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<title>Abstract</title> <p> Background Fungal empyema is a rare condition associated with high mortality, due to inadequate pleural drug penetration and intrinsic antifungal resistance. In patients with nephrotic syndrome, the combination of hypoalbuminaemia, lymphopenia, and corticosteroid use causes both quantitative and qualitative immune deficits, leaving them vulnerable to opportunistic pathogens. Case presentation A 70-year-old man with nephrotic syndrome on prednisone and a documented sulphonamide allergy presented with spontaneous pneumothorax and was treated with closed thoracic drainage and empirical antibiotics. Bronchoalveolar lavage fluid grew Acinetobacter baumannii and Aspergillus fumigatus; his condition improved after directed therapy, and he was discharged with an indwelling pleural catheter. He was readmitted with a dislodged catheter, and pleural fluid cultures grew Microascus gracilis with high minimum inhibitory concentrations to multiple antifungals; intravenous caspofungin and oral posaconazole were started. Over the next two weeks he developed progressive pneumonia with type 1 respiratory failure, and metagenomic sequencing of bronchoalveolar lavage fluid revealed Pneumocystis jirovecii and cytomegalovirus co-infection. Because of his sulphonamide allergy, he received clindamycin and primaquine for PJP and ganciclovir for CMV, together with adjunctive thymosin α1 and intravenous immunoglobulin. Serial flow cytometry showed a marked decline in CD4 <sup>+</sup> PD-1 <sup>+</sup> T cells from 86.6% to 14.2% in blood, coinciding with clinical and microbiological recovery. He was discharged on terbinafine and posaconazole, and follow-up CT at six months showed complete resolution of the right upper lobe lesion with no pneumothorax or pleural effusion. Conclusion The patient's immunosuppressive status and inappropriate management of the IPC likely played key roles in the pleural seeding of M. gracilis. BALF mNGS is warranted for glucocorticoid-treated patients with progressive pneumonia, as it can identify PJP and CMV co-infection.The sequential antifungal regimen of caspofungin plus posaconazole, followed by terbinafine plus posaconazole, resulted in sustained microbiological clearance. Serial CD4 <sup>+</sup> PD-1 <sup>+</sup> profiling may serve as a bedside marker of immune recovery during adjunctive immunomodulation. Clinicians and microbiologists should remain alert to the possibility of this infection in immunocompromised hosts at risk for opportunistic infections, and should consider using mNGS alongside immune profiling to guide targeted therapy. </p>

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pleural posaconazole patients immune fluid

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