Effectiveness of a Multicomponent Intervention to Reduce Multidrug-Resistant Organisms in Nursing Homes

Key Points Question What is the effect of a multicomponent infection prevention intervention on multidrug-resistant organisms in nursing homes? Findings In this cluster randomized clinical trial of 6 nursing homes, including 245 patients, a multicomponent intervention consisting of enhanced barrier precautions, chlorhexidine bathing, microbial surveillance, and staff engagement statistically significantly reduced the odds of multidrug-resistant organism contamination in patients’ environments. Meaning These findings suggest that multicomponent interventions can be tailored to reduce multidrug-resistant organisms burden and transmission potential in nursing homes.

practices. Some questions pertaining to knowledge regarding hand hygiene, indwelling devices, 122 or environmental cleaning may be perceived to be intrusive. Random observations of HCWs as 123 they perform device care may be also be perceived as intrusive. We will structure our questions 124 and observations to minimize such intrusiveness. We will also ensure HCWs of confidentiality.

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While we will collect demographic data and identifiers from each HCW; only aggregate data on 126 compliance and adherence will be reported to the facility leadership.

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There is no direct, individual benefit that can be guaranteed as a result of participation in 128 this research study. There is a societal benefit, as this study will provide information about the 129 transmission of bacteria that could ultimately reduce the risk of bacterial infection for other NH 130 patients. All patients, HCWs and family/visitors will be given the opportunity to have their 131 questions answered by the study coordinators or investigators as needed. Given the minimal 132 risks to the participants, the benefits outweigh the risks.

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This study will be conducted in compliance with the current protocol approved by the 135 Institutional Review Board and according to Good Clinical Practice standards. All study 136 documents will be located on a restricted access shared folder on the university server. The 137 current protocol will also be posted there. E-mail alerts to all study personnel will be generated 138 with each change in the version of the protocol. These will include a summary of the 139 modifications. All approval letters from local Institutional Review Boards will be posted on the 140 folder. Current consent forms will also be posted. No deviation from the protocol will be 141 knowingly implemented without the prior review and approval of the IRB except where it may be 142 necessary to eliminate an immediate hazard to a research subject. In such a case, the deviation 143 will be reported to the IRB as soon as possible. 6 intervention and three will serve as control sites. Data gathered from our previously defined risk-160 stratification model will be crucial in informing the population to target for this intervention, the

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Enrolled patients will be assigned to the high-risk category for acquiring an MDRO based on a 181 previously described risk-stratification model:

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 Functional disability: patients needing moderate to total assistance with dressing, 183 bathing, toileting, or grooming.

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 Presence of indwelling devices: urinary catheter and/or feeding tube.

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Enrolled patients will receive study visits at baseline, at 7 days, 14 days, 21 days, 30 days, and 189 monthly thereafter for up 6 months. Each patient will be followed from the enrollment through a 190 minimum of 7 days to a maximum of six months, death, or discharge from the facility.

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We are requesting a partial consent waiver for recruitment to allow the study coordinator to 220 review the medical record of potential participants to determine initial eligibility, medical

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Because cognitive impairment is common in the nursing home population, the patient will 239 be evaluated for his/her ability to give informed consent. The patient must be alert and able to 240 communicate in order to give informed consent. If the potential participant is considered 8 9 assure that HCWs are not coerced into participating, we will not report participation to 288 supervisors. There will be no penalties or loss of benefits for not participating.

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The HCW will be told about the study by the study coordinator following the Consent Form for 291 healthcare workers. If the HCW is willing to participate, the study staff will provide a copy of the 292 informed consent. The HCW will not be required to sign the informed consent document, as this 293 is the only study document that will link the HCW to the research study. We are requesting a

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Approximately ten environmental swabs from common use areas such as dining rooms, living 315 rooms, rehab gym, and common equipment will be obtained from each facility monthly. These 316 samples will be swabbed onto Bile Esculin Agar containing 6 g/mL vancomycin, Mannitol Salt

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Agar, and MacConkey Agar and phenotypically unique colonies will be identified by standard 318 methods.

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We will randomize NH facilities instead of participants using cluster randomization as 322 randomizing participants can lead to contamination by HCW experiences learned while caring 323 for the intervention group. Similarly, randomizing individual HCWs can also introduce bias due 324 to contamination. Therefore, NHs will serve as the unit of randomization. We will enroll six services, environmental) and informal caregivers (family and visitors) will be in-serviced on 335 indications for hand hygiene, glove and gown use when providing care for all patients. Tools 336 such as personalized posters, demonstration of hand hygiene techniques, and simplified 337 tailored infection prevention education will be provided. Structured observations will be 338 conducted to monitor compliance.

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We will discuss our aggregated results with HCWs during their in-services, with infection

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Enhanced barrier precautions will include hand hygiene, glove use, and gown use for HCW 345 when providing ADL assistance, care for indwelling devices, or wound care to high-risk patients.
13 intervention sites will also be introduced to other resources from various national infection 462 prevention societies.
antibiotic usage (type and duration), hospitalization along with diagnoses at transfer, presence 469 of wounds including pressure ulcers, falls, and antipsychotic use will be obtained [ Table 1].

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Facility-level data such as staffing patterns, bathing practices, cohorting based on risk factors,

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presence of shared and private rooms, frequency, and room-cleaning time will also be collected.

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Outcome data on the presence of MDROs, infection control knowledge, and adherence to 473 standard and enhanced standard precautions, hand hygiene, and chlorhexidine bathing will be 474 collected as described above.

Adverse Event Reporting
prevalence, we will use univariable and General mixed effect models with multivariable logistic 539 regression to predict the presence of each MDRO individually (MRSA, VRE, and R-GNBs). We 540 will additionally predict the presence of any of the three MDROs. This analysis will be done Patient and environment visit-level data will be combined as a composite outcome. We 544 will use generalized mixed effect modeling with logistic regression. To assist in the modeling of 545 dyadic outcomes (e.g., MDRO prevalence in both patient and environment samples), we will 546 adjust for multilevel data by considering two random effects, the dyad and the 547 patient/environment within the dyad. This will be performed to account for the potential that an 548 intervention can influence both a patient and his/her partner (e.g., patient room environment 549 samples).

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To evaluate the impact of this intervention on MDRO acquisition, we will test subsamples 551 of patients with more than one sampling visit. These subsamples will only include patients who 552 are free of the MDRO of interest (e.g., MRSA, VRE, R-GNB) on admission. We will use 553 univariable and multivariable Cox regression modeling to predict the acquisition for new 554 acquisition of each MDRO and the combined MDRO outcome. Given our interest in 555 environmental contamination, we will additionally include patient room environment 556 contamination data into the multivariable Cox regression model to identify whether the identify 557 effect holds after accounting for the influence of the patient room on MDRO transmission.

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Acquisition rates will be calculated and defined as new acquisition events per 1,000 patient-559 days.

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For our exploratory analyses, we intend to collect data on the onset of physician-defined 561 onset of new healthcare-associated infections. Although this study was not powered to test for 562 the intervention effect on infection data, we intend to report the longitudinal patterns on patients 563 and compare infection rates.

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Based on a previously described risk-stratification model, we expect to identify patients at the 566 highest risk of new acquisition. We expect this pool to be 955 (44% of all new admits) from six 567 facilities over two years. We assume that 50% of patients or their DPOA will give informed 568 consent (=478). Our previously conducted risk stratification analyses call for at least a 90-day 569 follow-up. We expect 50% of these patients to stay more than 90 days, giving estimated high-570 risk study population to be 239 patients in all six NHs or 119/each cohort enrolled over two 571 years and followed up to six months. Based on a 42% reduction in MRSA transmission in acute 572 care, we expect to have a conservative 30% reduction in new MDRO acquisition as a result of 573 our intervention. The expected proportion of new MDRO acquisition (π 0 ) in the high-risk control 574 group is 0.6. The proportion of new MDRO acquisition in the high-risk intervention group with 575 30% reduction (π 1 ) is 0.42. The desired power of the study is 80% (z 2 = 0.84); the desired 576 significance level is 0.05 (z 1 = 1.96).

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The Principal Investigator is responsible to ensure the accuracy, completeness, legibility, and 605 timeliness of the data reported. Data collection is the responsibility of the study staff.

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Paper records or case report forms will be filled out at the participating community-based 607 NH. Copies of the paper records or case report forms will serve as source documents and 608 maintained for recording data for each subject enrolled in the study. All source documents will 609 be completed in a legible manner to ensure accurate interpretation of data. Black ink is required 610 to ensure clarity of reproduced copies. When making changes or corrections, the original entry 611 will be crossed out with a single line, and the change initialed and dated. Erasing, overwriting, or 612 use of correction fluid or tape will not be done.

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All source documents and laboratory reports will be reviewed by the clinical team and data 614 entry staff, who will ensure that they are accurate and complete. AEs must be graded, assessed 615 for severity and causality, and reviewed by the PI or designee.

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Confidentiality will be maintained to the fullest extent permitted by law. All clinical data will 617 be collected on case report forms that will be scanned into a password protected relational 618 database which will be kept on a research server that has a level and scope of security that database on a regular basis (approximately quarterly). Site-specific data edit reports will be 665 generated for missing, out-of-range, unusual and inconsistent values. Study staff must respond 666 to each data edit and make modifications to the study form and database as needed.