Pediatr Transplantation 2014: 18: 393–397

© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Pediatric Transplantation DOI: 10.1111/petr.12263

Antifungal prophylaxis in pediatric lung transplantation: An international multicenter survey Mead L, Danziger-Isakov LA, Michaels MG, Goldfarb S, Glanville AR, Benden C and International Pediatric Lung Transplant Collaborative (IPLTC). Antifungal prophylaxis in pediatric lung transplantation: An international multi-center survey.

Lee Mead1, Lara A. Danziger-Isakov2, Marian G. Michaels3, Samuel Goldfarb4, Allan R. Glanville1, Christian Benden5 and International Pediatric Lung Transplant Collaborative (IPLTC)

Abstract: Fungal infections create a significant risk to pediatric lung transplant recipients. However, no international consensus guidelines exist for fungal infection prevention strategies. It was the aim to describe the current strategies of antifungal prophylaxis in pediatric lung transplant centers. A self-administered, web-based survey on current practices to prevent fungal infection was circulated to centers within the IPLTC. Twenty-one (88%) IPLTC centers participated, predominantly from Europe and the US. More than 50% of respondents perform adult and pediatric lung transplant operations. Twenty-four percent use universal prophylaxis, 28% give prophylaxis to all patients but stratify the antifungal coverage based on pretransplant risk, and 48% target prophylaxis to only the children with CF or pretransplantation fungal colonization. Commonly, centers aim to target Aspergillus and Candida infection. Monotherapy with either voriconazole or inhaled amphotericin B is used in the majority of centers. Institutions utilize prophylactic therapy for variable time periods (40% 3–6 months; 30% ≥12 months). Alternative drugs were prescribed for lack of tolerance, toxicity, or positive surveillance culture. TDM (itraconazole/voriconazole) was used in 86% of centers. The survey revealed a wide range of antifungal prophylaxis strategies as current international practice in pediatric lung transplant recipients.

1

Lung transplantation in children is an accepted therapeutic option, offering carefully selected children a survival benefit (1). Recently, a significant improvement has been made with regard to post-transplant results (2). However, complications after lung transplantation are frequent, most prominently including the development of chronic lung allograft dysfunction and infections. The most common underlying diagnosis for pediatric lung transplantation is end-stage CF lung disease; many of these children are chronically colonized with fungal pathogens. Thus, pretransplant chronic fungal colonization is of importance. Prior studies in

Abbreviations: CF, cystic fibrosis; IPLTC, International Pediatric Lung Transplant Collaborative; ISHLT, International Society for Heart and Lung Transplantation; TDM, therapeutic drug monitoring.

St Vincent’s Hospital, Sydney, NSW, Australia, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA, 3Children’s Hospital of Pittsburgh of UPMC, PA, USA, 4Children’s Hospital of Philadelphia, PA, USA, 5University Hospital Zurich, Zurich, Switzerland 2

Key words: lung transplantation – pediatrics – children – antifungal prophylaxis Christian Benden, MD, FCCP, Medical Director of Lung Transplantation, Division of Pulmonary Medicine, University Hospital Zurich, Raemistr 100, CH-8091 Zurich, Switzerland Tel.: +41 44 255 111 Fax: +41 44 255 8997 E-mail: [email protected] Accepted for publication 26 February 2014

pediatric lung transplant recipients revealed that pretransplant fungal colonization was more common in patients with CF. Rates of post-transplant pulmonary fungal infections are higher in recipients with pretransplant colonization compared to those not colonized (3), and pulmonary fungal infections are associated with a decreased one-yr survival in pediatric lung transplant recipients (4). Despite the significant risk that fungal infections pose to children undergoing lung transplantation, there are currently no internationally agreed-upon guidelines for antifungal prophylaxis in pediatric lung transplantation. The aim of the study was to describe the current strategies of antifungal prophylaxis in pediatric lung transplant centers. The information obtained provides the background information required to develop standardized and internationally agreed-upon protocols. 393

Mead et al. Methods In 2012, clinicians at each of the 24 centers within the IPLTC were invited by email to participate in a self-administered, web-based survey on the current practice of pediatric antifungal prophylaxis at their center (www.rationalsurvey.com). The email invitation included the web link and online password for the web-based survey. The survey included a combination of multiplechoice and free-text answers. Centers in Australia, Europe, and North America collaborating within the IPLTC currently perform >90% of lung transplant operations each year in children 20 adult lung transplants yearly. The primary prevention strategies were not associated with the number of transplants performed at each center. Universal prophylaxis

Twenty-four percent of centers (three European, two North American) reported using universal prophylaxis for all pediatric lung transplant recipients. Rationales documented included increased risk of invasive fungal infection in pediatric lung transplantation (4), desire to standardize regimens (2), and maximization of cost–benefit ratios (1). All centers target Aspergillus infections while two additionally target Candida species. Duration of therapy varied widely from 3–6 months ≥12 months ≤3 months ≤3 months >6–12 months

Antifungal prophylaxis in lung transplantation Risk-stratified universal prophylaxis

Six centers (29%; three North American, two European, one Australian) reported prophylaxis to all recipients with adjustment of the agent or duration based on pretransplant risk assessment. Standardizing the approach (4), fear of posttransplant fungal infections (6) and maximizing the cost–benefit ratio (1) were the reported rationales for prevention strategy choice. All targeted Aspergillus infections; non-Aspergillus molds (2), Candida species (4) and histoplasmosis (1) were also aims of prophylaxis in this group. Higher and lower risks were defined by each reporting center (Table 2). Duration of therapy varied widely from one month to more than 12 months, while the antifungal agents employed were also variable with only one center using combination therapy (Table 2). Five centers employed TDM of itraconazole/voriconazole at least once during prophylaxis. Prophylaxis with the centers’ second-line regimens was initiated secondary to positive cultures (5), intolerability including photosensitivity (5), drug interactions (1), or for insurance issues (1). Targeted prophylaxis

Ten centers (five North American, four European, one Australian) report using targeted prophylaxis for either patients with CF (n = 4) or those with pretransplant colonization (n = 9). The majority of centers initiate prophylaxis immediately after transplant, while four centers consider initiation of prophylaxis in the pretransplant period for known colonizations. All centers using targeted prophylaxis target Aspergillus with other considerations being non-Aspergillus mold (5), Candida species (3), Zygomycetes (2), Cryptococcus (1), and Scedosporium (1) species. Voriconazole monotherapy use was reported by the majority of centers (7) with others using

itraconazole with or without inhaled amphotericin B; duration of prophylaxis ranged from

Antifungal prophylaxis in pediatric lung transplantation: an international multicenter survey.

Fungal infections create a significant risk to pediatric lung transplant recipients. However, no international consensus guidelines exist for fungal i...
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