Universal Glove and Gown Use and Acquisition of Antibiotic-Resistant Bacteria in the ICU: A Randomized Trial

Importance  Antibiotic-resistant bacteria are associated with increased patient morbidity and mortality. It is unknown whether wearing gloves and gowns for all patient contact in the intensive care unit (ICU) decreases acquisition of antibiotic-resistant bacteria.

Objective  To assess whether wearing gloves and gowns for all patient contact in the ICU decreases acquisition of methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE) compared with usual care.

Design, Setting, and Participants  Cluster-randomized trial in 20 medical and surgical ICUs in 20 US hospitals from January 4, 2012, to October 4, 2012.

Interventions  In the intervention ICUs, all health care workers were required to wear gloves and gowns for all patient contact and when entering any patient room.

Main Outcomes and Measures  The primary outcome was acquisition of MRSA or VRE based on surveillance cultures collected on admission and discharge from the ICU. Secondary outcomes included individual VRE acquisition, MRSA acquisition, frequency of health care worker visits, hand hygiene compliance, health care–associated infections, and adverse events.

Results  From the 26 180 patients included, 92 241 swabs were collected for the primary outcome. Intervention ICUs had a decrease in the primary outcome of MRSA or VRE from 21.35 acquisitions per 1000 patient-days (95% CI, 17.57 to 25.94) in the baseline period to 16.91 acquisitions per 1000 patient-days (95% CI, 14.09 to 20.28) in the study period, whereas control ICUs had a decrease in MRSA or VRE from 19.02 acquisitions per 1000 patient-days (95% CI, 14.20 to 25.49) in the baseline period to 16.29 acquisitions per 1000 patient-days (95% CI, 13.48 to 19.68) in the study period, a difference in changes that was not statistically significant (difference, −1.71 acquisitions per 1000 person-days, 95% CI, −6.15 to 2.73; P = .57). For key secondary outcomes, there was no difference in VRE acquisition with the intervention (difference,  0.89 acquisitions per 1000 person-days; 95% CI, −4.27 to 6.04, P = .70), whereas for MRSA, there were fewer acquisitions with the intervention (difference, −2.98 acquisitions per 1000 person-days; 95% CI, −5.58 to −0.38; P = .046). Universal glove and gown use also decreased health care worker room entry (4.28 vs 5.24 entries per hour, difference, −0.96; 95% CI, −1.71 to −0.21, P = .02), increased room-exit hand hygiene compliance (78.3% vs 62.9%, difference, 15.4%; 95% CI, 8.99% to 21.8%; P = .02) and had no statistically significant effect on rates of adverse events (58.7 events per 1000 patient days vs 74.4 events per 1000 patient days; difference, −15.7; 95% CI, −40.7 to 9.2, P = .24).

Conclusions and Relevance  The use of gloves and gowns for all patient contact compared with usual care among patients in medical and surgical ICUs did not result in a difference in the primary outcome of acquisition of MRSA or VRE. Although there was a lower risk of MRSA acquisition alone and no difference in adverse events, these secondary outcomes require replication before reaching definitive conclusions.

Trial Registration  clinicaltrials.gov Identifier: NCT0131821

Antibiotic resistance is associated with considerable morbidity, mortality, and costs.^1,2 Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) are primary causes of health care–associated infections (HAIs) that are associated with worse outcomes than those caused by antibiotic-susceptible S aureus and Enterococcus.^3,4 The estimated cost of antibiotic-resistance in the United States is more than $4 billion per year.¹ Health care–associated infections are the most common complication of hospital care, affecting an estimated 1 in every 20 inpatients.²

Numerous studies have shown that health care workers acquire bacteria on their hands and clothing by touching patients.^5,6 Current interventions focus on hand hygiene; however, despite decades of efforts to improve hand hygiene compliance, hand hygiene compliance rates remain low.⁷ The use of gloves and gowns may reduce acquisition of antibiotic-susceptible and antibiotic-resistant bacteria by health care workers and decrease subsequent transmission to other patients.

The Centers for Disease Control and Prevention (CDC) recommend use of contact precautions (wearing gloves and gowns) when caring for patients colonized or infected with antibiotic-resistant bacteria.⁸ However, colonization with MRSA, VRE, or other antibiotic-resistant bacteria often is not detected, and contact precautions, therefore, are not applied. Small, nonrandomized trials suggest that wearing gloves and gowns for all patient contact may decrease acquisition of antibiotic-resistant bacteria and HAIs.^9-12 However, the use of contact precautions has also been associated with fewer health care worker-patient contacts and an increase in adverse events.^13-15

We conducted a cluster randomized trial to assess whether wearing gloves and gowns for all patient contact in the intensive care unit (ICU) compared with the use of contact precautions only for patients with known antibiotic-resistant bacteria reduces colonization acquisition rates of MRSA and VRE. We hypothesized that the intervention would decrease MRSA or VRE acquisition.

The study was a matched pair cluster randomized trial with the ICU as the level of randomization and inference. In the intervention group, health care workers wore gloves and gowns for all patient contact and when entering any patient room. In the control group, health care workers wore gloves and gowns according to CDC guidelines, ie, for patients with known antibiotic-resistant bacteria. From September 2011 to December 2011, ICUs collected baseline data on the primary outcome of MRSA or VRE acquisition. The ICUs were pair-matched based on baseline MRSA or VRE acquisition rates as a composite outcome. Within each pair, 1 ICU was randomized to the intervention and the other to the control group by the statistician (M.S.) using a computer-generated sequence.¹⁶ The study period was January 4, 2012, to October 4, 2012. The trial was conducted in accordance with CONSORT guidelines.¹⁷ A cluster randomized trial was necessary to answer these questions because a behavioral infection control intervention could not be studied using traditional patient-level randomization.^18,19

We recruited medical, surgical, or combined medical-surgical ICUs for adult patients from academic and community hospitals in the United States through the Society for Healthcare Epidemiology of America (SHEA) Research Network (Figure).²⁰ The only exclusion criterion was that ICUs could not screen patients for MRSA or VRE (active surveillance culturing). Patients were eligible for inclusion in the analysis of the primary outcome if they had a negative admission culture for MRSA or VRE and a discharge culture collected (as described below).

The University of Maryland School of Medicine served as the central institutional review board (IRB). All participating ICUs received approval from their local IRBs, and each determined this to be a minimal-risk study and granted approval of the study along with a waiver of consent and Health Insurance Portability and Accountability Act (HIPAA) waiver.

The intervention occurred at the cluster level of ICU. During the study period, all health care workers (nurses, physicians, respiratory therapists, etc) in the 10 ICUs assigned to the intervention groups were required to wear gloves and gowns for all patient contact and when entering any patient room.^8,21 The 10 control ICUs followed their usual standard of care, which consisted of health care workers’ following CDC contact precautions guidelines (gloves and gowns) for patients known to have infection or colonization with antibiotic-resistant bacteria such as VRE and MRSA.⁸

Each site designated a study coordinator and physician champion to lead implementation. All sites were trained via webinar on proper technique for collecting and shipping cultures, and study coordinators from each site attended a study initiation meeting, where they received in-person training on all data collection requirements. Training for the Institute for Healthcare Improvement (IHI) Global Trigger Tool²² included completion of 5 standardized cases from IHI and another 5 standardized cases from the coordinating center with feedback. To ensure that infection control and prevention staff at each ICU determined HAIs according to CDC definitions, staff were required to view standardized Microsoft Powerpoint presentations developed by the CDC on National Health Safety Network definitions and complete a test on these definitions.^23-26 Biweekly conference calls were held with site coordinators to discuss questions, challenges, and solutions with meeting minutes and frequently asked questions with the answers distributed to sites. Additionally, all sites received at least 1 visit from study investigators. To improve admission and discharge culture compliance, sites received weekly feedback of their compliance rates compared with other sites.

All patients had ICU admission and ICU discharge surveillance cultures for MRSA (nasal swab) and VRE (perianal swab). The primary outcome was acquisition of either MRSA or VRE as a composite. Key secondary outcomes were MRSA and VRE acquisition as 2 separate outcomes. For each eligible patient, acquisition was defined as having an initial ICU surveillance culture that was negative for an antibiotic-resistant pathogen with a subsequent discharge surveillance culture within the same ICU admission that was positive for the same antibiotic-resistant pathogen. The ICUs did not receive results of the surveillance cultures. Specimens were shipped to and processed at the University of Maryland using a method that did not affect bacterial yield.²⁷ The specimens were enriched in both Enterococcosel broth and trypticase soy broth with 6.5% sodium chloride (Remel) broth and plated to bile esculin azide agar with 6 μg/mL Vancomycin agar for VRE and Spectra MRSA agar (Remel) for MRSA. Antibiotic resistance was confirmed by the detection of the resistance genes, mecA for MRSA and vanA or vanB for VRE by polymerase chain reaction (PCR), during the study and baseline periods.^28,29 However, due to a short amount of time between the baseline period and the randomization and notification of sites to the intervention or control group, confirmation of MRSA by PCR was not performed for the baseline period prior to site randomization assignment. Baseline MRSA rate by culture method was equal in both groups, although PCR identified more false-positive MRSA tests in the control group leading to the intervention group having a higher baseline MRSA acquisition rate.

In addition to MRSA or VRE acquisition, secondary outcomes included the following:

1. Health care–associated infections: These were recorded at the cluster level. Central line–associated bloodstream infection, catheter–associated urinary tract infection, and ventilator–associated pneumonia rates were measured in a standardized fashion at the ICU level using CDC National Healthcare Safety Network definitions.³⁰

2. Adverse events: A random selection of charts was reviewed, and ICU adverse events were recorded to calculate ICU adverse event rates using the IHI Global trigger tool.²² The trigger tool defines adverse events as “unintended physical injury resulting from or contributed to by medical care that requires additional monitoring, treatment, or hospitalization or that results in death.” Ninety charts per ICU in both intervention and control groups were reviewed using a standardized data extraction sheet. We selected patients who had been in the study ICU for at least 24 hours and had been discharged for 30 days. Nurse, physician, and coordinator primary clinical reviewers at each site completed chart review worksheets and patient summaries. Reviewers sent chart reviews to the coordinating center as PDFs. Two physicians (A.D.H. and D.J.M.) independently reviewed all summaries and adverse events in a blinded fashion for adequate evidence of adverse event independently and then met together for concurrence, as done previously.³¹

3. Frequency of health care worker room entry and hand hygiene compliance: Compliance with hand hygiene, glove and gown compliance, and the frequency of health care worker visits were measured by 30-minute direct observation periods on a random sample of rooms. Site study staff covertly observed health care workers. Two hours per week of observations occurred at varied times of day over the entire study period. Hand hygiene was monitored on room entry and room exit. The recording form used was based on one from the IHI.³²

Initial power calculations determined that 18 ICUs were necessary to detect a 25% relative reduction in acquisition of MRSA or VRE in the intervention group vs no reduction in the control group (or relative rate ratio of 0.75) based on a presumed rate of 50 acquisitions per 1000 patient days. We calculated this rate using preliminary data from ICUs at the University of Maryland Medical Center. We enrolled 20 ICUs to account for expected attrition of 10%. These power calculations were then revised based on actual baseline-period data from this study as follows: The observed mean rate of MRSA or VRE acquisition during the baseline period was 30 new acquisitions per 1000 person-days. The monthly standard deviation in the baseline period was 15 new acquisitions per 1000 person-days and the longitudinal intraclass correlation coefficient (correlation between adjacent monthly acquisitions rates in the same ICU) was 0.38. We assumed no decrease in acquisition in ICUs assigned to standard control and a 25% relative rate reduction (which corresponds with an absolute reduction of 30 × 0.25 = 7.5 new acquisitions per 1000 person-days) in ICUs assigned to the intervention. We also assumed an autoregressive correlation, 9 months of follow-up during the study period, and a 25% gain in efficiency due to matching. The 20 ICUs (10 per group) were sufficient to reach 80% power to reject the null hypothesis of no difference in changes in MRSA or VRE acquisition rates between ICUs assigned to the standard control group and ICUs assigned to the intervention group using a 2-sided t test with 5% type I error.

Analyses of all outcomes were conducted at the ICU level, followed the intention-to-treat approach, and accounted for the matched-pair design. All tests were 2-sided with 5% type I error. For acquisition of either MRSA or VRE and other outcomes with baseline period data, weighted paired t tests compared changes in rates from baseline (prerandomization) to the end of the study between the intervention and control ICUs.¹⁶ For outcomes without baseline period data, weighted paired t tests compared study period rates or means between intervention and control ICUs.¹⁶ Weighting accounted for differences in cluster sizes (eg, patient-time at risk) between ICUs with each pair weighted according to the inverse variance of the estimated effect size.³³ Testing and estimation were performed on the log scale to account for different ICU sizes³⁴; estimated rates and 95% confidence intervals were obtained by exponentiating. A prespecified secondary analysis of the primary outcome and key secondary outcomes was performed, adjusting for ICU admission prevalence of MRSA or VRE. For each pair, the weight was the inverse variance of the estimated effect after adjusting for admission prevalence of MRSA or VRE. All weighted paired t tests had 9 degrees of freedom.^16,33,34 The statistical plan is in the Supplement.

Twenty ICUs participated in the study and none withdrew. There were 26 180 patient admissions including 6324 patients during the baseline period and 19 856 patients during the study period. A total of 92 241 swabs were collected for detection of MRSA and VRE, including 20 646 swabs during the baseline period and 71 595 swabs during the study period. Table 1 shows the characteristics of the ICUs and proportion of patients colonized at admission. During the study period, compliance with obtaining nasal cultures at admission was 95.73%; perianal cultures, 94.92%. Compliance with obtaining nasal cultures at discharge was 84.44%; perianal cultures, 85.07%. Overall, during the study period 1700 of 9920 admissions were ineligible for analysis in the control ICUs, and 1540 of 9936 admissions were ineligible for analysis in the intervention ICUs because admission or discharge cultures were not obtained. The difference in proportions of admissions that were ineligible due to missing cultures, comparing intervention with control ICUs, was not statistically significant (P = .18). Compliance with wearing gloves in the intervention ICUs was 86.18% (2787 of 3234) and compliance with gowns was 85.14% (2750 of 3230). In the control group, 10.52% of patients were on contact precautions. In the control ICUs, for patients on contact precautions, compliance with wearing gloves was 84.11% (556 of 661) and compliance with gowns was 81.21% (536 of 660).

The effects of the intervention on the primary outcome and the key secondary outcomes are shown in Table 2. Intervention ICUs had a decrease in the primary outcome of MRSA or VRE from 21.35 acquisitions per 1000 patient-days (95% CI, 17.57 to 25.94) in the baseline period to 16.91 acquisitions per 1000 patient-days (95% CI, 14.09 to 20.28) in the study period, whereas control ICUs had a decrease in MRSA or VRE from 19.02 acquisitions per 1000 patient-days (95% CI, 14.20 to 25.49) in the baseline period to 16.29 acquisitions per 1000 patient-days (95% CI, 13.48 to 19.68) in the study period, a difference in changes that was not statistically significant (difference, −1.71 acquisitions per 1000 person-days; 95% CI, −6.15 to 2.73; P  = .57). Regarding the key secondary outcome of VRE, intervention ICUs had a decrease from 15.18 acquisitions per 1000 patient-days (95% CI, 10.50 to 21.95) in the baseline period to 13.59 acquisitions per 1000 patient-days (95% CI, 10.26 to 17.99) in the study period, whereas control ICUs had a decrease in VRE from 14.37 acquisitions per 1000 patient-days (95% CI, 10.31 to 20.02) in the baseline period to 11.88 acquisitions per 1000 patient-days (95% CI, 8.65 to 16.33) in the study period, a difference in changes that was not statistically significant (difference, 0.89 VRE acquisitions per 1000 person-days; 95% CI, −4.27 to 6.04, P = .70). For the other key secondary outcome of MRSA, intervention ICUs had a decrease from 10.03 acquisitions per 1000 patient-days (95% CI, 8.05 to 12.50) in the baseline period to 6.00 acquisitions per 1000 patient-days (95% CI, 4.63 to 7.78) in the study period, whereas control ICUs had a decrease in MRSA from 6.98 acquisitions per 1000 patient-days (95% CI, 4.50 to 10.83) in the baseline period to 5.94 acquisitions per 1000 patient-days (95% CI, 4.59 to 7.67) in the study period, a statistically significant difference in rates of change (difference, −2.98 MRSA acquisitions per 1000 person-days; 95% CI, −5.58 to −0.38; P  = .046). This was a 40.2% relative reduction in MRSA acquisition compared with a 15.0% reduction in control ICUs. The results did not qualitatively differ after adjusting for admission prevalence of MRSA or VRE. After adjustment, results were still not statistically significant for acquisition of MRSA or VRE (P = .60) and VRE (P = .57), and the decrease in MRSA acquisition remained significantly larger in the intervention group than in the control group (P = .007).

Health care worker behaviors were affected by the intervention (Table 3). The mean number of health care worker visits per hour in the in the intervention group was 4.28 (95% CI, 3.95 to 4.64) vs 5.24 (95% CI, 4.46 to 6.16) in the control group, for a mean difference of −0.96 visits per hour (95% CI, −1.71 to −0.21; P = .02). Hand-hygiene compliance upon room entry did not significantly differ between the intervention and control groups (56.1% in the intervention group vs 50.2% in the control group; difference, 5.91%; 95% CI, −6.91% to 18.7%, P = .42), but compliance upon exit was 15.4% higher in the intervention group (78.3% vs 62.9%; 95% CI, 8.99% to 21.8%, P = .02).

Changes in central line–associated urinary tract infection, catheter–associated urinary tract infection, and ventilator-associated pneumonia rates did not differ significantly between the 2 groups (all P > .10), and ICU mortality did not significantly differ between the groups (P = .81; Table 4). The ICU adverse events were lower in the intervention group, but this was not significant (58.7 events per 1000 patient days vs 74.4 events per 1000 patient days; difference, −15.7; 95% CI, −40.7 to 9.2; P = .24). Preventable, nonpreventable, severe, and not severe ICU adverse events were all nonsignificantly lower in the intervention group than in the control group (all P >.20; Table 4).

Our results show that health care workers wearing gloves and gowns for all ICU patient contact did not reduce the composite primary outcome of VRE or MRSA acquisition. Regarding key secondary outcomes, the intervention did not reduce VRE acquisition, but it did reduce MRSA acquisition. Better hand hygiene compliance on room exit occurred in the intervention ICUs. The intervention led to fewer health care worker–patient visits and did not increase the frequency of adverse events.

To the best of our knowledge, this study is the first cluster randomized trial to assess the potential benefit of universal glove and gown use. Other smaller studies suggest that this intervention may have benefits. A quasiexperimental study conducted in response to an Acinetobacter baumannii outbreak found that universal glove and gown use in a medical ICU was associated with a decrease in MRSA and VRE acquisition.⁹ In a single-center trial of 70 pediatric patients, fewer infections occurred when health care workers were randomized to use gloves and gowns on individual patients.¹⁰

The decrease in our key secondary outcomes of MRSA acquisition rates but not in VRE acquisition rates was surprising and should be considered hypothesis generating given the negative primary outcome. Interventions may have differing effects on specific antibiotic-resistant bacteria. For example, chlorhexidine bathing was shown to decrease VRE acquisition but not MRSA acquisition.¹⁹ Also, different bacteria have shown differential methods of transmission.^35,36 The lack of effect on VRE may represent the effect of antibiotic selective pressure on the intestinal microbiome and the potential underdetection of VRE on admission surveillance culture.³⁵ In other words, patients thought to acquire VRE may have had low, undetectable levels at admission that increased to the level of detection with antibiotic use before discharge. The effect of universal glove and gown use on other pathogens such as carbapenem-resistant Enterobacteriaceae is not known. One plausible explanation for the observed reduction in MRSA is that intervention ICUs had a greater decrease in MRSA owing to regression to the mean. However, intervention ICUs also had higher admission prevalence of MRSA (colonization pressure), a known risk factor for MRSA transmission in ICUs, suggesting that the higher acquisition rates may not be aberrant but rather accurately reflect endemic rates in those ICUs. Comparing changes in rates and secondarily adjusting for admission prevalence helped to partially overcome this baseline imbalance. Nevertheless, replication is warranted.

Twenty to fifty percent of patients hospitalized in ICUs who are colonized with antibiotic-resistant bacteria develop infection with the same organism.^36,37 We previously demonstrated that 19% of patients who carried MRSA when admitted subsequently developed CDC-defined infection with MRSA on the same admission.³⁷ In the current study, we did not find an effect on overall HAI rates, but the study was not powered for this rare outcome.

We found that the use of gloves and gowns led to fewer health care worker visits and greater hand hygiene on exit. This was found both in the intervention group and in those patients on contact precautions in the control group. We did not find a corresponding difference in adverse events between control and intervention patients. In fact, we observed fewer adverse events in the intervention group, although this was not statistically significant. Our findings are consistent with reports that contact precautions are associated with less health care worker–patient contact and better hand hygiene.¹³ However, the finding of no difference in adverse events contrasts with at least 1 retrospective study reporting more falls, pressure ulcers, and electrolyte disturbances in patients on contact precautions.¹⁵ Our results suggest that the changes in health care worker behavior may not increase adverse events when contact precautions or universal glove and gown use are implemented.

It is important to place our study in context with other similar intervention studies aiming to decrease transmission of MRSA and VRE. Climo et al¹⁹ showed that chlorhexidine bathing decreased VRE acquisition in ICU patients. Huang et al³⁸ found that universal chlorhexidine bathing and intranasal mupirocin reduced MRSA clinical cultures in ICU patients. However, the use of chlorhexidine or mupirocin may increase bacterial resistance and thus could have long-term adverse effects.^39,40 Many experts advocate active surveillance and some states have mandated active MRSA surveillance but the efficacy of this practice has not been established.^18,36 Universal glove and gown use will not increase antimicrobial resistance and could eliminate costs of active surveillance, chlorhexidine, and mupirocin.

This study had several limitations. First, we were unable to blind ICUs to intervention status. Although adverse events were coded in a blinded fashion, other outcomes could have been influenced by a lack of blinding. Second, the mechanism of the intervention’s effect is not completely clear. Universal glove and gown use increased hand hygiene on room exit and decreased health care worker–patient visits. Fewer visits with better hand hygiene may explain some of the effect on MRSA acquisition. Third, we did not have adequate power to detect relatively large differences in adverse events as measured by the IHI trigger tool. However, we observed fewer adverse events in the intervention group.

Our study also had many strengths. The cluster randomized design provides stronger evidence than most studies currently used to support infection control interventions, and the primary outcome measurement of MRSA or VRE acquisition was more objective than clinical culture positivity as used in other studies.⁴¹ In addition, all ICUs enrolled completed the study, which is rare in a study of this size, and compliance with the intervention was high, which demonstrates the feasibility of implementing and sustaining the intervention. Moreover, our results represent a broad set of hospitals because the study was conducted in medical, surgical, and medical-surgical ICUs varying in size from 9 to 36 beds and located across the United States in rural, urban, academic, and nonacademic settings.

The use of gloves and gowns for all patient contact compared with usual care among patients in medical and surgical ICUs did not result in a difference in the primary outcome of acquisition of MRSA or VRE. Although there was a lower risk of MRSA acquisition alone and no difference in adverse events, these secondary outcomes require replication before reaching definitive conclusions.

Corresponding Author: Anthony D. Harris, MD, MPH, University of Maryland School of Medicine, 10 S Pine St, MSTF 330, Baltimore, MD 21201 (aharris@epi.umaryland.edu).

Published Online: October 4, 2013. doi:10.1001/jama.2013.277815.

Author Contributions: Dr Harris had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Harris, Pineles, Belton, Shardell, Dembry, Braun, Perencevich, Hall, Morgan, Zervos.

Acquisition of data: Harris, Pineles, Belton, Johnson, Braun, Morgan, Shahryar, Price, Gadbaw, Drees, Kett, Muñoz-Price, Jacob, Herwaldt, Sulis, Yokoe, Maragakis, Lissauer, Zervos, Warren, Carver, Anderson, Calfee, Bowling, Safdar.

Analysis and interpretation of data: Harris, Pineles, Belton, Johnson, Shardell, Loeb, Newhouse, Dembry, Perencevich, Morgan, Kett, Sulis, Zervos, Warren, Carver, Anderson, Calfee, Bowling.

Drafting of the manuscript: Harris, Pineles, Belton, Johnson, Shardell, Perencevich, Morgan.

Critical revision of the manuscript for important intellectual content: Harris, Pineles, Belton, Shardell, Loeb, Newhouse, Dembry, Braun, Perencevich, Hall, Morgan, Shahryar, Price, Gadbaw, Drees, Kett, Muñoz-Price, Jacob, Herwaldt, Sulis, Yokoe, Maragakis, Lissauer, Zervos, Warren, Carver, Anderson, Calfee, Bowling, Safdar.

Statistical analysis: Harris, Pineles, Shardell, Loeb, Morgan.

Obtained funding: Harris, Belton, Dembry, Perencevich, Morgan.

Administrative, technical, or material support: Pineles, Belton, Johnson, Newhouse, Dembry, Braun, Hall, Morgan, Price, Maragakis.

Study supervision: Harris, Belton, Morgan, Shahryar, Price, Drees, Kett, Muñoz-Price, Jacob, Sulis, Yokoe, Maragakis, Lissauer, Zervos, Warren, Carver, Anderson, Calfee, Bowling, Safdar.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Harris reported that he serves as a consultant for Premier, Cubist, and Sanogiene and is an editor for UpToDate, Online. Dr Johnson reported that she has received research support from Nanosphere, Bio-Fire, and Bio-Med. Dr Morgan reported that he serves as a consultant for Welch Allyn and Sanogiene. Dr Kett reported that he serves as a consultant for Pfizer and Astellas; has received honoraria or speaking fees from Pfizer, Astellas, and GlaxoSmithKline; and research support from Pfizer and Akers Bioscience. Dr Muñoz-Price reported that she has received speaking fees from Sage and Steris. Dr Zervos reported that he has received grants from Cubist and Pfizer; received speaker honoraria from Sunovion and Cubist; and is a consultant for Optimer. Dr Warren reported that he has received research support from Cubist and Biomerieux; payment for a lecture from 3M Healthcare; and serves as a consultant for Centene Corp and Sagentia. Dr Anderson reported that he received research support from Robert Wood Johnson Foundation, and Merck and royalties from UpToDate, Online. No other disclosures were reported.

Funding/Support: This study was supported by grants HHSA290200600015 from the Agency for Healthcare Research and Quality (AHRQ), 5K25AG034216-03 (Dr Shardell) and 5K24AI079040-05 (Dr Harris) from the National Institutes of Health, and 1K08HS18111-01 (Dr Morgan) from the AHRQ.

Role of the Sponsor: The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or in the preparation, review, and approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of AHRQ.

Additional Contributions: We thank the following people for their outstanding contributions: Leslie Norris, University of Maryland School of Medicine, for invaluable administrative support; Gwen Robinson, MPH,* University of Maryland School of Medicine, for managing the thousands of specimens received in the clinical microbiology laboratory; Tamara Rasner, RN, BS, CIC, Scripps Health, San Diego; Marc-Oliver Wright, MT, MS, CIC, Northshore University Health System; W. Charlie Huskins, MD, Mayo Clinic; Michael L. Terrin, MD, CM, MP, and J. Kathleen Tracy, PhD, University of Maryland School of Medicine; Mary E. Johantgen, RN, PhD,* University of Maryland School of Nursing; and Valerie Burgest, MUPP, MA,* The Joint Commission, for technical and administrative support in study design and implementation. We thank the BUGG study coordinators for their outstanding efforts in data collection, compliance and site management: Kerry Bommarito, MPH,* Barnes Jewish Hospital; Lauren A. Howard, MPH, CCRC,* and Jennifer Coukos,* Boston Medical Center; Afrin Nuzhad,* and Nate Johnson,* Brigham & Women’s Hospital; Patty McGraw, RN, MS, CCRC,* Christiana Hospital; Amy Irwin, DNP, MS, RN,* Denver Health Medical Center; Lauren Knelson, MSPH,* Duke Infection Control Outreach Network; Anna LaFae, MPH,* Emory University Hospital Midtown; Daniela Moreno, MS,* and Rachel Giordano,* Henry Ford Hospital; G. Fernando Cubillos, MD,* and Paola Ballesteros, MPH,* Jackson Memorial Hospital & University of Miami Hospital; Elena Staicu,* Johns Hopkins Hospital; Barbara Gerrish, RN,* Lawrence & Memorial Hospital; Kirsis Ham, FNP,* Cornell Clinical Trials Unit; Renata Schwartz, MBA, RN, BSN,* St Luke’s Medical Center; Melissa A. Ward, MS,* University of Iowa Hospitals; Mindy Ralls, BS, ADN, RN,* Dawn Calderone, BSN, RN, CCRN, CNII,* Holly Howes, RNC, BSN,* and Jessica Warren, BSN, RN,* University of Maryland Medical Center; Timothy J. Houlihan, RN,* University of Texas Health Science Center at San Antonio; Susan Valentine, RN, MS,* University of Wisconsin Hospital and Clinics; and Nina Casserly,* WakeMed Hospital. We thank the ICU physician and nurse directors at the participating sites for their leadership and engagement: Warren Isakow, MD, and Michele Gatzert, RN, Barnes Jewish Hospital; Suresh Agarwal, MD, and Christina Denenberg, RN, Boston Medical Center; Anthony Massaro, MD, and Kathleen Leone, BSN, MBA, RN, Brigham & Women’s Hospital; Gerard Fulda, MD, Cindy Peters, RN, Christiana Hospital; Clay Cothren Burlew, MD, and Nicole Stafford, RN, Denver Health Medical Center; Lisa Pickett, MD, Louise Saladino, RN, BSN, MHA, and Sandy Hawk, RN, BSN, CRN, CNIV, Durham Regional Hospital; Michael Russell, MD, and Angela Bullock, RN, Duke Raleigh Hospital; Ken Leeper, MD, and Georgia Jackson, BSN, RN, MPH, Emory University Hospital Midtown; Michael Eichenhorn, MD, and Nancy Price, RN, BSN, Henry Ford Health System; Latoya Lewis-Pierre, RN, MSN, Jackson Memorial Hospital; Roy Brower, MD, and Pam Bollinger, MS, RN, Johns Hopkins Hospital; Robert J. Keltner, MD, Kelly Smith, Lawrence & Memorial Hospital; David Berlin, MD, and John “Chip” Holmes, RN, New York Presbyterian Hospital; Carol Loftin RN, CMCN, St Luke’s Medical Center; Kent Pearson, MD, Sara Caven, BSN, RN, University of Iowa Hospitals & Clinics; Cindy Dove, BSN, RN, University of Maryland Medical Center; Tanira Ferreira, MD, and Doreen Ashley, DrNP, University of Miami Hospital; Stephanie Levine, MD, amd Ronald Estrella, BSN, RN, CCRN, University Hospital, San Antonio; Jeffrey A. Wells, MD, and Ann Malec, MS, RN, ACNP, University of Wisconsin Hospital & Clinics; Ted S. Feinson, MD, Sabrina Tyndall, RN, MSN, NE-BC, and Chris Smith, RN, WakeMed Hospital. We would also like to thank the champions and infection prevention staff at each site. *Received compensation.