Elsevier

Transplantation Proceedings

Volume 43, Issue 6, July–August 2011, Pages 2463-2471
Transplantation Proceedings

Fungal infection
Italian Guidelines for Diagnosis, Prevention, and Treatment of Invasive Fungal Infections in Solid Organ Transplant Recipients

https://doi.org/10.1016/j.transproceed.2011.06.020Get rights and content

Abstract

Use of various induction regimens, of novel immunosuppressive agents, and of newer prophylactic strategies continues to change the pattern of infections among solid organ transplant (SOT) recipients. Although invasive fungal infections (IFIs) occur at a lower incidence than bacterial and viral infections in this population, they remain a major cause of morbidity and mortality worldwide. In March 2008, a panel of Italian experts on fungal infections and organ transplantation convened in Castel Gandolfo (Rome) to develop consensus guidelines for the diagnosis, prevention, and treatment of IFIs among SOT recipients. We discussed the definitions, microbiological and radiological diagnoses, prophylaxis, empirical treatment, and therapy of established disease. Throughout the consensus document, recommendations as clinical guidelines were rated according to the standard scoring system of the Infectious Diseases Society of America and the United Stated Public Health Service.

Section snippets

Definitions

In 2002, a consensus group of the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group (EORTC) and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (MSG) published definitions for IFIs in clinical and epidemiological research. The original definitions were restricted to patients with cancer and to recipients of hematopoietic stem cell transplantations. However, IFIs are known to affect other populations. For this

Microbiological Diagnosis

An early, specific microbiological diagnosis is essential to guide treatment of IFIs and to minimize exposure to nonessential antimicrobial agents. Invasive diagnostic procedures are often required for an accurate, timely diagnosis.2 Currently available laboratory methods to diagnose IFIs involve traditional (microscopic direct test, culture with identification genus and species, susceptibility tests), histopathologic, immunologic (β-1-3-D-Glucan, galactomannan test, and glucuronoxylomannan),

Microbiological Screening of Organ Donors

Fungal infections have been transmitted via organ and tissue allografts. Pretransplantation screening is designed to prevent serious posttransplantation infections, either by excluding a donor or by defining the need for specific antimicrobial therapy after grafting.1, 26 The first step in screening donors to detect unknown infections is a thorough medical history and physical examination (by the surgical team as well) during the procurement process (AII; Table 1). The initial evaluation,

Radiological Diagnosis

The challenge of fungal infections supports a rapid diagnostic approach. The clinical suspicion for these pathogens should be investigated by imaging studies, biopsies, and cultures. The radiological procedures may include ultrasound or computed tomography (CT) scan or magnetic resonance imaging (MRI) to highlight suspicious lesions for guided biopsies. The radiological appearance of Aspergillus or other mould infections of the central nervous system (CNS) is variable; it depends upon the

Treatment Strategies

Transplant recipients are complex and fragile. Successful treatment of an established fungal infection requires an early diagnosis, aggressive debridement when possible, reduction in immunosuppression, and fungicidal therapy. Amphotericin B (AmB) deoxycholate has been regarded as the gold standard for therapy, but its administration is often associated with renal toxicity and infusion-related side effects. The lipid-associated amphotericin compounds, mainly the liposomal formulation, have the

Prophylaxis

The use and choice of agents for antifungal prophylaxis for SOT recipients remains controversial. Large randomized trials are lacking; single-center experiences have insufficient numbers of patients. Given these circumstances, the ability to develop evidence-based recommendations for antifungal prophylaxis in SOT recipients is extremely limited.

Pre-Emptive Treatment

The low frequency of IFIs in patients undergoing solid organ transplantation, and the absence of reliable surrogate markers for a prompt diagnosis, follow-up, and monitoring of response to therapy are the major limiting factors for pre-emptive treatment in this patient population (CIII; Table 1).

Empirical Treatment

Criteria for starting empirical antifungal therapy in non-neutropenic patients remain poorly defined. Early initiation of antifungal therapy may reduce morbidity, mortality, and length of stay in the hospital in SOT recipients, but the widespread use of these agents must be balanced against their toxicities, costs, and emergence of resistance. Empirical antifungal therapy should be considered for critically ill patients with risk factors for IFIs and no other known cause of fever. It should be

Treatment of an Established Infection

There are no randomized studies of IFI treatment among SOT recipients. Thus, therapeutic approaches to these patients are generally based on large randomized studies in a heterogeneous group of patients that include organ transplant recipients as a small component. Treatment of IFI in SOT recipients should be based on the pathogen recovered as well as on the clinical syndrome and site(s) of involvement. Clinicians should become familiar with strategies to optimize efficacy through understanding

Candida Infections

Fluconazole (loading dose of 800 mg [12 mg/kg], then 400 mg [6 mg/kg] daily) remains the standard therapy for SOT recipients with candidemia. It is considered to be the first-line therapy among patients with mild to moderate illness, who are clinically stable, with no recent azole exposure and with infection due to an organism that is likely to be susceptible to fluconazole, eg, C albicans, C parapsilosis, and C tropicalis (AIII; Table 1). The echinocandin caspofungin (loading dose of 70 mg,

Aspergillus Infections

Voriconazole (loading dose of 6 mg/kg every 12 hours for 2 doses, then 4 mg/kg every 12 hours) is now regarded to be the drug of choice for primary treatment of IA in all hosts, including SOT recipients, (AI; Table 1), independent of the site of involvement (AIII; Table 1). Voriconazole is formulated as a tablet or as a sulfobutyl-ether cyclodextrin solution for intravenous (IV) administration. The parenteral formulation is recommended for seriously ill patients (AIII; Table 1). Because the

Non-Aspergillus Mold Infections

Infections caused by non-Aspergillus molds have become increasingly common among SOT recipients in the past decade.11, 56 The reasons for this trend are not exactly known. It may be a consequence of the current antifungal prophylaxis or changes in the type and potency of immunosuppression. Nonetheless, these changes are worrisome because many of these fungi are resistant to conventional therapy.

Therapy of zygomycosis involves extensive debridement of necrotic tissue, control of predisposing

Acknowledgments

Editorial assistance was provided by Luca Giacomelli and Siobhan Ward.

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