BACKGROUND : Pulmonary tuberculosis (TB) is among the top 10 causes of death worldwide. Prolonged use and noncompliance with TB treatment have a potential risk for pulmonary fungal coinfection. This study aimed to evaluate fungal coinfection in pulmonary TB patients in Indonesia referred to the Clinical Microbiology Laboratory, Faculty of Medicine, Universitas Indonesia, Jakarta, during 2018–2022. METHODS : A cross-sectional study was conducted to compare 5 years of data collected at the Clinical Microbiology Laboratory, Faculty of Medicine, Universitas Indonesia. A total of 7,440 sputum specimens from various clinical sites were examined from 2018 to 2022. Sputum specimens from TB patients were prepared for microscopic examination using ZN staining to detect AFB. Culture and antimicrobial susceptibility of TB were performed on LJ agar. Fungal detected on microscopic examination and culture were assessed as coinfections. RESULTS : ZN staining to detect M. tuberculosis in clinical specimens has high specificity (98.4%) but low sensitivity (60.6%). Drug resistance in TB patients remains a problem, which can increase the risk of fungal infections. In 2018–2019, TB and fungal coinfections were more common in polyresistant TB cases. In 2020–2021, TB and fungal coinfections were found in all resistant TB cases, most commonly in XDR-TB cases. In 2022, TB and fungal coinfections were found in monoresistant and polyresistant patients. Candida spp. was found in 6.2% of positive TB cases, and all were found in resistant TB. CONCLUSIONS Increasing MDR- and XDR-TB are risk factors for fungal coinfection and must be detected early for better TB management in Indonesia.
antimicrobial susceptibility ; culture ; fungal infections ; sputum ; tuberculosis

Invasive fungal infections (IFIs) are a group of diseases caused by fungal pathogens, primarily Candida, Aspergillus, and Cryptococcus, which invade the body, proliferate in deep tissues, organs, or the bloodstream, and lead to localized or systemic severe infections. These infections impose significantclinical and economic burdens due to their high mortality rates, the high cost and limited availability of antifungal drugs, and the frequent adverse effects. Invasive fungal pathogens invade the host through hyphae, spores, and secreted adhesive proteins, primarily triggering disease via signal cascades resulting from the binding of fungal membrane ligands to host receptors, as well as through secreted substances and intrinsic toxins. Macrophages, as the first line of defense against invasive fungal pathogens, play a crucial role in combating IFIs. They combat fungal pathogens through mechanisms such as antigen recognition, phagocytosis, oxidative killing, polarization, and the regulation of various bioactive substances. This article reviews recent research progress on the mechanisms by which macrophages contribute to innate immunity against invasive fungal infections. Additionally, it discusses the immune evasion strategies employed by invasive fungal pathogens to counteract macrophages, aiming to provide new insights for the prevention and treatment of invasive fungal infections.
Humans ; Immunity, Innate ; Macrophages/immunology* ; Invasive Fungal Infections/microbiology* ; Animals ; Phagocytosis/immunology*

OBJECTIVE: To investigate the efficacy and safety of diagnostic-driven therapy for invasive fungal disease(IFD) in patients with myeloid hematologic malignancies. METHODS: A retrospective analysis was conducted on the clinical data of 91 patients with myeloid hematologic malignancies who received diagnostic-driven therapy for IFD at the Second Hospital of Anhui Medical University from January 1, 2020 to December 31, 2023. The patients were divided into two groups based on medication: 44 patients in the caspofungin group and 47 patients in the voriconazole group. The clinical efficacy and adverse reactions of the two groups were compared and analyzed. RESULTS: The overall response rates in the caspofungin and voriconazole groups were 67.4% and 60.0%, respectively. Among patients who transitioned to diagnostic-driven therapy following prophylactic or empirical treatment with triazole antifungal agents, the response rate of the caspofungin group was significantly higher than that of the voriconazole group (76.9% vs 35.3%, P <0.05). A total of 9 patients in both groups experienced adverse reactions, and no grade III or higher adverse reactions occurred. The incidence of grade I-II adverse reactions in the caspofungin group was lower than in the voriconazole group (2.3% vs 17.0%, P <0.05). CONCLUSION In patients with myeloid hematologic malignancies, caspofungin and voriconazole demonstrate comparable clinical efficacy in diagnostic-driven therapy for IFD, but caspofungin is associated with a lower incidence of adverse reactions. Caspofungin exhibits significant effectiveness when initiating diagnostic-driven therapy after prophylactic or empirical treatment with broad-spectrum triazole antifungal agents.
Humans ; Retrospective Studies ; Hematologic Neoplasms/complications* ; Antifungal Agents/therapeutic use* ; Voriconazole/therapeutic use* ; Caspofungin/therapeutic use* ; Invasive Fungal Infections/diagnosis* ; Male ; Female ; Mycoses/drug therapy* ; Middle Aged ; Treatment Outcome ; Aged ; Adult

In 2005, the Chinese Invasive Fungal Infection Working Group published the first guidelines for the diagnosis and treatment of invasive fungal disease (IFD) in patients with hematological disorders and cancers, with the sixth revision released in 2020. Numerous advances in the fields of hematological oncology treatment and the diagnosis and management of IFD have significantly influenced the corresponding strategies. Therefore, the Chinese Invasive Fungal Infection Working Group has reviewed key research advances from 2020 to 2024 and released the seventh revision of the Chinese guidelines. Major revisions include: changes in the epidemiology of IFD; evaluation of novel diagnostic methods (especially PCR and metagenomic next-generation sequencing); updated recommendations on therapeutic drug monitoring and in vitro drug sensitivity test; management of breakthrough IFD; targeted therapy of Pneumocystis jiroveci pneumonia and cryptococcosis; and updated recommendation on the duration of antifungal therapy.
Humans ; Invasive Fungal Infections/drug therapy* ; Hematologic Diseases/complications* ; Antifungal Agents/therapeutic use* ; Neoplasms/complications* ; Hematologic Neoplasms/complications* ; Mycoses/therapy* ; China

Introduction: Histoplasmosis is a disease of global distribution with diverse manifestations caused by the dimorphic fungus Histoplasma capsulatum. It is frequently described in severely immunocompromised and Human Immunodeficiency Virus (HIV)-positive individuals. Despite being widely reported in Southeast Asia, few cases have been reported in the Philippines. Case Report: A 53-year-old Filipino male who presented with umbilicated papules resembling molluscum contagiosum, and a previous history of a left lung mass with initial complaints of cough and hemoptysis. Gram stain of his sputum revealed the presence of fungal elements, otherwise not specified. In relation to this, a fine-needle aspiration biopsy of the suspected lung mass was done. However, findings were negative for malignant cells and fungi. Dermoscopy revealed central ulceration and necrosis with faint peripheral arborizing telangiectasia and surrounding superficial scaling. Histopathologic analysis revealed a diffuse granulomatous dermatitis, and Periodic acid-Schiff (PAS) and Grocott methenamine silver (GMS) stains showed numerous small yeast-like structures measuring approximately 3.74µm in diameter. Tissue culture of the skin lesion on the right thigh isolated fungal elements but was not specified. As histoplasmosis is an AIDS-defining infection and often found in immunocompromised states, screening for HIV was done which revealed negative results. Interestingly, disease distribution of histoplasmosis in the Philippines was frequently found in HIV-negative patients. Due to persistent serum creatinine elevation of over 300 µmol/L, renal biopsy was also done and revealed similar fungal elements. With these findings, a diagnosis of disseminated histoplasmosis was made. After a month of treatment with oral itraconazole, there was marked improvement of the patient’s skin lesions. Conclusion This case highlights the importance of recognizing cutaneous manifestations and maintaining a high index of suspicion for histoplasmosis in HIV-seronegative patients.
systemic fungal infections ; disseminated histoplasmosis ; itraconazole

Humans ; Antifungal Agents/therapeutic use* ; Consensus ; Hematopoietic Stem Cell Transplantation ; Invasive Fungal Infections/drug therapy*

This article reports two cases of children with B-cell acute lymphoblastic leukemia (B-ALL) complicated by invasive fungal disease (IFD) who received bridging treatment using blinatumomab. Case 1 was a 4-month-old female infant who experienced recurrent high fever and limb weakness during chemotherapy. Blood culture was negative, and next-generation sequencing (NGS) of peripheral blood, bronchoalveolar lavage fluid, and cerebrospinal fluid were all negative. Chest CT and cranial MRI revealed obvious infection foci. Case 2 was a 2-year-old male patient who experienced recurrent high fever with multiple inflammatory masses during chemotherapy. Candida tropicalis was detected in peripheral blood and abscess fluid using NGS, while blood culture and imaging examinations showed no obvious abnormalities. After antifungal and blinatumomab therapy, both cases showed significant improvement in symptoms, signs, and imaging, and B-ALL remained in continuous remission. The report indicates that bridging treatment with blinatumomab in children with B-ALL complicated by IFD can rebuild the immune system and control the underlying disease in the presence of immunosuppression and severe fungal infection.
Child, Preschool ; Female ; Humans ; Infant ; Male ; Antibodies, Bispecific/therapeutic use* ; Invasive Fungal Infections/drug therapy* ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Remission Induction

Central nervous system (CNS) fungal infections are challenging and difficult to diagnose and treat. This article introduces the high risk factors, pathogen spectrum and laboratory indicators that cause CNS fungal infection. As patients with CNS fungal infections are often accompanied by immunodeficiency, it is especially necessary for clinical early detection, early prevention, and early diagnosis, and timely and effective implementation of optimized diagnosis and treatment programs to prevent further deterioration of the disease.
Central Nervous System ; Central Nervous System Fungal Infections/microbiology* ; Central Nervous System Infections ; Fungi ; Humans ; Risk Factors

Child ; Humans ; Invasive Fungal Infections/diagnosis* ; Lung ; Lung Diseases, Fungal/diagnosis*

Child ; Consensus ; Humans ; Invasive Fungal Infections/diagnosis* ; Lung Diseases, Fungal