (12.5%) had lung transplantation. The most common causes of PNTA included local radiotherapy (10/16, 62.5%), repeated chemotherapy (7/16, 43.8%) and recurrent intervention therapy by bronchoscope (4/16, 25.0%). Aspergillus fumigatus was the most frequent pathogen (62.5%, 10/16). The main clinical manifestations included progressive dyspnea (14/16, 87.5%) and irritable cough (12/16, 75.0%). The trachea was involved in 9/16 patients (56.3%), right main bronchus in 10/16 (62.5%). All 16 patients were treated with systemic anti-aspergillosis agents, local anti-aspergillosis agents with amphotericin B inhalation and direct perfusion of amphotericin B by bronchoscope, and interventional treatment by bronchoscope to ensure an unobstructed airway. The total efficiency was 31.3%.

<b>CONCLUSIONSb>PNTA is an infectious disease caused by aspergillus and it mainly involves the trachea, primary bronchus and segmental bronchus. A. fumigatus is the most common pathogen. PNTA can pose a severe clinical threat and often occurs after systemic immunodeficiency and/or local airway damage, with the main symptoms including dyspnea and irritable cough. Bronchoscopic findings supply the main evidence for diagnosis of PNTA. Treatment of PNTA is difficult and requires a long course. Systemic and local anti-aspergillosis agents plus bronchoscopy debridement can improve the prognosis of the disease.

Adult ; Aged ; Amphotericin B ; therapeutic use ; Antifungal Agents ; therapeutic use ; Aspergillosis ; diagnosis ; drug therapy ; Bronchoscopy ; Echinocandins ; therapeutic use ; Female ; Humans ; Itraconazole ; therapeutic use ; Lipopeptides ; Lung Diseases, Fungal ; diagnosis ; drug therapy ; Male ; Middle Aged ; Pyrimidines ; therapeutic use ; Triazoles ; therapeutic use ; Voriconazole

PURPOSE: Amphotericin B is considered the treatment of choice for systemic candidiasis, but adverse effects may limit its use. An alternative option for the treatment of candidiasis includes lipid preparations of amphotericin B. This study investigated the safety and efficacy of AmBisome(R), a lipid formulation of amphotericin B containing liposomal structures, for the treatment of systemic candidiasis in very low birth weight infants (VLBWI). MATERIALS AMD METHODS: Data from 26 VLBWI treated with AmBisome(R) in the study group (AmBisome group) from October 2003 to July 2006 were compared with data from 20 VLBWI treated with amphotericin B as a historical control (Amphotericin group). This study was a prospective, historical control, multi-center trial. RESULTS: Candida spp. was isolated in 73% (19/26) of the cases for the AmBisome group and 90% (18/20) of the cases for the Amphotericin group. The fungal eradication rate and the time to eradication was 84% (16/19) and 9+/-8 days in the AmBisome group, and 89% (16/18) and 10+/-9 days in the Amphotericin group, respectively (p=0.680 vs p=0.712). The major adverse effects were lower in the AmBisome group (renal toxicity, 21% vs 55%, p=0.029; hepatotoxity, 25% vs 65%, p=0.014, AmBisome group vs Amphotericin group, respectively). There was no significant difference in mortality attributed to systemic candidiasis (12% in the AmBisome group, 10% in the Amphotericin group, p=0.868). CONCLUSION: AmBisome(R) is effective and safe for treating systemic fungal infections in VLBWI.
Amphotericin B/adverse effects/*therapeutic use ; Candidiasis/*drug therapy ; Female ; Humans ; Infant, Newborn ; *Infant, Very Low Birth Weight ; Male