Fungal infections and critically ill adults Martin Beed FRCA FFICM DM Richard Sherman MRCP FRCA FFICM 1A02,2C03 Stephen Holden MSc FRCPath Key points Although there are many different species of oropharynx, or upper and lower airways. It can fungi, relatively few are responsible for human ill- sometimes be difficult to tell whether or not a The incidence of fungal nesses. Fungal infections associated with critical positive fungal culture is indicative of invasive diseases in critically ill patients is thought to be illness are thought to be increasing in incidence, disease or simply the result of the capture of increasing, most commonly possibly as a result of the increasing population of normal flora. involving Candida and immunocompromised individuals, more aggres- Aspergillus species. sive medical interventions and procedures, and Fungal infections in the Risk factors for invasive fungal increased use of anti-bacterial therapies. critically ill infections include: A list of risk factors for fungal infections can be immunocompromised states, including neutropaenia; Structure and classification foundinTable1. Admission to intensive care unit intravascularorother of fungi (ICU) has been identified as a risk factor asso- catheters (especially if ciated with invasive fungal infection, and there is parenteral nutrition is Fungi are eukaryotes (i.e. having membranes evidence suggesting higher rates of non-infective involved); prostheses; that cover the nucleus and other intracellular fungal colonization and of horizontal transmission anatomical barrier loss organelles); this makes them structurally similar occurring within critical care areas. The fungi (for example, burns); broad- to animals and plants, but different from prokar- most commonly associated with infections in spectrum antimicrobial usage. yotes such as bacteria. Fungi have rigid cell the critically ill are Candida and Aspergillus. Delays in commencing walls containing chitin, chitosan, mannan, and Less common causes include Zygomycetes, antifungal therapies are glucan. Fungi also have cell membranes struc- Histoplasma, Cryptococcus, Blastomyces,and associated with worse turally different from that of animals as they Coccidioides. These names often do not describe outcomes, and as a result of contain ergosterol rather than cholesterol. specific fungi, rather a species or class of fungi. As the difficulties associated with The simplest subclassification of fungi respon- fungi are opportunistic, the list of rare examples confirming fungal infections, sible for human infections is as either moulds identified as human pathogens continues to grow. empirical therapy is often (e.g. Aspergillus species) or yeasts (e.g. Candida Symptoms associated with mycoses (diseases commenced in high-risk species). Under the microscope, yeasts are small patients. caused by fungi) are often non-specific general- rounded cells that can bud, while moulds demon- ized inflammatory responses (for example, Geographicalvariationinthe strate a stranded, filamentous appearance caused pyrexia and tachycardia), or specific end-organ prevalence of fungal species by hyphae. Some fungi can exist in both forms damage (for example, hypoxia or confusion). In will affect the choice of (these are said to be dimorphic, e.g. Blastomyces), antifungal therapy. neutropaenic or immunocompromised patients, and some yeasts can develop pseudo-hyphae (e.g. white cell counts are often unhelpful. Cutaneous Candida species). When the hyphae of filament- Martin Beed FRCA FFICM DM and mucous membrane stigmata can be asso- ous fungi develop a matted, intermeshed network, ciated with systemic fungal infections (for Consultant in Intensive Care and 1 Anaesthesia this is referred to as a mycelium. example, oral candidiasis, or cutaneous eschars Nottingham University Hospital Fungi are slow-growing, with cell-doubling caused by invasive Aspergillus), but these are Nottingham NG5 1PB, UK times often as long as days, which can affect the Tel: þ44 (0) 115 9691169 uncommon. A high-index of suspicion is Fax: þ44 (0) 115 9936563 ability to identify clinically relevant infections. required to identify fungal infections, especially E-mail: [email protected] Reproduction may be sexual, asexual, or both; as delays in treatment are associated with worse (for correspondence) and may result in the production of ‘daughter outcomes.2 Richard Sherman MRCP FRCA FFICM cells’ or spores. Many fungi and spores are envir- Consultant in Intensive Care and onmentally ubiquitous, for example, Aspergillus Candida Anaesthesia species are commonly found in soil, and their Nottingham University Hospital spores are prevalent in the atmosphere. Candida species are responsible for the majority Nottingham NG5 1PB, UK Several fungi are common human flora (for of fungal infections in critically ill patients, with Stephen Holden MSc FRCPath example, Candida occur within the human gut) Candida albicans being the most common or- Consultant Microbiologist or are able to colonize structures such as the gut, ganism in the UK. The Candida genus also Nottingham University Hospital Nottingham NG5 1PB, UK doi:10.1093/bjaceaccp/mkt067 Advance Access publication 18 December, 2013 Continuing Education in Anaesthesia, Critical Care & Pain | Volume 14 Number 6 2014 & The Author [2013]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. Downloaded 262from https://academic.oup.com/bjaed/article-abstract/14/6/262/247636 by guest All rights reserved. For Permissions, please email: [email protected] on 13 November 2017 Fungal infections and critically ill adults Table 1 Risk factors thought to affect the incidence of fungal disease Candida spp. are often isolated from respiratory secretions Immunocompromise Human immunodeficiency virus obtained from critically ill patients, although true infection of the Haematological malignancy lower respiratory tract is rare. Growth of Candida spp. from respira- Haematopoietic stem cell transplant tory specimens alone should not prompt the use of antifungal Neutropaenia Chemotherapy therapy in most patients. Candiduria is also difficult to interpret and Immunosuppressant usage, for example: can represent conlonization of urinary catheters or the lower urinary Solid organ transplant tract in the absence of symptoms. Alternatively, Candida spp. may Long-term steroid usage Liver disease cause an ascending pyelonephritis frequently complicated by the de- Diabetes velopment of fungal balls, or spread to the urinary tract by haema- Renal failure and haemodialysis togenous dissemination. The presence of pyuria is of limited value Burns Malnutrition in determining the significance of candiduria as it may represent bacterial co-infection in as many as 25% of cases. In severely im- Respiratory compromise Suppurative diseases, for example: Cystic fibrosis munocompromised patients, fever and candiduria may be a surrogate Bronchiectasis marker of disseminated disease and require treatment; in other Chronic obstructive pulmonary disease patient groups removal of predisposing factors such as indwelling Tracheal intubation and mechanical ventilation catheters may be sufficient.4 Invasive procedures Central venous catheters Candida commonly colonizes urinary catheters and intravascular Parenteral nutrition Urinary catheterization devices (especially in the presence of parenteral nutrition) and Intra-peritoneal dialysis catheters removal of the indwelling device is often required to enable the Implanted prosthetics and devices, for example: eradication and cure of any associated infection. An often-debated Heart valves topic is the need for central venous line removal in cases of candi- General Increased use of broad-spectrum antibiotic therapy daemia. In non-neutropaenic patients, there is evidence of improved Gut lumen contamination of body compartments, for example: outcomes after early line removal, regardless of the putative source. Faecal peritonitis Where C. parapsilosis is the causative organism, line removal Oesophageal perforation should be undertaken whenever possible as the organism is thought I.V. drug misuse to form resistant biofilms. The two most commonly cited complications of disseminated can- didiasis are infective endocarditis and ocular involvement. This has led to recommendations that patients with candidaemia should contains other species that cause human infection, including: undergo both echocardiography and dilated retinal examination. Candida tropicalis, Candida parapsilosis, Candida glabrata, However, a more targeted approach has also been suggested whereby Candida krusei, and Candida dublinsiensis; these are collectively persistently positive blood cultures despite treatment and removal of known as ‘non-albicans’ species. The incidence of non-albicans an infected focus indicate the need to investigate for endovascular Candida varies with geographical location and overall appears to be involvement. Although patients who report new visual disturbance increasing, possibly related to the increased use of the antifungal should be prioritized for ophthalmological review, early ophthalmo- agent fluconazole, which might select out resistant non-albicans logical review is required even in the absence of symptoms as infec- Candida species, such as C. glabrata and C. krusei. tion may be clinically silent, especially in critically ill patients.5 Candida infections (candidiasis or candidosis) are mostly superfi- cial, affecting mucous membranes or skin. Invasive candidiasis Aspergillus occurs when Candida