Although the management of invasive fungal infections has made considerable progress in recent years, the prevalence of these infections continues to significantly increase, which warrants close attention from medical care providers. The incidence rate of fungal bloodstream infections in ICU patients in developing countries is 4 to 15 times higher than that in developed countries.In this study, the prevalence of fungal bloodstream infections in ICUs in the three hospitals surveyed in Meizhou from 2008 through 2017 was 0.38%. Compared with fungal bloodstream infections in ICU in developing countries, where the prevalence ranges from 0.22 to 4.1%[5–8], those in Meizhou were low and more comparable to the prevalence among developed countries, where the rates are reported to be 0.024–0.687%[9–11].
Our study results showed that the prevalence of fungal bloodstream infections was lowest in 2008 and highest in 2016, with an overall increasing trend. This might be related to the large-scale use of broad-spectrum antibiotics, corticosteroids, and immunosuppressive agents and to the rapid increase in immunocompromised populations in recent years. In addition, ICU stays are associated with various invasive procedures that carry increased risk of bloodstream infections, such as indwelling catheters, tracheotomy, mechanical ventilation, and hemodialysis[4,12–15].
The 98 strains of fungi isolated from ICU blood cultures were predominantly Candida spp., accounting for 90.8% (89/98) of all strains. Nearly one-half were C. albicans (42.9%), leaving 48.0% that comprised C. tropicalis, C. glabrata, and C. parapsilosis. The proportion of non-albicans species increased over the study period to comprise mainly C. tropicalis and C. parapsilosis, which is similar to the results of other reports[9,12–15].
Candida albicans were more sensitive to azole drugs, such as fluconazole, than other Candida spp. Because azole drugs are those most commonly used for clinical fungal treatment, this might explain the increase in the proportion of non-albicans infections. Candida tropicalis has a high infection rate in tropical Asia[8,32].The Meizhou area is located in the southern part of China and has a subtropical climate, which might contribute to the high rate of ICU fungal infections in that area. Other reports show that C. parapsilosis is frequently carried on the hands of medical staff and has a tendency to form a biofilm on medical devices, which might explain its increasing prevalence in the area[16–17].
In this study, nine patients were also infected with Cr. neoformans, Ta. marneffei, Pi. pastoris, and S. cerevisiae. Although the pathogenic ability of Cr. neoformans and Ta. marneffei was strong, that of Pi. pastoris and S. cerevisiae was weak. Pichia pastoris is used mainly as a research vector and is rarely isolated from human blood.
Most guidelines recommend the use of echinomycin for antifungal infections; however, fluconazole is the most commonly used antifungal drug, and although it has a high mortality rate when used to treat candidemia, it is still widely used in developing countries. In an Indian multicenter study of ICU-acquired candidemia, 64% of the patients were treated with fluconazole.In this study, although most Candida spp. were more sensitive to azole drugs, the susceptibility of C. glabrata to azole drugs was relatively low, which suggests that testing for antimicrobial susceptibility is necessary for the correct selection of antifungal drugs.
ICU patients have a relatively high mortality rate, often from infections. In addition, a variety of invasive procedures such as indwelling catheter, tracheotomy, mechanical ventilation, and hemodialysis, as well as organ transplantation and other new technologies, have become more common. The lack of early fungal diagnostic techniques in many hospitals has affected the early diagnosis and treatment of fungal bloodstream infections; consequently, the incidence of fungal bloodstream infections has rapidly increased, resulting in a higher mortality rate[17–20].
Age is a significant risk factor for nosocomial infections, particularly fungal infections of the bloodstream [22, 23]. Candida parapsilosis more frequently infects younger populations, while C. glabrata and C. tropicalis are more common among the elderly. In this study, age was an independent risk factor for infection, and the mortality risk increased with age (Table 4) for several reasons. First, older patients are more likely to have underlying diseases, low immunity, and decreased organ function, which would make them more susceptible to fungal bloodstream infections. Second, older patients might be given fewer antifungal treatments than younger patients, the practice of which is independently associated with a poor prognosis.When the patient’s condition deteriorates, the elderly patient or his or her guardian might decide to stop treatment if the patient’s chance of recovery is low, the costs are higher if treatment is continued, or the patient’s medical insurance does not cover the antifungal drug. Poor care of elderly patients by society and family members, as well as the relatively lagging development of the medical insurance industry, are important problems that affect the health of the elderly in China. To effectively reduce the high mortality rate for elderly patients with fungal disease, measures should be taken to resolve the above-mentioned problems and ensure that antifungal treatment is administered.
Studies have shown that diabetes, tumors, neutropenia, and chronic renal insufficiency are risk factors for fungal bloodstream infections[24, 25]. In this study, diabetes, cardiovascular disease, and three or more underlying diseases were strongly associated with mortality from the infection (Table 3). Logistic multiple regression analysis showed that three or more underlying diseases were among the independent risk factors (Table 4), which might be associated with patients with multiple long-term underlying diseases and many iatrogenic invasive procedures. Treatments such as recent surgery, solid organ transplantation, hemodialysis, longer ICU stay (≥7 d), mechanical ventilation, use of cardiovascular catheters, total parenteral nutrition, and catheters are other suggested risk factors for fungal bloodstream infections[26,27]. We found that length of stay in the ICU was also an important risk factor for mortality.
The APACHE II score is an important system used to determine the severity of a disease and estimates of mortality and plays an important role in judging the prognosis of bloodstream infections. The higher the APACHE II score, the lower the patient’s immune function; the higher the probability of infecting pathogens, such as fungi; and the higher the chance of death. Serum albumin levels are also important factors that affect bloodstream infections in hospitals[29–31]and are associated with increased mortality from candidemia. Low serum albumin levels affect the body’s immune function, including barrier function, leukocyte phagocytosis, and complement function, resulting in prolonged infection time, anti-infective effects, and increased mortality. Hypoalbuminemia can lead to serious complications, such as sepsis and septic shock[29–30]. The results of this study showed that the APACHE II score and serum albumin levels were two important independent mortality risk factors in ICU fungal infections (Table 4). According to our findings, we recommend that patients with APACHE II scores > 19 and serum albumin < 25 g/L should receive immediate clinical attention and increased vigilance for possible cases of fungal bloodstream infections.