Case Report: Introduction: Pseudomembranous Aspergillus Tracheobronchitis (PMAT) is an uncommon manifestation of invasive pulmonary aspergillosis (IPA). Patients are typically immunocompromised although sporadic cases have been reported in previously immunocompetent individuals.1Aspergillus flavus is the second most frequent Aspergillus species causing bronchopulmonary disease and isolates typically display MICs to amphotericin B (amB) which are two-fold dilution steps higher than A.fumigatus.2 Although the clinical significance of in vitro antifungal susceptibility is debated, there is evidence to suggest that A. flavus isolates demonstrating resistance to amB are associated with increased mortality.3 We present two cases of A. flavus PMAT with raised MICs to amB and contrasting host risk-factors. Methods: Susceptibility testing was performed using E-test on RPMI agar and confirmed at a reference laboratory using brothmicrodilution in accordance with CLSI methodology. As no species-specific breakpoints have been established for A. flavus, resistance was defined as ≥2mg/L based on expected MIC ranges.3 Results: Patient 1: A 39-year-old male was admitted for an Allogeneic Haematopoetic Stem Cell Transplant for Acute Lymphoblastic Leukaemia. Post-transplant, his medications included prophylactic liposomal amB. On day 4, he became febrile with an undetectable neutrophil count. Therapeutic doses of liposomal amB were subsequently added due to persistent fevers. Chest CT showed bronchial narrowing suggestive of mucous plugging and bronchoscopy revealed pseudomembranous tracheobronchitis. Bronchoalveolar-lavage (BAL) cultured A. flavus with an MIC to amB of 4.0mg/L. His antifungal regimen was changed to IV voriconazole and caspofungin. He required admission to ICU due to respiratory failure but died at 31 days post-transplant. Patient 2: A 51-year-old previously immunocompetent male presented to hospital with fevers and progressive shortness of breath. Chest X-ray showed patchy infiltrates and he was commenced IV co-amoxiclav, clarithromycin and oseltamivir. By day 2, he required admission to ICU due to respiratory failure. A nasopharyngeal aspirate PCR returned positive for Influenza A RNA and IV hydrocortisone was added as an adjunct to his antiviral therapy. Bronchoscopy showed a pseudomembranous tracheobronchitis and brushings cultured A.flavus with an MIC of 2.0mg/L to amB. He received dual antifungal therapy with IV voriconazole and amphotericin B but died at 31 days post admission.
Conclusion: These cases contrast a neutropenic patient with classical risk-factors for IPA with a patient who was not immunocompromised but was diagnosed with PMAT following Influenza infection. Diagnosis may be delayed by the absence of clearly distinguishable symptoms, laboratory parameters or imaging findings, and cases may be refractory to antifungal therapy. Our experience is consistent with evidence demonstrating poor outcomes in patients with A.flavus infections with invitro resistance to amB, and underline the importance of performing susceptibility testing to guide antifungal therapy. References: 1. Khalid S et al. Pseudomembranous aspergillar tracheobronchitis in a non-neutropenic critically ill patient in the intensive care unit. J Community Hosp Intern Med Perspect. March 2017p.43-45 2. Van Der Linden, J. W.M et al. Aspergillus species intrinsically resistant to antifungal agents. Medical Mycology,Vol.49, Issue Supplement_1, April 2011,p.S82–S89 3. Inès Hadrich et al. Amphotericin B in vitro resistance is associated with fatal Aspergillus flavus infection, Medical Mycology, Vol.50, Issue 8, November 2012,p829–834
Full conference title:
- TIMM (2019)