In the past, systemic fungal infections have been considered to be a problem only for neutropenic patients. However, beyond the risk factor of neutropenia, more recent data suggests that half of all hospital-acquired fungal infections have occurred in critically-ill surgical patients.
species account for greater than 80% of all fungal nosocomial isolates [62
] unlike Aspergillus
species and the less common Fusarium
species which comprise only 10% of the remaining nosocomial isolates. Invasive candidiasis is the most frequently occurring invasive fungal infection and occurs most commonly in immunocompromised solid organ transplant recipients, those receiving chemotherapy, and those having multiple, complex abdominal surgical procedures.
As stated earlier, Candida
species have become the fourth most common nosocomial bloodstream isolate, exceeded only by coagulase negative Staphylococcus
, Staphylococcus aureus
, and Enterococci
. This fact is particularly important when it is recognized that less than half of these cases with invasive Candidemia documented at autopsy have had a positive premortem blood culture for Candida
infections have a mortality rate averaging between 25 and 38%. The specific Candida
species accounting for Candidemia in high-risk populations have shifted over the last decade from C
to more nonalbicans species, with approximately half the reported cases being due to the nonalbicans species [5
]. More importantly these nonalbicans species (C
, and C
) have a greater mortality rate, account for the greater length of stay in ICUs, and are associated with greater rates of renal failure, thrombocytopenia, malignancy, and mechanical ventilation. The risk factors recognized for Candidemia in general include complicated abdominal operations, second operations, parenteral nutrition, the use of broad-spectrum antibiotics, the use of multiple vascular catheters, prior recognized Candida
colonization, mechanical ventilation, and renal replacement therapy [58
In a prospective clinical trial examining the risk factors for Candida
bloodstream infections in more than 4,000 surgical patients, those identified included previous surgery (RR = 7.3), acute renal failure (RR = 4.2), parenteral nutrition (RR = 3.6), and the presence of a triple lumen catheter (RR = 5.4) [58
]. Other risk factors identified in other studies included ICU hospitalization >4 days, diabetes mellitus, HIV infections, central lines, neutropenia, chemotherapy, cancer (especially hematologic cancers), use of broad-spectrum antibiotics, the use of 3 or more antibiotics, and mechanical ventilation >2 days.
The initial response to a suspected Candidemia is to institute antifungal therapy with either voriconazole or an echinocandin and the removal of all vascular lines. It is important to recognize that blood cultures are positive in cases of invasive Candidemia in less than 50% of the time. Invasive Fusarium infections, similar to Candida infections, are detectable with blood culture in less than half of the cases. Worse invasive Aspergillus infections are rarely identifiable with blood cultures.
First line therapy for Candidemia remains controversial as studies have reported similar efficacy rates with amphotericin, fluconazole, echinocandins, and voriconazole [65
]. With the increasing frequency of nonalbicans species especially in critically-ill patients the use of a broad-spectrum agent such as voriconazole, an echinocandin, or amphotericin may be more appropriate at least until the specific Candida
species is identified to avoid the increased mortality occurring in cases wherein an inappropriate therapeutic agent is initially started. The limitation of intravenous voriconazole is its formulation with cyclodextrin which accumulates in individuals with impaired renal function. The many adverse effects of amphotericin identified earlier limit its use. Among the echinocandins, only anidulafungin has shown superiority over fluconazole [55
]. Moreover, its efficiency, safety, and lack of cytochrome P450 metabolism suggest that it should be considered as a first line option for invasive candidiasis infection. Regardless of the choice of a specific echinocandin over fluconazole, echinocandins are recommended for use in individuals who are either critically ill or hemodynamically unstable.
Candidemia is associated with an increased cost of hospitalization estimated at $68,311 (95% CI $57,513–$79,108) and longer length of stay estimated at 23.1 days of hospitalization (95% CI 19.3–26.8 days) as compared to that of a DRG identified control population without Candidemia [70
The incidence of invasive fungal infections in solid organ transplant recipients ranges from 5–42% [73
]. Depending upon the organ being transplanted, being lowest for pancreas recipients and greatest for liver graft recipients.Candida
species, and to a lesser degree Aspergillus
, account for the vast majority of invasive fungal agents in solid organ transplant recipients [14
and endemic mycoses occur late, typically a year or more after transplantation.
Currently, most liver transplant centers use antifungal prophylaxis in the early postoperative period in individual recipients having either a complicated or repetitive posttransplant surgical procedures [74
]. The principal problem associated with the use of azole therapy in transplant recipients is the interaction with calcineurin inhibitor agents that consequently requires a dose adjustment in one or the other agents.