Fungal infections after lung transplantation
Introduction
Infectious complications after lung transplantation (LT) are frequent as a direct consequence of the use of the aggressive immunosuppression employed in these receptors, as well as the presence of impaired mucociliary clearance, ischemic airway injury, altered alveolar macrophage phagocytic function, and direct communication of the transplanted organ with the enviroment. Moreover, pulmonary infections in LT recipients besides their direct impact on morbidity and mortality have an indirect effect with immunological consequences implicated in the genesis and clinical course of acute and chronic rejection.
Fungal infections (FIs) are associated with a high mortality rate in lung transplant recipients for several reasons: the difficulty of establishing an early diagnosis, the lack of effective treatment for infections by some filamentous fungi, the toxicity and interactions of some antifungal agents with immunosuppressive drugs, the scarce published experience about the use of prophylaxis with antifungal drugs in this setting, and finally, the loss of grafts as the result of reducing immunosupression to cure these infections.
Fungal infection occurs in 15% to 35% of patients after LT, and more than 80% are caused by Candida spp and Aspergillus spp, with an overall mortality rate of nearly 60% [1], [2], [3], [4], [5], [6]. Unusual moulds such as Scedosporium spp are increasingly recognized as important opportunistic pathogens in LT; other moulds such as Zygomycetes and species of Fusarium have less relevant role in LT, but in all cases, their infection is associated with a high rate of dissemination and poor outcome [7], [8]. However, the overall incidence of invasive mycoses in LT has declined over the past decade. This may be related to improved surgical techniques, decreases in the length of operations, units of blood transfused, more effective prophylactic strategies, and refinements in immunosuppressive regimens.
This review highlights changing spectrum of invasive FIs (IFIs), risk factors, antifungal prophylaxis, diagnosis, and treatment after LT.
Section snippets
Risk factors for IFIs
In general, risk factors for invasive mycoses in solid organ transplantation (SOT) are concentrated in specific subpopulations of transplant recipients. Risk factors for Candida infection are well known and usually are related with a complicated postoperative course in the intensive care unit during the early postoperative period (Candida colonization, central vascular lines, broad-spectrum antibiotics, total parenteral nutrition, and hospital length of stay), and they do not differ in LT
Aspergillus spp infection in recipients of LT
Aspergillus is a filamentous fungus with a wide environmental distribution [17]. Aspergillus infections remain among the most significant opportunistic infections after LT. Aspergillus fumigatus, the most pathogenic species, produces the most infections; however, Aspergillus flavus, Aspergillus terreus, and Aspergillus niger have been increasingly reported in IFI. Data from the compilation and synthesis of existing studies give a variable incidence of AI of 6% in the published series (range,
Diagnosis
The diagnosis of invasive mycoses in immunosuppressed patients poses significant clinical challenges. In fact neither radiological findings (patchy infiltrates or consolidation) nor respiratory samples have a high specificity. Symptoms of invasive mycoses are nonspecific, and initially, about 30% of cases are asymptomatic. Besides, Aspergillus is cultured from sputum in only 8% to 34%, and from bronchoalveolar lavage fluid (BAL) up to 62% of patients with invasive disease. Moreover, post LT
Prophylaxis
Several prophylactic strategies with antifungal drugs have been reported to result in a decreased incidence and mortality of fungal disease in LT recipients [93], [94], [95]. However, there has not been a uniform approach, data are limited, and besides, there is a considerable variation in antifungal prophylaxis practices among lung transplant centers throughout the world. Most lung transplant programs are using universal antifungal prophylaxis in the postoperative period; about 30% use a
Antifungal therapy and management
AmBd has been the gold standard antifungal therapy for opportunistic FI for more than 4 decades. However, it is associated with undesirable toxicities and is commonly ineffective, predominantly in those patients with advanced immunosuppression. In addition, outcomes of salvage therapy after progression of infection or toxicity after initiation of AmB are extremely poor. For these reasons, antifungal agents with better tolerability and efficacy have been needed without delay. In the last decade,
Immune reconstitution syndrome
Although host immunity is crucial in the eradication of any infection, immunological recovery can also be detrimental and may contribute toward worsening disease expression [118]. The concept of immune reconstitution syndrome (IRS) and its precise diagnosis in the context of opportunistic mycoses remain poorly characterized. Immune reconstitution syndrome is best considered as a collection of localized and systemic inflammatory reactions of varying degrees that have both beneficial and noxious
Conclusion
This review highlights the risk factors and changing spectrum of IFI after LT. Despite the increasing impact of viral infections in LT, FIs still have a main role in LT. In fact, they remain a common cause of morbidity and mortality in the early and late post-transplant periods. Aspergillus spp and Candida spp account for most IFI, but recent epidemiological and clinical studies suggest the emergence of mycelial fungi other than Aspergillus as well as resistant strains of Candida in these
References (121)
- et al.
Aspergillus infections in lung transplant recipients: risk factors and outcome
Clin Microbiol Infect
(2005) - et al.
Aspergillus infections after lung transplantation: clinical differences in type of transplant and implications for management
J Heart Lung Transplant
(2003) - et al.
Zygomycoses in solid organ transplant recipients in a tertiary transplant center and review of the literature
Am J Transplantation
(2006) - et al.
Aspergillus airway colonization and invasive disease after lung transplantation
Chest
(1997) - et al.
Demolition of a hospital building by controlled explosion: the impact on filamentous fungal load in internal and external air
J Hosp Infect
(2002) - et al.
The clinical spectrum of pulmonary aspergillosis
Chest
(2002) - et al.
Aspergillus infection in lung transplant recipients with cystic fibrosis
Chest
(2003) - et al.
Spectrum of Aspergillus infection in lung transplant recipients. Case series and review of the literature
Chest
(2001) - et al.
Voriconazole prophylaxis in lung transplant recipients
Am J Transplant
(2006) - et al.
Infectious complications in pulmonary allograft recipients
Clin Chest Med
(1990)
Infectious complications following isolated lung transplantation
Chest
Infections in lung transplant recipients
Clin Chest Med
Disruption of the aortic anastomosis after heart-lung transplantation
Ann Thorac Surg
Emerging and less common fungal pathogens
Infect Dis Clin North Am
Emerging fungal diseases: the importance of the host
Clin Lab Med
Mucormycoses: an emerging disease?
Clin Microbiol Infect
Invasive zygomycoses: update on pathogenesis, clinical manifestations, and management
Infect Dis Clin North Am
Mucormycoses of the bronchial anastomosis: a case of successful medical treatment and historic review
J Heart Lung Transplant
Successful treatment of disseminated scedosporium infection in 2 lung transplant recipients: review of the literature and recommendations for management
J Heart Lung Transplant
Scedosporium apiospermum fungemia in a lung transplant recipient
Chest
Scedosporium apiospermum (Pseudallescheria boydii) infection in lung transplant recipients
J Heart Lung Transplant
Disseminated Scedosporium apiospermum infection in a cystic fibrosis patient after double-lung transplantation
Heart Lung Transplant
Fusarium, a significant emerging pathogen in patients with hematologic malignancy: ten years' experience at a cancer center and implications for management
Blood
Primary pulmonary involvement of Fusarium solani in a lung transplant recipient
Chest
Successful treatment of Fusarium proliferatum pneumonia with posaconazole in a lung transplant recipient
J Heart Lung Transplant
Clinical and radiological factors associated with pulmonary nodule etiology in organ transplant recipients
Am J Transplant
Prospective assessment of Platelia Aspergillus galactomannan antigen for the diagnosis of invasive aspergillosis in lung transplant recipients
Am J Transplant
Microbiological procedures for diagnosing mycoses and for antifungal susceptibility testing
Enferm Infecc Microbiol Clin
Significant reduction in the number of fungal infections after lung-, heart-lung, and heart transplantation using aerosolized amphotericin B prophylaxis
Transplant Proc
Antifungal prophylaxis during the early postoperative period of lung transplantation. Valencia Lung Transplant Group
Chest
Pulmonary complications of solid organ and hematopoietic stem cell transplantation
Am J Respir Crit Care Med
Current approaches to diagnosis and treatment of invasive aspergillosis
Am J Respir Crit Care Med
Fungal infections in solid organ transplantation
Expert Opin Pharmacother
Infectious complications of lung transplantation
Transpl Infect Dis
Opportunistic mycelial fungal infections in organ transplant recipients: emerging importance of non-Aspergillus mycelial fungi
Clin Infect Dis
Aspergillus infections in transplant recipients
Clin Microbiol Rev
Risk factors for invasive aspergillosis in solid-organ transplant recipients: a case control study
Clin Infect Dis
Aspergillosis in lung transplantation: incidence, risk factors, and prophylactic strategies
Transpl Infect Dis
Pathogenic Aspergillus species recovered from a hospital water system: a 3-year prospective study
Clin Infect Dis
Cryptococcosis in liver and kidney transplant recipients receiving anti-thymocyte globulin or alemtuzumab
Clin Infect Dis
Infectious complications associated with alemtuzumab use for lymphoproliferative disorders
Clin Infect Dis
Fungal infections in transplant recipients
Eur Respir J
Anastomotic infections in lung transplant recipients
Ann Transplant
Late-onset invasive aspergillosis in organ transplant recipients in the current era
Med Mycol
Incidence, clinical characteristics and risk factor late infection in solid organ transplant recipients. Data from RESITRA study group
Am J Transplant
Combination of voriconazole and caspofungin as primary therapy for invasive aspergillosis in solid organ transplant recipients: a prospective. Multicenter, observational study
Transplantation
Infectious complications in heart-lung transplantation. Analysis of 200 episodes
Arch Intern Med
Infection after lung transplantation
Semin Respir Infect
Lung transplantation
Am J Respir Crit Care Med
Infectious complications of lung transplantation. Impact of cystic fibrosis
Am J Respir Crit Care Med
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