Excess Mortality in CRKp: A Non-Randomized (Fortunately) Trial

Understanding the burden of antimicrobial resistance is critically important if we are to appropriately target research and clinical resources. For years, lack of proper estimates of the morbidity, mortality and costs associated with multidrug-resistant bacteria greatly limited the attention paid to these pathogens. This changed with the 2013 CDC Antibiotic Resistance Threats Report which provided the public with the number 23,000.  In the report, carbapenem-resistant Klebsiella pneumoniae (CRKp) was estimated to cause 7,900 infections and 520 deaths per year. But questions remain: Is the 6.5% (520/7900) mortality estimate high or low and how can we estimate the burden of resistance since we can't (fortunately) perform randomized trials where we randomly infect patients?

To answer these important questions, a group of investigators formed The Consortium on Resistance against Carbapenems in K. pneumoniae (CRACKLE) and just published a cohort study in Clinical Microbiology and Infection. This group, of what appears to be 18 Great Lakes hospitals, prospectively collected CRKp BSI (N=90), pneumonia (N=49), and UTI (N=121) isolates along with a control group (N=223) of patients with CRKp urinary tract colonization. The use of patients colonized but not infected with the pathogen as controls is interesting. The authors explain that they chose these controls since "non-infection-associated contribution to overall mortality is relatively larger in patients colonized with CRKp compared with patients colonized with more susceptible organisms, since risk factors for mortality such as chronic and acute illness, overlap with risk factors for CRKp colonization. An estimate of this non-infection-related mortality may be approximated in patients who are colonized, but not infected with CRKp." This is another way of saying that they wanted to isolate the attributable mortality risk of infection, not underlying disease.

The primary outcome was time-to-hospital-mortality from the time of the first positive CRKp culture as calculated by an adjusted hazard ratio using Cox proportional hazard models. I've included the unadjusted outcomes below. The full paper includes separate models and Kaplan-Meier curves for each infection, which don't differ greatly from the unadjusted outcomes.

As you can see, 39% of both BSI and pneumonia patients died or were transferred to hospice care compared to 12% of controls giving an attributable mortality of 27% for CRKp infection. In the Cox models, the adjusted hazard ratio was 2.59 (1.52-4.50) for BSI and 3.44 (1.80-6.48) for pneumonia. In contrast CRKp UTI was protective in both the unadjusted (3% lower mortality) and adjusted (aHR=0.68, p=0.33) analyses. This is further evidence that we need to rethink our definitions and focus on UTI.

Overall, a very nice study that utilized a novel control group of patients colonized but not infected with the organism of interest. It is likely that this approach when coupled with multivariable analysis reduced the effects of measured and unmeasured confounders. And it looks like CDC should increase the attributable mortality from 6.5% in their 2013 report to something a bit higher - say 27%.

The unfolding M. chimaera debacle: June 2016 update

It’s time for some updates about the evolving global outbreak of invasive M. chimaera infections linked to heater-cooler units (HCUs—see prior posts here). Notable developments in June include:

Release of an FDA Safety Alert regarding the Sorin 3T HCU: In this alert, the FDA references the Eurosurveillance study we recently discussed, recognizing the evidence for factory-source contamination of 3T units, stating that “if your facility purchased and used a 3T prior to September 2014, be aware that the units may have been shipped from the factory contaminated with M. chimaera”. FDA now recommends all such facilities (1) inform surgeons about their patients’ infection risk, and (2) “determine a method for patient follow-up and establish patient surveillance” (per CDC recommendations). 

Do you know if your hospital uses the 3T units? If so, are you alerting clinicians and working on a surveillance approach?

Meeting of the FDA Circulatory System Devices panel (June 2-3, 2016): During this meeting, the risks of bio-aerosol generation by HCUs were discussed at length. Slides and other materials from this meeting are here. Although all slide sets are available at this site, a quick 24-hour summary is here. Here are a few of my own random observations from this meeting:

• Awareness of this issue is still very limited, a point made by several panel members who should have already heard about fatal infections linked to HCU bio-aerosol generation. Broader notification is needed.
• HCU models differ dramatically in their design, and in their risk for production of aerosols (for example, the range of air movement by the HCU fans is an astonishing 20->700 cubic feet of air per minute, and the location and containment of the water source also varies). 
• Routine culturing of HCU water for mycobacterial contamination isn't particularly useful and will likely not be recommended outside of outbreaks or clusters of infection. Only a small number of labs can do the cultures properly, negative results can be falsely reassuring, and the cultures take 8 weeks to return. Our own experience confirms this--we've had consecutive samples from the same unit yield different results, as have others. However, routine bacterial cultures ("heterotrophic counts") will continue to be recommended as a monitor for effectiveness of disinfection.
• No obvious near-term solution is evident. Replacement or recall of all 3T units is not possible given that it has 60% market share, and the panel felt that removal of the HCUs from the OR is not practical (despite the fact that some EU countries have done so). A rapidly-implementable engineering solution is desperately needed.

Thus there are undoubtedly many M. chimaera-contaminated 3T units being operated inside ORs, which really is an untenable situation. If your hospital can’t engineer a solution to remove this device from the OR (or otherwise separate the 3T HCU exhaust air from OR air), then you should seek to replace them with other makes/models not linked to this global outbreak. 

Publication of the first US case series of invasive M. chimaera infections. Three cases have been reported from Mayo Clinic, preprint available from OFID here. The cases have similar clinical presentations to those reported already from Europe, and larger case series are undoubtedly to follow. Notably, two of the three patients in the Mayo series died, and the third (a 66 year old with aortic graft infection) is being treated medically due to the risk of graft replacement.

Based upon what I’ve heard from other clinicians caring for these patients, I propose this as an open question: once a patient has a device-associated invasive/systemic infection due to M. chimaera, is cure possible? Given the very long incubation period for this syndrome, this question is not currently answerable. The criteria for cure would require 24+ months without symptoms (and with negative cultures), after device replacement and 18 months of therapy. Stay tuned.

Image: The Chimaera of Arezzo

Even with the Hawthorne Effect, Hand Hygiene Compliance Still Hideous

One way to deal with low hand hygiene compliance

A recurring theme has emerged in hand hygiene science - when you really look, compliance is very very low. A study 5 years ago reported that compliance was below 10% when hidden video monitoring was utilized. Our group has quantified the impact of the Hawthorne Effect, improved behavior when subjects know they're being observed, on hand hygiene compliance. In a multicenter study, we found that both measured exit and entry compliance increased the longer direct observers remained on the unit.

There is a report of a new APIC abstract in ABC-News that further quantifies that impact of the Hawthorne Effect and highlights the lack of investment in hand hygiene programs. Investigators from Santa Clara, California compared compliance measured by well-recognized Infection Prevention nurses, to observations collected by unknown high-school and college-aged volunteers who were trained to use the same surveillance methods. Here are their findings:

So, what do I make of these findings? First, even 57% is too low. Second, hospitals and healthcare systems continue to throw hand hygiene programs under the rug. We are much happier to report compliance rates of 100% collected by nurse managers on the floor (or compliance of 57% by recognized IPs) and ignore the problem than spend time and money detecting compliance rates of 22%, which would then require additional investments in proven hand hygiene interventions.

Any administrator, who thinks compliance in their hospital is higher than 70% or 90%, won't invest in hand hygiene programs. Since hospitals are happier to report compliance of 90% to the Joint Commission, we also won't invest in technological and socio-adaptive interventions that will finally improve the safety of our hospitals. We must work to create a safety culture where it is better to report hand hygiene compliance of 20% than falsely high compliance rates of 90%.

image source: montonara.com

Does CAUTI Exist?

A previous post with this title written by two guest bloggers was removed at the authors' request. The owners of this blog did not request the original post nor the post's removal. We take this issue very seriously and are considering guest-post policy changes going forward in order to avoid similar situations in the future.

Why I love the new NEJM CAUTI study!

This week, Sanjay Saint's group at Michigan published the kingdaddy of CAUTI studies in the New England Journal (free full text here). And yesterday, one of the authors guest blogged for us on the study.

Although it's not a randomized controlled trial, it's just about everything else you'd want to see in a CAUTI intervention study:

• Large and multicenter (over 900 units in 603 hospitals across 32 states)
• Well designed
• Well executed
• Conceptually similar to the CLABSI Keystone study, arguably the most important study in our field since Semmelweiss, which demonstrated a huge (2/3) reduction in CLABSI   
• Bundled interventions, including daily assessment of catheter necessity, catheter avoidance, aseptic insertion, proper catheter maintenance, feedback on CAUTI rates, and multifaceted training via in-person or virtual training, monthly content calls, and monthly coaching calls

Now the results:

• Overall there was a statistically significant reduction in CAUTIs of 14% after the intervention
• Absolute rate reduction was 0.35 CAUTI/1,000 catheter days
• When hospital units were stratified (ICU vs non-ICU), all of the reduction was found to be in non-ICUs. There was no significant change in CAUTI rates in ICUs.

So let's bring this study a little closer to home. We'll assume that a 700-bed hospital has 35,000 catheter days yearly. If they implemented this intervention with the same results, the number of avoided infections would be 12.2 annually. If 1% of CAUTI patients become bacteremic (see here and here), they would avoid 0.12 secondary BSIs per year. And if 11% of bacteremic UTIs result in death, they would avoid 0.01 deaths per year. Expressed another way, this comprehensive, bundled intervention would result in saving 1 life every 100 years. Saving any life is a noble goal. But context is key. CLABSIs have an attributable mortality of 25%. In other words, CLABSIs kill people relatively commonly. CAUTIs rarely do. And there are many other nosocomial events that kill more than 1 person every 100 years. 

The take home message is that a superb study designed by the world's CAUTI experts didn't yield much impact. This is no fault of the investigators. It's due to two reasons: (1) the attributable morbidity and mortality of CAUTI are relatively small; and (2) CAUTIs have low preventability (at least in 2016). 

Dan Livorsi and Eli Perencevich summed it all up in their ICHE editorial last year when they questioned whether an NHSN-defined CAUTI is an episode of preventable harm. Is the work we do on surveillance and prevention of CAUTI an opportunity or an opportunity cost? I think the answer is clear. 

Lastly, one point made in the guest post yesterday really bothers me: "how a hospital addresses CAUTI likely says much about how such a facility attacks other endemic and mundane harms such as falls, delirium and pressure sores." This is a specious argument. As the Chief Quality Officer of an academic medical center, I spend a great deal of time deciding where to best utilize our resources to prevent both infectious and non-infectious adverse outcomes. In fact, the hospital's leadership team actively engages in setting our quality and safety targets. As a utilitarian, I'm duty bound to attempt to have the greatest impact for our patients. And the reason why I love this study so much is that it makes the decision to focus on issues other than CAUTI even easier.  

Preventing Catheter-Associated Urinary Tract Infection in Acute Care

Dr. Mohamad Fakih

This guest post is by Mohamad Fakih, MD, MPH, Senior Medical Director of the Ascension Center of Excellence for Antimicrobial Stewardship and Infection Prevention; Sarah Krein, PhD, RN, Research Scientist and Research Professor at VA Ann Arbor Healthcare System and University of Michigan; and Sanjay Saint, MD, MPH, Chief of Medicine, VA Ann Arbor Healthcare System and University of Michigan Medical School

Catheter-associated urinary tract infection (CAUTI) – sometimes jokingly referred to as the “Rodney Dangerfield” of healthcare-associated infections – finally got respect in 2008 when the Centers for Medicare & Medicaid Services stopped reimbursing for these events if associated with a hospitalization. Since then, hospitals have attempted to decrease their CAUTI rates, with this work taking on more urgency now that CAUTI is publicly reported and associated with a reduction in compensation through value-based purchasing.

CAUTI, however, presents not only a financial risk to hospitals, but a substantial safety risk to patients, especially with prolonged – and often unnecessary -- use of the catheter. The “On the CUSP Stop CAUTI” initiative attempted to implement best practices to reduce CAUTI in hospitals across the United States. The program was modeled after a successful statewide initiative in Michigan that found a 25% reduction in catheter use and CAUTI, and included a qualitative assessment to better understand the socio-adaptive aspects of CAUTI prevention. The national program focused on sharing best practices to reduce urinary catheter risk, and helping healthcare workers change their behavior to adopt measures that reduce CAUTI. This effort, sponsored by the Agency for Healthcare Research and Quality (AHRQ), included a collaboration of professional societies, academic researchers, government agencies -- including the CDC -- and state hospital associations. The program was led by the Health Research and Educational Trust with the support of faculty from the University of Michigan, St. John Hospital and Medical Center, the MHA Keystone Center, and Johns Hopkins Medicine Armstrong Institute for Patient Safety and Quality.

The newly published NEJM article presents the results of the first 4 (of 9) cohorts that participated in the initiative, and encompasses 926 units in 603 hospitals across 32 states, the District of Columbia, and Puerto Rico.  These results showed a 32% reduction in CAUTI in the non-intensive care units (ICUs), but no change in ICUs. In addition, a 7% reduction in catheter use was seen in non-ICUs. Early in the work, we evaluated the indications for catheter use and found marked differences between the ICU and non-ICU. Catheter use was reported to be indicated ~ 94% of the time in the ICUs compared to ~65% for the non-ICUs. In addition, the primary indication for using the catheter in the ICU was for fluid monitoring in the critically ill. The newly released Ann Arbor criteria for urinary catheter use may help better clarify the appropriate indications in critically ill patients.

The main elements of the initiative that helped to produce these results were to: 
1) integrate evaluation for catheter use as part of healthcare worker’s daily routine, particularly nurses
2) avoid catheter use by considering alternative urine collection methods
3) ensure that aseptic practices are used when inserting and maintaining the catheter such as hand hygiene.

Additional elements included regular feedback on performance related to catheter use and CAUTI events. Identified gaps were addressed and mitigated. A key component was ensuring adoption of best practices and buy-in from different stakeholders. This was achieved by addressing  catheter harm for specific stakeholders, ensuring leadership support of the essential disciplines, underscoring the collaborative nature of CAUTI prevention, and identifying champions within the organization to lead the effort.

The “On the CUSP Stop CAUTI” initiative demonstrates that scaling up complex interventions --with technical and socio-adaptive components -- to a national level is achievable at least in non-ICUs. CAUTI is certainly not a “sexy” healthcare-associated condition but how a hospital addresses CAUTI likely says much about how such a facility attacks other endemic and mundane harms such as falls, delirium and pressure sores. We are currently extending our CAUTI prevention program to long-term care and to those hospital units – both ICU and non-ICU – that have persistently elevated CAUTI rates. We hope to share those results soon.