Introduction
Pulmonary talaromycosis, caused by Talaromyces marneffei, is increasingly recognized beyond traditional Southeast Asian endemic regions and among HIV-negative patients. This case report from Shandong Province details a 50-year-old male welder with rapid progression to acute respiratory failure (ARF) without HIV infection, emphasizing diagnostic hurdles, imaging findings, and an integrated antifungal approach that led to recovery.
Clinical Presentation and Initial Management
The patient, a previously healthy 50-year-old man from Zibo, presented with a 15-day history of fever, chills, night sweats, cough, headache, sore throat, and myalgias. Chest imaging showed bilateral diffuse lesions with pleural effusions. Laboratory tests revealed leukocytosis with neutrophilia and markedly elevated CRP, yet HIV testing was negative. Despite broad-spectrum antibiotics and supportive care, his condition worsened, developing significant dyspnea and hypoxemia (oxygenation index 203 mmHg on FiO2 33%).
CT imaging demonstrated multiple diffuse hyperdensities in both lungs with bilateral effusions, compatible with a severe infectious process. Routine testing for common pathogens (including TB, influenza, RSV, and bacterial cultures) yielded negative results, prompting bronchoscopy and lung biopsy to elucidate the etiology.
Diagnostic Challenge and Key Findings
Bronchoscopy with BAL and biopsy was performed. Routine bacterial and fungal cultures, TB-DNA, GM testing, and metagenomic NGS of BAL fluid were negative, while histopathology of the biopsy did not initially reveal a definitive pathogen. A sputum fungal culture on day 11 grew Talaromyces marneffei, establishing the diagnosis of pulmonary talaromycosis. Notably, NGS had not detected T. marneffei in BAL or tissue samples, a discrepancy discussed below.
Eligibility for mNGS-based diagnosis remains imperfect. Nitpicking the negative mNGS result, clinicians recognized that mNGS can fail to detect intracellular fungi like T. marneffei, especially with low organism load or sample handling delays. Given the epidemiologic history (prior residence in an endemic area) and the imaging pattern, the team judged pulmonary talaromycosis as the leading diagnosis pending culture confirmation.
Treatment Strategy
Initial empiric therapy with moxifloxacin and oseltamivir did not improve the patient’s status. After confirming T. marneffei from sputum culture and with worsening respiratory failure, the team initiated antifungal therapy using a two-drug strategy due to drug availability and rapid clinical deterioration.
Voriconazole was started at a loading dose of 6 mg/kg every 12 hours for the first day, followed by 4 mg/kg every 12 hours. Because amphotericin B and itraconazole were not readily available, amphotericin B was introduced on day 3 with a cautious ramp, starting at 1 mg/day and increasing to 25 mg/day over the first week, while continuing voriconazole. After seven days of combination therapy, chest CT showed improvement. Voriconazole was then discontinued, and amphotericin B maintenance followed by itraconazole 0.2 g twice daily was continued. The total antifungal course spanned 13 days for amphotericin B-based induction, with a transition to itraconazole for consolidation and maintenance.
The patient’s respiratory distress gradually improved, enabling discharge on the second day of itraconazole therapy. A three-week follow-up CT demonstrated significant radiographic improvement, corroborating clinical recovery.
Discussion: Why This Case Matters
HIV-negative talaromycosis can present as a localized pulmonary disease with ARF, challenging clinicians in non-endemic regions. The case highlights several teaching points:
- Pulmonary talaromycosis should be considered in severe pneumonia with negative routine etiologies, especially in patients with exposure history or residence in endemic areas.
- Imaging often shows diffuse bilateral lesions, nodules, and effusions, but findings are nonspecific; histopathology and culture remain gold standards.
- mNGS can yield false negatives for T. marneffei due to intracellular localization and sample factors; culture and targeted testing remain essential.
- In HIV-negative patients, treatment strategies are extrapolated from HIV-positive data; amphotericin B induction followed by itraconazole remains a cornerstone, with voriconazole as a viable alternative or adjunct when amphotericin B access is limited.
Outcome and Follow-Up
The patient recovered with respiratory support and antifungal therapy, was discharged on itraconazole, and remained relapse-free at a three-year follow-up by telephone, returning to full work capacity. The case underscores the importance of multidisciplinary collaboration, timely diagnosis, and context-aware treatment decisions in managing talaromycosis outside classic endemic regions.
Conclusion
This report documents a rare instance of HIV-negative pulmonary talaromycosis presenting with acute respiratory failure in northern China. It emphasizes that clinicians should maintain vigilance for talaromycosis in patients with compatible imaging and exposure history, even in non-endemic areas, and that culture remains indispensable for definitive diagnosis. A flexible antifungal strategy, balancing drug availability and patient status, can lead to favorable outcomes in this challenging infection.
