Integrated Molecular Diagnostics Unmask Legionella Pneumophila and Fungal Coinfection in an Immunocompromised Host: A Case Study of Precision Antimicrobial Stewardship
Abstract
BACKGROUND: Legionella pneumophila poses significant diagnostic challenges in immunocompromised hosts due to its fastidious growth requirements and nonspecific clinical presentation. Conventional culture methods have limited sensitivity (30-80%), while molecular diagnostics require multi-platform validation to ensure reliability.
CASE DESCRIPTION: A 57-year-old woman with rheumatic heart disease, chronic renal failure, and immunosuppression presented with acute respiratory failure. Initial investigations revealed leukocytosis (19.03×109/L), hyponatremia (127 mmol/L), elevated procalcitonin (42.55 ng/mL), and bilateral pulmonary infiltrates. Bronchoalveolar lavage fluid (BALF) analysis employed three molecular methods: isothermal amplification for screening (positive for L. pneumophila on ICU admission), digital PCR (dPCR, 4,455 copies/mL after 10-fold dilution) reconfirmed L. pneumophila infection, and metagenomic next-generation sequencing (mNGS; 384,661 Legionella reads alongside 3,474 Candida glabrata reads). Subsequent fungal β-D-glucan testing (674.8 pg/mL) and culture validated Candida glabrata coinfection. Antimicrobial therapy from targeted moxifloxacin/azithromycin to co-infection therapy with carbapenem escalated from Imipenem-cilastatin to sulbactam/cefoperazone for suspected gram-negative coinfection and fluconazole escalated to amphotericin B for resistant candidiasis guided by CRP/PCT trends.
CONCLUSION: Integrated molecular diagnostics enable rapid pathogen…
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