Time to Positivity Doesn't Predict Mortality in Bloodstream Infections With Enterococci

Marcia Frellick

August 26, 2021

A short time to positivity (TTP), the period from incubation to blood culture positivity, may help predict mortality rates for patients with Enterococcus faecalis and vancomycin-sensitive E faecium (VSEfm) bloodstream infections (BSIs), but it is not an independent predictor of risk for death from bloodstream infections caused by enterococci, new research indicates.

Katharina Michelson, of the Institute of Microbiology, Jena University Hospital, Jena, Germany, and colleagues conducted a single-site study at Jena University Hospital that included 244 patients with monomicrobial BSIs to assess the value of TTP as a prognostic or diagnostic tool.

Death in the hospital was the primary endpoint considered in the study, which was conducted from January 2014 through December 2016. The shortest TTP of blood cultures was compared among groups.

Findings were published online in April in Diagnostic Microbiology and Infectious Disease.

Among the 244 patients with monomicrobial BSIs, 22.1% of cases were caused by E faecalis, 55.3% were caused by VSEfm, and 22.5% were caused by vancomycin-resistant E faecium (VREfm).

Average TTP of Enterococcus BSI (E-BSI) was 11.6 hours. The researchers found no significant association between risk for death and time to positivity with bloodstream infections with E faecalis, VSEfm, or VREfm, or its cutoffs.

The mortality rate of patients with bloodstream infections with E faecalis was 16.7%; for VSEfm, 26.7%; and for vancomycin-resistant E faecium, 38.2%. Cutoffs showed a significantly higher death rate when TTP was longer but were not risk factors in survival analysis.

The authors explain that "in literature, TTP has not always been proven to be a reliable parameter."

Sam Aitken, PharmD, MPH, who is a pharmacy specialist for infectious diseases at Michigan Medicine, in Ann Arbor, Michigan, told Medscape Medical News that the main message from the article is that the TTP of E faecalis is quite different from that of E faecium and that "that's in line with what we know about generally with how these organisms come about in patients.

"This paper reinforces the differences that are sometimes underappreciated between these organisms because they are both enterococci," he said.

The authors say appropriate antimicrobial therapy can lead to misinterpretation of TTP, so only patients who received inappropriate antimicrobial therapy on the day of positive blood culture were included in the study.

However, Aitken said that methodology doesn't account for "immortal time bias."

"They didn't account for the fact that patients who tend to get active antibiotics are the ones who live longer. So unless you account for it, you're necessarily going to find that patients who get active antibiotics have improved survival," he said.

The authors point out that finding new methods for quickly identifying patients with E-BSI is a high priority.

The mortality rates of E-BSI vary between 20% for E faecalis and 50% for E faecium.

Resistance to vancomycin is common in E faecium infections and is associated with high mortality, longer hospital stays, and increased costs. Vancomycin-resistant E faecium is part of a group of bacteria that is associated with multidrug resistance and nosocomial infections.

Aitken said that rather than TTP, "the best risk predictors are going to be in the microbiome studies we're seeing. If there is a future for figuring out who's going to get significant E faecium infections, at least, it's going to be in the microbiome."

Limitations of the study include its small size; the possibility of missing data, owing to the fact that the study was retrospective; potential delays to incubation; and the possibility of contamination of blood cultures.

The authors and Aitken have disclosed no relevant financial relationships.

Diagn Microbiol Infect Dis. 2021 Apr 20;101:115396. Abstract

Marcia Frellick is a freelance journalist based in Chicago. She has previously written for the Chicago Tribune and Nurse.com and was an editor at the Chicago Sun-Times, the Cincinnati Enquirer, and the St. Cloud (Minnesota) Times. Follow her on Twitter at @mfrellick.

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