An article published in the Journal of Mushrooms Analysis of bloodstream infections by fungi of the genus Candida and comparison of data for the periods 2010–11 and 2017–18 in Brazil shows that despite advances in therapeutic practice, extremely high mortality rates persist. Candidemia is the most common nosocomial (hospital-acquired) invasive fungal infection worldwide. Incidence varies worldwide from 0.33 to 6.51 episodes per 1,000 admissions.
For the comparative analysis, data from 616 cases treated in 11 public and private hospitals (369 in the first period and 247 in the more recent period) were used.
Treatment with echinocandins, the current initial antifungal drugs of choice, increased from 13% to 41% but had no effect on mortality rates, indicating that other factors should be examined.
“We have a late diagnosis problem. Diagnosis still depends solely on blood culture. Fungal culture and identification in the laboratory takes time and the sensitivity of this method is low, with up to 50% false negative results. Time is critical to patient survival.” “We need to save time by investing in better techniques that are not culture dependent, including molecular diagnosis and the use of biomarkers,” said Caroline Agnelli, first author of the article. She is Ph.D. Candidate specializing in Research on Infectious and Parasitic Diseases at the Federal University of São Paulo (UNIFESP).
Another shocking revelation in the article is the number of people who are not receiving any treatment at all. “Two out of ten are not treated due to a lack of diagnostic resources. At least half of those who receive treatment die. The data was collected by colleagues in Porto Alegre.” [state capital of Rio Grande do Sul] from more than 120 Latin American medical centers shows that only one in ten hospitals has the resources for an effective diagnostic approach in medical mycology – and this is true for several fungal infections,” said Arnaldo Colombo, last author of the article and professor at UNIFESP.
For the researchers, the study shows that despite the accumulated knowledge about the natural history of invasive infections caused by Candida, unlike other neglected fungal diseases, mortality rates have not decreased. “Patient prognosis is multifactorial, but we know what can make all the difference: early administration of antifungal drugs combined with timely and effective control of the source of infection, including removal of the midline catheter,” said Agnelli.
Candidemia is a complication that usually occurs in critical patients who are hospitalized for long periods, particularly in intensive care units (ICUs), are taking broad-spectrum antibiotics and corticosteroids, or require an invasive procedure such as dialysis or surgery, especially in the abdomen. The use of central venous catheters represents a risk factor, but the rate of early removal in candidemia cases remained below 50% throughout the study period.
“The decision to remove a midline should of course be made on an individual basis for reasons of safety, disease severity and clinical condition. However, it should be given priority whenever possible to improve the patient’s prognosis,” said Agnelli.
The fungus that causes hospital-acquired candidemia is the same one that naturally colonizes the gastrointestinal tract and is known to women as the cause of vaginal candidiasis (yeast infection). “It’s harmless if your immune system is fine and you’re not in the hospital, where it can go from colonization to invasive disease, particularly due to the use of antibiotics that promote dysbiosis – an imbalance in the gut with an increase in …” of the Candida population – and the use of invasive medical procedures to treat the patient. Under conditions associated with low immunity and a hospital environment, “living with the enemy” in good health becomes dangerous living with the enemy,” Colombo said.
Profile change and further studies
Mortality rates were unacceptably high and remained unchanged throughout the study period, despite the wider use of echinocandins. For the researchers, this was likely linked to changes in the at-risk population and treatment strategies that could be improved. “There was a profile change. We found that age did not increase, but the quality of aging was different. Recently, there have been more comorbidities. Patients who are hospitalized have been hospitalized before, sometimes multiple times,” Agnelli said.
The mean age of the patients was similar in both periods (62 and 65) and there were no significant differences in initial clinical severity. More recently, however, the number of patients with more than three comorbidities has doubled (to 29%, versus 16% in 2010), as has the proportion of patients on dialysis (15%, versus 8% in 2010). More recent patients presented with candidemia earlier and 40% had been previously hospitalized (compared to 21% in 2010).
“We found a 14-day mortality rate of about 35% and a 30-day mortality rate of about 50%. Those are very high rates. A few years ago we asked why and compared them to rates in other countries,” Colombo said, citing a study conducted in collaboration with researchers in Spain. Mortality was significantly lower among the Spanish patients, although they were older than the Brazilians.
“Diagnosis was a factor here too, but it was clear that they removed the central lines sooner, controlled the focus of infection effectively and started administering the right antifungal earlier. In Brazil, the recommended bacterial sepsis protocol for patients in intensive care units is often ignored.” “The timing of initiation of therapy is critical to prognosis. The study showed this very clearly,” said Agnelli.
methodology and challenges
The collection of medical history and laboratory data up to 30 days after confirmation of candidemia was based on a routine, laboratory-based surveillance protocol, including demographic data, underlying medical conditions, risk factors, and conditions associated with candidemia, such as use of broad-spectrum antibiotics. Chemotherapy, steroids, prior abdominal surgery, central venous catheter at time of diagnosis, parenteral nutrition, identification of Candida species, clinical severity, antifungal medications prescribed, time to initiation of treatment, time to catheter removal, and all-cause mortality at 14 years 30 days post the diagnosis of candidemia. The species was identified by a local laboratory and the material was sent to UNIFESP’s Specialized Laboratory for Mycology for confirmation.
The group has a long history of conducting epidemiological surveillance research in collaboration with hospitals to enable similarity between clinical records. “However, collecting this data accurately is not an easy task. It requires oversight and testing and careful analysis to bring databases together and make correct comparisons,” said Colombo.
“The technology isn’t advanced enough to help merge databases. It is necessary to constantly review the criteria to adjust all variables so that populations and samples are comparable,” Agnelli said.