Overview
Candidemia is the isolation of Candida from one or more blood specimens. While it is more convincing to have two or more positive cultures, even a single culture should not be ignored.
An important debate took place for many years regarding the possibility that candidemia could be an insignificant finding. It is possible for any organism in a blood culture to represent contamination of the specimen during the collection process, and early reports also suggested that candidemia was often a trivial process that could simply be ignored [664]. This idea was gradually reversed by reports showing that candidemia was associated with significant morbidity and mortality. Mortality rates of 26-75 percent are reported in series containing mostly non-cancer patients [762, 993, 1212, 1446, 1790, 1904], while mortality rates of 30-72 percent are reported for series that contain mostly cancer patients [762, 1062, 1224, 2332].
Thus, it cannot be disputed that there are individual cases where candidemia resolves satisfactorily without treatment [664, 762]. However, there is no ready way for a clinician to know which patient will have no further problems and which patient will soon begin to deteriorate. Given the high mortality and morbidity of candidemia, a recent international consensus conference concluded that essentially all patients with candidemia should receive therapy [649].
Epidemiology
Candidemia has become one of the most important nosocomial infections over the last two decades. An increment in its frequency of more than 400 times as agent causing bloodstream infections, was noted during the 1980’s [168]. During the 1990’s Candida spp. were the fourth most common agent causing nosocomial bloodstream infection [646].
C. albicans has historically been the most frequent cause of candidemia. However, the frequency of candidemia due to non-albicans species of Candida rose during the 1990s [4, 1641, 1846, 2444, 2445] and recent surveys find that C. albicans causes only about half of all cases of candidemia [1717, 1779]. The species that have grown in frequency have been C. tropicalis, C. glabrata, and C. parapsilosis [993, 1150, 1453, 1778, 2465]. While C. tropicalis and C. glabrata have increased in frequency in the adult populations, C. parapsilosis seems to have a special affinity for pediatric (and especially neonatal) settings [1327, 1718, 1871]. Among bone marrow transplant patients, C. krusei has also been noted to increase in frequency [2444].
The causes of this change in epidemiology are not entirely clear [2422]. The use of fluconazole in prophylactic regimens for severely immunosuppressed patients has been strongly associated with the changes in the etiology of candidemia in this population [4, 2444, 2445]. However, the same phenomenon has occurred in populations not exposed to this agent [1525].
The clinical manifestations of candidemia range from nothing more than fever to overt and life-threatening sepsis. When candidemia is detected, it is also helpful to consider it in the context of one of the four overlapping forms of invasive candidiasis.
Candidemia in patients with HIV/AIDS
Despite oropharyngeal candidiasis being the most frequent fungal infection affecting patients with HIV and AIDS, the invasive forms of candidiasis are rare in this immunosuppressed population. Isolated case reports and a single retrospective study have been published on candidemia in HIV-infected adults [1282, 1303, 2263]. These cases have occurred in patients with end-stage-AIDS (CD4+ counts < 50 cells/mm3) and extensive prior therapy with fluconazole. Other than that, the risk factors for HIV-infected individuals who develop candidemia are similar to those in non-HIV-infected individuals: central venous catheters, parenteral nutrition, and previous use of broad spectrum antibiotics. Hence, this complication appears to represent a typical nosocomial infection rather than a condition related to the presence or absence of HIV. From a therapeutic perspective, the frequent use of azoles in HIV-infected patients means that amphotericin B should be used as the first-line antifungal agent when invasive candidiasis is seen [1303].
Therapy
Treatment of candidemia has two fundamental elements. First, the most likely source of the fungemia should be identified and treated, if possible. In the non-neutropenic patient, an intravascular catheter is the most likely source and removal of such catheters is often valuable. The reader is referred to our discussion of intravascular catheters and candidemia.
Other common sources are the urinary tract and localized infections [1904]. If possible, the local conditions at these sites should be treated (e.g., eliminate urinary obstruction, drain an abscess).
Second, an antifungal agent should be employed. Of the available antifungal agents, only amphotericin B and fluconazole are readily available in the parenteral formulations required for treating critically ill patients. To date, two large randomized trials [1790, 1904] and two large observational series [71, 1642] have examined the relative utility of these agents and found that they are generally comparable, particularly as treatment of C. albicans fungemia in non-neutropenic patients. Outside of this setting, the choice of therapy is less certain and follows the (A):general rules for treatment of invasive candidiasis. The recently licensed intravenous preparation of itraconazole is currently being studied as therapy for invasive candidiasis, but no data on its relative utility are yet available.