ReviewCandidemia and invasive candidiasis: A review of the literature for the burns surgeon
Introduction
The ultimate goal of burn wound management is closure and healing of the wound. Early surgical excision of burned tissue, with extensive debridement of necrotic tissue and grafting of skin or skin substitutes, greatly decreases mortality rates associated with severe burns. Moreover, advances in patient care including increasing use of broad-spectrum antibiotics, immunosuppressive and anti-neoplastic agents, prosthetic devices and total parenteral nutrition (TPN) [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], have been associated with an increased incidence of life-threatening opportunistic fungal infections [4], [6], [11] as patients with impaired host defenses, including severe burns, now survive longer.
Candida species (spp.) are commensal and opportunistic pathogens present on virtually all humans. Candida spp. are frequently isolated from mucosal sites where they are generally considered to be colonizing organisms [1], [2], [12], [13], [14]. However, bloodstream infections (BSIs) due to Candida spp. with or without disseminated candidiasis are now major causes of morbidity and mortality in hospitalized patients, including severe burns patients, worldwide.
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Epidemiology
Patients at highest risk of Candida bloodstream infections (BSIs) are in neonatal, surgical, hematological and burn units [2]. The precise incidence rates of candidemia remain difficult to establish, partly due to the use of different denominators between published studies. However, since the 1980s, Candida spp. have ranked fourth as the most common cause of BSI in data from the US Centers for Disease Control (CDC) National Nosocomial Infections Surveillance (NNIS) system; also accounting for
Significance of candida sepsis
The attributable mortality rate of candidemia from various studies is estimated to be >30% (range 24–60%, median 38%), with a crude mortality rate of >50% (range 13–90%, median 55%) reported, amongst widely divergent patient cohorts [1], [4], [5], [10], [11], [14], [15], [17], [18], [19], [20], [23], [24], [25], [26], [27], [34], [36], [37], [41], [42], [43], [45], [46], [47], [48], [49], [50], [51], [52]. Patient outcomes appear worst for C. glabrata and C. tropicalis infections, and to a
Risk factors
There are many risk factors for candidal colonization and infection including: host barrier disruption (e.g., major burn), acute or chronic graft versus host disease particularly with gut involvement, antibiotics, neutropenia, cancer, invasive procedures, ICU admission, steroids and hyperglycemia, severe catabolism secondary to injury, total parenteral nutrition (TPN), mechanical ventilation, prolonged hospitalization, malnutrition, multiple medical co-morbidities and stress ulcer prophylaxis
Pathogenesis
Candida spp. infections typically originate from the patient's endogenous microflora [3], [5], [10], [13], [29]. The major steps in the pathogenesis of invasive candidiasis include: (1) increasing fungal colonization, characteristically secondary to broad-spectrum antimicrobials; (2) failure of skin and mucosal barriers, often a result of the use of intravascular devices, severe burns or recent surgery and; (3) immune dysfunction (e.g., neutropenia) that enables fungal access and ultimately
Candidiasis in burns
Invasive candidiasis occurs in 2–21% of burn patients, with a crude mortality of 30–90% [7], [44]. Up to 30–63% of burn patients have at least one positive culture for Candida spp. and there is a 3–5% incidence of candidemia [23]. Burn wounds are a major risk factor for fungal infections; rising further with increases in burn wound size and depth, and patient age [32], [33], [59], [63]. Burn patients with central venous catheters (CVCs) have amongst the highest risk for candidemia of any
Diagnosis
Candida species can cause disease anywhere, thus presenting a very wide spectrum of clinical manifestations (see Table 3) [5], [8], [11], [15], [16], [27], [29], [35], [46], [65]. Clinical presentation with candidiasis also depends on the patients’ immune status, chiefly the ability to produce adequate inflammatory responses. These factors can make candida infection difficult to diagnose. Diagnosis is additionally often delayed by low-levels and intermittent presence of Candida species in
Prevention
The most important measures against candidiasis are to minimize modifiable predisposing factors. Skin and gastrointestinal tract are the major reservoirs of Candida species [41]. Invasive procedures result in disruption of the integrity of the cutaneous barrier [41]. While administration of broad spectrum antibiotics select for Candida spp. at mucosal surfaces, ineffective antibacterial therapy in the critically ill with septicemia likely increases patient mortality [2]. Reduction in Candida
Therapy of candidemia and invasive candidiasis
The best treatment strategy for serious Candida spp. infections remains contentious. Conventional amphotericin B deoxycholate (cAmB-D) has served as the gold-standard treatment, but its toxicity underscores the need for alternative antifungals. Newer options for patients with candidemia or invasive candidiasis include lipid formulations of amphotericin (L-AmB), fluconazole and broader-spectrum triazoles such as voriconazole, and the echinocandins (caspofungin, micafungin and anidulafungin). The
Topical therapy
Given increased rates of fungal infections have occurred in burn patients, in recent years, use of topical antifungals is an appealing way to prevent invasive candida wound infection. Traditional topical antimicrobial agents that contain silver, such as silver sulfadiazine, confer wide antimicrobial coverage and are most useful for deeper burns (e.g., third-degree burns). Four widely used topical antimicrobial agents in burns—silver sulfadiazine cream, mafenide acetate cream, silver nitrate
Conclusions
Candidiasis is an emerging infectious disease. Due to difficulty in diagnosis and its high associated high mortality rates, approaches to prophylactic or empirical therapy in high-risk patients have been proposed; however, prophylactic and pre-emptive antifungal therapy in burn patients remains controversial. When used, the choice of antifungal agent depends upon local patterns of resistance and incidence of non-albicans Candida isolates, previous exposure to antifungals, patient
Conflict of interests
There are no conflicts of interests or funding directly related to this article. However, Dr. Chris Heath is/has been on Antifungal Advisory Boards for Gilead Sciences, Pfizer Australia, Merck Sharp and Dohme, Australia, and Schering-Plough, Australia, and has received honoraria for lectures and/or travel assistance to scientific meetings from Gilead Sciences, Australia, Merck Sharp and Dohme, Australia, Basilea Pharmaceutica Ltd, Switzerland, and Schering-Plough, Australia.
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