Scedosporium apiospermum and Lomentospora prolificans in lung transplant patients – A single center experience over 24 years

Abstract

Introduction: Scedosporium apiospermum and Lomentospora prolificans (Scedosporium/ Lomentospora) species are emerging, multi-resistant pathogens that cause life-threatening illnesses among lung transplant (LTx) recipients. The current epidemiology and management in LTx are unknown. Methods:We performed a retrospective single center audit of all sputum/bronchoscopy samples for Scedosporium/Lomentospora species in LTx patients over a 24-year period . Patients were diagnosed as colonized or with invasive fungal disease.Results: From a cohort of 962 LTx recipients, 30 patients (3.1%) cultured Scedosporium/ Lomentospora (1.2%, 1.9%, respectively). There were no isolates from 1995 to 2013, with multiple yearly isolates thereafter. Nineteen (63%) cases were classified as IFD, and 11 (37%) as colonization. The median time to first culture from transplantation was 929 days (Interquartile-range [IQR] 263-2960). Most patients (63%) had received antifungals prior to the first positive culture of Scedosporium/Lomentospora for other fungal infection. The most common antifungal used for treatment of Scedosporium/ Lomentospora was posaconazole (n = 16; 53%). Median duration of therapy was 364 days . Treatment was associated with improved lung function over 6 months (median FEV1 increased from 1.3L[IQR 0.9-1.8L] to 1.8L[IQR 1.1-2.3] P = .05). Six patients cultured Scedosporium/Lomentospora prior to transplantation, and no survival disadvantage was seen as compared to our whole LTx cohort (P = .8). Conclusion:Our single center 24-year experience suggests that the incidence of Scedosporium/Lomentospora is increasing. Scedosporium/Lomentospora is typically isolated several years after LTx, and requires prolonged anti-fungal treatment that is usually associated with improved in lung function. Culture of Scedosporium/ Lomentospora prior to LTx did not pose a survival disadvantage. Further surveillance is required to fully characterize implications of these organisms for LTx recipients.

Lomentospora prolificans: An Emerging Opportunistic Fungal Pathogen

“…Distinguishing between colonization and infection can be difficult [ 1 ]. Colonization is defined as the presence of fungus or fungal elements in respiratory secretions without symptoms and in the absence of radiological or endobronchial changes [ 48 ]. Colonization has been studied in detail in lung transplant recipients and patients with cystic fibrosis.…”

“…Structural changes in the airways, long-term immunosuppression, and previous exposure to antifungal agents contribute to the higher prevalence of L. prolificans in this group of patients [ 48 , 49 , 50 ]. It is worth noting that L. prolificans colonization constituted a contraindication to lung transplantation in several centers [ 51 ], while in a more recent study, colonization was not associated with worse survival rates [ 48 ]. Symptoms of respiratory infection include cough, dyspnea, fever and pleuritic chest pain [ 52 ].…”

Management of Multidrug Resistant Infections in Lung Transplant Recipients with Cystic Fibrosis

“…prolificans —formerly known as S. prolificans ) are reported in up to 4% of CF patients, and multiple single-center studies demonstrate similar rates in CF-LTx patients. 80 , 85 S. apiospermum/L. prolificans are intrinsically multiresistant pathogens that often require complex surgical debridement and prolonged multidrug regimens with significant morbidity/mortality.…”

“…prolificans are intrinsically multiresistant pathogens that often require complex surgical debridement and prolonged multidrug regimens with significant morbidity/mortality. 85 , 86 Treatments for these fungi are based on expert opinion and retrospective data. S. apiospermum is treated either with voriconazole monotherapy, or in conjunction with terbinafine.…”

“… 92 Subsequently, two recent meta-analyses reveal no difference in the odds of fungal infection with universal prophylaxis compared to no prophylaxis following LTx. 93 , 94 Long-term exposure to antifungal medication has been reported as the major risk factor in the emergence of multiresistant fungal infections post-LTx 85 and the question remains as to whether universal prophylaxis risks breeding increased resistance to first-line antifungal medication without a mortality benefit.…”