Skip to main content

Real-world experience of how chlorhexidine bathing affects the acquisition and incidence of vancomycin-resistant enterococci (VRE) in a medical intensive care unit with VRE endemicity: a prospective interrupted time-series study

Abstract

Background

Critically ill patients in intensive care units (ICUs) often acquire opportunistic infections or are colonized by vancomycin-resistant enterococci (VRE), which limits therapeutic options and results in high case-fatality rates. In clinical practice, the beneficial effects of universal chlorhexidine gluconate (CHG) bathing on the control of VRE remain unclear. This study aimed to investigate whether 2% CHG daily bathing reduced the acquisition of VRE in the setting of a medical ICU (MICU) with VRE endemicity.

Methods

This quasi-experimental intervention study was conducted in a 23-bed MICU of a tertiary care hospital in Korea from September 2016 to December 2017. In a prospective, interrupted time-series analysis (ITS) with a 6-month CHG bathing intervention, we compared the acquisition and incidence of VRE and the incidence of methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Acinetobacter baumannii (CRAB) between the pre-intervention and intervention periods. The primary and secondary outcomes were a change in the acquisition of VRE and incidence of VRE, MRSA, or CRAB between the two periods, respectively.

Results

All the adult patients admitted to the MICU were enrolled in the pre-intervention (n = 259) and intervention (n = 242). The overall CHG daily bathing compliance rate was 72.5%. In the ITS, there was a significant intervention effect with a 58% decrease in VRE acquisition (95% CI 7.1–82.1%, p = 0.038) following the intervention. However, there was no significant intervention effects on the incidence trend of VRE, MRSA, and CRAB determined by clinical culture between the pre-intervention and intervention periods.

Conclusion

In this real-world study, we concluded that daily bathing with CHG may be an effective measure to reduce VRE cross-transmission among patients in MICU with a high VRE endemicity.

Background

In this era of antimicrobial resistance, patients in intensive care units (ICUs) who are critically ill often contract opportunistic infections or are colonized by multidrug-resistant organisms (MDROs) such as vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA), and carbapenem-resistant Acinetobacter baumannii (CRAB) [1,2,3]. The MDRO burden in ICUs is also affected by highly antimicrobial-resistant pathogens, for which there are extremely limited treatment options, and which lead to high morbidity and mortality rates [4, 5]. VRE are often endemic in ICUs, where VRE colonization or acquisition is associated with VRE-related infections with significant mortality and morbidity [6, 7]. The persistence of VRE in ICUs is determined through the selective pressure of antibiotic usage, colonization pressure, and patients vulnerable to colonization or infection. Skin contamination can increase the risk of infection through indwelling medical devices or wounds and contribute to cross-transmission of VRE via environmental shedding and the contaminated hands of healthcare workers (HCWs) [8, 9].

In South Korea, infectious diseases due to six types of MDROs have been legally designated for sentinel surveillance since December 2010 [10]. According to the annual report of the Korean National Healthcare-associated Infection Surveillance (KONIS) at 301 ICUs in 216 participating hospitals from July 2018 through June 2019, a total of 4672 major pathogens were isolated from patients with healthcare-associated infections. Of these, 785 (16.8%) isolates were Enterococcus faecium, with a vancomycin resistance rate of 55.9% [11]. Our institution has been further challenged by the higher incidence of VRE in ICUs along with an influx of patients from outside hospitals, despite the routine application of evidence-based control measures, such as antibiotic stewardship programs, hand hygiene monitoring, active surveillance cultures (ASC) for rectal VRE, cohort isolation, and environmental surface cleaning [12, 13]. Therefore, we needed an additional, more stringent approach to reduce the cross-transmission of VRE in our ICUs.

Preventing the spread of VRE colonization or infection remains an ongoing challenge. Regimens and efficacy concerning decolonization protocols for patients with VRE have not yet been established [9]. Nevertheless, recent studies have demonstrated that decolonization through the use of chlorhexidine gluconate (CHG) bathing for patients in ICU can prevent hospital-acquired infections (HAIs) and reduce the acquisition rate of MDROs including VRE, MRSA, and multidrug resistant-gram negative bacteria (MDR-GNB) [14,15,16]. Therefore, further research is needed to evaluate the effects of routine CHG bathing on MDROs in a real-world setting. In this study, we developed a daily bathing protocol using 2% CHG and performed an intervention study in the medical ICU (MICU) to investigate changes in the acquisition of VRE and the incidence of VRE, MRSA, and CRAB using a prospective interrupted time-series (ITS) analysis.

Methods

Study design and subjects

During a prospective sequential period, ITS analysis was conducted to evaluate the effects of daily CHG bathing in a 23-bed MICU at Korea University Anam Hospital, a 1048-bed tertiary care teaching hospital in South Korea, from September 2016 to December 2017. We employed a pre-intervention and intervention, quasi-experimental design with equivalent assessment timing to evaluate the effect of CHG bathing implementation after completion of the intervention. We checked the achieved effects and assessed the unexpected effects of the intervention. This enabled detection of changes in real-world data that might be attributable to the intervention.

The study comprised two periods: the pre-intervention period from September 2016 to February 2017 (26 weeks) and intervention period from July 2017 to December 2017 (26 weeks). A 6-month intervention with 2% CHG daily bathing was performed, whereas standard bed baths using soap and water were provided twice a week during the pre-intervention periods. An intervening period between two periods was excluded from the analysis, which corresponded to the preparation of the customized CHG bathing protocol and pilot trial (9 weeks), and the following wash-out period (8 weeks). The subjects included patients aged ≥ 19 years, who had been admitted to the MICU for > 72 h (Fig. 1). The primary outcome was a change in the acquisition rate of rectal VRE, as determined using active surveillance culture (ASC). The secondary outcome included a change in the incidence of VRE, MRSA, or CRAB, as determined using clinical cultures.

Fig. 1
figure1

Flowchart of the patients included during the pre-intervention and intervention of the study period. CHG: chlorhexidine gluconate; ICU: intensive care unit

Customized 2% chlorhexidine daily bathing protocol

Infection control unit staff nurses developed the CHG bathing protocol based on a previously published CHG decolonization protocol [17]. Commercial CHG cloth-compatible products were not available in South Korea; therefore, cotton wipes impregnated with 2% CHG were prepared daily, using 5% CHG solution (Green Pharmaceutical Co., Ltd, Seoul, South Korea) and warm, sterile distilled water prior to use. Six clean CHG cloth wipes were used to bathe the whole body below the jawline, concentrating on each area of six body sites sequentially (neck, arms, groin/perineum, right leg/foot, left leg/foot, and back of neck, back, and buttocks). Partial bathing was performed for patients who had medical conditions in which they were unable to move easily or moved with pain. CHG bathing was performed once daily by two trained ICU assistants during the entire ICU stay. All the patients were tested for skin contact irritation or allergic reactions to CHG exposure prior to bathing. Patients with MDRO isolation were bathed last. Patients in critical condition, dermatitis, or abnormal skin conditions were also excluded from CHG daily bathing, depending on the patient’s condition.

CHG bathing compliance was assessed daily, based on documentation provided by an infection control practitioner. A patient receiving full or partial bathing was considered “compliant”. Compliance rate was calculated through dividing the total number of the “compliant” patient-days by the total number of patient-days.

Skin swab cultures of the body sites at high risk of MDRO acquisition were monitored in a small number of randomly selected patients prior to the pilot trial (n = 4) and during the 6-month intervention (two patients per month, n = 12), including patients who had a longer ICU stay of > 30 days and MDRO isolates from the clinical culture (Additional file 1: Table S1).

Routine infection control and prevention program in the ICU

The hospital runs a routine ICU infection control and prevention program, including ASC on ICU admission for rectal VRE and nasal MRSA, a follow-up weekly surveillance rectal culture for VRE acquisition, single room or cohort isolation of patients with VRE, monitoring of hand hygiene adherence for HCWs, monitoring of HAIs, and the electronic antibiotic stewardship program. Patients with a previous MDRO colonization were placed on contact precautions and cohort isolation on admission to the ICU. The infection control staff monitored all the measures on a monthly basis.

Data collection

Demographic and clinical data concerning patients in the ICU were collected through reviewing hospital electronic medical records. We collected data on age, sex, admission department, length of ICU and hospital stay, Acute Physiology and Chronic Health Evaluation (APACHE) II score, medical devices used (mechanical ventilator, urinary catheter, and central venous catheter), and recent surgery and clinical outcomes.

Microbiological data were collected from hospital electronic medical records. Data on MDRO surveillance and ICU-acquired device-associated infections (DAIs) were also obtained from the infection control unit database. The acquisition of rectal VRE using ASC and incidence of VRE, MRSA, and CRAB in clinical cultures were collected weekly for ITS analysis.

Definitions

The compliance rate with the CHG bathing intervention was calculated as the total number of CHG bathing days divided by the total number of patient-days as denominator and expressed in percentage. Since the patients with a stay ≤ 72 h in ICUs were excluded, the patient-days for these patients were subtracted from the denominator. VRE acquisition was evaluated for all the patients who had no previous VRE isolation, a negative ASC result for VRE on ICU admission, and a positive follow-up weekly ASC result for VRE. The incidence of VRE, MRSA, and CRAB was defined as newly acquired positive clinical cultures obtained > 48 h after ICU admission. Clinical cultures were obtained depending on a patient’s clinical status, as determined by the medical staff. Only the first isolate from a single body site per patient was included in the analysis. Identification and susceptibility determination of MDROs were undertaken in the hospital microbiological laboratory. The laboratory definition of each MDRO was determined according to the Clinical and Laboratory Standards Institute criteria [18].

The definitions of MICU-acquired DAIs, including central line-associated bloodstream infection (CLA-BSI), catheter-associated urinary tract infection (CA-UTI), and ventilator-associated pneumonia (VAP), were used based on those of the KONIS national surveillance program, as our hospital has been participating in the ICU module of the program since 2006 [19,20,21].

Statistical analyses

We compared continuous variables, expressed as median and inter-quartile range (IQR), using Student’s t- or the Mann–Whitney U tests, depending on their distribution. Categorical variables were analyzed using χ2- or Fisher’s exact tests. The VRE acquisition rate and the incidence rates of MDROs were calculated as the total number of episodes divided by the total number of patient-days as denominator and expressed per 1000 patient-days. DAI rates were calculated as the total number of cases per 1000 device-days.

ITS was used to statistically measure the changes in the level and slope of the trends over time for the acquisition of rectal VRE and incidence of MDROs between the pre-intervention and intervention periods. We calculated the final multivariable model with a significant parameter (the use of mechanical ventilator) using stepwise backward variable selection. The outcome and offset parameters were the weekly number of cases and the logarithmized patient days, respectively. Overdispersion was tested for the distribution of cases, including potential confounding parameter such as the use of mechanical ventilators. Since there was no overdispersion, we calculated the change in the level and slope of the series using a segmented Poisson regression model. The model used for the analysis is as follows:

Log[E(YX1,X2,X3,X4)] = β0 + β1log(X1) + β2log(X2) + β3log(X3) + β4log(X4) + et

(X1: time, X2: intervention, X3: time after intervention, and X4: covariates), where log[E(YX1,X2,X3,X4)] was the VRE acquisition and MDRO incidence per patient-days, time was the number of weeks starting in September 2016, β0 estimated the intercept at the beginning of the time series, β1 estimated the log-linear trend of the pre-intervention period, where X1 was a continuous variable indicating the time in weeks at time t from the initiation of the study period, β2 estimated the level changes in incidence, where interventiont = 0 was pre-intervention, and interventiont = 1 was intervention, β3 estimated the change in weekly trend from pre-intervention to intervention, β4 estimated the effects of significant covariates, and et was the random error at time t.

Incidence rate ratio (IRR) and the percent change as two standardized effect sizes were obtained as a ratio of change in level and trend between the pre-intervention and intervention periods [22]. A change in level represented how the outcome level had changed from the last observation prior to the intervention to the first one after, based on the Poisson model predictions and not on a difference between observed versus predicted levels. Moreover, a change in level represented a direct change, whereas a change in slope represented a sustained effect (if slope goes down) or unsustainable effect (if slope goes up, after level change down) [23]. A negative change in the level and slope indicated a reduction in the infection rates. A p-value of < 0.05 was interpreted as a significant association with intervention efficacy. ITS analysis was performed using package R version 3.6.1 (R Foundation for Statistical Computing, Vienna, Austria) software.

Results

Compliance to 2% CHG bathing

A total of 501 patients were enrolled (pre-intervention, n = 259; intervention, n = 242). The overall compliance with the 2% CHG daily bathing was 72.5%, including full (66.6%) and partial bathing (5.9%). The most common body site excluded from the partial CHG bathing was the back, followed by the upper trunk and extremities in decreasing order of frequency. No patient had an allergic reaction to chlorhexidine. The reasons for non-compliance to daily bathing were identified: the barriers to CHG bathing in the MICU setting included patient in critical conditions, the presence of dermatitis and/or abnormal skin conditions, patient’s refusal to bathe, and the absence during the bathing time in decreasing frequency (Table 1).

Table 1 Compliance with 2% CHG bathing and reasons for failure to perform CHG bathing in 242 patients in MICU during the intervention period

HCW hand hygiene adherence

HCW hand hygiene adherence in the ICU was routinely monitored using the World Health Organization’s Five Moments for Hand Hygiene protocol in the daytime by a validated and trained observer and adherence was reported on a monthly basis  [24]. The total number of hand hygiene opportunities for HCWs observed in the MICU in pre-intervention and intervention periods were 3165 and 2193, respectively. There was no significant difference in the overall hand hygiene adherence rates among the registered nurses, nurse aids, and medical doctors between the two periods (registered nurses, 67.97 ± 4.72% vs. 70.41 ± 5.44%, p = 0.425; nurse aids, 80.4 ± 8.03% vs. 86.32 ± 3.04%, p = 0.139; medical doctors, 63.52 ± 3.71% vs. 71 ± 9.06%, p = 0.091: Additional file 1: Table S2).

Baseline characteristics

The baseline characteristics of the patients in MICU were compared between the pre-intervention and intervention periods (Table 2). No significant differences were observed in terms of sex, age, comorbidities, and a receipt of surgery between the two periods. The patients in intervention presented higher APACHE II scores than those in pre-intervention [18 (IQR 13 − 23) vs. 24 (IQR 16–32), p < 0.001]. The overall in-hospital mortality was 34.9% during the study period, which did not differ significantly between the two periods. The median length of MICU stay in pre-intervention and intervention was 13 days each (IQR 11–15, p = 0.723). The rectal VRE carriage rates among the patients at the time of admission to the MICU, determined using ASC were 6.6% (17/259) in pre-intervention and 4.5% (11/242) in intervention (p = 0.326). The percentages of patients who received at least one follow-up ASC in pre-intervention and intervention were 82.2% (213/259) and 81.4% (197/242), respectively (p = 0.809). The device utilization ratio for urinary catheter and central line in pre-intervention was higher than that in intervention period, although the difference was not significant. The ventilator utilization ratio was significantly higher in intervention than in pre-intervention (p < 0.001). There was no significant difference in the incidence of CLA-BSI and CA-UTI between the two periods, and no patients with VAP were reported in either period of the study.

Table 2 Baseline demographics, rates of the device-associated infections, and acquisition and incidence of MDROs in patients in the MICU during the study period

Interrupted time-series analysis

Outcomes

The overall rectal VRE acquisition rate decreased significantly between pre-intervention and intervention periods (20.17 vs. 9.34 per 1000 patient-days, p < 0.001: Table 2). The overall incidence of MRSA and CRAB per 1000 patient-days in clinical cultures were not significantly different between the two periods. The ITS analysis revealed the IRR and percent change calculated from the IRR for the model effects (Table 3). In the VRE acquisition, there was a significant intervention effect (β2) with a 58% decrease (95% CI 7.1–82.1%) following the intervention (p = 0.038). However, there was no significant difference in the trend (β3) of VRE acquisition between the pre-intervention and intervention periods. There was no significant difference in the intervention effect (β2) and trend (β3) on the incidence of VRE, MRSA, and CRAB by clinical cultures between the two periods (Fig. 2).

Table 3 Incidence Rate Ratio and associated percent changes for an interrupted time series analysis model of the VRE acquisition and incidence of MDROs in the MICU during the study periods
Fig. 2
figure2

Interrupted time-series analysis of VRE acquisition and MDROs incidence in MICU patients after daily CHG bathing. A VRE acquisition, B VRE incidence, C MRSA incidence, and D CRAB incidence. CRAB: carbapenem-resistant Acinetobacter baumannii; MICU: medical intensive care unit; MRSA: methicillin-resistant Staphylococcus aureus; VRE: vancomycin-resistant enterococci

Discussion

This quasi-experimental, intervention study investigated whether daily bathing with 2% CHG as an adjunctive intervention could reduce the VRE acquisition and the incidence of VRE, MRSA, or CRAB in a VRE-endemic MICU. In the ITS analysis, we have shown a significant intervention-associated reduction in the acquisition of rectal VRE, following the intervention of 2% CHG daily bathing at a compliance rate of 72.5%. These results suggest that daily CHG bathing could reduce cross-transmission of VRE in patients in the MICU setting with a high VRE endemicity.

Patients with rectal VRE carriage on ICU admission often lead to subsequent colonization of other patients, which may play an important role in the spread and persistence of VRE in the ICU [25]. High VRE endemicity has become stabilized in our ICU settings despite weekly active surveillance for rectal VRE and other infection control measures. However, our hospital has been faced with a constant influx of patients colonized with MDROs from outside healthcare facilities since 2016, when it was designated a regional emergency center [13, 26]. Therefore, the infection control staff developed a daily CHG bathing protocol to overcome the challenges of priority VRE control.

In this study, ITS analysis showed that daily CHG bathing reduced the acquisition rate of rectal VRE, but not the incidence of VRE in clinical cultures between the pre-intervention and intervention periods. Our results are consistent with those of two previous studies on the effect of CHG bathing in the ICU settings [27, 28]. A quasi-experimental, multi-center trial performed in six ICUs reported a significant decrease of 45% in the acquisition of VRE by the end of the intervention [27]. Another prospective clinical trial at a single center reported a significant decrease the incidence of VRE acquisition decreased from 26 colonizations per 1000 patient-days to 9 per 1000 patient-days in the setting of MICU following the intervention [28]. Furthermore, two meta-analyses showed that patients with CHG bathing had a significantly lower risk of VRE colonization [29, 30].

A higher compliance rate with the CHG bathing protocol might have further improved the decrease in colonization of MDROs and the HAI rate. In this study, the compliance rate of 72.5%, including full and partial daily CHG bathing was compatible with the reported compliance rates ranging from 70 to 100% in previous studies [31,32,33]. We evaluated that CHG daily bathing compliance was affected due to multiple barriers in MICU settings. A trained ICU assistant helping patients with CHG bathing was likely to reduce the likelihood of a patient declining to undertake a CHG bath; however, other multiple barriers to CHG daily bathing mostly related to a patient’s clinical severity, which reduced the compliance rate. In our study, the continuing efforts to monitor and provide feedback to staff nurses with increasing compliance rate of CHG daily bathing reflected a real-world setting in the MICU with heterogeneous population and health outcomes. The findings from our real-world study provide further evidence-based information concerning the advantages and disadvantages of daily CHG bathing, as used in an ICU setting.

At our institute, the overall proportions of MRSA and CRAB in the clinical isolates in the MICU were high throughout the study period, accounting for approximately 81.5% (172/211) of all Staphylococcus aureus isolates and 86.3% (233/270) of all Acinetobacter baumannii isolates, respectively. However, the ITS analysis failed to show a significant reduction in MRSA and CRAB incidence in clinical cultures after the intervention. There have been two, randomized controlled studies targeting MRSA and/or VRE in ICUs following a CHG daily bathing intervention. Huang et al. reported a significant decrease in the prevalence of MRSA clinical isolates following targeted or universal decolonization, including CHG bathing and intranasal mupirocin for 5 days [17]. Another multicenter randomized controlled trial by Climo et al. demonstrated a significant decrease in the acquisition of VRE and MRSA in patients in ICU following interventions involving CHG bathing and active surveillance cultures for perirectal VRE and nasal MRSA [27]. These two studies reported a compliance rate of approximately 85%. Unlike these studies, our study protocol focused primarily on VRE control, which included active surveillance cultures on admission and on a weekly basis and single room or cohort isolation in addition to a CHG daily bathing intervention at a compliance rate of 72.5%. On the other hand, our protocol did not specifically include MRSA-targeted strategies, such as active surveillance culture for MRSA nasal carriage and decolonization with intranasal mupirocin. For the effective control of MDROs in ICU settings with CHG daily bathing, we speculate that it is necessary to prepare strategy protocols targeting the specific pathogens, considering the magnitude of the compliance rate and duration of the intervention.

In our study, CHG bathing was not associated with significant reductions in the incidence of DAIs (CLA-BSI and CA-UTI). This might be related to the low number of DAIs during the entire study period. The previous studies have reported inconsistent results of the effect of CHG bathing on the incidence of DAIs in ICUs [34,35,36]. In a single-center randomized controlled trial performed in 5 ICUs, the intervention of CHG bathing did not reduce the incidence of HAIs (CLA-BSIs, CA-UTIs, VAP, and Clostridium difficile infections) in patients [34]. In another study, no significant decrease was reported in the incidence of ICU-acquired CLA-BSI between the control and CHG bathing periods [35]. In contrast, Popovich et al. reported a significant decrease in CLA-BSI following CHG bathing [36]. It is unclear whether the effect of CHG bathing is dependent on the baseline incidence rate of HAIs.

This study has several limitations. First, the study was conducted in a single center; therefore, generalizing the potential effects of CHG bathing to other hospitals’ settings might be difficult. A multicenter study with real-world ICU settings can provide the potential effects of CHG bathing against MDRO control. Second, not all the analyzed patients could receive at least one follow-up weekly VRE surveillance during the study periods. Approximately eighteen percent of the analyzed patients failed to follow-up with VRE surveillance cultures due to ICU stay < 7 days, death, or transfer to general wards. Third, in the setting of MICU of our study, the proportions of patients with ≤ 72 h-ICU stay for pre-intervention and intervention periods were 48.3% (n = 247) and 42.8% (n = 214), respectively. However, the proportions of the patient-days for the two periods were 12.1% (522 patient-days) and 8.4% (369 patient-days), respectively. Fourth, this was a quasi-experimental study, which was susceptible to bias and confounding. We did not consider the randomization and control arm in the study design. Fifth, the pre-intervention and intervention periods did not cover the same months and seasons, which could have played a role in the effect of intervention. Last, our study did not investigate MDROs for development of CHG resistance. Future studies are needed to evaluate MDRO isolates for CHG-resistance.

In this era of antibiotic resistance, MDROs are prevalent worldwide. Multiple intervention strategies are needed for optimal infection control of MDROs, including continuing education, antibiotic stewardship, active surveillance, contact precautions, and environmental control measures [37]. Effective measures for MDRO decolonization remain limited in ICU settings. CHG bathing, as a universal decolonization strategy might be an adjunctive control measure to reduce cross-transmission of VRE until more effective measures become available [38].

Conclusions

This real-world intervention study showed that daily bathing with 2% CHG at a compliance rate of 72.5% could be an effective adjunctive control measure to reduce the acquisition rate of VRE in the ICU where VRE is endemic.

Availability of data and materials

The original contributions presented in the study are included in the article/Additional file 1; further inquiries can be directed to the corresponding author.

Abbreviations

ASC:

Active surveillance cultures

CA-UTI:

Catheter-associated urinary tract infection

CHG:

Chlorhexidine gluconate

CI:

Confidence interval

CLA-BSI:

Central line-associated blood stream infection

CoN-staphylococci:

Coagulase-negative staphylococci

CRAB:

Carbapenem-resistant Acinetobacter baumannii

DAIs:

Device-associated infections

HAIs:

Hospital-acquired infections

HCWs:

Healthcare workers

IQR:

Interquartile range

ITS:

Interrupted time-series

KONIS:

Korean national healthcare-associated infections surveillance system

MDR-GNB:

Multidrug resistant-gram negative bacteria

MDROs:

Multidrug-resistant organisms

MICU:

Medical intensive care unit

MRSA:

Methicillin-resistant Staphylococcus aureus

RC:

Regression coefficient

SD:

Standard deviation

VAP:

Ventilator-associated pneumonia

VRE:

Vancomycin-resistant enterococci

IRR:

Incidence rate ratio

References

  1. 1.

    MacVane SH. Antimicrobial resistance in the Intensive Care Unit: a focus on Gram-negative bacterial infections. J Intensive Care Med. 2017;32:25–37.

    Article  Google Scholar 

  2. 2.

    Doyle JS, Buising KL, Thursky KA, Worth LJ, Richards MJ. Epidemiology of infections acquired in intensive care units. Semin Respir Crit Care Med. 2011;32:115–38.

    Article  Google Scholar 

  3. 3.

    Stefani S, Goglio A. Methicillin-resistant Staphylococcus aureus: related infections and antibiotic resistance. Int J Infect Dis. 2010;14:S19-22.

    Article  Google Scholar 

  4. 4.

    Barrasa-Villar JI, Aibar-Remón C, Prieto-Andrés P, Mareca-Doñate R, Moliner-Lahoz J. Impact on morbidity, mortality and length of stay of hospital-acquired infections by resistant microorganisms. Clin Infect Dis. 2017;65:644–52.

    Article  Google Scholar 

  5. 5.

    McCann E, Srinivasan A, DeRyke CA, Ye G, DePestel DD, Murray J, et al. Carbapenem-nonsusceptible Gram-negative pathogens in ICU and non-ICU settings in US hospitals in 2017: a multicenter study. Open Forum Infect Dis. 2018;5:ofy241.

    Article  Google Scholar 

  6. 6.

    Ziakas PD, Thapa R, Rice LB, Mylonakis E. Trends and significance of VRE colonization in the ICU: a meta-analysis of published studies. PLoS ONE. 2013;8:e75658.

    CAS  Article  Google Scholar 

  7. 7.

    Bhavnani SM, Drake JA, Forrest A, Deinhart JA, Jones RN, Biedenbach DJ, et al. A nationwide, multicenter, case–control study comparing risk factors, treatment, and outcome for vancomycin-resistant and -susceptible enterococcal bacteremia. Diagn Microbiol Infect Dis. 2000;36:145–58.

    CAS  Article  Google Scholar 

  8. 8.

    Siegel JD, Rhinehart E, Jackson M, Chiarello L, Health care infection control practices advisory committee. 2007 guideline for isolation precautions: preventing transmission of infectious agents in health care settings. Am J Infect Control. 2007;2007(35):S65-164.

    Article  Google Scholar 

  9. 9.

    Muto CA, Jernigan JA, Ostrowsky BE, Richet HM, Jarvis WR, Boyce JM, et al. SHEA guideline for preventing nosocomial transmission of multidrug-resistant strains of Staphylococcus aureus and enterococcus. Infect Control Hosp Epidemiol. 2003;24:362–86.

    Article  Google Scholar 

  10. 10.

    Uh Y. Improvement plan for the Korean nationwide surveillance of antimicrobial resistance program. Infect Chemother. 2014;46:141–2.

    Article  Google Scholar 

  11. 11.

    KONIS. Korean national healthcare-associated infections surveillance system (KONIS) report: Data summary from July 2018 through June 2019; 2019. Retrieved from: http://konis.cafe. [cited 31 Jun 2019]. Retrieved from: http://24.com/xe/reports_icu_y

  12. 12.

    Yoon YK, Kim HJ, Lee WJ, Lee SE, Yang KS, Park DW, et al. Clinical prediction rule for identifying patients with vancomycin-resistant enterococci (VRE) at the time of admission to the intensive care unit in a low VRE incidence setting. J Antimicrob Chemother. 2012;67:2963–9.

    CAS  Article  Google Scholar 

  13. 13.

    Yoon YK, Lee MJ, Ju Y, Lee SE, Yang KS, Sohn JW, et al. Determining the clinical significance of co-colonization of vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus in the intestinal tracts of patients in intensive care units: a case–control study. Ann Clin Microbiol Antimicrob. 2019;18:28.

    Article  Google Scholar 

  14. 14.

    Musuuza JS, Sethi AK, Roberts TJ, Safdar N. Implementation of daily chlorhexidine bathing to reduce colonization by multidrug-resistant organisms in a critical care unit. Am J Infect Control. 2017;45:1014–7.

    CAS  Article  Google Scholar 

  15. 15.

    Ruiz J, Ramirez P, Villarreal E, Gordon M, Saez I, Rodríguez A, et al. Daily bathing strategies and cross-transmission of multidrug-resistant organisms: impact of chlorhexidine-impregnated wipes in a multidrug-resistant gram-negative bacteria endemic intensive care unit. Am J Infect Control. 2017;45:1069–73.

    Article  Google Scholar 

  16. 16.

    Cassir N, Thomas G, Hraiech S, Brunet J, Fournier PE, La Scola B, et al. Chlorhexidine daily bathing: impact on health care-associated infections caused by gram-negative bacteria. Am J Infect Control. 2015;43:640–3.

    CAS  Article  Google Scholar 

  17. 17.

    Huang SS, Septimus E, Kleinman K, Moody J, Hickok J, Avery TR, et al. Targeted versus universal decolonization to prevent ICU infection. N Engl J Med. 2013;368:2255–65.

    CAS  Article  Google Scholar 

  18. 18.

    Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing. 27th ed. CLSI supplement M100. Wayne, PA: Clinical and Laboratory Standards Institute; 2017.

  19. 19.

    Kwak YG, Choi JY, Yoo HM, Lee SO, Kim HB, Han SH, et al. Validation of the Korean National Healthcare-associated Infections Surveillance System (KONIS): an intensive care unit module report. J Hosp Infect. 2017;96:377–84.

    CAS  Article  Google Scholar 

  20. 20.

    Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control. 2008;36:309–32.

    Article  Google Scholar 

  21. 21.

    Choi JY, Kwak YG, Yoo H, Lee SO, Kim HB, Han SH, et al. Trends in the incidence rate of device-associated infections in intensive care units after the establishment of the Korean Nosocomial Infections Surveillance System. J Hosp Infect. 2015;91:28–34.

    CAS  Article  Google Scholar 

  22. 22.

    Ellingson K, Muder RR, Jain R, Kleinbaum D, Feng PJ, Cunningham C, Squier C, Lloyd J, Edwards J, Gebski V, Jernigan J. Sustained reduction in the clinical incidence of methicillin-resistant Staphylococcus aureus colonization or infection associated with a multifaceted infection control intervention. Infect Control Hosp Epidemiol. 2011;32:1–8.

    Article  Google Scholar 

  23. 23.

    Ramsay CR, Matowe L, Grilli R, Grimshaw JM, Thomas RE. Interrupted time series designs in health technology assessment: lessons from two systematic reviews of behavior change strategies. Int J Technol Assess Health Care. 2003;19:613–23.

    Article  Google Scholar 

  24. 24.

    WHO Guidelines on Hand Hygiene in Health Care: First Global Patient Safety Challenge Clean Care Is Safer Care. Geneva: World Health Organization; 2009. http://whqlibdoc.who.int/publications/2009/9789241597906_eng.pdf. Accessed 15 May 2021.

  25. 25.

    Austin DJ, Bonten MJM, Weinstein RA, Slaughter S, Anderson RM. Vancomycin-resistant enterococci in intensive-care hospital settings: transmission dynamics, persistence, and the impact of infection control programs. Proc Natl Acad Sci USA. 1999;96:6908–13.

    CAS  Article  Google Scholar 

  26. 26.

    Yoon YK, Ryu JM, Lee MJ, Lee SE, Yang KS, Lee CK, et al. Active surveillance at the time of hospital admission for multidrug-resistant microorganisms among patients who had recently been hospitalized at health care facilities. Am J Infect Control. 2019;47:1188–93.

    Article  Google Scholar 

  27. 27.

    Climo MW, Sepkowitz KA, Zuccotti G, Fraser VJ, Warren DK, Perl TM, et al. The effect of daily bathing with chlorhexidine on the acquisition of methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, and healthcare-associated bloodstream infections: Results of a quasi-experimental multicenter trial. Crit Care Med. 2009;37:1858–65.

    CAS  Article  Google Scholar 

  28. 28.

    Vernon MO, Hayden MK, Trick WE, Hayes RA, Blom DW, Weinstein RA, Chicago Antimicrobial Resistance Project (CARP). Chlorhexidine gluconate to cleanse patients in a medical intensive care unit: the effectiveness of source control to reduce the bioburden of vancomycin-resistant enterococci. Arch Intern Med. 2006;166:306–12.

    CAS  Article  Google Scholar 

  29. 29.

    Xiao G, Chen Z, Lv X. Chlorhexidine-based body washing for colonization and infection of methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus: an updated meta-analysis. Infect Drug Resist. 2018;11:1473–81.

    CAS  Article  Google Scholar 

  30. 30.

    Frost SA, Alogso MC, Metcalfe L, Lynch JM, Hunt L, Sanghavi R, Alexandrou E, Hillman KM. Chlorhexidine bathing and health care-associated infections among adult intensive care patients: a systematic review and meta-analysis. Crit Care. 2016;20:379.

    Article  Google Scholar 

  31. 31.

    Derde LPG, Cooper BS, Goossens H, Malhotra-Kumar S, Willems RJL, Gniadkowski M, et al. Interventions to reduce colonisation and transmission of antimicrobial-resistant bacteria in intensive care units: an interrupted time series study and cluster randomised trial. Lancet Infect Dis. 2014;14:31–9.

    Article  Google Scholar 

  32. 32.

    Kettelhut V, Van Schooneveld T, McClay J, Fruhling A, Dempsey K. The utility of electronic health record-based hygiene notes for chlorhexidine bathing practice evaluation. J Infect Prev. 2017;18:72–7.

    Article  Google Scholar 

  33. 33.

    Rupp ME, Cavalieri RJ, Lyden E, Kucera J, Martin M, Fitzgerald T, et al. Effect of hospital-wide chlorhexidine patient bathing on healthcare-associated infections. Infect Control Hosp Epidemiol. 2012;33:1094–100.

    Article  Google Scholar 

  34. 34.

    Urbancic KF, Mårtensson J, Glassford N, Eyeington C, Robbins R, Ward PB, et al. Impact of unit-wide chlorhexidine bathing in intensive care on bloodstream infection and drug-resistant organism acquisition. Crit Care Resusc. 2018;20:109–16.

    PubMed  Google Scholar 

  35. 35.

    Noto MJ, Domenico HJ, Byrne DW, Talbot T, Rice TW, Bernard GR, et al. Chlorhexidine bathing and health care-associated infections: a randomized clinical trial. JAMA. 2015;313:369–78.

    Article  Google Scholar 

  36. 36.

    Popovich KJ, Hota B, Hayes R, Weinstein RA, Hayden MK. Effectiveness of routine patient cleansing with chlorhexidine gluconate for infection prevention in the medical Intensive Care Unit. Infect Control Hosp Epidemiol. 2009;30:959–63.

    Article  Google Scholar 

  37. 37.

    Backman C, Taylor G, Sales A, Marck PB. An integrative review of infection prevention and control programs for multidrug-resistant organisms in acute care hospitals: a socio-ecological perspective. Am J Infect Control. 2011;39:368–78.

    Article  Google Scholar 

  38. 38.

    Huang SS. Chlorhexidine-based decolonization to reduce healthcare-associated infections and multidrug-resistant organisms (MDROs): Who, what, where, when, and why? J Hosp Infect. 2019;103:235–43.

    CAS  Article  Google Scholar 

Download references

Acknowledgements

We acknowledge Yoojung Jeong at the Institute of Emerging Infectious Diseases, Korea University for managing the administrative processes used in this study.

Funding

This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant number: HI17C0665).

Author information

Affiliations

Authors

Contributions

MJK devised the project and designed and implemented the research. NHK, MJL, and SEL developed the protocol and technical details, carried out the experiments, and prepared the experimental database. BCC and JWS performed data analyses using the interrupted time-series method. JWS and MJK worked on the manuscript. JL cleared the experimental database and performed numerical calculations for the suggested experiments. CKL, JHK, SBK, YKY, and JWS worked out the practical details of the experimental process. All the authors discussed the results and commented on the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Min Ja Kim.

Ethics declarations

Ethics approval and consent to participate

This study was approved by the Institutional Review Board of Korea University Anam Hospital (IRB Number 2020AN0357).

Consent for publication

Not applicable.

Competing interests

The authors disclose that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1:

Detailed information concerning the MDRO distribution from skin swab cultures prior to the pilot study and during the six-month intervention of 2% CHG bathing, the hand hygiene adherence rate for healthcare workers in the MICU during the study period, and the isolation of microorganisms from patients with DAIs in the MICU during the study period. Table S1. Skin swab cultures for MDROs from the representative body sites of patients in MICU prior to the pilot trial and during the six-month intervention of 2% CHG daily bathing. Table S2. Hand hygiene adherence rate for HCWs in the MICU observed at the World Health Organization’s Five Moments of Hand Hygiene during the study period. Table S3. Isolation of microorganisms from the patients with device-associated hospital-acquired infections in the MICU during the study period.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Suh, J.W., Kim, N.H., Lee, M.J. et al. Real-world experience of how chlorhexidine bathing affects the acquisition and incidence of vancomycin-resistant enterococci (VRE) in a medical intensive care unit with VRE endemicity: a prospective interrupted time-series study. Antimicrob Resist Infect Control 10, 160 (2021). https://0-doi-org.brum.beds.ac.uk/10.1186/s13756-021-01030-6

Download citation

Keywords

  • Chlorhexidine gluconate
  • Baths
  • Vancomycin-resistant enterococci
  • Acquisition
  • Intensive care unit
  • Interrupted time-series analysis