key: cord-0914705-55ehw0j9
authors: Kabbani, Dima; Goldraich, Livia; Ross, Heather; Rotstein, Coleman; Husain, Shahid
title: Outbreak of invasive aspergillosis in heart transplant recipients: The role of screening computed tomography scans in asymptomatic patients and universal antifungal prophylaxis
date: 2017-12-26
journal: Transpl Infect Dis
DOI: 10.1111/tid.12808
sha: 02a00e8886d61aa7a24f7a40e01b6b39b4eaf45f
doc_id: 914705
cord_uid: 55ehw0j9

BACKGROUND: Delays in diagnosing pulmonary invasive aspergillosis (IA), a significant cause of morbidity and mortality among heart transplant recipients (HTRs), may impact on successful treatment. The appropriate screening strategy for IA in these patients remains undefined, particularly in the setting of nosocomial outbreaks. We describe our experience employing chest computed tomography (CT) scans as a screening method for IA. In addition, we comment on antimicrobial prophylaxis in HTRs in the setting of an outbreak. METHODS: Screening CT scans of the chest and serum galactomannan (GM) were performed in HTRs during an outbreak that followed the index case of IA. Abnormal CT findings prompted a diagnostic workup. Antimicrobial prophylaxis for new transplants recipients included intravenous micafungin while hospitalized, followed by outpatient inhaled amphotericin B for up to 3 months. RESULTS: During a 10‐month period, five cases of IA were identified among HTRs. Two additional asymptomatic patients were diagnosed with IA among 15 asymptomatic HTRs who underwent screening chest CT scans. Among the five cases of IA in HTRs, two of five (40%) had a partial response and the other three failed voriconazole therapy. Complete response to voriconazole therapy assessed at 12 weeks was achieved in these two asymptomatic HTRs diagnosed via screening CTs. Serum GM was positive only in one of the symptomatic cases. The negative predictive value of CT scans was 100% (95% confidence interval, 71.5%‐100%). CONCLUSIONS: In an outbreak setting, screening CT scans of the chest may aid in early detection of asymptomatic HTRs with IA and improve outcome.

Background: Delays in diagnosing pulmonary invasive aspergillosis (IA), a significant cause of morbidity and mortality among heart transplant recipients (HTRs), may impact on successful treatment. The appropriate screening strategy for IA in these patients remains undefined, particularly in the setting of nosocomial outbreaks. We describe our experience employing chest computed tomography (CT) scans as a screening method for IA. In addition, we comment on antimicrobial prophylaxis in HTRs in the setting of an outbreak.

Methods: Screening CT scans of the chest and serum galactomannan (GM) were performed in HTRs during an outbreak that followed the index case of IA. Abnormal CT findings prompted a diagnostic workup. Antimicrobial prophylaxis for new transplants recipients included intravenous micafungin while hospitalized, followed by outpatient inhaled amphotericin B for up to 3 months.

Results: During a 10-month period, five cases of IA were identified among HTRs. Two additional asymptomatic patients were diagnosed with IA among 15 asymptomatic HTRs who underwent screening chest CT scans. Among the five cases of IA in HTRs, two of five (40%) had a partial response and the other three failed voriconazole therapy. Complete response to voriconazole therapy assessed at 12 weeks was achieved in these two asymptomatic HTRs diagnosed via screening CTs. Serum GM was positive only in one of the symptomatic cases. The negative predictive value of CT scans was 100% (95% confidence interval, 71.5%-100%).

In an outbreak setting, screening CT scans of the chest may aid in early detection of asymptomatic HTRs with IA and improve outcome.

heart transplant, imaging, invasive aspergillosis, outbreak, screening

Pulmonary invasive aspergillosis (IA) remains a significant cause of morbidity and mortality in solid organ transplantation (SOT). IA has been reported in 1.6%-14% of heart transplant recipients (HTRs), with most the cases occurring within the first 3 months post transplant. 1 Nosocomially acquired IA has been noted in setting of outbreaks, and has been linked to construction work within the hospital settings or surroundings. Delay in establishing an early diagnosis remains a major impediment to the successful treatment of IA. Data in hematological malignancies suggest that computed tomography (CT) scans of the chest may detect the diseases earlier than serum galactomannan (GM). 2 However, the appropriate screening strategy for IA in the setting of an outbreak in HTRs remains undefined.

From February to October 2013, an unusually high number of IA cases were noted in HTRs at our institution. The present retrospective report describes our experience utilizing CT scans of the chest, as an early detection screening method for IA in asymptomatic HTRs in the setting of an institutional outbreak. In addition, we describe the antimicrobial prophylaxis undertaken and the outcomes at the end of prophylactic period.

This retrospective cohort study evaluated all consecutive HTRs between January 2013 and September 2014. Institutional ethics approval was obtained. As a part of the outbreak investigation, F I G U R E 1 From February to October 2013, five heart transplant recipients (HTRs) were diagnosed with invasive aspergillosis (IA). An outbreak was declared and two interventions were undertaken simultaneously. In HTRs transplanted between February and October of 2013, serum galactomannan (GM) and screening chest computed tomography (CT) scans were performed, and if the CT scan of the chest was normal, they were started on inhaled amphotericin (Inh Ampho) for 3 months. From October 2013 onward, all new HTRs were started on micafungin 50 mg intravenously daily while the patients were hospitalized, followed by inhaled amphotericin 20 mg twice a day for 3 months. 1: Screening CT, 2: Antifungal prophylaxis 

Thirty-eight heart transplantations were performed during the study period ( Figure 1 ). Mean age at transplant was 54 ± 13 years and 79.5% were male. Approximately half of them were bridged to transplant with mechanical circulatory support devices. HTRs had abnormal initial CT scans, two of which were diagnosed with IA (Figure 2A and B 

Our study underscores the high mortality rate (43%, 3/7) associated with IA in HTRs in an outbreak setting. Munoz et al 1 described a similarly adverse outcome, with two deaths of three patients affected during an outbreak of IA in a major heart surgery unit. In addition, similar to other SOT studies, 1 the sensitivity of serum GM in detecting cases of IA was poor; only one HTR with IA had a positive serum GM. Hence, we could not rely on the latter as a screening tool, and performed low radiation dose CT scans of the chest on asymptomatic HTRs. This helped to identify two asymptomatic HTRs with IA, who achieved complete response to therapy at 12 weeks, as compared to partial response or failure to therapy in the rest of cohort, including three deaths. Although this screening strategy might be costly and expose patient to increased radiation, it helped identify asymptomatic HTRs early in the course of disease.

The concept of early diagnosis and improved outcomes has been shown in patients with hematological malignancy and invasive fungal infection. 2, 6 This strategy also helped in following patients who did not tolerate prophylaxis because of side effects, and ensureing that these HTRs did not develop IA.

Our study possesses several limitations. Despite our limited single-center, retrospective, small cohort, and the absence of a control group, we have shown that, in an outbreak setting, early diagnosis of IA by CT scanning of the chest may be an effective screening strategy in HTRs and improve outcomes. The negative predictive value of CT scans in diagnosis IA was 100%; 95% confidence interval (71.5%-100%). Based on our experience during an outbreak of aspergillosis, we propose a combination of screening thoracic CT scans on patients transplanted during the same period as the index cases, in addition to universal prophylaxis on all new HTRs.

However, since this study represents the experience of a single center in the context of an outbreak, larger studies will be needed before our strategy can be recommended for generalization.

The best screening and prophylaxis strategies in the setting of an outbreak of IA in HTRs remain unclear. CT scans of the chest as a screening procedure prior to the institution of antifungal prophylaxis may aid in the early detection of IA, which is associated with better outcomes.

The authors have no conflicts of interest to disclose. 

Invasive aspergillosis among heart transplant recipients: A 24-year perspective

Galactomannan does not precede major signs on a pulmonary computerized tomographic scan suggestive of invasive aspergillosis in patients with hematological malignancies

working formulation for the standardization of definitions of infections in cardiothoracic transplant recipients (consensus document)

Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group

Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses Study Group and European Organization for Research and Treatment of Cancer consensus criteria

Outbreak of invasive aspergillosis in heart transplant recipients: The role of screening computed tomography scans in asymptomatic patients and universal antifungal prophylaxis