Overview
This case report details a 50-year-old male welder from Zibo, Shandong, who developed pulmonary talaromycosis with acute respiratory failure (ARF) despite being HIV-negative. The report highlights diagnostic challenges, treatment decisions in a resource-limited setting, and a positive radiographic response to a sequential antifungal strategy. It also emphasizes the growing recognition of talaromycosis in non-endemic regions and in patients without overt immunosuppression.
Clinical Presentation and Initial Management
The patient presented with a 15-day history of fever, chills, night sweats, cough, headache, sore throat, and myalgias, progressing to severe chest distress. Chest imaging from a local hospital showed bilateral lung lesions. Laboratory data indicated leukocytosis with neutrophilia and markedly elevated CRP, suggesting a strong inflammatory process. Despite empiric antibiotics and supportive care, fever and dyspnea persisted, and the patient developed hypoxemia with an Oxygenation Index of 203 mmHg, signaling ARF.
Key Investigations
- CT scan: diffuse hyperdense lesions with bilateral pleural effusions.
- HIV test: negative; basic labs showed elevated ESR and CRP, mild anemia, and hypoalbuminemia. ANA was weakly positive (1:100).
- Extensive infectious workup: negative for TB, common bacteria, viruses, and fungi in initial assays.
- Bronchoscopy and right-lung biopsy: cultures (bacterial/fungal/TB-DNA) and GM tests were negative; NGS of BAL fluid did not detect T. marneffei. PAS and acid-fast stains were negative on the biopsy material.
Definitive Diagnosis
Day 11 of admission yielded a pivotal finding: sputum fungal culture grew Talaromyces marneffei. This organism is unusual in northern China and even more so in HIV-negative patients. Despite negative mNGS results from BAL fluid and tissue, the culture-confirmed pathogen established the diagnosis of pulmonary talaromycosis with respiratory compromise. The case underscores that mNGS, while powerful, may fail to detect some fungal pathogens due to intracellular localization, low fungal load, or technical delays, reinforcing the importance of complementary culture and histology alongside molecular methods.
Treatment Strategy
Initial management combined moxifloxacin and oseltamivir with nutritional support. As respiratory status deteriorated, the team initiated a staged antifungal approach using voriconazole first due to drug availability and then added amphotericin B once accessible, aiming to balance efficacy with potential toxicity in a patient with ARF.
- Voriconazole: 6 mg/kg IV every 12 hours on day 1, then 4 mg/kg IV every 12 hours.
- amphotericin B: started at 1 mg daily, titrated to 25 mg over a week.
- After stabilization, combination therapy led to radiographic improvement on chest CT, and voriconazole was stopped after four days of combination therapy.
- Itraconazole: 0.2 g twice daily continued after IV therapy for maintenance.
The patient was discharged two days after starting itraconazole, with follow-up CT showing substantial improvement three weeks later. A 3-year telephone follow-up reported ongoing physical activity without relapse.
Discussion and Implications
Acute respiratory failure attributable to localized pulmonary talaromycosis in an HIV-negative patient is rare, particularly in Shandong and other non-endemic regions. This case illustrates several important considerations:
- The need to consider talaromycosis in differential diagnoses for ARF with diffuse pulmonary lesions, even in HIV-negative patients and non-endemic areas.
- The value—and limitations—of mNGS in detecting T. marneffei, highlighting reliance on culture and histology as gold standards in certain contexts.
- Flexibility in antifungal therapy when drug access is limited, including staggered use of voriconazole and amphotericin B, followed by itraconazole maintenance, aligned with current but not uniformly standardized guidelines for HIV-negative talaromycosis.
Conclusion
This case supports heightened clinical suspicion for pulmonary talaromycosis in HIV-negative individuals presenting with ARF and compatible imaging, even in non-endemic regions. Timely culture confirmation and adaptive antifungal therapy can yield favorable outcomes, as demonstrated by this patient’s recovery and durable remission at follow-up.
