Sustained reduction of catheter-associated bloodstream infections with enhancement of catheter bundle by chlorhexidine dressings over 11 years

Despite the successful widespread implementation of catheter bundles, central line-associated bloodstream infections remain an important cause of preventable nosocomial infections in patients requiring intensive care unit (ICU) management [1‐4]. The multimodal strategies included in these bundles (i.e., standardization of procedures and care, skin preparation, hand hygiene, aseptic techniques and maximal barrier precaution for insertion) successfully addressed most recognized risk factors for catheter infections [5, 6]. However, the efficacy of these recommended bundles seems to plateau around 1.0 episode per 1000 catheter-days [7‐11]. This translates into the persistence of a significant number of preventable catheter-related infections in high-volume ICUs complying with the benchmark [12‐14].

By controlling bacterial load at the site of insertion, dressings continuously releasing chlorhexidine gluconate (CHG) decreased the rate of central line-associated infections in two large prospective multicenter randomized trials among critically ill patients [15, 16]. These results were confirmed by a meta-analysis including nine randomized controlled trials comparing either CHG sponge or CHG gel dressings (55,915 catheter-days) with regular dressings (54,583 catheter-days) [17].

Based on these studies, recommendations for the use of CHG dressings have been included in the CDC and NHS guidelines [18, 19]. However, studies confirming the effectiveness of these antiseptic-containing dressings in a real-world setting are still lacking. Moreover, the two types of CHG dressings have never been directly compared.

We took advantage of a prospective bloodstream infection surveillance program for an ongoing catheter bundle to evaluate the impact of the progressive introduction of two types of CHG dressings on all arterial and central venous catheters inserted in patients admitted to a large mixed ICU over a 13-year period. For the first 2 years we collected baseline data, and during the following 7 years, we introduced the CHG dressings in four different steps. The objectives of the study were to assess whether the progressive introduction of CHG dressings to an ongoing catheter bundle could further reduce the rate of catheter-associated bloodstream infections and to compare the effectiveness of two different types of CHG dressing (CHG sponge + transparent dressing versus CHG gel all-in-one dressing) on the rate of catheter-associated bloodstream infection.

The stepwise introduction of two types of CHG dressings over a 7-year period achieved a sharp and sustained reduction in all types of catheter-related infections, despite increased workload, catheter use and severity of illness.

For the first time, a real-world data study, consisting of prospective surveillance of 155,242 catheter-days, confirms that the addition of CHG dressings to existing catheter bundles provides a significant decrease in the rate of catheter-related bloodstream infections in a real-world setting. Post-study surveillance data showed a persistent low rate of infections over an additional 4-year period.

CRBSI are considered the most preventable nosocomial infection [4]. Over the last 2 decades, catheter bundles, aiming at reducing contamination during insertion procedures and subsequent hub handling, resulted in a substantial decrease in CLABSI rates, down to values between one and two episodes per 1000 catheter-days [3, 12, 14].

By adding an antimicrobial agent to control the bacterial load at the insertion site, chlorhexidine dressings can further reduce the CLABSI rate. Timsit et al. conducted two milestone prospective randomized controlled trials on this topic. The first study [15] tested the same CHG sponge dressing we used in periods B, C and D. It evaluated 1636 patients for a total of 28,931 catheter-days. Compared with standard dressings, the CHG sponge dressings achieved a decrease in catheter-related infections (defined as either catheter-related clinical sepsis without bloodstream infection or CRBSI) from 1.4 to 0.6 episodes per 1000 catheter-days (hazard ratio: 0.39; 95% CI 0.17–0.93; p = 0.03). The second study [16] tested the same CHG gel dressing we used in periods D and E. It evaluated 1879 patients for a total of 34,339 catheter-days. Compared with non-chlorhexidine dressings, the CHG gel dressings achieved a decrease in CRI (defined as in the previous study) from 2.1 to 0.7 episodes per 1000 catheter-days (hazard ratio: 0.328; 95% CI 0.174–0.619; p = 0.0006) and a decrease in CRBSI from 1.3 to 0.5 episodes per 1000 catheter-days (hazard ratio: 0.402; 95% CI 0.186–0.868; p = 0.02).

Our data not only confirm these results in a real-word setting, but also provide additional evidence to support the recommendation endorsed by the guidelines for the generalized use of CHG dressings in acutely ill patients [18, 19]. Comparing the initial period, during which the state-of-the-art bundle was in use, and the last period during which the CHG gel dressing was used for all patients and catheters, we observed a sixfold reduction in the CABSI rate, corresponding to 16 (95% CI 13.6–19.3) episodes avoided every year.

Moreover, the enhanced bundle impacted CRBSI and primary bacteremia similarly, independently of case mix variation. This suggests that primary bacteremia might be correlated with catheter infection in situations such as ours where catheter tip cultures are not systematically performed.

Our study has several strengths. First, it is a large real-world data study including > 18,000 patients and 160,000 catheter-days over 9 years. This is comparable to the recent meta-analysis including nine studies with antiseptic dressings [17]. Second, the observation was done in a mixed tertiary ICU admission with severely critically ill patients, as assessed by high severity scores and workload required to manage them. The single-center design limits the external validity on one hand but ensures a higher degree of consistency of processes of care on the other. Third, the sustained decrease in infection rate was achieved despite a continuous increase in case mix severity over time. Finally, the recording of the data was performed without changes in the setting of the surveillance, in the definitions of infections or in the staff in charge of catheter-bundle training and maintenance.

Our study also has several limitations. First, it is monocentric and without randomization and therefore does not qualify for a pragmatic trial. Hence, we cannot discriminate between the relative impact of the ongoing bundle over time and the precise contribution of CHG dressings. However, data from the literature suggest that if catheter bundles have a sustainable effect, this seems to be limited to stabilization of the rate of infection rather than permitting a continuous further decrease over time [7, 8, 22, 23]. Second, the study design did not allow determining the effect of the generalization of alcoholic 2% chlorhexidine for skin preparation introduced in period D. Third, although systematic education and continuous bedside teaching to comply with the catheter bundle were provided, we never formally assessed compliance. Fourth, the absence of systematic catheter culture may result in an underestimation of the true rate of CRBSI. Episodes may have been scored as primary bacteremia and then included in CABSI already defined as the primary end point. Finally, the improved results might result not only from the use of chlorhexidine dressings on top of the bundle, but also from the creation of an environment and culture of quality improvement commitment among staff, generated by the long-lasting chain of quality improvement initiatives, with breakthrough interventions, supported by educational tools and data feedback.

Our data suggest that CHG gel may be more effective than CHG sponge to prevent CABSI in adult patients requiring ICU management. Comparing periods C (CHG sponge on all catheters) and E (CHG gel on all catheters), the CABSI and CRBSI incidence density rates almost reached the significance level of 0.017 accounting for multiple comparisons (p = 0.019 and 0.018, respectively; see Table 2a). Due to the small numbers of infections, the power to detect a difference between those periods was only 77% and not the usual 80% targeted. For period D during which both dressings were used concomitantly and where the effect of the ongoing catheter bundle was identical, the difference did not reach significance either (two episodes, hazard ratio: 0.13; 95% CI 0.03–0.50, versus nine episodes, hazard ratio: 0.43; 95% CI 0.23–0.83, per 1000 catheter-days, p = 0.059). The absence of significant difference may be due to low power to assess a significant difference in this comparison (49%) or to random chance. A potential significant superiority of the gel could further improve infection control and decrease rates of CABSI. This hypothesis should however be addressed by a sufficiently powered prospective controlled study.

Calculation of cost-effectiveness was beyond the scope of the study. However, the stepwise implementation of the enhanced catheter bundle has changed the empirical management of patients developing sepsis of unknown origin. First, systematic catheter change (guidewire exchange or insertion at new sites) was no longer required, thus avoiding the risk associated with new catheterization. Second, for the same reason, vancomycin was not systematically added in empirical antibiotic treatment of sepsis of unknown origin to treat an eventual CABSI, thus contributing to reducing antibiotic exposure. Finally, these changes in patient management combined with a sustained reduction in CABSI might have resulted in cost reduction as suggested by Maunoury et al. [5, 24].

We conclude that the addition of chlorhexidine dressings to all CVC and arterial lines to an ongoing catheter bundle in all patients requiring ICU admission resulted in a sustained and probably cost-effective 11-year reduction of catheter-associated bloodstream infections.