A 73-year-old gentleman, known patient of chronic obstructive pulmonary disease (COPD), on tablet prednisolone 5 mg for the past one month (after a recent tapering from 30 mg/day) and inhaled salmeterol with fluticasone 25/250 mcg for almost 3 years. He presented with gradually worsening shortness of breath for one week in the emergency room. He had mucoid sputum production but no fever. On presentation, he had SaO2 of 88 % on room air, with low pressures of 100/60 mmHg, no fever, and a pulse rate of 90/min. He also had bilateral crepitations associated with a wheeze. Chest X-ray and CT chest (Fig. 2, Fig. 3 respectively) showed infiltrates and cavity formation. The total leucocyte count on presentation was 18.2 x 109/L. The patient was started empirically on piperacillin/tazobactam and vancomycin. Later, therapy was switched to deoxycholate amphotericin B, and vancomycin was continued according to his culture which grew MRSA, Aspergillus flavus, and Syncephalastrum species. Both A. flavus and Syncephalastrum spp. were identified on gross and microscopic morphology. Identification to genus level was performed for Syncephalastrum spp. as speciation was not possible with available laboratory capacity.
Serum Beta D glucan level performed on day 5 of admission was 62.14 pg/mL, where levels <60 pg/ml were considered negative, 60-80 pg/ml borderline, and >80 pg/ml as positive as per manufacturer [Fungitell (Cape Cod, USA)]. Serum Aspergillus galactomannan index [Platiella (Biorad, France)] sent on the same day was 0.26, where a single value of >0.7 or two consecutive samples with a value of >0.5 were considered positive while a value <0.5 was deemed negative. The patient's creatinine clearance declined to 27 mL/min after 7 days of therapy so doses were adjusted by reducing deoxycholate amphotericin B to 0.8 mg/kg/day from 1 mg/kg/day and trough levels for vancomycin were maintained between 10-20 mg/L. After 8 days of therapy on adjusted doses, the patient suddenly developed tachypnea, hypoxia, and hypotension. CT chest showed empyema so emergency video-assisted thoracic surgery (VATS) with decortication was performed. Chest tubes were also placed. Histopathology of pleural tissue performed showed moderate acute and chronic inflammatory cells with no evidence of granuloma formation or malignancy in the available material. Although gram stain and PAF were not performed on paraffin-embedded tissue sections, the sample was also sent to Microbiology for smear and culture. Gram stain of the tissue performed showed only gram positive cocci and cultures grew MRSA. No fungal culture was sent at that time. Acid-fast stain, GeneXpert MTB/RIF, and mycobacterial cultures were later reported negative. The patient received vancomycin and deoxycholate amphotericin B for MRSA and Syncephalastrum pneumonia for two weeks. He improved clinically after the surgery and was discharged after 44 days of stay on oral voriconazole as subsequent cultures grew Aspergillus flavus. Vancomycin was switched to oral linezolid with an early follow-up. His chest X-ray improved (Fig. 4) on day 50 of therapy. The patient was advised regular follow-ups. He eventually got better after 6 weeks of outpatient therapy. He was treated for total twelve weeks (including both in- and out-patient duration).
The diagnosis was made in both cases after the sputum culture reports were finalized, but at the initial presentation the differential diagnosis, keeping in view the immune status and recent hospitalization, included viral pneumonia, atypical and multi drug-resistant bacterial pneumonia, fungal pneumonia as with Pneumocystis jiroveci, and primary disease progression. In both cases, diagnosis of co-infection with MRSA and Syncephalastrum was considered.
Both cases were treated with deoxycholate amphotericin B, case 1 for 10 days, and case 2 for two weeks. In both cases, deoxycholate amphotericin led to acute kidney injury. However, in case 2, follow-up sputum cultures were sent 26 days after the the initial positive culture which came out negative for fungi. Due to limited data present and unavailability of management guidelines, it is unclear whether the negative culture report depicted that two weeks were sufficient enough for treatment or that the pathogen was a contaminant. A third sputum sample for culture sent at 34 days grew Aspergillus flavus, so voriconazole alone was continued for the next 6 weeks.