Objective: To investigate the clinical manifestations, treatments, and prognosis of pediatric patients with Talaromyces marneffei infection. Methods: 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: 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: 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

BACKGROUNDOnychomycosis is a fungal infection of the nail plate and subungual area. In this study, we examined the efficacy of laser treatment using self-controlled study programs involving a long-pulsed Nd:YAG 1064-nm laser combined with oral medication.

METHODSSelf-controlled strategies were followed in this study. The patients received treatment with oral itraconazole in conjunction with long-pulsed Nd:YAG 1064-nm laser treatment at the nails of the unilateral limb once a week for a total of four times. A total of 84 affected nails were divided into Group A (mild to moderate) and Group B (severe) according to disease severity. Affected nails with the same Scoring Clinical Index for Onychomycosis scores were selected to compare the therapeutic effects of the pure medication treatment group and the combination treatment group with a 24-week follow-up period.

RESULTSIn Group A, at the 8th, 16th, and 24th weeks of follow-up, the efficacies in the pure medication treatment group were 81.0%, 81.0%, and 90.5%, respectively, while those in the combination treatment group were 100%, 95.2%, and 90.5%, respectively. The differences between groups were not significant (8th week: χ2 = 4.421, P> 0.05; 16th week: χ2 = 2.043, P> 0.05; 24th week: χ2 = 0.00, P > 0.05). In Group B, at the 8th, 16th, and 24th weeks of follow-up, the efficacies in the pure medication treatment group were 61.9%, 66.7%, and 52.4%, respectively, while those in the combination treatment group were 95.2%, 90.5%, and 100%, respectively. The differences between groups at the 8th and 24th weeks of follow-up were statistically significant (8th week: χ2 = 6.929, P< 0.05; 24th week: χ2 = 13.125, P < 0.05).

CONCLUSIONSFor patients with mild or moderate onychomycosis, we recommended a pure medication treatment or combination treatment with medication and laser. For those patients with severe onychomycosis, we recommended a combination of medication and laser therapy.

Adolescent ; Adult ; Aged ; Antifungal Agents ; therapeutic use ; Combined Modality Therapy ; Female ; Humans ; Itraconazole ; therapeutic use ; Laser Therapy ; Lasers, Solid-State ; therapeutic use ; Male ; Middle Aged ; Onychomycosis ; drug therapy ; therapy ; Treatment Outcome ; Young Adult

To compare clinical features, diagnosis and therapeutic effect between pulmonary histoplasmosis and progressive disseminated histoplasmosis.
 Methods: A retrospective analysis for 12 cases of hospitalized patients with histoplasmosis, who was admitted in Xiangya Hospital, Central South University during the time from February 2009 to October 2015, was carried out. Four cases of pulmonary histoplasmosis and 8 cases of progressive disseminated histoplasmosis were included. The differences of clinical features, imaging tests, means for diagnosis and prognosis were analyzed between the two types of histoplasmosis.
 Results: The clinical manifestations of pulmonary histoplasmosis were mild, such as dry cough. However, the main clinical symptoms of progressive disseminated histoplasmosis were severe, including recurrence of high fever, superficial lymph node enlargement over the whole body, hepatosplenomegaly, accompanied by cough, abdominal pain, joint pain, skin changes, etc.Laboratory examination showed pancytopenia, abnormal liver function and abnormal coagulation function. One pulmonary case received the operation of left lower lung lobectomy, 3 cases of pulmonary histoplasmosis and 6 cases of progressive disseminated histoplasmosis patients were given deoxycholate amphotericin B, itraconazole, voriconazole or fluconazole for antifungal therapy. One disseminated case discharged from the hospital without treatment after diagnosis of histoplasmosis, and 1 disseminated case combined with severe pneumonia and active tuberculosis died ultimately.
 Conclusion: As a rare fungal infection, histoplasmosis is easily to be misdiagnosed. The diagnostic criteria depends on etiology through bone marrow smear and tissues biopsy. Liposomeal amphotericin B, deoxycholate amphotericin B and itraconazole are recommended to treat infection for histoplasma capsulatum.
Abdominal Pain ; etiology ; Amphotericin B ; therapeutic use ; Antifungal Agents ; therapeutic use ; Biopsy ; Cough ; epidemiology ; Death ; Deoxycholic Acid ; therapeutic use ; Diagnostic Errors ; Drug Combinations ; Fever ; etiology ; Hepatomegaly ; etiology ; Histoplasma ; Histoplasmosis ; complications ; diagnosis ; mortality ; therapy ; Humans ; Invasive Fungal Infections ; complications ; diagnosis ; therapy ; Itraconazole ; therapeutic use ; Lung ; microbiology ; surgery ; Lung Diseases, Fungal ; diagnosis ; surgery ; therapy ; Pneumonia ; complications ; mortality ; Recurrence ; Retrospective Studies ; Splenomegaly ; etiology ; Treatment Outcome ; Tuberculosis ; complications ; mortality

Korea is not known as an endemic area for Histoplasma. However, we experienced a case of histoplasmosis in a person who had never been abroad. A 65-year-old female was admitted to the hospital for evaluation of multiple lung nodules. A computed tomography (CT) scan of the chest showed multiple ill-defined consolidations and cavitations in all lobes of both lungs. The patient underwent a CT-guided lung biopsy, and a histopathology study showed findings compatible with histoplasmosis. Based on biopsy results and clinical findings, the patient was diagnosed with chronic cavitary pulmonary histoplasmosis. The patient recovered completely following itraconazole treatment. This is the first case report of pulmonary histoplasmosis unconnected with either HIV infection or endemicity in Korea.
Aged ; Antifungal Agents/therapeutic use ; Biopsy ; Female ; Histoplasma/*isolation & purification ; Histoplasmosis/*diagnosis/drug therapy/microbiology ; Humans ; *Immunocompromised Host ; Itraconazole/therapeutic use ; Lung Diseases, Fungal/*diagnosis/drug therapy ; Republic of Korea ; Tomography, X-Ray Computed ; Treatment Outcome

Korea is not known as an endemic area for Histoplasma. However, we experienced a case of histoplasmosis in a person who had never been abroad. A 65-year-old female was admitted to the hospital for evaluation of multiple lung nodules. A computed tomography (CT) scan of the chest showed multiple ill-defined consolidations and cavitations in all lobes of both lungs. The patient underwent a CT-guided lung biopsy, and a histopathology study showed findings compatible with histoplasmosis. Based on biopsy results and clinical findings, the patient was diagnosed with chronic cavitary pulmonary histoplasmosis. The patient recovered completely following itraconazole treatment. This is the first case report of pulmonary histoplasmosis unconnected with either HIV infection or endemicity in Korea.
Aged ; Antifungal Agents/therapeutic use ; Biopsy ; Female ; Histoplasma/*isolation & purification ; Histoplasmosis/*diagnosis/drug therapy/microbiology ; Humans ; *Immunocompromised Host ; Itraconazole/therapeutic use ; Lung Diseases, Fungal/*diagnosis/drug therapy ; Republic of Korea ; Tomography, X-Ray Computed ; Treatment Outcome

OBJECTIVETo explore the efficacy and safety of intravenous itraconazole for patients undergoing intensive chemotherapy or hematopoietic stem cell transplantation in different strategies.

METHODSBased on multicenter, observational data, the efficacies of antifungal therapy for patients with persistent fever and suspected IFD in different strategies were calculated retrospectively, and the factors associated with the response of antifungal therapy were explored by logistic analysis.

RESULTSIn accordance with the latest published diagnostic criteria and treatment consensus in China, there were 2 patients who were diagnosed as proven IFD ultimately, 20 probable IFD, 19 possible IFD and 133 undefined IFD, respectively. Accordingly, the response rates in targeted therapy for proven/probable IFD patients, diagnostic-driven therapy for possible and undefined IFD patients with clinical or microbiological evidence of IFD, and empirical therapy for undefined patients without any evidence of IFD were 50.0%, 57.4% and 13.5%, respectively (P<0.01). And the multivariable analysis indicated that the presence of radiological or microbiological evidence of IFD before or after the initiation of antifungal therapy was markedly associated with the response to antifungal therapy (P<0.01). The incidence of itraconazole related adverse effect was only 2.9%.

CONCLUSIONItraconazole injection was an effective and safe agent in targeted and diagnostic- driven antifungal therapy for immunocompromised or neutropenic febrile patients with hematological malignancies.

Adolescent ; Adult ; Aged ; Antifungal Agents ; therapeutic use ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Itraconazole ; therapeutic use ; Male ; Middle Aged ; Multicenter Studies as Topic ; Observational Studies as Topic ; Retrospective Studies ; Treatment Outcome ; Young Adult

PURPOSE: To identify prognostic factors for the outcomes of empirical antifungal therapy, we performed a multicenter, prospective, observational study in immunocompromised patients with hematological malignancies. MATERIALS AND METHODS: Three hundred seventy-six patients (median age of 48) who had neutropenic fever and who received intravenous (IV) itraconazole as an empirical antifungal therapy for 3 or more days were analyzed. The patients with possible or probable categories of invasive fungal disease (IFD) were enrolled. RESULTS: The overall success rate was 51.3% (196/376). Age >50 years, underlying lung disease (co-morbidity), poor performance status [Eastern Cooperative Oncology Group (ECOG) > or =2], radiologic evidence of IFD, longer duration of baseline neutropenic fever (> or =4 days), no antifungal prophylaxis or prophylactic use of antifungal agents other than itraconazole, and high tumor burden were associated with decreased success rate in univariate analysis. In multivariate analysis, age >50 years (p=0.009) and poor ECOG performance status (p=0.005) were significantly associated with poor outcomes of empirical antifungal therapy. Twenty-two patients (5.9%) discontinued itraconazole therapy due to toxicity. CONCLUSION: We concluded that empirical antifungal therapy with IV itraconazole in immunocompromised patients is effective and safe. Additionally, age over 50 years and poor performance status were poor prognostic factors for the outcomes of empirical antifungal therapy with IV itraconazole.
Antifungal Agents/adverse effects/*therapeutic use ; Female ; Hematologic Neoplasms ; Humans ; Immunocompromised Host ; Itraconazole/adverse effects/*therapeutic use ; Male ; Middle Aged ; Prospective Studies ; Republic of Korea

We assessed the success rate of empirical antifungal therapy with itraconazole and evaluated risk factors for predicting the failure of empirical antifungal therapy. A multicenter, prospective, observational study was performed in patients with hematological malignancies who had neutropenic fever and received empirical antifungal therapy with itraconazole at 22 centers. A total of 391 patients who had abnormal findings on chest imaging tests (31.0%) or a positive result of enzyme immunoassay for serum galactomannan (17.6%) showed a 56.5% overall success rate. Positive galactomannan tests before the initiation of the empirical antifungal therapy (P=0.026, hazard ratio [HR], 2.28; 95% confidence interval [CI], 1.10-4.69) and abnormal findings on the chest imaging tests before initiation of the empirical antifungal therapy (P=0.022, HR, 2.03; 95% CI, 1.11-3.71) were significantly associated with poor outcomes for the empirical antifungal therapy. Eight patients (2.0%) had premature discontinuation of itraconazole therapy due to toxicity. It is suggested that positive galactomannan tests and abnormal findings on the chest imaging tests at the time of initiation of the empirical antifungal therapy are risk factors for predicting the failure of the empirical antifungal therapy with itraconazole. (Clinical Trial Registration on National Cancer Institute website, NCT01060462)
14-alpha Demethylase Inhibitors/adverse effects/therapeutic use ; Adolescent ; Adult ; Aged ; Antifungal Agents/adverse effects/*therapeutic use ; Aspergillosis/complications/*drug therapy ; Candidiasis/complications/*drug therapy ; Coccidioidomycosis/complications/drug therapy ; Febrile Neutropenia/complications/drug therapy ; Female ; Hematologic Neoplasms/complications/drug therapy/*microbiology ; Humans ; Itraconazole/adverse effects/*therapeutic use ; Male ; Mannans/blood ; Middle Aged ; Prospective Studies ; Treatment Outcome ; Young Adult

OBJECTIVETo evaluate the efficacy and safety of antifungal prophylaxis of itraconazole in patients with acute myeloid leukemia (AML) to probe the relationship of the antifungal effect and the adverse events with serum concentration.

METHODSFrom April 2009 to May 2011, a total of 310 courses from 112 patients referred to our institute were enrolled in this study; of them, 297 courses were eligible for analysis. Eligible cases were randomized into oral group and injection/oral group according to different chemotherapy of induction and consolidation. Blood samples were collected at different time points for measurements of serum itraconazole levels. The morbidity of IFI and the adverse events were analyzed.

RESULTSThe morbidities of IFI in injection/oral and oral groups were 10.1% and 20.9%, respectively (P=0.010). 7 and 9 cases in injection/oral and oral groups, respectively were withdrawn from the study because of adverse events, and the difference between these two groups was of no significance. Serum itraconazole levels of injection/oral and oral groups were 672(299-1097) μg/L and 534(210-936) μg/L, respectively (P<0.01).

CONCLUSIONAntifungal prophylaxis with itraconazole in AML patients was effective and safe. Prophylactic effect with injection/oral itraconazole was superior to oral itraconazole solution; moreover, prophylactic effect of itraconazole was highly correlated with its serum level.

Adolescent ; Adult ; Antibiotic Prophylaxis ; Antifungal Agents ; therapeutic use ; Female ; Humans ; Itraconazole ; blood ; therapeutic use ; Leukemia, Myeloid, Acute ; drug therapy ; microbiology ; Male ; Middle Aged ; Mycoses ; etiology ; prevention & control ; Young Adult

OBJECTIVETo evaluate the efficacy and safety of itraconazole for secondary prophylaxis of previous proven or probable invasive fungal infection (IFI) in patients undergoing chemotherapy or allogeneic hematopoietic stem cell transplantation (HSCT) in agranulocytosis state.

METHODSA phase IV prospective, open-label, multicenter trial was conducted to evaluate itraconazole (200 mg q12h intravenously d1-2, 200 mg/d) as secondary antifungal prophylaxis in patients (18-65 years old) undergoing chemotherapy or HSCT with previous proven or probable IFI. Itraconazole was started when patients' neutrophils＜1.5 × 10⁹/L, and stopped when chemotherapy patients' neutrophils ＞0.5 × 10⁹/L and stem cell transplant recipients' neutrophils＞1.0 × 10⁹/L. The primary end-point of the study was the incidence of proven, probable or possible IFI.

RESULTSSeventy one patients from November 2008 to September 2010 were enrolled in the trial. The median duration of itraconazole prophylaxis was 14 (4-35) days. No patients died of drug-related toxicity within trial. Five cases occurred IFI during the trial. The cumulative incidence of invasive fungal disease was 7.0%. One patient was withdrawn from the study due to treatment-related adverse events (liver malfunction and severe phlebitis).

CONCLUSIONItraconazole appears to be safe and effective for secondary prophylaxis of systemic fungal infection after chemotherapy and allogeneic HSCT. The observed incidence of 7.0% is considerably lower than the relapse rate reported in historical controls, suggesting that itraconazole is a promising prophylactic agent in this population.

Adolescent ; Adult ; Aged ; Antifungal Agents ; therapeutic use ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Itraconazole ; therapeutic use ; Male ; Middle Aged ; Mycoses ; prevention & control ; Prospective Studies ; Treatment Outcome ; Young Adult