By Richard R. Watkins, MD, MS, FACP, FIDSA, FISAC
Professor of Internal Medicine, Northeast Ohio Medical University, Rootstown, OH
SYNOPSIS: A systematic review and meta-analysis found differential time to positivity (DTP) was a useful measurement in confirming or excluding central line-associated bloodstream infections (CLABSIs). However, DTP was not as accurate for CLABSIs resulting from Staphylococcus aureus (lower sensitivity) or Candida spp. (lower specificity) compared to other organisms.
SOURCE: Dhaliwal M, Daneman N. Utility of differential time to positivity in diagnosing central line-associated bloodstream infections: A systematic review and meta-analysis. Clin Infect Dis 2023;77:428-437.
A central line-associated bloodstream infection (CLABSI) is a serious event that leads to significant healthcare costs. Reducing CLABSIs in hospitalized patients has become a high priority for healthcare stakeholders, including payers and the Centers for Medicare & Medicaid Services (CMS).1 Differential time to positivity (DTP) is a technique that has been investigated previously for diagnosing CLABSIs. When a CLABSI is suspected, significantly faster growth in a blood culture drawn from a central line suggests there is a higher bacterial load in the catheter, thus indicating the need for catheter removal. Dhaliwal and Daneman sought to elucidate the usefulness of DTP in determining CLABSIs through a systematic review and meta-analysis of the existing literature.
Studies were included in the analysis if they reported the sensitivities, specificities, predictive values, or likelihood ratios of DTP for the diagnosis of CLABSI, or if they provided the raw data that allowed for these values to be calculated. Case reports and conference abstracts that did not have an associated publication were excluded. Two hours was used as the DTP threshold for the analysis. Catheter colonization within the CLABSI definition was added as a post hoc subgroup after the investigators found that multiple studies included catheter colonization in the absence of bacteremia in their results.
Twenty-eight articles were included in the systemic review and 23 were included in the meta-analysis. The meta-analysis included 2,526 cases of suspected CLABSI. There was no evidence of publication bias in the meta-analysis (P = 0.25). However, 19 of 28 articles were found to have a high risk of bias related to patient selection, index test, reference standard, or flow and timing. Most of them (26/28) were single-center studies.
DTP showed a sensitivity of 81.3% (95% confidence interval [CI], 72.8% to 87.7%), a specificity of 91.8% (95% CI, 84.5% to 95.8%), a positive likelihood ratio (PRL) of 9.89 (95% CI, 5.14-19.00), and a negative likelihood ratio (NLR) of 0.20 (95% CI, 0.14-0.30). Covariate analysis found no significant differences based on organism, study design, catheter duration, or immune status. Furthermore, studies that included catheter colonization yielded a sensitivity of 77.9% (95% CI, 67.4% to 85.8%) and a specificity of 91.4% (95% CI, 81.9% to 96.2%). Covariate analysis determined this was not a statistically significant difference when compared to the primary analysis.
However, the findings were somewhat different for Staphylococcus aureus and Candida CLABSIs. The two studies in the meta-analysis that specifically looked at S. aureus CLABSIs found sensitivities of 41.1% (95% CI, 29.1% to 55.9%) and 36.7% (95% CI, 19.9% to 56.1%), while specificities were 100% (95% CI, 59.0% to 100%) and 77.2% (95% CI, 64.2% to 87.3%). Similarly, another study had a subgroup of only S. aureus CLABSIs and reported a sensitivity of 33.9% (95% CI, 22.6% to 46.7%) and a specificity of 87.5% (95% CI, 61.7% to 98.5%). In two studies on Candida CLABSIs, the sensitivities were 100% (95% CI, 69.2% to 100%) and 85.3% (95% CI, 73.8% to 93.0%), while the specificities were 33.3% (95% CI, 9.9% to 65.1%) and 81.6% (95% CI, 65.7% to 92.3%).
COMMENTARY
Deciding whether to remove a central line can be a challenge for physicians at the bedside. Thus, Dhaliwal and Daneman should be commended for their study because it helps clarify this important clinical conundrum. Although not foolproof, DTP is a straightforward and low-resource method that can be useful for diagnosing a CLABSI. The study showed that DTP has a high sensitivity and specificity that is able to confirm or exclude CLABSI. Pragmatically, this could mean that further testing (e.g., imaging) to look for an alternative infectious source can be eliminated if the DTP is positive, and the central line can be retained if the DTP is negative. This also lends support to the practice of drawing paired catheter blood cultures when a CLABSI is suspected, even though there is a risk for blood culture contamination. The risk can be mitigated by implementing current best practices for drawing blood cultures from catheters.
Previous studies have shown a lower sensitivity of DTP for CLABSIs caused by S. aureus, so a similar finding from the current study is not unexpected. One hypothesis is that the myriad virulence factors of S. aureus allow it to disseminate very quickly, thereby raising the bacterial load and decreasing the time to positivity of blood cultures. This leads to lower DTP and more false-negative results. The studies on Candida and DTP should be interpreted with caution because of their small sample size, although it seems that DTP does not perform as well for Candida CLABSIs. Regardless, current guidelines recommend that all lines be removed with Candida fungemia as well as S. aureus bacteremia.2
The study had a few limitations. First, the search strategy focused on bacterial causes of CLABSIs, so reports on fungal causes may have been missed. Second, many of the studies included in the meta-analysis were small and of poor quality. Third, nine of the 28 studies included patients with positive central line blood cultures but negative peripheral ones and classified these as a positive DTP. How DTP was measured in these studies is not explained by the investigators in the current study.
Given its relatively high sensitivity and specificity, DTP can be a helpful and convenient clinical tool for diagnosing CLABSI. Preventing unnecessary line removal and superfluous testing would save healthcare resources and could reduce patient harm.
REFERENCES
- Centers for Medicare and Medicaid Services. Hospital-Acquired Condition Reduction Program. Last updated Sept. 6, 2023. https://www.cms.gov/medicare/quality-initiatives-patient-assessment-instruments/value-based-programs/hac/hospital-acquired-conditions
- Mermel LA, Allon M, Bouza E, et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 Update by the Infectious Diseases Society of America. Clin Infect Dis 2009;49:1-45.
