Epidemiology and antifungal resistance in invasive candidiasis

In 2001, McNeil et al. reported that (in the USA) "from 1980 through 1997, the annual number of deaths in which an invasive mycosis was listed on the death certificate (multiple-cause mortality) increased from 1557 to 6534" (Table 1, Figure 1) [1]. Augmentation of fungal infections had been published earlier i.e. by Beck-Sague and Jarvis [2] and Edmond et al. [3] for the USA and by Lamagni et al. [4] for England and Wales (Figure 2). There are several possible reasons for this change. An important one might be the increase in lifespan in the populations of the developed world and the age related loss of immune-competence. An increase of systemic fungal infections is probably also due to more intensive treatment schemes for hematological and oncological patients causing prolonged neutropenic phases. Finally, more effective antibacterial treatments allow patients with infections to survive longer without necessarily overcoming the underlying diseases and thus leaving them susceptible to other opportunistic infections. Eggimann et al. [5] summarized prior surgery, acute renal failure, previous yeast colonization, neutropenia, antibacterial therapy, parenteral nutrition, and central venous catheters as risk factors for invasive Candidia infections.The increase in incidence of Candida infections barely preceded the introduction of fluconazole in 1990. This azole agent combined good activity against Candida albicans with reduced toxicity as compared to i.e. polyene anti-fungals. It is orally and parentally available and has a reliable that means linear pharmacokinetic profile [6], which makes it easy to handle. Not surprisingly, fluconazole became the agent of choice for many fungal infections as well as for prophylactic purposes, at that time often being applied in rather low doses. Although there is inconclusive evidence, many experts in the field believe that it was the selective pressure exerted by this therapeutic concept that caused changes in the epidemiology [7].