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Candidemia standard-of-care questioned

Reuters Health • The Doctor's Channel Daily Newscast

NEW YORK (Reuters Health) – In managing hospitalized patients who develop candidemia, the standard practice of promptly removing a central venous catheter does not improve outcomes, according a report in Clinical Infectious Diseases published online June 25.

“These findings suggest an evidence-based re-evaluation of current treatment recommendations,” the authors state.

Lead investigator Dr. Marcio Nucci, at the Universidade Federal do Rio de Janeiro in Brazil, pointed out via email that central venous catheter (CVC) removal became standard of care in the 90s when some studies found an association between CVC removal and better outcome, and vice versa. However, the studies lacked multivariate analysis and so did not account for possible confounders.

Later studies that did include multivariate analysis had other methodological problems. Early deaths were included, which could have led to a bias favoring CVC removal “simply because patients who died earlier did not have the opportunity to have their CVC removed,” Dr. Nucci explained. Furthermore, the studies included late removal of the CVC, which again favors the strategy “because patients who have their CVC removed late (e.g. on day 10 of candidemia) survived this period, compared with those who died earlier.”

To resolve these issues, Dr. Nucci and an international team looked at data on 842 patients treated for candidemia in two phase III trials and who had a CVC in place at diagnosis. The CVC was removed within 48 hours of starting treatment in 354 of the patients.

On univariate analysis, early catheter removal had no effect on treatment success but it was associated with better survival at 28 and 42 days. For example, 28-day survival was 76.7% when the catheter was removed within 24 hours, compared with 70.4% when it was not removed within that period.

However, on multivariate analysis, this improvement in survival was lost.

“In the present paper we provide convincing evidence that the association between early CVC removal and better outcome seems not to be true,” Dr. Nucci said.

“This does not mean that retaining a CVC is beneficial to the treatment of candidemia,” he continued. “But it provides compelling evidence that if the clinician does not remove the catheter ‘promptly’ it is very unlikely that he is doing harm to the patient and the patient will die.”

As for the team’s call for a re-evaluation of current treatment recommendations, this evoked a caution from the authors of an accompanying editorial. “Several considerations need to be taken into account in deriving conclusions from this retrospective analysis,” write Drs. Eric P. Brass and John E. Edwards, Jr. at Harbor/University of California Los Angeles (UCLA) Medical Center.

After discussing these considerations and other issues, they conclude, “The theoretical risks of not removing a CVC in a patient with candidemia are clear, and the expert guidelines remain the current best synthesis of the available data.”

Meanwhile, Dr. Nucci said the current data “provide evidence to favor a more rational approach in which clinicians have time to think (and not just blindly follow a guideline).”

He offered this strategy: “The key questions are: 1. Is a CVC needed? If not, remove the line. 2. If it is needed, is candidemia catheter related? (If it is, it is more likely that CVC removal will be beneficial). 3. If not CVC-related, (there are ways to try to diagnose without pulling the line), it is reasonable to start antifungal treatment and wait for some days. If the patient is not responding, consider removing the catheter.”

Reference:

Early Removal of Central Venous Catheter in Patients with Candidemia Does Not Improve Outcome: Analysis of 842 Patients from 2 Randomized Clinical Trials

Clin Infect Dis 2010;51.