Summary Critically ill patients and patients with haematological cancer are HIV-negative populations at high risk of invasive fungal infections. In intensive-care units, candidaemia and intra-abdominal candidiasis predominate, but aspergillosis has emerged as a lethal, under-recognised cause of pneumonia. In patients with haematological malignancies or who have undergone stem-cell transplantations, pulmonary disease due to aspergillus and other mould diseases predominate. In this Series paper, we provide an update on risk assessment, new diagnostic strategies, and therapeutic approaches. New concepts have emerged for use of risk prediction rules and an evidence base now exists for inclusion of biomarkers (eg, galactomannan, 1,3-β-D-glucan, and PCR assays for Aspergillus spp) into early diagnostic and therapeutic strategies. Imaging techniques remain helpful for early diagnosis of pulmonary mould diseases, with PET techniques offering potential improvements in diagnostic specificity and evaluation of clinical response. Echinocandins and triazoles have been validated extensively for prophylaxis, empirical therapy, and targeted therapy, but an increase in intrinsically resistant fungi and emergence of secondary resistance as a result of drug-induced selection pressure are of major concern. Echinocandins remain a major component of treatment of invasive candidiasis and new triazoles are the best alternative for prophylaxis and therapy of invasive aspergillosis.

Candida and invasive mould diseases in non-neutropenic critically ill patients and patients with haematological cancer

To describe concisely the current standards of care, major recent advances, common beliefs that have been contradicted by recent trials, areas of uncertainty, and clinical studies that need to be performed over the next decade and their expected outcomes with regard to Candida and Aspergillus infections in non-neutropenic patients in the ICU setting. A systematic review of the medical literature taking account of national and international guidelines and expert opinion. Severe invasive fungal infections (IFIs) are becoming increasingly frequent in critically ill patients. Approximately 80% of IFIs are due to Candida spp. and 0.3–19% to Aspergillus spp. Recent observations emphasize the necessity of building a worldwide sentinel network to monitor the emergence of new fungal species and changes in susceptibility. Robust data on the attributable mortality are essential for the design of clinical studies with mortality endpoints. Although early antifungal therapy for Candida has been recommended in patients with risk factors, sepsis of unknown cause, and positive Candida serum biomarkers [β-1 → 3-d-glucan (BDG) and Candida albicans germ tube antibody (CAGTA)], its usefulness and influence on outcome need to be confirmed. Future studies may specifically address the optimal diagnostic and therapeutic strategies for patients with abdominal candidiasis. Better knowledge of the pharmacokinetics of antifungal molecules and tissue penetration is a key issue for intensivists. Regarding invasive aspergillosis, further investigation is needed to determine its incidence in the ICU, its relationship with influenza outbreaks, the clinical impact of rapid diagnosis, and the significance of combination treatment. Fundamental questions regarding IFI have to be addressed over the next decade. The clinical studies described in this research agenda should provide a template and set priorities for the clinical investigations that need to be performed.

Intensive care medicine research agenda on invasive fungal infection in critically ill patients

PURPOSE OF REVIEW: Apparently immunocompetent critically ill patients represent an increasing population at risk for invasive pulmonary aspergillosis (IPA). The current review gives an update on the epidemiology, diagnosis, and management of IPA in the ICU. RECENT FINDINGS: Patients without apparent severe immunosuppression (e.g. chronic obstructive pulmonary disease, decompensated liver disease, etc.) represent the majority of ICU IPA cases. IPA diagnosis is problematic and the true incidence of IPA is difficult to be estimated because of the nonspecific clinical presentation. A user-friendly clinical diagnostic algorithm for IPA is valuable, particularly through a high negative predictive value. IPA carries a poor prognosis and has an important impact on hospital costs. Timely diagnosis and prompt administration of appropriate treatment may improve the outcomes. Intravenous voriconazole is the recommended primary IPA treatment, but liposomal amphotericin B also has clinical utility. Voriconazole presents bioavailability and toxicity issues, and drug level monitoring is advocated. Caspofungin or antifungal combinations are recommended as salvage therapy. SUMMARY: A high level of suspicion in critically ill patients presenting with Aspergillus-positive respiratory tract cultures or nonresolving pulmonary infection may lead to earlier IPA diagnosis. Dosage individualization may decrease treatment discontinuation and improve clinical efficacy.

Approach to invasive pulmonary aspergillosis in critically ill patients.

Contrary to hospital exposure, little is known about the indoor fungal exposure of hematology patients at home. The aim of our study was to investigate the mold exposure of hematology patients both at home and at hospital to assess their invasive aspergillosis (IA) risk. Fungal exposure was assessed by quantifying opportunistic molds at hospital during hospitalization and in homes of 53 hematology patients. IA was diagnosed in 13 of 53 patients and invasive fungal infection (IFI) in one patient. In hospital, no opportunistic species, or low levels of opportunistic species, were found in 98% of weekly controls. Only 2% of hematology intensive care unit (ICU) controls showed a high level of Aspergillus fumigatus spores in corridor air. Five patients IA were hospitalized during these periods. Seven dwellings of 53 (5/14 dwellings of patients with IA/IFI and 2/39 dwellings of non-IA patients) had a percentage of A. fumigatus and Aspergillus flavus to total mold (significant predictor variable of IA/IFI in our study, general linear model, P-value = 0.02) as high as 15%. Maintaining a 'zero Aspergillus' goal at hospital is essential, and establishing specific and individually opportunistic mold monitoring at home could help to further reduce the IA risk through continuous surveillance.

Evaluation of invasive aspergillosis risk of immunocompromised patients alternatively hospitalized in hematology intensive care unit and at home

This study aimed to consider the effects of incubation temperature (15, 25, and 37°C) and the type of growth media on fungal index microbial airborne (IMA) in a hospital building. Because there weren't any integrated guidelines for these variables, the results weren't comparable. Moreover, some studies have investigated the effects of ambient temperature and other factors by the active sampling method. Therefore, we tried to indicate the difference between use of several media and incubation temperature by passive method. Sampling was taken by an open plate during (1hr, 1 m above the ground). Results were shown that IMA was 112–552 CFU/m2/hr., while its highest level was detected in the dialysis ward at 15°C. The predominant fungal species were A.niger and Cladosporium. Besides, the distribution of IMA in indoor air of the hospital was verified base on the Fourier model (R2 = 0.41 and RMSE = 81.65). Moreover, there were significant differences between IMA at various temperatures (p

The effect of incubation temperature and growth media on index microbial fungi of indoor air in a hospital building in Shiraz, Iran

Summary

Invasive aspergillosis (IA) seems to be an emerging condition in intensive care units (ICUs). However, little attention has been given to the role of environmental factors that could increase the risk for IA in the ICU. The objective of this study was to determine the concentration of airborne fungi in three Brazilian ICUs, in an attempt to correlate fungal burden with the frequency of Aspergillus spp isolation from clinical samples of patients hospitalised in these units. During a 1-year period we quantitatively evaluated the presence of fungi in the air of three ICUs in Porto Alegre, Brazil. The quantity of fungi was correlated with environmental factors. Only one of the ICUs studied showed equal concentrations of Aspergillus conidia in the indoor air, in comparison with the outdoor environment. All cases of Aspergillus colonisation and IA cases observed during the study occurred in that particular ICU. Environmental factors have a direct influence on fungal spore concentration in the air in ICUs, as well as air filtration systems in air conditioners. Fungal contamination of the indoor air may influence the frequency of AI in ICU patients.

Cristiane Boff

Papers

The indoor air as a potential determinant of the frequency of invasive aspergillosis in the intensive care.

Technical note: the effect of different incubation temperatures on the recovery of Aspergillus species from hospital air.