Differential time to positivity showed high sensitivity and specificity for identifying central line-associated bloodstream infections.


“Differential time to positivity (DTP) for the diagnosis of central line-associated bloodstream infections (CLABSI) is a simple diagnostic technique that can provide additional information without requiring line removal,” Manreet Dhaliwal explains. “However, most studies looking at the diagnostic characteristics of DTP for CLABSI have been small, with contradictory results.”

DTP for diagnosing CLABSI has the potential to reduce healthcare expenditures because of the significant costs associated with line removal, according to Dhaliwal, and could decrease “unnecessary investigations” conducted to identify the cause of bacteremia. “Thus, we felt there was a need to pool together all available information to better understand the diagnostic characteristics of DTP for CLABSI so clinicians can appropriately apply DTP to patients.”

For a study published in Clinical Infectious Diseases, Dhaliwal and Nick Daneman, MD, FRCPC, MSc, of the University of Toronto and Sunnybrook Research Institute, performed a systematic review of the diagnostic characteristics associated with DTP for CLABSI, including sensitivity, specificity, and likelihood ratios. “We also looked into whether there was an explanation for the significant differences between the results of prior studies,” Dhaliwal says. “We specifically looked at whether DTP performance differed in certain populations, such as individuals who were immunocompromised or had long-term catheters. The study was conducted systematically with predefined search criteria and two independent screeners.”

DTP Shows High Sensitivity & Specificity

The study team assessed 274 study records and included 23 that met the criteria for meta-analysis. The 23 studies described a total of 2,526 suspected CLABSI.

DTP showed a summary sensitivity of 81.3% (95% CI, 72.8% to 87.7%), a specificity of 91.8% (95% CI, 84.5% to 95.8%), a positive likelihood ratio of 9.89 (95% CI, 5.14-19.0), and a negative likelihood ratio of 0.20 (95% CI, 0.14-0.30).

“The positive and negative likelihood ratios are important to stress, as they can significantly shift the probability of a CLABSI depending on the pretest probability,” Dhaliwal says. “The important methodological differences that make this assessment more reliable, compared with prior reviews, include a systematic approach, the number of studies included, and the covariate analysis.”

In the covariate analysis, which was based on catheter duration, study design, and patient immune status, the researchers identified no significant differences, according to the study results. However, when compared with other organisms, DTP performed worse for Staphylococcus aureus, with low sensitivity but high specificity, and Candida, with high sensitivity but low specificity.

“Previously documented findings reflecting poorer performance of DTP in S. aureus and Candida CLABSI were supported by this review,” Dhaliwal notes. “Although the covariate analysis by organism did not show a significant difference, it was limited by the small number of studies focusing on specific organisms. Ultimately, this review reinforces the importance of removing all lines in S. aureus and Candida bacteremia.”

Value of DTP in Decision Making About Central Lines

The results indicate that “DTP can be used to help rule out line infections in certain clinical scenarios and allow retention of the line,” Dhaliwal says.

“We hope that physicians utilize these results to order a DTP for patients with sepsis of an unclear origin and a central line in place,” she continues. “DTP is easy to request because it does not require any additional expensive technology. If the central line culture is positive more than 2 hours before the peripheral vein culture becomes positive, then the central line is the likely source of infection and should be removed. If the central line blood culture does not become positive more than 2 hours before the peripheral culture, the line can be retained in certain clinical situations.”

Future research should examine clinical outcomes, such as the retention of a central line, when DTP is used, Dhaliwal notes, in order “to document that line retention does not result in an increased risk for treatment failure or recurrent infection.”

Further, he says, “quality improvement studies focused on blood culture collection and labelling are needed to ensure accurate calculation of DTP, as well as implementation studies encouraging greater use of DTP in clinical decision making.”

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