Real‐world challenges and unmet needs in the diagnosis and treatment of suspected invasive pulmonary aspergillosis in patients with haematological diseases: An illustrative case study

Recent years have seen important advances in the diagnosis of invasive pulmonary aspergillosis (IPA), complemented by the introduction of new therapies. Despite this, IPA remains a major cause of infection‐related mortality in patients with haematological diseases. There are two main reasons for this. First, diagnosis of IPA remains a challenge, since risk factors and the clinical, radiological and mycological presentations vary not only by fungal disease stage, but also by patient group (eg neutropenic vs non‐neutropenic patients). Diagnosis is particularly challenging in patients receiving mould‐active prophylactic or empirical treatment, which reduces the sensitivity of all diagnostic tests for IPA. Second, treatment of IPA is complex due to unpredictable pharmacokinetic profiles of antifungal agents, small therapeutic window in terms of exposure and adverse events, and multiple drug‐drug interactions through the CYP450 system. Here we report a case of a 23‐year‐old male with severe aplastic anaemia and subpleural nodules. Diagnostic tests for IPA obtained during ongoing mould‐active empirical treatment were negative. Intravenous voriconazole was stopped after visual disturbances and hallucinations. The patient then had an anaphylactic reaction to liposomal amphotericin B and was switched to intravenous posaconazole, which had to be discontinued due to a significant increase in transaminase levels. He was treated with oral isavuconazole with reduced dosage, triggered by increasing transaminases under the standard dosage. Even under reduced dosage, blood concentrations of isavuconazole were high and treatment was successful. The case illustrates real‐world challenges and unmet needs in the diagnosis and treatment of IPA in patients with haematological diseases.     

Direct comparison of galactomannan performance in concurrent serum and bronchoalveolar lavage samples in immunocompromised patients at risk for invasive pulmonary aspergillosis

Invasive pulmonary aspergillosis (IPA) is a life‐threatening infection mainly affecting immunocompromised patients. Early diagnosis is critical, but the diagnostic gold standard (histopathology and culture) is time consuming and cannot offer early confirmation of IPA. Fungal biomarkers like galactomannan (GM) are a promising extension to the diagnostic repertoire. However, it still remains under discussion if biomarker analysis from the site of the infection is superior to testing blood samples. We retrospectively evaluated the diagnostic performance of concurrent serum GM and bronchoalveolar lavage (BAL) GM (obtained within 24 h) of immunocompromised patients at high risk of IPA. Twenty‐six proven/probable patients and eight patients with no IPA according to the EORTC/MSG 2008 criteria were included in this study. Sensitivity, specificity, positive predictive value, negative predictive value and diagnostic odds ratio were for BAL GM: 85%, 88%, 96%, 64% and 38.5, and for serum GM: 23%, 88%, 88%, 26% and 2.1 respectively. BAL GM proved to be significantly more sensitive for the detection of IPA compared to same‐day serum GM in patients at high risk of IPA (P < 0.0001). Our data show that BAL GM testing is significantly superior to serum GM implying that diagnostic efforts should focus on specimens from the site of infection.     

Testing the performance of a prototype lateral flow device using bronchoalveolar lavage fluid for the diagnosis of invasive pulmonary aspergillosis in high‐risk patients

The diagnosis of invasive pulmonary aspergillosis (IPA) increasingly relies on non‐culture‐based biomarkers in bronchoalveolar lavage (BAL) fluid. The Aspergillus lateral flow device (LFD) is a rapid immunoassay that uses a novel Aspergillus monoclonal antibody to gain specificity. The objective of the study is to compare specificity and sensitivity of the prototype LFD and the galactomannan (GM) enzyme immunoassay in BAL fluid in high‐risk patients. A total of 114 BAL samples from 106 patients at high risk for IPA were studied: 8 patients had proven/probable IPA, 16 had possible IPA and 82 did not have IPA. In patients with proven/probable IPA, specificity of LFD was 94% and GM was 89%; sensitivity of LFD was 38% and GM was 75%. Negative predictive value (NPV) for LFD was 94% and for GM was 98%; positive predictive value (PPV) was 38% for both tests. The use of anti‐mould prophylaxis did not affect specificity but resulted in decreased NPV of both LFD and GM. Union and intersection analysis showed no improvement in the performance by using both tests. Among patients at risk for IPA, the diagnostic performance of LFD and GM in BAL fluid appears comparable; specificity is high, but sensitivity of both LFD and GM is poor.     

Diagnosis and antimicrobial therapy of lung infiltrates in febrile neutropenic patients (allogeneic SCT excluded): updated guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO)

Up to 25% of patients with profound neutropenia lasting for >10 days develop lung infiltrates, which frequently do not respond to broad-spectrum antibacterial therapy. While a causative pathogen remains undetected in the majority of cases, Aspergillus spp., Pneumocystis jirovecii, multi-resistant Gram-negative pathogens, mycobacteria or respiratory viruses may be involved. In at-risk patients who have received trimethoprim–sulfamethoxazole (TMP/SMX) prophylaxis, filamentous fungal pathogens appear to be predominant, yet commonly not proven at the time of treatment initiation. Pathogens isolated from blood cultures, bronchoalveolar lavage (BAL) or respiratory secretions are not always relevant for the etiology of pulmonary infiltrates and should therefore be interpreted critically. Laboratory tests for detecting Aspergillus galactomannan, β-d-glucan or DNA from blood, BAL or tissue samples may facilitate the diagnosis; however, most polymerase chain reaction assays are not yet standardized and validated. Apart from infectious agents, pulmonary side-effects from cytotoxic drugs, radiotherapy or pulmonary involvement by the underlying malignancy should be included into differential diagnosis and eventually be clarified by invasive diagnostic procedures. Pre-emptive treatment with mold-active systemic antifungal agents improves clinical outcome, while other microorganisms are preferably treated only when microbiologically documented. High-dose TMP/SMX is first choice for treatment of Pneumocystis pneumonia, while cytomegalovirus pneumonia is treated primarily with ganciclovir or foscarnet in most patients. In a considerable number of patients, clinical outcome may be favorable despite respiratory failure, so that intensive care should be unrestrictedly provided in patients whose prognosis is not desperate due to other reasons.     

Primary prophylaxis of invasive fungal infections with posaconazole or itraconazole in patients with acute myeloid leukaemia or high‐risk myelodysplastic syndromes undergoing intensive cytotoxic chemotherapy: A real‐world comparison

This is an observational‐retrospective study comparing the real‐world outcomes associated with posaconazole vs itraconazole as prophylaxis treatments. Two hundred and ninety‐three patient admissions attributable to 174 patients were included in the study. Patients were treated with itraconazole (n = 114 admissions; 39%) or posaconazole (n = 179; 61%). Antifungal prophylaxis failure (APF) due to treatment‐related adverse events (in 34 out of 293 patient admissions; 11.6%) was more frequent in the posaconazole group (6.1% vs 15.1%; P = .024). There were 9 patient admissions for episodes of APF due to probable/proven breakthrough fungal infection (primary endpoint): 6 and 3 in the itraconazole and posaconazole group respectively (5.3% vs 1.7%; P = .095). All of them were associated with invasive pulmonary aspergillosis (IPA). APF was more frequent with itraconazole (65% vs 30%; P < .001), along with failure due to possible/probable/proven IPA (25% vs 10%; P = .002) and overall failure by any of the 3 different causes of prophylaxis failure (70% vs 38%; P < .001). In agreement with clinical trial data, this real‐world evidence supports the use of posaconazole over itraconazole in AML or MDS patients undergoing intensive chemotherapy.     

Performance of lateral flow device and galactomannan for the detection of Aspergillus species in bronchoalveolar fluid of patients at risk for invasive pulmonary aspergillosis

Early diagnosis of invasive pulmonary aspergillosis (IPA) remains difficult due to the variable performance of the tests used. We compared the performance characteristics of Aspergillus lateral flow device (LFD) in bronchoalveolar lavage (BAL) vs. BAL‐galactomannan (GM), for the diagnosis of IPA. 311 BAL specimens were prospectively collected from patients who underwent bronchoscopy from January to May 2013. Patients at risk for IPA were divided into haematological malignancy (HEM) and non‐HEM groups: solid organ transplants (SOT) (lung transplant (LT) and non‐LT SOT); chronic steroid use (CSU); solid tumour (STU) and others. We identified 96 patients at risk for IPA; 89 patients (93%) were in the non‐HEM groups: SOT 57 (LT, 46, non‐LT SOT, 11); CSU 21; STU 6, other 5. Only three patients met criteria for IA (two probable; one possible). Overall sensitivity (SS) was 66% for both and specificity (SP) was 94% vs. 52% for LFD and GM respectively. LFD and GM performance was similar in the HEM group (SS 100% for both and SP 83% vs. 100% respectively). LFD performance was better than GM among non‐HEM SOT patients (P = 0.02). Most false‐positive GM results occurred in the SOT group (50.8%), especially among LT patients (56.5%). LFD performance was superior with an overall SP of 95.6% in SOT (P < 0.002) and 97% in LT patients (P = 0.0008). LFD is a rapid and simple test that can be performed on BAL to rule out IPA.     

Radiological findings of early invasive pulmonary aspergillosis in immune‐compromised patients

Data on the radiological features of invasive pulmonary aspergillosis (IPA) in early stages is scanty. Detection of Aspergillus (ASP) species in broncho‐alveolar (BAL) fluid by polymerase chain reaction (PCR) enables early diagnosis of IPA. This study describes the radiological features of early stages of IPA. Chest computerized tomography (CT) films of 22 consecutive immune‐compromised patients with IPA diagnosed with the aid of ASP PCR testing from BAL fluid were characterized and compared to that of 18 similar patients diagnosed with traditional bacteriological methods and to data from the literature. It was found that patients diagnosed with the aid of ASP PCR testing tended to have focal disease as manifested by more 11–30 mm nodules with halo (68% vs. 33%, p = 0.04), more focal ground glass (single area 32% vs. 6%, p = 0.05, patchy 32% vs. 0%, p = 0.01) and less diffuse ground glass (0% vs. 22%, p = 0.03), less cavitations (5% vs. 28%, p = 0.05) and less consolidations (segmental 14% vs. 50%, p = 0.02 and diffuse 14% vs. 67%, p = 0.001). It was concluded that the radiological appearance of early IPA diagnosed with the aid of PCR testing included mainly discrete small nodules with halo and focal ground glass, representing the early stage of the disease. Copyright © 2009 John Wiley & Sons, Ltd.     

Invasive pulmonary aspergillosis: A rare complication after microwave ablation

Three cases are reported of invasive pulmonary aspergillosis (IPA) occurring after microwave ablation (MWA) for lung tumours. This is a rare complication that has not previously been described in the literature. The diagnosis of IPA was based on the following factors: host factors, clinical manifestations and mycological findings. The first case was a 63-year-old man treated for primary lung squamous carcinoma. Significant tumour regression was achieved by 18 days after MWA, medical treatment with itraconazole for 6 weeks, and postural drainage. The second case, a 65-year-old man, was confirmed with primary lung squamous cell carcinoma. Voriconazole administration using intravenous infusion combined with intracavitary lavage was therapeutically effective after MWA at 1 year follow-up. The third case was a 61-year-old woman with primary lung adenocarcinoma. Delayed pneumothorax and bronchopleural fistula secondary to IPA persisted. The patient died from secondary multiple organ function failure. Despite its very low incidence, the significance of early diagnosis and early administration of antifungal therapy should be highlighted because of the relentless severity of IPA in patients undergoing MWA.     

Role of bi‐weekly serum galactomannan screening for the diagnosis of invasive aspergillosis in haematological cancer patients

Invasive aspergillosis (IA) is a life‐threatening infection affecting haematological cancer patients with chemotherapy‐induced neutropenia. The diagnosis of IA often relies on the detection of galactomannan (GM) in serum or bronchoalveolar lavage fluid (BAL). Bi‐weekly serum GM screening has been proposed for a pre‐emptive therapeutic approach of IA in patients not receiving mold‐active prophylaxis. We have analysed all IA cases among patients with haematological malignancies and prolonged chemotherapy‐induced neutropenia (>14 days) in our institution over a 10‐year period (2007‐2017). Serum GM was measured twice weekly and mold‐active prophylaxis was not routinely administered. Thirty IA cases were observed and a positive serum GM was the first indicator of IA in 10 (33%) of them, which represents a need of approximately 500 GM tests for the detection of a single IA case. In the other 20 (67%) cases, suggestive chest CT lesion was the first sign of IA and bronchoscopy was required in 15 (50%) cases with negative serum GM for establishing the diagnosis of probable/proven IA. A positive serum GM was associated with a worse prognosis (57% 12‐week survival vs 100% among serum GM‐negative patients, P = .006), irrespective of the timing of GM positivity compared to CT. We concluded that bi‐weekly serum GM screening demonstrated limited benefit in this population.     

Posaconazole therapeutic drug monitoring in clinical practice and longitudinal analysis of the effect of routine laboratory measurements on posaconazole concentrations

Posaconazole is indicated for prophylaxis and treatment of invasive aspergillosis. Therapeutic drug monitoring (TDM) of posaconazole is used to optimise drug exposure. The aim of this study was to analyse and describe the TDM practices and exposure of posaconazole tablets. Patients who received posaconazole for treatment or prophylaxis of fungal infections were included in the study. The following therapeutic window was defined: if concentration was low (<0.7 mg/L for prophylaxis or < 1.5 mg/L for treatment) or high (>3.75 mg/L), the hospital pharmacist provided the physician with dosage advice, which implementation to patient care was analysed. A longitudinal analysis was performed to analyse if different confounding variables had an effect on posaconazole concentrations. Forty‐seven patients were enrolled resulting in 217 posaconazole trough concentrations. A median of 3 (IQR 1‐7) samples was measured per patient. The median concentration was 1.7 mg/L (IQR 0.8‐2.7) for prophylaxis and 1.76 mg/L (IQR 1.3‐2.3) for treatment. Overall, 78 posaconazole concentrations were out of the therapeutic window. For 45 (54%) of these concentrations, a dosage change was recommended. In the longitudinal analysis, the laboratory markers and patient baseline variables did not have an effect on posaconazole concentrations. Adequate posaconazole exposure was shown in 64% (affected 28 patients) of the measured concentrations. TDM practice of posaconazole can be improved by increasing the implementation rate of dose recommendation by a multidisciplinary antifungal stewardship team.     

Utility of galactomannan antigen detection in bronchoalveolar lavage fluid in immunocompromised patients

Diagnosis of invasive pulmonary aspergillosis (IPA) is a challenging process in immunocompromised patients. Galactomannan (GM) antigen detection in bronchoalveolar lavage (BAL) fluid is a method to detect IPA with improved sensitivity over conventional studies. We sought to determine the diagnostic yield of BAL GM assay in a diverse population of immunocompromised patients. A retrospective review of 150 fiberoptic bronchoscopy (FOB) with BAL for newly diagnosed pulmonary infiltrate in immunocompromised patients was performed. Patient information, procedural details and laboratory studies were collected. BAL and serum samples were evaluated for GM using enzyme‐linked immunoassay. Of 150 separate FOB with BAL, BAL GM was obtained in 143 samples. There were 31 positive BAL GM assays. In those 31 positive tests, 13 were confirmed as IPA, giving a positive predictive value of 41.9%. There was one false negative BAL GM. Of the 18 false positive BAL GM, 4 were receiving piperacillin–tazobactam and 11 were receiving an alternative beta‐lactam antibiotic. BAL GM assay shows excellent sensitivity for diagnosing IPA. There was a significant number of false positive BAL GM assays and several of those patients were receiving beta‐lactam antibiotics at the time of bronchoscopy.     

急性白血病并发侵袭性肺曲霉病的临床分析

[目的]探讨急性白血病（AL）并发侵袭性肺曲霉病（IPA）的临床特点、诊断及治疗。[方法]回顾性分析7例AL并发IPA病例的临床资料。[结果]7例AL患者强烈化疗后第8.6d（4～11d）出现中性粒细胞（ANC）缺乏（ANC〈0.5×10^9/L）,粒细胞缺乏持续时间达15d（6～20d）,并在此期间出现持续发热、咳嗽、少痰、痰中带血、胸痛等症状;在发热后6d（3～10d）行CT检查均发现胸膜下结节或肺内多发结节影,呈晕征改变,2例伴有类圆形空洞病灶;4例行痰培养发现烟曲霉菌。4例患者予两性霉素B治疗,2例好转,1例疗效欠佳改用卡泊芬净后好转,1例因并发肾功能衰竭死亡;另外3例患者予伏立康唑治疗后好转。6例好转者随访中位时间18个月未见复发。[结论]粒细胞缺乏是IPA发病的高危因素,CT检查有助于IPA的早期诊断。伏立康唑是治疗IPA的首选药物,其有效性及安全性均优于两性霉素B。     

Aspergillus galactomannan testing in patients with long-term neutropenia: implications for clinical management.

We carried out a prospective study on galactomannan enzyme immuno assay (GEI) (Platelia Aspergillus EIA, Bio-Rad) testing for diagnosis of invasive aspergillosis (IA) in serum and broncho-alveolar lavage (BAL) in 200 patients with hematological malignancies and profound neutropenia. The incidence of proven and probable IA was 6% and 5.5%, respectively. In patients with fever or pneumonia, a single-positive GEI test result (galactomannan index >or= 0.5) had excellent specificity (100%). Sensitivity was relatively low (40%) at onset of fever, but increased to 94.7% after 6 days of fever. In patients with infiltrates in chest X-ray or computed tomography scan (n = 48), GEI testing in BAL had a favorable diagnostic accuracy as compared with GEI testing in serum (sensitivity 100% versus 71%). Our findings indicate that antifungal therapy should be started immediately at onset of fever in neutropenic patients with positive GEI tests. In patients with fever refractory to broad-spectrum antibiotics (>or=6 days of fever), the high diagnostic accuracy makes GEI testing a valuable diagnostic tool and questions the common strategy to carry out antifungal treatment irrespective of diagnostic testing in this situation. Our data also show that GEI testing in BAL can be useful for early diagnosis of IA in patients with hematological malignancies and pulmonary infiltrates.     

泊沙康唑预防或挽救性治疗血液病患者侵袭性真菌病的临床研究

目的 探讨泊沙康唑预防或挽救性治疗血液病患者侵袭性真菌病(IFD)的疗效及安全性.方法 回顾性分析2014年2月至2015年2月接受泊沙康唑预防或挽救性治疗IFD的25例血液病患者临床资料,患者平均年龄32.6岁(16～64岁).其中18例接受了泊沙康唑预防性治疗,7例接受了泊沙康唑挽救性治疗.结果 18例接受预防性治疗的患者在治疗期间或治疗结束后12周内,均没有出现IFD的临床表现(即无突破性真菌感染的病例),预防性治疗的平均疗程为21 d(14～35 d).7例接受挽救性治疗的患者均为伏立康唑治疗无效或不耐受者,挽救性治疗的总有效率为6/7,其中4例治愈,2例有效.所有患者中没有发现与泊沙康唑相关的明显不良反应.结论 泊沙康唑用于预防或挽救性治疗血液病患者IFD,均能够获得较好的临床疗效.     

Posaconazole prophylaxis – impact on incidence of invasive fungal disease and antifungal treatment in haematological patients

Since two large‐scale, randomised studies on posaconazole prophylaxis have demonstrated a clear benefit for patients at high risk for contracting invasive fungal disease (IFD), posaconazole prophylaxis has been adopted as standard of care for this patient collective. Several years on from implementation at our institution, we wanted to evaluate its impact on the incidence and use of empirical antifungal therapy in a real‐life setting. We analysed retrospectively incidence and severity of IFD in high‐risk patients with prophylaxis, using a historical cohort as comparator. A total of 200 patients had either received the extended spectrum triazole posaconazole in prophylactic dosage of 200 mg tid or empirical antifungal therapy. Disease events were analysed by application of the revised EORTC/MSG definitions for IFD. Before posaconazole prophylaxis, we recorded 57/100 cases of IFD which was reduced to 28/100 with prophylaxis. The empirical use of antifungal drugs was reduced to 41% from 91% in the non‐prophylaxis cohort. Furthermore, we observed a shift in the categorisation of IFD according to EORTC/MSG criteria. Our data suggest that posaconazole was effective in reducing the rate and probability of invasive fungal disease in high‐risk patients.     

Increasing volume and changing characteristics of invasive pulmonary aspergillosis on sequential thoracic computed tomography scans in patients with neutropenia.

PURPOSE: In patients with neutropenia, thoracic computed tomography (CT) halo and air-crescent signs are recognized as major indicators of invasive pulmonary aspergillosis (IPA). Nevertheless, the exact timing of CT images is not well known. PATIENTS AND METHODS: Seventy-one thoracic CT scans were analyzed in 25 patients with neutropenia with surgically proven IPA. RESULTS: On the first day of IPA diagnosis with early CT scan (d0), a typical CT halo sign was observed in 24 of 25 patients. At that time, the median number of thoracic lesions was two (range, one to six), and pulmonary involvement was bilateral in 12 cases. The halo sign was present in 68%, 22%, and 19% of cases on d3, d7, and d14, respectively. Similarly, the air-crescent sign was seen in 8%, 28%, and 63% of cases on the same days. Otherwise, a nonspecific air-space consolidation aspect was seen in 31%, 50%, and 18% of cases on the same days. The analysis of calculated aspergillary volumes on CT showed that, despite antifungal treatment, the median volume of lesions increased four-fold from d0 to d7, whereas it remained stable from d7 to d14. Overall, 21 patients (84%) were cured by the medical-surgical approach. CONCLUSION: In patients with neutropenia, CT halo sign is a highly effective modality for IPA diagnosis. The duration of the halo sign is short, and it demonstrates the value of early CT. The increase of the aspergillosis size on CT in the first days after IPA diagnosis is not correlated with a pejorative immediate outcome when using a combined medical-surgical approach.     

Antifungal prophylaxis in newly diagnosed AML patients–Adherence to guidelines and feasibility in a real life setting

Antifungal posaconazole prophylaxis for AML patients receiving induction chemotherapy has been routine at our centre since 2009. This retrospective study examined the feasibility and practicability of our prophylaxis guidelines in clinical practice. Data sets of 90 patients undergoing induction‐chemotherapy for AML between 2011 and 2014 were evaluated regarding adherence to local guidelines for the administration of antifungal prophylaxis with posaconazole. 75.5% of the 90 patients received posaconazole prophylaxis. All but eight patients received the recommended dosage. A total of 77.95% on prophylaxis had serum galactomannan measured twice weekly. Contradicting our guidelines, 89.70% of patients received concomitant therapy with PPI. Overall, 16.17% of patients had prophylaxis discontinued and started empirical antifungal treatment in the absence of diagnostic criteria for IFI. The breakthrough IFI rate was 36.76% (proven, probable and possible) with 7.35% of infections being classified as proven or probable. Although limited by a small sample size, our study demonstrates the feasibility of local guidelines in a real life setting and outlines areas for improvement in both guidelines and clinical practice. We also highlight the importance of ensuring awareness of guidelines and raise questions about a uniform approach to antifungal prophylaxis in AML patients.     

Treatment cost development of patients undergoing remission induction chemotherapy: a pharmacoeconomic analysis before and after introduction of posaconazole prophylaxis

Prior clinical trials have demonstrated efficacy and effectiveness of posaconazole in the prophylaxis of invasive fungal diseases in high‐risk patients. Controversy exists about the cost‐effectiveness of this approach. We performed an analysis comparing the direct costs of posaconazole prophylaxis against polyene mouthwash (thrush) prophylaxis in patients with acute myelogenous leukaemia (AML). Data of AML patients receiving remission‐induction chemotherapy were extracted from the CoCoNut (Cologne Cohort of Neutropenic Patients) database to compare hospital costs of patients before (2003–2005) and after (2006–2008) introduction of posaconazole prophylaxis. Treatment on general ward, intensive care unit (ICU), mechanical ventilation, diagnostic procedures, and all anti‐infectives were calculated. Patient groups were well matched according to age, gender and duration of neutropenia. The mean costs per patient in the posaconazole group (n = 76) and the polyene mouthwash group (n = 81) were €21 040 (95% confidence interval (CI): €18 204–€23 876) and €23 169 (95% CI: €19 402–€26 937) per patient. Antifungal treatment costs were €4580 (95% CI: €3678–€5482) and €4019 (95% CI: €2825–€5214). Duration on the ICU was 2582 (95% CI: 984.1–4181.7) and 5517 (95% CI: 2206–8827.3) min. In our hospital, primary antifungal prophylaxis by posaconazole was cost‐effective. There was a trend towards cost savings, which was primarily caused by a shorter overall length of stay and the less frequent ICU treatment.     

Use of posaconazole delayed‐release tablets for treatment of invasive aspergillosis

A 65‐year‐old man developed Aspergillus brain abscesses following surgical resection of a sinus aspergilloma. He was treated with voriconazole for 1 year but infection recurred. We elected to treat with posaconazole delayed‐release tablets, currently only indicated as antifungal prophylaxis in high‐risk patients. A maintenance dose of 300 mg Q24 h resulted in a therapeutic serum concentration and appears safe and clinically effective thus far. This is the first report of successful use of posaconazole tablets for treatment of invasive aspergillosis.     

Pulmonary fungal infections in patients with acute myeloid leukaemia: is it the time to revise the radiological diagnostic criteria?

The definition of pulmonary fungal infections (PFI) according to the EORTC‐MSG criteria may lack diagnostic sensitivity due to the possible presentation of PFI with different radiological pictures. We evaluated the hypothesis to apply less restrictive radiological criteria to define PFI in patients with acute myeloid leukaemia (AML) submitted to chemotherapy. Overall, 73 consecutive episodes of pulmonary infiltrates associated to positive serum galactomannan test or fungal isolation or galactomannan detection from respiratory specimens were considered. CT scans acquired at the onset of symptoms (time‐0) and within 4 weeks (time‐1) were analysed to identify specific (group A) or aspecific radiological signs (group B). Pulmonary infiltrates fulfilled the EORTC‐MSG criteria in 49 patients (group A), whereas in 24 patients (group B) they did not reach the criteria due to aspecific CT findings at time‐0. Eleven of 21 (52.4%) patients of the group B evaluable for the evolution of the radiological findings fulfilled EORTC‐MSG criteria at time‐1. All the analysed clinical and mycological characteristics, response to antifungal therapy and survival were comparable in the two groups. Our study seems to confirm the possibility to extend the radiological suspicion of PFI to less restrictive chest CT findings when supported by microbiological criteria in high‐risk haematological patients.