In the United States, ∼75,000 patients die in the hospital annually as a result of healthcare-associated infections (HAIs). Reference Warren, Turner and Smith1 These infections contribute to significant morbidity, mortality, extended length of hospital stay, and costs to the healthcare system and the patient. Reference Stone, Braccia and Larson2,Reference Sievert, Ricks and Edwards3 Most HAIs are caused by epidemiologically important pathogens (EIPs), Reference Burnham, Olsen and Kollef4 and it is now well established that the healthcare environment plays a crucial role in the transmission of EIPs. Reference Weber, Anderson and Rutala5 Healthcare personnel may contaminate their hands by touching environmental surfaces, which can lead to the transmission of EIPs to patients. Reference Han, Sullivan, Leas, Pegues, Kaczmarek and Umscheid6 Hence, effective surface disinfection remains a cornerstone to preventing transmission of EIPs and reducing HAI. Reference Han, Sullivan, Leas, Pegues, Kaczmarek and Umscheid6
Despite increasing evidence that disinfecting the environment can reduce the transmission of infectious pathogens, most surfaces in hospital settings are inadequately cleaned. Reference Rutala and Weber7–Reference Cadnum, Pearlmutter and Jencson9 Though newer technologies, such as ultraviolet devices and hydrogen peroxide systems, are available to optimize terminal cleaning in patient rooms, there are challenges associated with the implementation of these approaches. Reference Weber, Kanamori and Rutala10 Furthermore, although surface disinfection reduces the bioburden, pathogens are repeatedly reintroduced onto a cleaned surface. Recontamination of environmental surfaces is multifactorial and could be affected by the prolonged survival of EIPs, suboptimal cleaning, the level of contamination of rooms related to pathogen shedding from both symptomatic and asymptomatic patients with EIPs, and suboptimal hand hygiene practices. Reference Lei, Jones and Li11,12 However, if daily cleaning can be done with a continuously active disinfectant (CAD) that remains active on the environmental surface for a longer duration by forming a multilayer protective shield, it has the potential to reduce the overall bioburden and prevent recontamination with EIPs. 13,Reference Rutala, Gergen and Sickbert-Bennett14
Although most studies evaluating CAD effectiveness have been performed in vitro, very few studies have been done in situ. Reference Schmidt, Fairey and Attaway15–Reference Warren, Turner and Smith18 Some major limitations of the studies conducted in the clinical setting include the fact that patient-level variables were not assessed, and most were not randomized trials. We conducted a randomized controlled trial to study the efficacy of a new CAD compared to a standard disinfectant to reduce environmental bioburden in the intensive care unit (ICU) setting.
Methods
Study design and setting
We conducted a parallel randomized controlled trial with a 1:1 allocation ratio. The study was conducted in the medical intensive care unit (MICU), a 29-bed unit, at the University of Maryland Medical Center (UMMC), where a single patient occupies each room. The study was approved by the University of Maryland Institutional Review Board (IRB) as exempt from IRB review, and a waiver of informed consent was obtained from this IRB. Enrollment for the study took place between November 2021 and April 2022.
A room was eligible for inclusion in the study if the patient currently in the room was aged >18 years, admitted to the MICU, and on contact precautions. Patients with confirmed or suspected Clostridioides difficile infections or confirmed or suspected COVID-19 were excluded. Patients who were incarcerated or had a discharge or transfer from the MICU planned within the next 24 hours were also excluded.
During the study period, a daily list of eligible patients on contact precautions in the MICU was automatically generated from the hospital’s electronic health record database based on the inclusion criteria. Eligible patients were randomized to the intervention arm or control arm using a pregenerated random allocation sequence. The random allocation sequence was implemented using a sequential number system, and the study arms were deidentified in the observation sheet and database during entries. All patients enrolled in the study were unique.
Intervention
The new CAD used in the intervention group is a persistent, organosilane quaternary ammonium product and the first and currently the only Environmental Protection Agency (EPA)–registered surface disinfectant with 24 hours of sustained antimicrobial activity marketed by Professional Disposables International (Woodcliff Lake, NJ). Rooms assigned to the control group were cleaned with the standard disinfectant which in this case was an accelerated hydrogen peroxide product marketed by Diversey.
Implementation
After a patient’s room was randomized, the research staff placed signage on the door to remind healthcare personnel (HCP) to only use the wipes available in the room. To ensure consistency of product application and to standardize cleaning, the research staff thoroughly wiped down all 5 high-touch environmental surfaces using 1 wipe per surface. Environmental samples were then obtained from the 5 high-touch surfaces at 1, 4, and 24 hours after cleaning by the research staff. At each sampling time, the research staff also documented whether the correct wipes were in the room and whether any other wipes were present.
Based on previous work on the transmission of EIPs, the 5 high-touch environmental surfaces selected for sampling included (1) bed rails, (2) bedside table, (3) trash can, (4) sink, and (5) supply cart. Reference O’Hara, Calfee and Miller19,Reference Jackson, Thom and Magder20 The samples were obtained using a sterile 25×25-cm (10×10-inch) stencil. Cellulose sponge sticks (3M, St. Paul, MN) with a neutralizing buffer that inactivates halogen disinfectants and quaternary ammonium compounds were used, and the CDC recommended technique for environmental surface sampling was followed. 21 In total, 20 swabs were obtained for each enrolled patient in the study (ie, 5 high-touch surfaces were sampled at 4 times).
Study outcomes
The primary outcome was the mean bacterial (pathogenic and nonpathogenic) bioburden measured in CFU/mL from all 5 environmental high-touch surfaces at 24 hours. The secondary outcome was the detection of any one of the EIPs (ie, Staphylococcus aureus and methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis, Enterococcus faecium, Pseudomonas aeruginosa, Klebsiella peumoniae, Acinetobacter baumannii, and Enterobacter aerogenes) from any of the 5 high-touch surfaces at 24 hours.
Blinding
The laboratory team was blinded to the study arm, time of sampling, and the surface from where the samples were obtained. It was not feasible to blind research staff and frontline HCP since the 2 disinfectant wipes were of different sizes, textures, and smells.
Microbiological methods
Each sponge was extracted using a stomacher for bacteria and plated on Pseudosel agar, Cetrimide agar, CHROMagar SA, Bile Esculin Azide agar with vancomycin, and MacConkey agar for identification of the specific pathogenic bacteria. Colonies were counted if growth was between 30 and 300 to calculate the average colony count, and the colonies were also subcultured in TSB enrichment media and incubated for 24 hours. Identification of the isolates was performed using the VITEK MS (bioMeriuex, France). On all isolates, the laboratory personnel performed susceptibilities using the appropriate Vitek antimicrobial susceptibility testing cards.
Sample size
Sample size calculations were done a priori to determine the number of rooms necessary for adequate statistical power. Using 2 sample means, it was determined that at least 40 rooms were necessary to obtain power >80% to detect an effect size difference of 150 CFU/mL at 24 hours between the 2 study arms (accounting for a crossover of 5% and 2% loss to follow-up). Reference Schmidt, Fairey and Attaway15
Statistical analysis
Results were analyzed on an intention-to-treat basis. We assessed statistical differences between the 2 groups using the χ2 test or Wilcoxon-Mann-Whitney test. The bioburden (CFU/mL) from the 5 high-touch surfaces was log-transformed (x+1) for the primary outcome analysis. A composite binary outcome variable of any detectable EIP on any of the 5 high-touch surfaces was created for the secondary outcome. We restricted our analyses to postcleaning samples at 1 hour, 4 hours, and 24 hours after cleaning. For the primary outcome, we used a general linear model for repeated measures with unstructured covariance to study the association between the log-transformed mean bioburden (CFU/mL) and the 2 disinfectants at 24 hours. For the secondary outcome, we used logistic regression to calculate the odds (OR) of EIP detection between the 2 disinfectants at 24 hours. All P values were 2-tailed, and analyses were performed using SAS version 9.4 software (SAS Institute, Cary NC).
Results
We enrolled 43 patient rooms during the study period between November 2020 to April 2021; 21 patients were randomized to receive the new CAD and 22 patients were randomized to receive the standard disinfectant. In total, 843 samples were obtained during the study. Some samples from 3 patients (2 in the control arm, and 1 in the intervention arm) were missing as the patients were lost to follow-up (Fig. 1). Removal of the environmental markers from the environmental surfaces in the patients’ room assessing the quality of cleaning by the environmental services staff was not significantly different between the new disinfectant and the standard disinfectant (41% vs 40%). To ensure standardized application of the assigned disinfectant to the environmental surfaces studied, research staff recleaned each surface until 100% of the environmental markers were removed. As illustrated in Table 1, the baseline characteristics of patients enrolled in the study were similar between the 2 study arms.
Figure 1. CONSORT flow diagram showing patient enrollment.
Table 1. Baseline Characteristics of Unique Medical Intensive Care Unit Patients (n=43)
a P value obtained using the χ2 test or Fisher exact test when cell count <5 for categorical variables and using the Wilcoxon-Mann-Whitney test or Student t test for continuous variables.
b Length of stay in days on the day of enrollment calculated by subtracting date of enrollment from date of admission.
c Comorbidities present at the time of current admission. Obtained using International Classification of Disease, Tenth Revision, Clinical Modification (ICD-10-CM) codes and standardized Agency for Healthcare Research and Quality (AHRQ) software to obtain the Elixhauser score.
d Characteristics documented during current admission.
e Current colonization, positive surveillance culture during current admission; past colonization or infection, positive surveillance culture from a previous admission and negative during current admission; current infection, positive clinical culture during current admission.
f Organism identified from clinical and/or surveillance culture during current admission.
Primary outcome
Figure 2 illustrates the overall mean bioburden for each sampling time by study arm. At all sampling times, the mean bioburden in the intervention arm was lower than in the control arm. At 24 hours, the mean bioburden recovered in the intervention arm was 52.0 CFU/mL (95% CI, 46.1–184.9) and was 92.0 CFU/mL (95% CI, 27.9–95.6) in the control arm. As shown in Figure 3, the mean bioburden was also lower in the intervention arm on 3 of 5 high-touch environmental surfaces. Table 2 shows the results of the multivariable analysis and suggests that the mean difference of the overall bioburden between the intervention arm and control arm was −0.59 (95% CI, −1.45 to 0.27).
Figure 2. Distribution of mean bioburden (CFU/mL) by time points stratified by study arm.
Figure 3. Distribution of mean bioburdn (CFU/mL) stratified by environmental high-touch surface and study arm at 24-hour timepont.
Table 2. Mean Difference in Bioburden (CFU/mL) Between Intervention and Control Arms
a Reference, control disinfectant, log (x+1) transformed.
Secondary outcome
Of the 843 samples analyzed, 57 (6.7%) had EIPs identified. Of 627 postcleaning samples, 38 (6.1%) EIPs were identified: 23 (3.7%) in the control arm and 15 (2.4%) in the intervention arm. At 24 hours, EIPs were identified on 17 (8.4%) of 202 samples: 8 (47.1%) from the intervention arm and 9 (52.9%) from the control arm (P = .80). Table 3 shows the distribution of the EIPs by study arm. Figure 4 shows EIPs detected by high-touch environmental surface at 24 hours. Multivariable models showed that the odds of EIP detection were 14% lower in the rooms cleaned with the intervention wipe compared to those cleaned with the standard wipe (OR, 0.86; 95% CI, 0.31–2.32; P = .76), though not statistically significant.
Table 3. Distribution of Epidemiologically Important Pathogens (EIPs) detected on environmental surfaces sampled (n=843)
Note. MRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillin-sensitive Staphylococcus aureus; E. faecium, Enterococcus faecium; K. pneumoniae, Klebsiella pneumoniae); E. faecalis, Enterococcus faecalis; A. baumannii, Acinetobacter baumanni; P. aeruginosa, Pseudomonas aeruginosa.
a P values obtained using the χ2 test or Fisher exact test.
b If any one of the specific pathogens were detected.
Figure 4. Distribution of EIP stratified by environmental high-touch surfaces and study arms at 24 hour timepoint.
Discussion
In this randomized controlled trial conducted in an ICU, we observed a 0.59 CFU/mL lower mean bioburden in the rooms cleaned with the new CAD compared to the standard disinfectant. Given that the 95% confidence interval ranged from −1.45 to 0.27, the mean bioburden may be 1.45 CFU/mL less in the rooms cleaned with CAD but also could be 27 CFU/mL higher in the rooms cleaned with the standard disinfectant. Similarly, while there were lower odds of EIP recovery from the rooms cleaned with the new CAD in comparison to the control disinfectant at 24 hours, this was not statistically significant.
The CAD product used in this study showed persistent decrease of bioburden in previously published studies. A study by Schmidt et al Reference Schmidt, Fairey and Attaway15 compared the CAD to 2 other disinfectants. This study was a nonrandomized, prospective, cohort study performed on a convenience sample of ICU patients, and the product was tested on a single high-touch surface (bed rail). Although each disinfectant was able to significantly reduce bioburden for the first hour, the CAD was associated with a significantly lower bioburden at 6 hours and 24 hours after cleaning. Reference Schmidt, Fairey and Attaway15 Tamimi et al Reference Tamimi, Carlino and Gerba17 performed a before-and-after intervention study with no control group. This study was performed in an ICU where high-touch and non-high touch surfaces were cultured before application and then at 1, 2, 4, 8, and 15 weeks after application of an organosilane-based quaternary ammonium compound. These researchers concluded that the average bacterial count on all treated surfaces was reduced by > 99% (2 logs) for at least 8 weeks after treatment. Antibiotic-resistant bacteria were found on 25% of the sites tested before treatment but were isolated at only 1 site during the 15 weeks after treatment. Reference Tamimi, Carlino and Gerba17 Ellingson et al Reference Ellingson, Pogreba-Brown, Gerba and Elliott22 also reported a decrease in environmental bioburden and a decrease in HAIs in six non-randomly selected units in 2 hospitals after application of a quaternary ammonium antimicrobial surface coating. The differences between the results presented here and prior studies may be ascribed to variations in study methodology, population, comparison groups, sampling techniques, surfaces sampled, and laboratory procedures.
Compared with previously published in vitro studies in which the CAD was effective in lowering environmental bioburden, we did not find similar results in a real-world clinical setting. Reference Rutala, Gergen and Sickbert-Bennett14,Reference Redmond, Cadnum and Silva23 Some postulated explanations for these discordant findings are (1) unintentional removal of CAD by HCP (using soap or other wipes) during patient care activities; (2) heterogeneity of the material composition of surfaces sampled; (3) uniform product application using the applicator in the laboratory environment compared to nonuniform application in real-world settings; and (4) more frequent recontamination of surfaces.
A major strength of this study was the randomized controlled trial design, which ensured exchangeability between the 2 study groups. Standardization of the cleaning in both arms of the trial was also ensured by having the research staff wipe down the environmental high-touch surfaces and the quality of cleaning was documented using environmental markers. Finally, patient-level variables were included in the analyses.
This study also had several limitations. It is possible that the study was underpowered. The observed effect sizes were smaller than those reported in a previous study that was used to inform parameters included in our power calculations. However, little is known about the effect size that is clinically meaningful to reduce bioburden on high-touch environmental surfaces in the clinical setting. In addition, our sample size calculation was based on a prior study evaluating a CAD on a single environmental surface. The generalizability of our results may be limited because enrollment was performed only in 1 unit. Finally, it is possible that crossover of cleaning products may have occurred because we were unable to monitor cleaning in the rooms throughout the full 24-hour period. However, at all data collection times, the research staff did not observe any deviations from study arm assignment. The research staff and other HCP were not blinded to the disinfectant; however, the laboratory personnel were blinded to the study arm, surface, and time they received the swabs.
In this randomized controlled trial, we evaluated the efficacy of a new CAD. The intervention was associated with a lower mean bioburden and a decreased detection of EIP compared to the standard disinfectant; however, the results were not statistically significant. Although the positive effect of the CAD in in vitro studies has been well established, larger multicenter randomized trials in the healthcare setting may be warranted to more accurately estimate the effect size and potential benefits of novel disinfectants with sustained activity to aid in the ongoing quest to limit the transmission of infectious diseases in healthcare settings.
Acknowledgments
We thank Scott Sorogon, Gwen Robinson, Lisa Pineles, Alison Lydecker, Indira French and Gwen Pasziewicz from the Genomic Epidemiology and Clinical Outcomes division at the University of Maryland for all their support in the planning, and implementation of this study. We would also like to thank Autumn Rosenblum (infection prevention manager) and Tiffany Taylor (environmental services manager) at the University of Maryland Medical Center for making implementation of this study a success.
Financial support
This study was funded by Professional Disposables International (Woodcliff Lake, NJ). The sponsor donated the product studied, but played no role in the design, conduct, interpretation, or summary of this investigation.
Competing interests
All authors report no conflicts of interest relevant to this article.
