Although new antifungal drugs such as caspofungin have been widely used in clinical treatment[16], the mortality of fungemia has not been significantly reduced[6], A predictive model for the 30-day mortality of fungemia in ICUs was developed, incorporating the following variables: age, renal failure, liver disease, glucocorticoid therapy, antifungal therapy, RR, INR and platelet count.
Patients with fungemia have an increased risk of death with age. Aging is a natural process which involves multiple factors and is characterized by “the accumulation of degenerative processes that are in turn underpinned by multiple alterations and damage within molecular pathways[17].Although many theories have been proposed to explain aging as a phenomenon, none of them has been able to fully explain the mechanisms that drive the fundamental process(es)[18].
Infectious diseases are considered important complications of renal failure[19].Fungemia is a serious BSI for patients with renal failure.Central venous catheterization is the only risk factor independently associated with BSIs due to non-albicans Candida species. Impairment of the innate and adaptive immunity predisposes patients with chronic kidney disease to BSIs.[20]In patients with fungemia, renal failure leads to difficulties in infection control and increases the mortality.Glucocorticoids reduce inflammation and immune activation[21] and are high risk factors for fungemia.Treatment of mice with mycosis using glucocorticoids leads to multiplying of fungi in large numbers and an increased mortality[22].
In this study, liver disease. is a risk factor for dying of fungemia within 30 days.The liver has important functions in the human body, including material metabolism, protein synthesis, detoxification, immune regulation and so on[23]. Liver disease may lead to pathological changes in other organs, such as hepatopulmonary syndrome and hepatorenal syndrome; on the other hand, metabolic syndrome and glucose intolerance in fatty liver can lead to cardiovascular disease[23]. When infection such as fungemia occurs, it can induce liver tolerance and desensitization to lipopolysaccharide and endotoxin, leading to immunosuppression[24, 25].
This study showed that the use of glucocorticoids in ICU patients with fungemia increased 30-day mortality. There is a consensus that glucocorticoid therapy is a high risk factor for invasive fungal infections[26]. Glucocorticoids are standard therapy for the control of inflammation and immunosuppression in patients with various immune diseases, such as allergy、asthma、arthritis、 inflammatory bowel disease and so on[21, 27]. However, they have many side effects, including osteoporosis, hyperglycemia, insulin resistance, hypertension, muscle atrophy, severe infection, Cushing's syndrome, peptic ulcer and neuropsychiatric disorder[21]. High-dose and prolonged systemic glucocorticoid therapy is associated with a high risk of invasive fungal and poor outcomes[26].
In this study, antifungal therapy improved the prognosis, however,the mortality was still high.SiriluckAnunnatsiriet et al.[28]reported that there was no difference in the mortality rate between patients receiving antifungal treatment and those not.Zengli Xiaoet al.[29]reported that there was no difference in the mortality among patients receiving antifungal treatment. Garnacho-Montero, J et al[30].found that the empirical use of an echinocandin in critically ill patients with documented candidemia reduced the 30-day and 90-day mortality rates significantly.Current antifungal therapies for fungemia are still controversial and have not been proved to be effective by randomized controlled trials.
This study shows that RR provides important information about the prognosis of fungemia.It is the first time for RR to be identified as a prognostic marker of fungemia.Our data indicate that its prognostic significance remains unchanged in the modern era of acute treatment.RR increases after acute lung injury to compensate for insufficient ventilation. During the critical stage, respiration is suppressed through the central nervous system and peripheral receptors.RR is an indicator of the severity of the damages to the respiratory system.It can also predict the outcome after acute myocardial infarction[31].
In this study, thrombocytopenia is associated with an increased mortality. Thrombocytopenia is common among critically ill patients, and has been reported to be associated with a poor prognosis[32].An acute reduction in platelet count is seen during the early phase of many diseases.Some mechanisms may lead to thrombocytopenia in patient with fungemia. Platelet production may be impaired by bone marrow depression caused by infectious fungi. Besides,ongoing consumption of platelets, for example, in the framework of disseminated intravascular coagulation and sepsis, may also play an important role. International normalized ratio (INR) was a risk factor for mortality in ICUs patients with fungemia. Coagulopathy is strongly associated with the severity and mortality of sepsis, and mortality increases with prolonged INR[33]. Platelets also play an important role in sepsis, where platelets and INR co-locate at the intersection of the immune system, the coagulation cascade, and endothelial cells[33].
There are three limitations in this study. Firstly, the sample size is relatively small because the data are from a single center and the incidence of fungemia is low, which may lead to nonuniversal findings.Secondly, this study is a retrospective study rather than a randomized controlled trial, which inevitably leads to bias. Lastly,death from candidemia was not differentiated from that from deterioration of underlying diseases because it could be very difficult to determine the exact cause of death in critically ill patients.
The 30-day mortality risk predictive model for ICU patients with fungemia constructed in this study has good predictive ability.Attested by the external validation results, this predictive nomogram boasts a relatively high accuracy in early identification of high-risk patients.Therefore, it is able to help control the risk of death from fungemia within 30 days in ICUs and may hopefully provide a 30-day mortality risk screening tool for ICU patients with fungemia.