To the Editor—Central venous catheter (CVC)–related bloodstream infections (CRBSIs) are clinically important healthcare-associated infections.Reference Magill, O’Leary and Janelle^1, Reference Battaglia and Hale² To reduce the burden of CRBSIs, many countries have implemented national surveillance programs.Reference Hallam, Jackson, Rajgopal and Russell^{3, 4} Reliable epidemiological data are provided not only by cohort studies but also by randomized controlled trials (RCTs),Reference Parienti, Mongardon and Mégarbane^5–Reference Hentrich, Schalk and Schmidt-Hieber⁷ which are considered the gold standard for assessment of clinically relevant questions.Reference Frieden⁸ However, patient populations included in RCTs are often highly selected, limiting the generalizability of study results. In contrast, clinical registries can provide useful data on rare conditions in the daily routine that may also be helpful in assessing quality of care. On the other hand, they are limited by substantial confounders and bias.Reference Frieden⁸

Our aim was to compare epidemiological data on CRBSIs in patients with hematological malignancies derived from a RCT (COAT,Reference Biehl, Huth and Panse⁶ ClinicalTrials.gov, no. NCT01544686) with data from a prospective registry (SECRECY,Reference Schalk, Hanus, Färber, Fischer and Heidel⁹ German Clinical Trial Register, no. DRKS00006551). We hypothesized that patients included in a CVC RCT profit from improved CVC care compared to patients under standard clinical care conditions, possibly resulting in different CRBSI rates. Thus, the primary aim of the present analysis was to compare the CRBSI incidences between these groups.

The COAT trial was a RCT carried out from February 2012 to September 2014 in 10 hematology/oncology departments in Germany to compare 2 different types of CVC dressings with respect to the associated CRBSI incidence in neutropenic patients.Reference Biehl, Huth and Panse⁶ The SECRECY registry began in March 2013 and is an ongoing CRBSI registry,Reference Schalk, Hanus, Färber, Fischer and Heidel⁹ now in 6 hematology/oncology departments in Germany.Reference Schalk, Toelle and Schulz¹⁰ In the present analysis, we included data from patients with nontunneled jugular and subclavian vein CVCs placed ≥1 day in situ. For CRBSI diagnosis, we used the 2012 definitions of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO), considering only definite or probable CRBSIs.Reference Hentrich, Schalk and Schmidt-Hieber⁷ Because the end points in the COAT trial referred to the 2008 AGIHO/DGHO definitions,Reference Wolf, Leithauser and Maschmeyer¹¹ the underlying data were reassessed, and the more recent definitions were applied to ensure the comparability of the 2 data sets.

According to the aforementioned inclusion criteria, we found 610 cases in the completed COAT trial data set and, as of May 2019, 2,390 cases in the SECRECY registry. In this entire cohort of 3,000 CVCs with 49,542 CVC days, underlying diseases were hematological malignancies and solid tumors in 2,719 (90.6%) and 158 (5.3%) cases, respectively. For a matched-pair analysis, the 610 patients from the COAT trial were matched with those patients from the SECRECY registry with regard to the use of chlorhexidine-coated CVC dressings, sex, and underlying disease with a high risk for CRBSI (ie, acute myeloid leukemia [AML], multiple myeloma, or non-Hodgkin lymphomaReference Schalk, Toelle and Schulz¹⁰).

Comparison of continuous variables was conducted using the Mann-Whitney U test, and categorical variables were compared using the Pearson χ² test or the Fisher exact test, when possible. CRBSI incidences were compared by χ² test. The Kaplan-Meier method was used for calculating the CRBSI probability over time, and the comparison between both groups was performed using the log-rank test and Cox regression. Two-sided P values <.05 were considered statistically significant. Statistical analyses were carried out using SPSS version 24 statistical software (IBM, Armonk, NY).

Patient and CVC characteristics as well as CRBSI features are shown in Table 1. Patients from the COAT cohort were younger than those from the SECRECY cohort (median, 58 vs 60 years; P < .001). There was a slight male predominance in both groups. COAT included fewer cases of AML than SECRECY (243 of 610 [39.8%] vs 300 of 610 [49.2%]; P = .001) but more cases of multiple myeloma (170 of 610 [27.9%] vs 123 of 610 [20.2%]; P = .002). In the COAT cohort, significantly fewer CVCs were inserted into the jugular vein, compared to the matched SECRECY cohort (41.8% vs 94.3%; P < .001). Although the median duration of CVC placement was significantly longer in the COAT trial than in the SECRECY registry (18 vs 15 days; P < .001), the median time to CRBSI onset was significantly shorter in the COAT cohort (12 vs 14 days; P = .040). We found no difference in the CRBSI rate between the COAT group and the SECRECY group (79 of 610 [13.0%] vs 71 of 610 [11.6%]; P = .542). Furthermore, the proportion of definite and probable CRBSIs was similar in both cohorts (P = .744). Regarding the primary aim of this analysis, the incidence of CRBSIs did not differ significantly with 7.0 CRBSIs per 1,000 CVC days in the COAT trial and 7.3 CRBSIs per 1,000 CVC days in the SECRECY registry (P = .794). Analyzing the CRBSI probability over time (ie, cumulative CRBSI incidence), we also found no significant differences at day 14 between these groups (10.4% in the COAT trail vs 9.6% in the SECRECY registry: hazard ratio, 1.12; 95% confidence interval, 0.74–1.71; P = .583). Finally, we detected no differences in the distribution of pathogen subgroups (P = .142), and coagulase-negative staphylococci were the most common causative pathogens for CRBSIs in both groups.

Table 1. Patient/CVC Characteristics and CRBSI Features

Note. CVC, central venous catheter; CRBSI, central venous catheter-related bloodstream infection; IQR, interquartile range; CRBSI14, cumulative CRBSI probability at day 14; 95% CI, 95% confidence interval.

^a Comparison COAT trial data vs matched-pair data from SECRECY registry; all P values are 2-sided.

^b Mann-Whitney U test.

^c Fisher’s exact test.

^d Pearson’s χ² test.

^e Underlying disease with high risk for CRBSI: acute myeloid leukemia, multiple myeloma or non-Hodgkin lymphoma.Reference Schalk, Toelle and Schulz¹⁰

^f log-rank test.

^g χ² test.

To the best of our knowledge, the present analysis is the first to provide comparative epidemiological data on CRBSIs from a RCT and a registry study in high-risk patients with hematological malignancies. Although limited by some differences in patient and CVC characteristics between both groups, this large matched-pair analysis did not show a reduced CRBSI incidence in patients treated in a RCT compared to patients in routine clinical care implicating a comparable quality of CVC care. Thus, epidemiological data on CRBSIs derived from RCTs may reliably be transferred to real-world settings.