Recently it has been shown that shorter time to blood cultures positivity in automated systems has been associated with worse prognosis in infections caused by bacteria (i.e., shorter times are associated with higher mortality) [9–11]. This has been shown for S. aureus, Streptococcus pneumoniae and Escherichia coli BSI . These findings prompted us to study the time to positivity of candidemia (C. albicans), since the studies analyzing time of positive Candida spp culture are rare and almost all were performed in vitro [19–21].
In our study, only the time to blood culture positivity was predictive of mortality for Candida albicans. The severity of illness (APACHE II, SAPS II and SOFA) was not significantly different between the two groups.
We identified in the medical literature only three clinical studies that analyzed the time to positivity for candidemia, but these had different goals: comparing the differential time to positivity between specimens obtained peripherally and via a central venous catheter ; quantifying the time between the collection of blood culture and its positivity ; and evaluating the time to positivity for detecting Candida species resistant to fluconazole .
Regarding Candida albicans BSI, our study showed the longer the time to positivity, the higher the mortality. We found only one report with a similar finding and this was for Staphylococcus aureus bacteremia . In this retrospective study they observed that a shorter time to positivity was associated with methicillin susceptibility and an endovascular source; multivariate analysis showed higher mortality both with time to positivity ≤ 12 or >48 hours .
Physicians often wait for the blood cultures to grow Candida prior to beginning antifungal therapy. However, even if the patient has a stable clinical condition and not receiving empirical antifungal treatment, this may be associated with a poor outcome.
Until the early 2000s, the vast majority of candidemia cases were diagnosed in intensive care units [3, 25]. Recent studies have shown a decrease in the proportion of Candida BSIs occurring in ICUs, especially in Latin America countries, with a fall between the years 2008 and 2009 from 64.9% to 42.6% .
We observed that only 22.5% of patients with candidemia (C. albicans) received adequate antifungal therapy in the first 24 hours after the suspected infection or collection of blood cultures. Although the reason for not instituting empiric treatment was not evaluated, we believe it has occurred at least in part, due to the delay in blood culture positivity. Other studies have also found that candidemia has one of the highest rates of inadequate empirical treatment in the first 24 hours after suspected infection [6, 7].
A multicenter study reported that the mean time for initiating empiric antifungal therapy was 3.8 days . These data emphasize the need to consider early initiation of empiric therapy given that blood cultures are slow to turn positive for Candida species.
Comparing the mean time to positivity for Candida albicans with other studies, we found that the automated BacT/ALERT® time growth is faster [8, 27]. Lai and colleagues (2012) reported similar time using the BACTEC® system . It should be noted that in our study we did not use specific culture medium for fungi. However another study also used specific culture medium for fungi (BACTECTM Myco/F Lytic) whose time to positivity is known to be shorter, especially in the identification of non-albicans Candida species. They showed differences between the mean time to positivity for Candida albicans between the specific culture medium for fungi versus a non-specific medium for fungi (aerobic culture), 34 ± 25 h vs. 42 ± 19 h, respectively .
Our study is limited by the retrospective nature of our analysis. In addition, because of the relatively small sample size of our study (n=89), a type II error could have occurred, which would limit the ability to detect a statistically significant difference in the other variables considered as predictors of mortality.