Screening, Decolonization and Environmental Decontamination for MRSA in Nursing Homes Doesn't Work

Just in the past couple of weeks, we've written about pneumonia prevention bundles, MDRO prevention bundles, and spread of S. aureus - all in nursing homes.  It's like no one cares about acute care facilities any more! (humor) There is now more great data for those charged with managing infection control in nursing homes.

Cristina Bellini and colleagues from Lausanne University Hospital in Switzerland just published the results of cluster-randomized trial of an MRSA prevention bundle in 104 nursing homes (53 intervention, 51 control) in the April ICHE. All residents in intervention and control nursing homes (NH), who gave consent, were screened for MRSA carriage at study entry and 12 months thereafter on a single day in each NH. Newly admitted or readmitted residents were screened when admitted to the NH. Screening included nasal, groin and ulcer swabs along with urine cultures if residents had an indwelling catheter. In the intervention NHs MRSA colonized residents underwent decolonization along with environmental decontamination.

The primary decolonization bundle included 5 days of nasal mupirocin, 5 days of CHG oral rinse twice per day, 5 days of CHG showers including CHG shampoo on day 1 and 5. Environmental disinfection included daily clothing changes for 5 days, new linens on day 1 and day 5, and daily bed/table/phone/remote/wheelchair/walker disinfection with 70% alcohol. A lot of steps.

Unfortunately, the MRSA decolonization and decontamination bundle was not successful. The baseline prevalence of MRSA was 8.9% in both groups. The rate declined in intervention units to 5.8% in the intervention unit and 6.6% on the control units after 12 months (p=0.66) Full stratified results are in Table 3 below, and as you can see, no matter how they analyzed the intervention, the MRSA bundle intervention did not reduce MRSA prevalence compared to controls. This was despite the fact that the participation rate was 87%.

A limitation of this study was that they only measured prevalence and not individual level acquisition of MRSA. It is possible that by measuring prevalence they missed detecting benefits of the intervention related to reduced patient-to-patient transmission of MRSA. In any case, as I said last week about the study in CID, congratulations to the authors and journal (this time ICHE) for publishing this important negative study.

Pneumonia Prevention Bundle in Nursing Homes: A Cluster-randomized Trail

If you're looking for another infection prevention bundle in long-term care, look no further than the March 15th issue of CID that included a cluster-randomized trial of a pneumonia prevention bundle in 36 Connecticut nursing homes by Juthani-Mehta and colleagues at Yale. (full text free)  Residents in the intervention nursing homes with at least one risk factor (impaired oral hygiene or swallowing difficulty) received a bundle that included manual tooth/gum brushing plus 0.12% chlorhexidine oral rinse, twice per day, plus upright positioning during feeding.

The primary outcome was development of first pneumonia defined as "presence of (1) a compatible infiltrate on chest radiograph (CXR) (if previous CXR was available, the infiltrate had to be new or worsened) and (2) at least 2 of the following clinical features within 72 hours of the CXR-documented infiltrate: fever, pleuritic chest pain, respiratory rate over 25 breaths/minute, worsening functional status (ie, decline in level of consciousness or activities of daily living), or new or increased cough, sputum production, shortness of breath, or chest examination findings."  The secondary outcome was first lower respiratory tract infection (LRTI).

After enrolling 834 participants (434 to the intervention arm and 400 to the control arm), the DSMB terminated the study for futility. Results showed no significant differences for cumulative incidence of first pneumonia (Figure 2A, below) or first LRTI between intervention and control arms. In fact, you can see that the intervention arm appears to have higher incidence of first pneumonia, which is concerning. Of note, adherence was 87.9% to chlorhexidine, 75.0% to toothpaste and 100% for upright feeding position in the intervention facilities. The authors offer several explanations for the study's failure, none of which are entirely convincing. For example, adherence at these levels should have still shown some benefit and not a trend toward harm, so it's unlikely that compliance explains the results. For those interested in reading more, there is an excellent commentary by Lona Mody, who we also mentioned last week. And congratulations to the authors and journal for publishing this important negative study.

MDRO Prevention Bundle in Nursing Homes: A Randomized Trial

In keeping with our long-term care theme (more on this later in the week), there is a new trial published in JAMA Internal Medicine by Lona Mody and colleagues at the University of Michigan. The team completed a cluster-randomized trial of a bundled intervention to prevent MDROs in nursing homes. Specifically, residents with indwelling urinary catheters, feeding tubes or both in 6 nursing homes were randomized to a targeted infection program (TIP) bundle that included (1) preemptive barrier precautions; (2) active surveillance for MDROs (baseline, day 15 and monthly at nares, oropharynx, feeding tube, supra-pubic catheter, groin, peri-rectal, and wound sites) and infections, with data feedback; and (3) NH staff education on key infection prevention practices, including minimum criteria for initiating antibiotics, and hand hygiene promotion. Inclusion required a signed inform consent. Six other nursing homes served as controls.

The outcomes assessed were quite broad. The primary outcome was "overall MDRO prevalence density rate, defined as each participant’s total number of MDRO-positive anatomic sites across all MDROs per visit averaged over the duration of his or her participation." This would result in residents "with persistent MDRO colonization (having) a higher prevalence than someone with intermittent or no colonization" and residents colonized at more sites (up to seven were tested) having a higher prevalence. Secondary outcomes included new MDRO acquisition and device-associated HAI both with 1000 device-day denominators.

For the primary outcome, 27% of swabs were positive in the intervention NH residents while 33% were positive in the control NH residents. The adjusted rate ratio was significant 0.77 (0.62-0.94). This outcome seems largely driven by lower MRSA colonization in residents with urinary catheters, feeding tubes, or both and lower ceftazidime-resistant GNR colonization in residents with urinary catheters in the intervention NHs. However, rates of VRE were higher in the feeding tube requiring residents but this increase was not significant. (see Table 3) Interestingly, new MRSA acquisition rates were lower in the intervention NH residents (see Table 4, below) and first new CAUTI rates were also lower in the intervention NH residents, HR 0.54 (0.30-0.97).

Overall, an important study and one that should be read closely. Clearly this was a very difficult RCT to undertake, especially with informed consent, and the research team should be congratulated. The primary outcome of MDRO prevalence density rate is an interesting choice and the authors make a compelling argument for why they chose it. However, it is unclear if the interventions in the TIP bundle are major components in the causal pathway for limiting MDRO colonization density or reducing CAUTI. However, the lower MRSA acquisition rate in the intervention NHs is an important outcome and does fit with how we expect barrier precautions to work. Minor quibbles aside, this RCT should be discussed widely and many components of it are worth testing in other settings in future trials. 

Close Proximity Interaction and S. aureus Spread in Long-Term Care

There is little doubt that S. aureus is transmitted between patients via contaminated hands, white coats or fomites carried by healthcare workers. Fortunately, that doesn't curb the enthusiasm of scientists seeking to understand the mechanisms of transmission in clinical settings. A case in point is a recent study in PLOS Computational Biology by Thomas Obadia and colleagues that tracked healthcare worker (HCW) and patient close proximity interactions (CPI) via small wireless sensors and correlated the interactions to incident S. aureus colonization.

The study was conducted in a 200-bed LTCF in France and utilized data collected from 329 patients and 261 HCWs over a 4-month period. Using weekly nasal swabs from all patients and HCW, they spa-typed and determined the resistance profiles to antibiotics of each detected S. aureus. Isolates were considered identical if they shared the same spa type and resistance profile. Incident cases were only considered in patients since HCWs could have been transiently colonized and missed by the weekly swab interval. Each incident case was evaluated to confirm that at least one time-consistent CPI in the prior three weeks with the same strain was possible. The 3-week interval was chosen since all but 4 cases could be linked to another patient with the same strain during that time period.

Without going into all of the statistical modeling methods, major findings include:

(1) When limiting the analysis to the 201 patients not already colonized on admission, 73 acquired S. aureus. The one-month acquisition rate was 33%.

(2) Time to acquisition among new admissions did not change based on the number of colonized neighbors in the preceding week using either raw number of CPIs nor cumulative duration of CPIs.

(3) There were 237 incident cases throughout the 4 months in 111 patients. Only 173 had candidate transmitters. The analysis was limited to 153 because sensors failed to record a CPI in the prior week in 20 cases.

(4) A CPI path existed for 149 of 153 episodes. As seen in the example figure above, P1 (patient) and H1 (HCW) were two-hops away from the incident case. P2 was three-hops away. In the same figure, distance between a transmitter and an incident case (black) was shorter than random simulations predicted (white). Additionally, a direct contact between candidate transmitter and incident case (i.e one hop away) occurred in 48% of cases vs. 30% expected by random chance. These findings supported that CPI predicts S. aureus incident colonization.

(5) HCWs spent about 20% of their shifts in direct contact with patients (110 minutes over 8 hours) and had CPIs with 15 unique individuals during their day (9 were patients, 6 other HCW) with 3.7 hours spent in contact with others. 36.3% of HCW were colonized with S. aureus.

(6) Interestingly, patients had CPIs with 12 unique individuals each day (half were other patients). Overall, patients spent half of their day (12.2 hours) in contact with another person.

A few thoughts. Studying social interactions and transmission in long-term care settings using these methods is quite brilliant. Given that LTCF cohorts are more stable with longer lengths of stay, it is easier to catch acquisition events through repeated screening. It is also important to note the huge amount of contact that LTCF residents have directly with each other - around 10 hours/day. This sort of social interaction among residents is not seen in acute care hospitals and goes a long way to explain why infection control in LTCF is so critical (and so extremely difficult). Given the richness of the CPI data, including frequency and duration of contacts, new mathematical models using these parameters could provide more accurate estimates of S. aureus transmission and effectiveness of candidate control strategies.

One issue that I think the authors might want to address in future studies is the use of spa typing to link transmission events. It is true that they also used susceptibility data, but it is my understanding (from one of Dan's earlier posts) that the discriminatory power of spa typing may be suboptimal. I hope Dan will provide his thoughts on this in the comments.

Additional reference: NPR Shots blog by Scott Hensley with comments from David Hartley on this study.