Radiology-based diagnosis of fungal pulmonary infections in high-risk hematology patients: are we making progress?

PURPOSE OF REVIEW: In patients with hematological malignancies, high-resolution computed tomography (CT) is the recommended imaging approach for diagnosis, staging and monitoring of invasive fungal disease (IFD) but lacks specificity. We examined the status of current imaging modalities for IFD and possibilities for more effective applications of current technology for improving the specificity of IFD diagnosis. RECENT FINDINGS: Although CT imaging recommendations for IFD are largely unchanged in the last 20 years, improvements in CT scanner technology and image processing algorithms now allow for technically adequate examinations at much lower radiation doses. CT pulmonary angiography can improve both the sensitivity and specificity of CT imaging for angioinvasive molds in both neutropenic and nonneutropenic patients, through detection of the vessel occlusion sign (VOS). MRI-based approaches also show promise not only for early detection of small nodules and alveolar hemorrhage but can also be used to detect pulmonary vascular occlusion without radiation and iodinated contrast media. 18F-fluorodeoxyglucose (FDG) PET/computed tomography (FDG-PET/CT) is increasingly used to monitor long-term treatment response for IFD, but could become a more powerful diagnostic tool with the development of fungal-specific antibody imaging tracers. SUMMARY: High-risk hematology patients have a considerable medical need for more sensitive and specific imaging approaches for IFD. This need may be addressable, in part, by better exploiting recent progress in CT/MRI imaging technology and algorithms to improve the specificity of radiological diagnosis for IFD.

Clinical features and prognostic factors of Magnusiomyces (Saprochaete) infections in haematology. A multicentre study of SEIFEM/Fungiscope.

BACKGROUND: Our multicentre study aims to identify baseline factors and provide guidance for therapeutic decisions regarding Magnusiomyces-associated infections, an emerging threat in patients with haematological malignancies. METHODS: HM patients with proven (Magnusiomyces capitatus) M. capitatus or (Magnusiomyces clavatus) M. clavatus (formerly Saprochaete capitata and Saprochaete clavata) infection diagnosed between January 2010 and December 2020 were recorded from the SEIFEM (Sorveglianza Epidemiologica Infezioni nelle Emopatie) group and FungiScope (Global Emerging Fungal Infection Registry). Cases of Magnusiomyces fungemia were compared with candidemia. RESULTS: Among 90 Magnusiomyces cases (60 [66%] M. capitatus and 30 (34%) M. clavatus), median age was 50 years (range 2-78), 46 patients (51%) were female and 67 (74%) had acute leukaemia. Thirty-six (40%) of Magnusiomyces-associated infections occurred during antifungal prophylaxis, mainly with posaconazole (n = 13, 36%) and echinocandins (n = 12, 34%). Instead, the candidemia rarely occurred during prophylaxis (p < .0001). First-line antifungal therapy with azoles, alone or in combination, was associated with improved response compared to other antifungals (p = .001). Overall day-30 mortality rate was 43%. Factors associated with higher mortality rates were septic shock (HR 2.696, 95% CI 1.396-5.204, p = .003), corticosteroid treatment longer than 14 days (HR 2.245, 95% CI 1.151-4.376, p = .018) and lack of neutrophil recovery (HR 3.997, 95% CI 2.102-7.601, p < .001). The latter was independently associated with poor outcome (HR 2.495, 95% CI 1.192-5.222, p = .015). CONCLUSIONS: Magnusiomyces-associated infections are often breakthrough infections. Effective treatment regimens of these infections remain to be determined, but neutrophil recovery appears to play an important role in the favourable outcome.

Impact of infectious comorbidity and overall time of hospitalization in total outpatient management of acute myeloid leukemia patients following venetoclax and hypomethylating agents.

Venetoclax (VEN) and hypomethylating agent (HMAs) regimens are emerging as the standard of care for unfit for chemotherapy acute myeloid leukemia (AML) patients, but the safety and feasibility of a total outpatient management have not been fully investigated. Fifty-nine AML patients with active disease received VEN and HMAs. Nineteen out of 59 (32.2%) patients received the first cycle as inpatients, whereas 40/59 (67.8%) patients were treated in the outpatient setting. No significant differences were observed with regard to incidence of adverse events (AEs), including tumor lysis syndrome (TLS), and the 30-day and 60-day mortality was comparable. Notably, an infectious prophylaxis inspired to that adopted during intensive chemotherapy resulted in a low infection rate with a reduced bacterial infections incidence in out- versus hospitalized patients (p < .0001). The overall time of hospitalization was significantly shorter in patients who received a total outpatient treatment as compared to those who received the first cycle as inpatients (5.9 vs. 39.7 days, p < .0001). Despite the adopted differences in treatment management, the efficacy was similar. These data indicate that a total outpatient management of VEN and HMAs is feasible in AML patients without negatively impacting on treatment efficacy and may yield pharmacoeconomic and quality-of-life benefits.

Beyond biomarkers: How enhanced CT imaging can improve the diagnostic-driven management of invasive mould disease.

CT imaging remains an essential diagnostic test for identification, staging and management of invasive mould infection (IMI) in patients with hematological malignancies. Yet the limited specificity of standard CT imaging can drive excessive antifungal use in patients, especially when more definitive diagnosis cannot be established through microbiology or invasive diagnostic procedures. CT pulmonary angiography (CTPA) is a complimentary, non-invasive approach to standard CT that allows for direct visualization of pulmonary arteries inside infiltrates for signs of angioinvasion, vessel destruction and vessel occlusion. Experience from several centers that are using CTPA as part of a standard diagnostic protocol for IMI suggests that a positive vessel occlusion sign (VOS) is the most sensitive and a specific sign of IMI in both neutropenic and non-neutropenic patients. CTPA is particularly useful in patients who develop suspected breakthrough IMI during antifungal prophylaxis because, unlike serum and/or BAL galactomannan and polymerase chain reaction (PCR) testing, the sensitivity is not reduced by antifungal therapy. A negative VOS may also largely rule-out the presence of IMI, supporting earlier discontinuation of empirical therapy. Future imaging protocols for IMI in patients with hematological malignancies will likely replace standard chest X-rays in favor of early low radiation dose CT exams for screening, with characterization of the lesions by CTPA and routine follow-up using functional/metabolic imaging such as 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (FDG-PET/CT) to assess treatment response. Hence, enhanced CT imaging techniques can improve the diagnostic-driven management of IMI management in high-risk patients with hematological malignancies.

Saprochaete clavata infections in patients undergoing treatment for haematological malignancies: A report of a monocentric outbreak and review of the literature.

Saprochaete clavata is a rare cause of fungaemia with deep organ involvement in patients with haematological malignancies with reported mortality rates of 60%-80%. We describe four cases of S clavata infection in a haematology unit over several months that were treated with voriconazole-based regimens. We also review the literature on factors that could contribute to earlier recognition and effective treatment of S clavata. We included all cases of culture-positive S clavata from sterile sites with associated signs of infection in patients undergoing treatment for a haematological malignancy. Isolates were identified by MALDI-TOF MS, and spectrum profiles were used to prepare clustering analysis of isolates. Susceptibility testing was performed using a commercial microtitre methods. Saprochaete clavata was isolated from the bloodstream in three cases and bronchial alveolar lavage (BAL) fluid in one case. Clustering analysis suggested strains of S clavata were clonal without evidence of divergence although a common source was not identified. Susceptibility testing yielded elevated MICs to fluconazole (8 mg/L) and echinocandins (>1-8 mg/L). All patients were treated with voriconazole-based regimens resulting in survival of 3/4 patients, who continued chemotherapy for their underlying malignancy without evidence of relapse. Saprochaete clavata is a rare but aggressive cause of breakthrough yeast infection in patients undergoing treatment for haematological malignancies, particularly patients with a prior history of echinocandin treatment. Timely initiation of appropriate treatment, aided by more rapid identification in microbiology laboratory, can reduce the risk of deep organ dissemination and patient death.

Successful treatment of bilateral endogenous Fusarium solani endophthalmitis in a patient with acute lymphocytic leukaemia.

Fusarium spp. are an uncommon cause of fungaemia in immunocompromised and neutropenic patients that may hematogenously disseminate to the eyes. Herein, we describe a patient with acute lymphoblastic leukaemia and a prior history of extensive corticosteroid exposure who developed disseminated Fusarium solani infection following chemotherapy despite posaconazole prophylaxis. She was successfully treated with combination liposomal amphotericin B and voriconazole, intraocular injections of voriconazole, topical amphotericin B and bilateral vitrectomy. We also review published literature describing the management of endogenous Fusarium endophthalmitis in immunocompromised hosts.

Retrospective Cohort Analysis of Liposomal Amphotericin B Nephrotoxicity in Patients with Hematological Malignancies.

We retrospectively examined the incidence, onset, risk factors, and outcomes of renal injury during 103 treatment courses of liposomal amphotericin B (L-AMB) in 97 adult patients with hematological malignancies. All the patients were analyzed before, during, and after the administration of L-AMB, and renal injury was graded according to the RIFLE criteria (risk, injury, failure, loss of function, end-stage renal disease). Most patients (87.3%) received L-AMB at 3 mg/kg of body weight/day. Nearly two-thirds (61.7%) of the treatment courses did not meet any RIFLE category for renal injury, while 19.4% of patients were classified at risk, 13.6% met an injury classification, and 5.8% were categorized as developing renal failure. However, 15% of the patients developed renal injury within 48 h of the onset of multiorgan failure associated with sepsis, bleeding, or progressing malignancy. When these patients were analyzed as a competing risk for L-AMB-associated renal injury (RIFLE category I or above) in a multivariate Cox regression model, receipt of cyclosporine (subhazard ratio [SHR], 2.62; 95% confidence interval [CI], 1.10 to 6.27; P = 0.03), cyclosporine plus furosemide at ≥40 mg/day (SHR, 5.46; 95% CI, 1.89 to 15.74; P = 0.002), or cyclosporine plus foscarnet (SHR, 9.03; 95% CI, 3.68 to 22.14; P < 0.0001) were the only comedications significantly associated with increased rates of renal injury. The cumulative incidence of L-AMB renal injury during the first 10 days of therapy was 7% overall but only 3% in patients who were not receiving cyclosporine. Hence, the renal risk of L-AMB therapy may be lessened if patients are switched to alternative agents after 7 to 10 days or if aggressive diuresis and/or foscarnet is avoided, especially among patients receiving calcineurin inhibitors.

Radiologic findings of Fusarium pneumonia in neutropenic patients.

In neutropenic patients, lungs are involved in 50%-80% of cases of fusariosis, but imaging of pulmonary fusariosis has been previously described as indistinguishable from other invasive mould diseases. Our attempt was to identify a radiological pattern that may distinguish pulmonary fusariosis from other mould diseases. We examined the CT findings of nine neutropenic haematology patients with invasive fusariosis. As control group for comparison, we examined 14 invasive mould diseases (11 aspergillosis, 3 mucormycosis) in haematology patients with similar underlying disease and timing of CT imaging. Chest-CT in invasive fusariosis showed small airways (7/9) or peribronchial (5/9) infiltrates, less frequently macronodular consolidations (4/9) with hypodense sign, but without halo sign or occluded-vessel sign. The control group presented macronodular consolidations with occluded-vessel sign in all of the cases; the halo and the hypodense signs were observed, respectively, in 100% and 82% of aspergillosis, and in 67% and 100% of mucormycosis. Sinusitis was documented by CT in 7/7 fusariosis, 2/2 mucormycosis and 5/7 aspergillosis; maxillary and ethmoid sinuses were involved in 7/7 fusariosis, in most of the cases with hyperdense opacification (rarely observed in the controls). We concluded that no radiological findings can discriminate between different mould infections, but invasive fusariosis should be suspected if chest-CT demonstrates pulmonary infiltrates with the hypodense sign, but without the halo or the occluded-vessel signs. Suspicion is greater in the presence of hyperdense maxillary and ethmoid sinusitis.

ITA-MNGIE: an Italian regional and national survey for mitochondrial neuro-gastro-intestinal encephalomyopathy.

Mitochondrial neuro-gastro-intestinal encephalomyopathy (MNGIE) is a rare and unavoidably fatal disease due to mutations in thymidine phosphorylase (TP). Clinically it is characterized by gastrointestinal dysfunction, malnutrition/cachexia and neurological manifestations. MNGIE diagnosis remains a challenge mainly because of the complexity and rarity of the disease. Thus, our purposes were to promote a better knowledge of the disease in Emilia-Romagna region (ERR) by creating an accurate and dedicated network; to establish the minimal prevalence of MNGIE in Italy starting from ERR. Blood TP activity level was used as screening test to direct candidates to complete diagnostic work-up. During the study period of 1 year, only 10/71 units of ERR recruited 14 candidates. Their screening did not show TP activity changes. An Italian patient not resident in ERR was actually proved to have MNGIE. At the end of study in Italy there were nine cases of MNGIE; thus, the Italian prevalence of the disease is ~0.15/1,000,000 as a gross estimation. Our study confirms that MNGIE diagnosis is a difficult process which reflects the rarity of the disease and, as a result, a low level of awareness among specialists and physicians. Having available novel therapeutic options (e.g., allogenic hematopoietic stem cell transplantation and, more recently, liver transplantation) and an easy screening test, an early diagnosis should be sought before tissue damage occurs irreversibly.

High resolution computed tomography angiography improves the radiographic diagnosis of invasive mold disease in patients with hematological malignancies.

BACKGROUND: Computed tomography pulmonary angiography (CTPA) may improve the diagnostic capabilities of CT imaging for invasive mold disease, but its performance relative to other signs (ie, halo sign, hypodense sign, pleural effusion, reversed halo sign) is unknown. METHODS: We prospectively compared the diagnostic performance of CTPA vs other CT imaging findings in 100 patients with hematological malignancies and possible invasive mold disease defined by EORTC/MSG criteria. After undergoing extensive diagnostic work-up, patients were upgraded to probable or proven mold disease based on galactomannan antigen, culture or histology; or remained as possible mold disease if an alternative diagnosis could not be established. RESULTS: In total, 46 /100 patients who underwent CTPA were upgraded to probable or proven mold disease. Excluding 8 CTPA cases that were nonevaluable by the radiologist, a positive occlusion sign identified by CTPA was 100% sensitive for the diagnosis of probable or proven mold disease (41/41). Among patients who could not be upgraded from the possible mold disease category (n = 51), 25 (49%) had evidence of vessel occlusion by CTPA with only one positive patient eventually reaching an alternative diagnosis (Staphylococcus aureus septic thrombosis). Intravenous and/or oral antifungal therapy was stopped earlier in patients with a negative vs positive CTPA results (P ≤ .001). CONCLUSIONS: Vessel occlusion detected by CTPA is a more sensitive and possibly more specific radiographic sign vs other common CT findings of invasive mold disease in patients with hematological malignancies.

Incidence and outcome of invasive fungal diseases after allogeneic stem cell transplantation: a prospective study of the Gruppo Italiano Trapianto Midollo Osseo (GITMO).

Epidemiologic investigation of invasive fungal diseases (IFDs) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be useful to identify subpopulations who might benefit from targeted treatment strategies. The Gruppo Italiano Trapianto Midollo Osseo (GITMO) prospectively registered data on 1858 consecutive patients undergoing allo-HSCT between 2008 and 2010. Logistic regression analysis was performed to identify risk factors for proven/probable IFD (PP-IFD) during the early (days 0 to 40), late (days 41 to 100), and very late (days 101 to 365) phases after allo-HSCT and to evaluate the impact of PP-IFDs on 1-year overall survival. The cumulative incidence of PP-IFDs was 5.1% at 40 days, 6.7% at 100 days, and 8.8% at 12 months post-transplantation. Multivariate analysis identified the following variables as associated with PP-IFDs: transplant from an unrelated volunteer donor or cord blood, active acute leukemia at the time of transplantation, and an IFD before transplantation in the early phase; transplant from an unrelated volunteer donor or cord blood and grade II-IV acute graft-versus-host disease (GVHD) in the late phase; and grade II-IV acute GVHD and extensive chronic GVHD in the very late phase. The risk for PP-IFD was significantly higher when acute GVHD was followed by chronic GVHD and when acute GVHD occurred in patients undergoing transplantation with grafts from other than matched related donors. The presence of PP-IFD was an independent factor in long-term survival (hazard ratio, 2.90; 95% confidence interval, 2.32 to 3.62; P < .0001). Our findings indicate that tailored prevention strategies may be useful in subpopulations at differing levels of risk for PP-IFDs.

[The role of iron metabolism in myelodysplastic syndromes]. / Il ruolo del metabolismo del ferro nelle sindromi mielodisplastiche.

Patients affected by myelodysplastic syndromes (MDS) with transfusion-dependent anemia are destined to develop iron overload. The main diagnostic tools for the diagnosis of transfusional iron overload are serum ferritin and transfusion history. In MDS several studies showed that iron overload is an independent negative prognostic factor. Deferasirox, an oral iron chelator, has shown efficacy and acceptable tolerability in MDS setting, and has also been shown to improve peripheral cytopenia in 10-20% of patients. Iron chelation therapy is recommended, after the transfusion of 20 red cell units, in low-risk MDS patients, and also in high-risk patients responding to treatment of the disease and/or candidates to receive allogeneic hematopoietic stem cell transplantation.

Molecular monitoring of BCR-ABL transcripts after allogeneic stem cell transplantation for chronic myeloid leukemia.

The monitoring of minimal residual disease (MRD) through low sensitivity real-time (RT) polymerase chain reaction (PCR) analysis of BCR-ABL transcripts allows early detection of chronic myeloid leukemia (CML) relapse after allogeneic hematopoietic stem cell transplantation (HSCT). The introduction of more sensitive techniques, such as RT quantitative (Q)-PCR, may lead to an overestimation of the risk of CML relapse. In this study, we reviewed the results of peripheral blood RT Q-PCR in CML patients who underwent allogeneic HSCT from 1983 to 2007. In our laboratory, RT Q-PCR analysis was routinely performed since 2002. Eighty-seven of 189 patients had available RT Q-PCR data; 63 patients had at least 3 RT Q-PCR analyses assessable. Fifty-two of 63 patients (83%) had, at least once, detectable transcript levels, but with an BCR-ABL/ABL ratio <.1% defined as .1% confirmed by the finding of Ph+ cells in bone marrow. No patients with persistent undetectable transcripts relapsed (P = .19). Relapse did not correlate with the number of occurrences of

Computed tomographic pulmonary angiography for diagnosis of invasive mold diseases in patients with hematological malignancies.

BACKGROUND: Invasive mold diseases (IMDs) of the lung remain a challenge for immunocompromised patients. Although timely diagnosis and treatment are crucial for the outcome of the infection, the poor sensitivity of microbiological techniques and the limited specificity of chest high-resolution computed tomography (HRCT) often delay definitive diagnosis of these infections. METHODS: To explore the diagnostic utility of computed tomographic pulmonary angiography (CTPA) for detecting angioinvasive patterns of pulmonary infection, we performed a single-center, prospective, nonrandomized trial involving 36 patients with hematological malignancies who had clinical suspicion of IMD, as defined by European Organization for Research and Treatment of Cancer/Mycosis Study Group diagnostic criteria. RESULTS: We found that 5 of 5 patients with proven IMD had CTPA-positive findings consistent with interruption of the arterial vessels (concordance, 100%). CTPA findings were positive in 5 of 7 patients with probable IMD (findings for 2 were considered false negative because lesions were too small or not evaluable). In 15 of 24 patients with a final diagnosis of possible IMD, CTPA findings were negative for 14 patients and were positive for 1 patient, who had septic emboli associated with Staphylococcus aureus bacteremia. CTPA findings were positive in the remaining 9 patients with a final diagnosis of possible IMD at the end of the study. CONCLUSIONS: We conclude that CTPA appears to be a promising tool to exclude the diagnosis of IMD in high-risk patients without specific findings on HRCT scans, and it is most useful in the presence of well-circumscribed lesions in which there is suspicion for IMD.

Management of drug-drug interactions of targeted therapies for haematological malignancies and triazole antifungal drugs.

Over the past 10 years, the number of targeted therapies for haematological malignancies has substantially increased, and many new drugs have entered the market. Many of these therapies have shown improved disease-free survival and reduced toxicity compared with existing treatments, especially in older patients. However, most of these new drugs undergo extensive hepatic metabolism and exhibit moderate to severe drug-drug interactions with triazole antifungal agents, which are essential for the prophylaxis and long-term treatment of invasive fungal infections. In this Review, we give a comprehensive overview of all known drug-drug interactions between new targeted drugs for haematological malignancies and antifungal drugs, in particular the triazoles. We begin with a general background on drug-drug interactions. Next, we provide a management strategy for the use of each targeted haematological drug, and discuss the possible role of therapeutic drug monitoring for both the triazole and the haematological drugs. This Review aims to provide practical guidance to clinical haematologists on managing the complex interplay between targeted therapies for haematological malignancies and triazole antifungal drugs, to pursue better outcomes for their patients.

Early low-dose computed tomography with pulmonary angiography to improve the early diagnosis of invasive mould disease in patients with haematological malignancies: A pilot study.

OBJECTIVE: High-resolution computed tomography (CT) is an essential diagnostic tool for invasive mould disease (IMD) in patients with haematological malignancies but is infrequently performed in the first 72 h of neutropenic fever until after chest X-ray (CXR). We hypothesised that early (< 48 h) low-dose CT (LD-CT; 90% reduction in radiation dose) combined with CT pulmonary angiography (CTPA) to detect the venous occlusion sign (VOS) inside suspected infiltrates could improve IMD diagnosis. METHODS: We prospectively studied 68 consecutive adult patients undergoing treatment for haematological malignancies who developed fever following chemotherapy or haematopoietic stem cell transplantation. Within 48 h of fever, patients underwent a standard CXR followed by LD-CT imaging and CTPA if eligible based on baseline imaging findings; the same protocol was performed in 42/68 (61.7%) of patients at day 7 follow-up. The diagnostic performance of CT signs for EORTC/MSG-defined proven, probable, and possible IMD was analysed at both imaging periods. RESULTS: The baseline LD-CT was positive for abnormalities in 43/68 (63%) of patients within 48 h of fever and 35/42 (83%) of patients at the follow-up exam. Amongst these 43 patients, CTPA was performed in 17/43 (39%) and in 18/35 (51%) at D + 7 follow-up. A positive VOS was associated with the highest estimated positive likelihood ratio for EORTC/MSG-defined proven, probable, or possible IMD at baseline (20.6; 95% CI 1.4-311.2) and at day 7 follow-up (19.0; 95% CI 0.93-300.8) followed by the baseline non-contrast enhanced hypodense sign (18.3; 0.93-361.7), reverse halo (11.0; 0.47-256.5), halo sign (8.68;3.13-24.01) and air-crescent sign at day 7 (16.7; 0.93-301.0). However, a negative VOS was the only CT sign at baseline or day 7 associated with sufficiently low negative likelihood ratio (0.05;0.001-0.8) to possibly support ruling-out IMD in patients with positive CT findings. CONCLUSIONS: Early LD-CT combined with CTPA shows promise for improving the early radiographic diagnosis of IMD.

Invasive aspergillosis in patients with acute myeloid leukemia: a SEIFEM-2008 registry study.

BACKGROUND: The aim of this study was to evaluate prognostic factors, treatments and outcome of invasive aspergillosis in patients with acute myeloid leukemia based on data collected in a registry. DESIGN AND METHODS: The registry, which was activated in 2004 and closed in 2007, collected data on patients with acute myeloid leukemia, admitted to 21 hematologic divisions in tertiary care centers or university hospitals in Italy, who developed proven or probable invasive aspergillosis. RESULTS: One hundred and forty cases of invasive aspergillosis were collected, with most cases occurring during the period of post-induction aplasia, the highest risk phase in acute myeloid leukemia. The mortality rate attributable to invasive aspergillosis was 27%, confirming previous reports of a downward trend in this rate. Univariate and multivariate analyses revealed that the stage of acute myeloid leukemia and the duration of, and recovery from, neutropenia were independent prognostic factors. We analyzed outcomes after treatment with the three most frequently used drugs (liposomal amphotericin B, caspofungin, voriconazole). No differences emerged in survival at day 120 or in the overall response rate which was 71%, ranging from 61% with caspofungin to 84% with voriconazole. CONCLUSIONS: Our series confirms the downward trend in mortality rates reported in previous series, with all new drugs providing similar survival and response rates. Recovery from neutropenia and disease stage are crucial prognostic factors. Efficacious antifungal drugs bridge the period of maximum risk due to poor hematologic and immunological reconstitution.

Identification of an invasive infection of R. oryzae in a haematological patient using a molecular technique.

We report a case of cerebral mucormycosis in a 28-year-old male who was affected by chronic myeloid leukaemia and underwent allogeneic bone marrow transplantation. Nine months post-transplantation, he was admitted to the hospital with fever, bilateral eyelid oedema and neutropenia. X-ray analysis showed numerous areas of pulmonary parenchymal thickening, and a computed tomography scan of the brain showed inflammation of the frontal, maxillary, ethmoidal and sphenoidal sinuses and diffuse swelling of the periorbital tissues. Sinus cultures were taken, and based on its characteristic rhizoid structure, we classified the isolated fungus as a member of the genus Rhizopus. The fungus was identified as an Rhizopus oryzae species, as assessed by sequencing of the internal transcribed spacer of the rRNA gene. Treatment with amphotericin B was ineffective, however, and the patient died 2 weeks after admission. This case highlights the potential severity of an invasive infection of R. oryzae, identified by molecular biology techniques.