We demonstrated that the incidence of candidemia in patients admitted to IMWs is increasing. Our patient population showed to be fragile being affected by multiple comorbidities. The mortality rate was 28% on day 30. Overall, these figures are quite alarming indicating a new group of patients who are at risk of developing this life-threatening infection.
In this study, we showed that specific clinical and microbiologic factors were associated with a negative outcome. In particular, the presence of neutropenia and pneumonia increased the risk of death by approximately seven- and two-fold, respectively. The first variable can be easily explained by the fact that neutrophils are key participants in the defense against fungal infections . We also can speculate that the occurrence of pneumonia, along with other clinical features (i.e., higher prevalence of cardiovascular diseases and solid tumors), worsens the overall clinical situation in a patient population in which the risk of death is already high. Data from the literature show that several underlying conditions in IMWs patients with candidemia might represent independent risk factors for mortality [4–9]. One study evaluated 274 patients and found that cirrhosis and neurologic diseases were independently associated with increased risk of death . Other clinical conditions such as chronic obstructive pulmonary disease and chronic kidney failure were predictors of mortality [7, 16]. Finally, the presence of solid tumors has been linked to a poor prognosis .
Mortality rate has been rarely related to the species of Candida. Here, we found that being infected with C. albicans represented an independent risk of mortality. It must be noted that C. albicans possesses virulence traits, such as the ability of transition from blastospore to hyphae, the presence of adhesins and the secretion of hydrolytic enzymes which make it more pathogenic than other species . Furthermore, the amount of biofilm produced by isolates of C. albicans is generally higher than those produced by other species including the new emerging MDR yeast C. auris . There are reports indicating as IMWs patients with candidemia due to C. tropicalis have a significantly higher mortality rate than patients infected with other species [7, 20]. It is interesting to note that C. tropicalis possesses well characterized virulence factors which resemble those of C. albicans .
Interestingly, we found that resistance was uncommon among isolates of Candida spp. causing infections in our patients. Only 2% of C. albicans isolates showed in vitro resistance to fluconazole. These data are in line with that recently observed in the literature. One international study investigated the in vitro activities of fluconazole and echinocandins against over 15,000 clinical isolates of Candida spp. and found that the overall resistance rate was rare. However, this study showed that a slow and steady emergence of resistance to both antifungal classes was observed in C. glabrata and C. tropicalis isolates .
Although our study was not designed to compare antifungal regimens, we observed that the choice of drug utilized as primary therapy (i.e.: fluconazole vs echinocandin) did not influence the outcome. Literature data report conflicting results on this issue [7, 15, 23–26]. A multicenter study investigated the role of antifungal therapy in the outcome of C. glabrata bloodstream infections and found that initial fluconazole treatment, a therapeutic drug regimen which might be suboptimal for infections caused by this species, was not associated with a poorer outcome than that obtained with echinocandins or L-AmB regimens . Similarly, one regional italian study involving 230 candidemic patiens admitted to IMWs, showed that the type of antifungal treatment did not influence the outcome . On the contrary, one recent study investigated the clinical characteristics, management and outcome of 111 patients with invasive candidiasis hospitalized in IMWs and found that fluconazole as initial therapy was associated with an increased risk of death at 90 days . Overall, these data further underline the discrepancy between the clinical practice and the results of randomized clinical trials. Indeed these studies, as well the international guidelines, indicate the superiority of echinocandins for the primary treatment of invasive candidiasis [25, 26].
The finding that 19% of our population did not undergo any therapy is worrying. This phenomenon, which has been already described in other studies [7, 27], is difficult to explain. One can speculate that the rapid clinical evolution of some patients along with a diagnostic delay might play a role in the lack of antifungal intervention. Another plausible reason is the efficiency of the antifungal stewardship in a given hospital/medical department. It has been recently demonstrated that the lack of any antifungal regimen in candidemic patients admitted to IMWs range from 6–12% and from 17–25% in hospitals where the infectious disease consultant is available or unaivalable, respectively . It is intriguing to note that the lack of any antifungal therapy did not affect the outcome. Although we observed a higher proportion of death in untreated vs treated patients (23% vs 17%), the difference was not significant. Whether these unexpected results were due to the fact that untreated patients were less clinically compromised or better managed in controlling the source of infection was not investigated.
Our study have several limitations. First, it is a retrospective observational study and the lack of a control group preclude any causality inference in this setting. Second, since our data come from a single-center experience, our findings may not be relevant to other patient populations. It must be noted, however, that several IMWs differing target populations were involved in this study thus increasing the heterogeneity in terms of patient care. Third, although we have made every attempt to collect and analyze as much clinical data as possible to reveal useful information for the patients management, some diagnostic procedures were performed according to the physician discretion and proportion of patients who underwent correct screening for secondary localizations was very low, so the real incidence of complications could not be determined.
In conclusion, we showed that patients admitted to IMWs are increasingly at higher risk of developing candidemia. Mortality rate remains high and significantly associated with both microbiologic- and host-related factors. Further prospective studies are strongly encouraged to investigate risk factors for development and management of candidemia in patients admitted to IMWs.