Risk factors for invasive fungal disease in heart transplant recipients

Abstract

BACKGROUND Heart transplant (HT) recipients are at risk for invasive fungal disease (IFD), a morbid and potentially fatal complication. METHODS We performed a retrospective cohort study to evaluate the incidence and risk factors for IFD in HT recipients from 1995 to 2012 at a single center. IFD cases were classified as proven or probable IFD according to current consensus definitions of the European Organization for Research and Treatment of Cancer/Mycoses Study Group. We calculated IFD incidence rates and used Cox proportional hazards models to determine IFD risk factors. RESULTS Three hundred sixty patients underwent HT during the study period. The most common indications were dilated (39%) and ischemic (37%) cardiomyopathy. There were 23 (6.4%) cases of proven (21) or probable (2) IFD, for a cumulative incidence rate of 1.23 per 100 person-years (95% CI 0.78 to 1.84). Candida (11) and Aspergillus (5) were the most common etiologic fungi. Thirteen cases (56%) occurred within 3 months of HT, with a 3-month incidence of 3.8% (95% CI 2.2 to 6.4). Delayed chest closure (HR 3.3, 95% CI 1.4 to 7.6, p = 0.01) and the addition of OKT3, anti-thymocyte globulin or daclizumab to standard corticosteroid induction therapy (HR 2.7, 95% CI 1.1 to 6.2, p = 0.02) were independently associated with an increased risk of IFD. CONCLUSIONS IFD incidence was greatest within the first 3 months post-HT, largely reflecting early surgical-site and nosocomial Candida and Aspergillus infections. Patients receiving additional induction immunosuppression or delayed chest closure were at increased risk for IFD. Peri-transplant anti-fungal prophylaxis should be considered in this subset of HT recipients.

Disseminated mucormycosis masquerading as rejection early after orthotopic heart transplantation

“…In 2011, the TRANSNET investigators reported a 12‐month cumulative incidence of 0.07% in SOT, compared with 0.29% in hematopoietic stem cell transplantation, across 23 institutions . In the two largest single‐center reviews of mucormycosis in SOT, invasive fungal infections occurred in 6%‐8% of patients post heart transplant, with the vast majority being Candida and Aspergillus . In the Stanford experience, only four cases of zygomycetes occurred among 108 fungal infections …”

“…Invasive fungal infections are reported to occur in 6%‐8% of patients post heart transplantation and are associated with significant morbidity and mortality . The majority of fungal infections following heart transplantation are caused by Candida and Aspergillus species .…”

Invasive fungal infections in paediatric patients treated with macromolecular immunomodulators other than tumour necrosis alpha inhibitors

“…21 A retrospective cohort study in heart transplant recipients found that utilisation of muromonab was associated with an increased risk of IFI (HR 2.68; 95% CI: 1.16-6.2), with IFIs being attributed mainly to Candida and secondarily, to Aspergillus. 22 In contrast, a randomised multicentre trial on adults with steroid-resistant acute GVHD revealed that muromonab use was correlated with a decreased (P=.059) incidence of IFIs as compared to high-dose steroids alone. 23 As regards to paediatric use (Table 1), a prospective, multicentre register study of children who underwent heart transplantation showed that patients who received induction had a lower risk for early fungal infections (HR 0.6; 91% CI: 0.40-0.91; P=.016).…”

“…In an uncontrolled study of infectious complications after muromonab induction in 122 adult liver transplant procedures, 19 IFIs (15.6%) were recorded, including 16 due to Candida spp, two cases of cryptococcosis and one case of aspergillosis . A retrospective cohort study in heart transplant recipients found that utilisation of muromonab was associated with an increased risk of IFI (HR 2.68; 95% CI: 1.16‐6.2), with IFIs being attributed mainly to Candida and secondarily, to Aspergillus . In contrast, a randomised multicentre trial on adults with steroid‐resistant acute GVHD revealed that muromonab use was correlated with a decreased ( P =.059) incidence of IFIs as compared to high‐dose steroids alone …”

Un nouveau concept

“…Ces différents agents fongiques sont susceptibles d'augmenter la mortalité et la morbidité des patients [8][9][10] ; (3) les traitements antibiotiques pourraient faciliter le développement des infections fongiques pulmonaires chez ces patients. De même, l'utilisation de traitements immunosuppresseurs (corticosté-roïdes au long cours ou autres) favorise le développement d'infections fongiques invasives et graves, en particulier dans un contexte de transplantation, mais éga-lement sur fond de pathologie chronique telle que la BPCO où des cas d'aspergillose semi-invasive ont été rapportés [11][12][13] ; (4) enfin, les champignons sont capables d'interagir notamment avec des bactéries [14]. Ils peuvent aussi former des biofilms et induire une résistance aux traitements anti-infectieux.…”