Progress on HAI progress: CDC portals and data

I spent about 2 hours with the new CDC HAI Progress Report – loosen your belt, it’s a big meal!  We probably had mixed perceptions about the recent alert to the 2016 HA progress report. Loads of information and analysis condensed down to a handful of bullets, all pointing to improvements in patient safety! The (very pleasant) surprise to me was that the format and delivery of the report has advanced to digital!! CDC has added the HAI progress report to the existing (and now updated) HAI AR Patient Safety Atlas Portal If you stop reading now – at least click on that link and explore and I will call this blog a success!

This report is several steps forward.  First, it pushes all of us to go to a place where we, being inquisitive minds, can wander and perhaps connect some dots within and between datasets. With the digitalization and visualization provided in the portal, the novice and experienced can more easily access and utilize these data. One can click through four distinct datasets, which now include state-summary statistics HAI infection rates/SIRs, inpatient stewardship activities, outpatient antibiotic prescribing rates, and inpatient antibiotic resistance metrics.

Now – the email alert. This year, well 2016 data, is the first to use the 2015 “re-baseline” efforts.

Unstated, but implied – the re-baseline effort includes the use of MBI (mucosal barrier injury) LCBSI as an event excluded from reported CLABSI rates, exclusion of yeasts (or low colony counts) from CAUTI rates, exclusion of “infection present on admission” for SSI (along with better patient-level risk adjustment), first use of risk adjusted metrics for VAE, and maybe slightly better models using more contemporary data for MRSA and CDI. 

With that said, 2016 performance suggests nationally patients are safer overall compared to the experience of 2015. Other than VAE which decreased by only 2%, everything else declined about 7-10% (I am rounding) compared to 2015. I understand many of the problems with risk adjustment and reporting bias that make these surveillance events poor performance measures for individual hospitals – but on the national level – I think these data do suggest fewer infections (o.k., perhaps some  widespread under-reporting—mixed reports on validation efforts in place).

Next – the overview of the current HAI Progress Report.   Although at first glance it seems the same as the info posted in the emails – CDC is offering more ways to track progress nationally – the number of states showing improvements (or worsening) compared to 2015, as well as the number states currently performing at levels better (or worse) then their 2016 contemporaries: 12 state perform better on at least 3 infection types compared to other states at the same time (2016). Now positive deviance nerds need to learn from these states to help the other states (or perhaps identify accuracy and validation issues at these states). The contemporary juxtaposition of SIRs is new, perhaps confusing (especially with CDC’s arcane explanation on how to interpret this: “SIRs statistically significantly lower than the 2016 national SIR are considered better than the 2016 national SIR”; curious if it ends up being useful to state programs. This year also is the first with more detail on inpatient rehabilitation facilities and long-term acute care facilities. Fewer data mean fewer statistical significant results, but these data are ripe for academic partners to latch onto as they try to partner with ARHQ, CDC, and state-programs to branch out into stewardship and prevention efforts in these types of facilities.

Finally, the portal – access it here.  Use the table view. No graphics to export for HAIs, only for other datasets. My pet peeve is that CDC still refused to list the no. of SSIs reported next to the number of surgical procedures reported to allow a crude attack rate. We still need to go to the technical tables for these values and calculate ourselves (see below). CDC, please stop making us jump through this hoop to be able to use attack rates for other purposes like planning studies, clinical trials, vaccine research! To all researchers and data nerds - the detailed technical tables should be downloaded examined (here), perhaps parsed out to our students and trainees, and used for different purposes that simply a “reporting requirement”.  I know there are many limitations to the accuracy of any one facilities reports and likely aggregate data up to the state or national level. However, as a long time national surveillance nerd all too familiar with the warts and ugliness of surveillance data, they do inform us, approximate the truth, and can help us ask the right questions and target the right populations. The more eyes using these data the more transparent the process will become, more uses of the data will be identified, patient safety should improve, and CDC will become more accountable to update (c’mon, where’s 2015 and 2016 NHSN AR data?! update the portal please!!),  maintain, and advance the public accessibility of useful data in our field.

Infection Prevention Summer Reading

With apologizes to our colleagues in the Southern Hemisphere, many of us are traveling a bit this summer and are looking for good things to read. At the top of my reading list is Ed Yong's new book, "I Contain Multitudes: The Microbes Within Us and a Grander View of Life." The book by the highly regarded UK science journalist (The Atlantic, National Geographic) digs into the relationship between microbes and animals. Unfortunately, the book won't appear until August 9th, so you'll have to be a bit patient and find something else to read.

In the meantime, I've listed five recently published journal articles/studies that will hopefully tide you over until "I Contain Multitudes" appears at your bookstore.

1) A Flawed Revision of the Common Rule (Joffe and Magnus, Annals 19 July 2016). The Common Rule is the regulatory framework that guides human subjects research, think IRB. Last September, 16 federal agencies released a Notice of Proposed Rulemaking outlining proposed changes to the Common Rule. There are several potentially important changes that could negatively impact infection prevention and stewardship studies. First, the Notice seeks to redefine all research on biospecimens, including de-identified specimens, as human subject research requiring "broad consent" before storing the specimens. The discussion didn't mentioned microbiology specimens specifically, but this requirement is concerning. Second, the Notice would only exclude QI research from review if it analyzed proven interventions and limited study endpoints to utilization outcomes (e.g. cost). However, QI projects such as quasi-experimental studies of the impact of CLABSI checklists on BSI rates or mortality WOULD require IRB review and potentially individual informed consent. (Yikes!)  My sense is this could drastically curtail important research in MDRO prevention and most infection control research. Stay tuned.

2) Control of an Outbreak of Middle East Respiratory Syndrome in a Tertiary Hospital in Korea (Park GE et al. Annals, 19 July 2016). From May to July 2015, 186 confirmed cases of MERS-CoV occurred in S. Korea. The authors provide an in-depth description of a 92-person outbreak in a single tertiary-care hospital in Seoul. Interestingly, 82 of the cases occurred after exposure to a single secondary patient cared for in their emergency department. All cases were identified through contact tracing and monitoring of exposed patients and healthcare workers and all in-hospital transmission was secondary to three patients with pneumonia and productive cough. The description of events was very sobering.

3) Colonization With Methicillin-resistant Staphylococcus aureus and Risk for Infection Among Asymptomatic Athletes: A Systematic Review and Meta-analysis (Karanika S et al, CID 15 July 2016). The results of this study suggest that you shouldn't be an athlete (6% MRSA colonization rate), especially a wrestler (22% MRSA colonization rate). Additionally, the authors reported that colonization increases the risk of subsequent skin and soft tissue infection 7 times. If only it were safer to lay around on the beach this summer.

4) Addressing Infection Prevention and Control in the First U.S. Community Hospital to Care for Patients With Ebola Virus Disease: Context for National Recommendations and Future Strategies (Cummings KJ et al. Annals 5 July 2016). Authors from the CDC, Texas Health Presbyterian Hospital in Dallas and other other institutions describe the massive infection prevention response that followed the infection of two MICU nurses who cared for the index patient from Liberia. The responses included protocols for specimen handling, managing medical waste and standardized PPE with education and monitoring. Nothing particularly novel in 2016, but the article certainly highlights the massive efforts and costs associated with the N=1 response that was required because of a chronically underfunded public health and infection prevention infrastructure.

5) A Novel Microbiome Therapeutic Increases Gut Microbial Diversity and Prevents Recurrent Clostridium difficile Infection (Khanna S et al. J Infect Dis 15 July 2016). The authors describe an alternative method to fecal transplants that could potentially avoid donor screening among other barriers. They tested SER-109, which is encapsulated spores captured from healthy human donor stool that was treated with ethanol to eliminate pathogens, for the prevention of recurrent CDI. The cohort of patients had to have had >3 CDI cases in the prior 12 months and a clinical response to antibiotic therapy for their current CDI episode immediately prior to dosing of SER-109. The 15 patients in cohort 1 received high-dose capsules (15 on day 0 and 15 on day 1) and 15 patients in cohort 2 received lower dose capsules on a single day. Overall, 87% achieved the endpoint of no CDI at 8 weeks. If you're interested in reading more, there is an excellent accompanying editorial.

Antimicrobial Stewardship and C. difficile Therapy: It's Complicated

The CDC's Get Smart About Antibiotics Week (November 16-22, 2015) is upon us. To do our part, we bloggers are using this (and hopefully other) posts to "Highlight Get Smart Week on your website" as CDC suggested as an Activity Idea. Of course, the problem with getting smart about antibiotics is that it's really complicated. Sure, reducing unnecessary antibiotic use (e.g. don't treat viruses) seems simple, but the toolkits necessary to assist primary care physicians aren't yet fully developed (e.g. improved rapid diagnostics). And don't even think about inpatient stewardship. I've yet to see antibiotic selection guided by the existence of bacterial multidrug efflux pumps, for example, but hopefully that's coming too. This is not meant to be discouraging, it's just to say that we have a long road ahead and we must keep pushing forward with stewardship-focused basic science studies and clinical trials including implementation science.

With all that in mind, I came across what appears to be an important paper in the November 15 issue of JID by Brittany Lewis and colleagues at Memorial Sloan-Kettering. The authors asked a fairly simple question - what happens to gut flora when it's treated with C. difficile specific therapies and how does antibiotic selection alter colonization resistance to C. difficile, VRE, CRE and E. coli challenges. The authors designed their study around a typical antimicrobial stewardship question: should we treat C. difficile infection (CDI) with metronidazole, vancomycin or both?

Using a mouse model (9 mice per treatment-time point), each was treated for 3 days with metronidazole, vancomycin or both. Fecal samples were then tested for bacterial population diversity (16s sequencing) and susceptibility to C. difficile spore inoculation at 1, 3, 7, 14 and 21 days. As you can see in the figure below, most metronidazole-treated mice could not support C. difficile growth (red circles) after seven days, while many who received vanco or vanco+metro remained susceptible to infection out to 3 weeks. At 7 days and 14 days, 11% and 0% of metronidazole-treated mice were susceptible, respectively. In those treated with vanco, 89% were susceptible at day 3 and 100% were susceptible at day 7. This suggests that vancomycin might increase risk for recurrent infection compared to metronidazole.

Given those findings, it is not surprising that mice treated with metronidazole alone maintained a relatively stable microbiota (See figure below - click to enlarge), which could explain their reduced susceptibility to C. difficile. Among those treated with vanco or vanco+metro, mice with higher levels of disrupted microbial communities were less able to suppress C. difficile growth.

Perhaps more importantly in our fight against antibacterial resistance, a second aim of their study (see figure below) found that mice treated with vancomycin (pink circles) were far more susceptible to VRE, carbapenem-resistant K. pneumoniae and E. coli than metronidazole treated (black circles) or untreated mice (open circles) for at least two weeks post therapy.

In summary, in this sophisticated mouse model, exposure to oral vancomycin was associated with higher risk of C. difficile, a prolonged highly disrupted microbiota and an elevated risk of VRE, CRKP and E. coli colonization compared to those treated with metronidazole alone. There seems to be an increased push to treat CDI patients with oral vancomycin, but given these findings, one wonders if increased utilization of PO vancomycin might be right for an individual patient (although there might be higher recurrence), but wrong for society with increased emergence of VRE, CRKP and other pathogens. After reviewing this study, I'm surely a bit smarter about antibiotics, but unsure of how to treat patients with CDI...and so it goes.

C. difficile and Hospital Process Measures: What Works?

One of the more difficult things to cover is a study that you've already written about in an accompanying editorial. It's quite hard to come up with anything "new" to write that you haven't already written. Such is the case with a very nice study examining hospital process measures and C. difficile infections just published in BMJ Quality and Safety by Nick Daneman and colleagues from Sunnybrook Health Sciences Centre in Toronto.

Using results of a mandatory CDI prevention practices survey they compared facility-level processes measures and patient level (via ICD-10 codes) CDI rates in 159 Ontario hospitals. Specifically, they looked at implementation of six hospital-level measures: (1) isolation at diarrhea onset, (2) audit of antibiotic use, (3) audit of environmental cleaning, (4) vancomycin as first line therapy and (5) on-site diagnostic testing and (6) reporting of rates to senior leadership. Somewhat surprisingly, none of the process measures were associated with lower risk of CDI.

In the editorial, Nasia Safdar and I wrote:

"First, the authors identified low self-reported implementation of most CDI prevention practices, with only 27% of facilities reporting isolation of all patients at onset of diarrhoea, and 16% reporting auditing of antibiotic stewardship practices. Low adherence rates for these two practices in particular are concerning because prompt institution of contact precautions is necessary to reduce nosocomial transmission of C. difficile. And antimicrobial stewardship is at least as important as infection prevention practices, if not more so, for reducing CDI."

"This study also highlights the importance of implementation science research to tackle the vexing yet pervasive problem of low and variable adherence to evidence-based interventions for reducing HAI, including CDI. The scope of this study did not extend to exploring barriers to implementation or an in-depth assessment of the self-reported practices that may help inform implementation strategies to increase uptake of proven practices."

and of course my favorite part:

"Last, increasing the evidence base for preventing CDI by undertaking pragmatic randomised controlled trials of novel interventions incorporating efficacy and effectiveness is essential to successfully bridge the quality chasm that currently exists in CDI prevention."

Reference: Daneman N. et al. BMJ Qual Saf. 2015 Apr 24 (open access)

Safety and efficacy of nontoxigenic C. difficile spores in preventing recurrent CDI

Lead Author: Dr. Dale Gerding

We have written and spoken often on the efficacy of fecal transplants in treating recurrent C. difficile infections. Wouldn't it be great if there was a way to prevent recurrent CDI in the first place? What if "good" C. difficile strains that lack toxin production genes could be used to out compete bad strains and prevent recurrent CDI?

There is a new study just published in JAMA that evaluates the safety and efficacy of a nontoxigenic C. difficile strain M3 (VP20621; NTCD-M3) in preventing recurrent CDI in those patients initially treated with metronidazole and/or oral vancomycin. In the four-arms of the phase 2, double-blind placebo-controlled trial they compared patients given oral liquid formulation of NTCD-M3, 10^4 spores/day for 7 days (n = 43), 10^7 spores/day for 7 days (n = 44), or 10^7 spores/day for 14 days (n = 42), or placebo for 14 days (n = 44).

Recurrent CDI occurred in 13/43 (30%) of placebo patients and only 14/125 (11%) of patients treated with NTCD-M3 patients (odds ratio [OR], 0.28; 95% CI, 0.11-0.69; P = .006). Fecal colonization with the NTCD-M3 strain was reported in 69% of treated patients and was associated with lower recurrence: 2/86 (2%) recurrence if colonized vs. 12/39 (31%) recurrence in treated but uncolonized patients (OR, 0.01; 95% CI, 0.00-0.05). Side effects such as abdominal pain, diarrhea and serious side effects were actually higher in the placebo groups. If this smaller study's findings are confirmed in larger trials, we may just have a new treatment for the prevention of recurrent CDI. Very cool.

Check out the video interview with lead author Dr. Dale Gerding, another related video and the JAMA Associate Editor's podcast covering this article and other important studies.

Toilet lids for infection prevention

Back on clinical service again and having more thoughts on poor hospital design. Last month I wondered why there were no stethoscope wipes available outside of every patient room. This month while caring for patients with C. difficile and viral gastroenteritis infections, I looked over and noticed toilets without lids. Of course most toilets in hospitals (and many public spaces) lack lids. Reasons given for lack of lids are (a) lids might be hard to lift for some folks and (b) lids would be another surface to clean. But lids also prevent the aerosolization of pathogens into the environment, as Mike discussed three years ago.

Lack of toilet lids in hospitals is a patient safety issue and there should be no excuse for not having and using them. First, most patients can and will close the lid before flushing if reminded to do so. In fact, there should be public services announcements in the media that remind us all to close the lid and kids should be taught to do this in school. Second, if a small minority of patients can't or won't close the lid, it's not a reasonable excuse for going lidless in hospitals. This would be like not providing seat belts because some folks can't or won't use them!

So here are my recommendations:

1) Put a plastic, cleanable lid on every toilet and train hospital staff to clean the lid daily
2) Create education campaigns to get patients and staff to close the lid before they flush
3) Put a big "CLOSE BEFORE YOU FLUSH" sign on both sides of the toilet seat in every bathroom in hospitals, including public spaces
4) Help start local "CBYF" campaigns in your cities
5) If hospitals are worried about patients not being able to open or close the lid, they should spend $6400 on this toilet that automatically opens and closes, among other features. Given the cost of HAI and the amount we spend on other HAI prevention interventions, the $6400 will easily be cost-effective or there's even a touch-free sensor toilet seat for ~$100.

It's time we give a crap about having and closing toilet lids.

image source: http://www.dudeiwantthat.com/household/bathroom/friendly-toilet-seat-reminder.asp

Stewardship Effective in C. difficile Prevention: A Meta-Analysis

As Dan mentioned last week, when 15% of asymptomatic hospitalized adults carry toxigenic strains of Clostridium difficile, it should alert us to focus on antimicrobial stewardship as a way to prevent CDI. But how effective are stewardship programs and does it matter what type of program you implement in your hospital? If only there was some sort of systematic review or meta-analysis to guide or decision making.

As if on queue, Leah Feazel and Marin Schweizer at University of Iowa published such a review and meta-analysis titled "Effect of antibiotic stewardship programmes on Clostridium difficile incidence" in JAC earlier this spring. Typical of projects completed by Marin and her group, they thoroughly combed the literature for papers. Here they identified 891 articles, reviewed 78 full articles and included 16 studies in their final analysis. Over all, stewardship programs were associated with a 52% reduction in CDI incidence. Importantly, programs appeared effective when implemented in whole hospital or geriatric settings and when utilizing a persuasive approach or a restrictive approach. I've provided the forest plot of studies below. An additional note is that the studies utilized various quasi-experimental study designs and based on the funnel plot, there appeared to be little publication bias.

Key points: (1) Stewardship works for CDI prevention, but it would have been nice if there was at least one funded RCT or cluster-RCT. (2) The meta-analytic approach, that Marin has pushed through her reviews of SSI bundles and hand hygiene interventions, is a fantastic way to guide medical decision making and should be considered for inclusion in future HAI guidelines. The reality is that infection prevention studies overwhelmingly utilize quasi-experimental designs. Why not identify the highest-quality QE studies and rigorously meta-analyze them as done here?

Patient - Wash Thy Own Hands!

There has been increasing attention over the past decade in engaging patients in patient safety. In infection control this trend has manifest through efforts to have patients monitor and encourage hand hygiene compliance among health care workers. In a related trend, there is also increased interest in patients washing their own hands in a framework called "patient-centered hand hygiene." My understanding of this approach is that having patients clean their own hands could potentially increase their engagement in infection control initiatives including encouraging health care workers to practice hand hygiene. This approach might also have the additional benefit in decreasing the organism burden on patients' hands and interrupting direct or indirect transmission of MDROs in healthcare settings.

It is with this background that Kundrapu and colleagues at CWRU and the Cleveland VA completed a randomized trial of soap and water versus alcohol hand rub in reducing C. difficile spore burden on patients' hands. Forty-four infected or colonized patients were included in the study. Hand cultures were positive in 32% of patients with CDI and 38% of colonized patients prior to hand hygiene. As you can see from the figure below, soap and water significantly reduce the proportion of positive cultures and mean CFUs, while alcohol hand rub did not. Interestingly, around 10% of patients still had C. difficile recovered after washing with soap and water. Seems like a trial is in order to determine the role of patient hands in transmission and whether cleaner patient hands reduces the incidence of CDI and other MDROs in hospital settings. One major limitation is that this intervention could not be implemented in settings where the need is the greatest, namely ICUs, since most patients would be too sick to wash their hands.

Using NHSN C. difficile Infection Rates? Mind your denominator!

Over here in the US hinterland we're completing a systematic review of MDRO outcomes for CDC in cooperation with investigators in Salt Lake City. At the moment we're tackling C. difficile and are busily pouring through the literature. We've come across many good studies, such as an ICHE paper from early 2013 by Gase and colleagues from the New York State Dept. of Health that compared NY State CDI surveillance to NHSN in 30 hospitals. The authors noted an 80% agreement between the methods and thus recommended that NY State adopt the NHSN LabID method because of ease of implementation.

Building on that study, Haley and colleagues also from the NY State Dept of Health completed an analysis of the sources of bias in NHSN "Hospital Onset" CDI rate calculations using data from 124 NY hospitals. Their findings were published in the January 2014 issue of ICHE and were accompanied by a nice editorial by two of my former Maryland colleagues Jessina McGregor and Anthony Harris. The NY authors looked at how auditing, including outside labs, age adjustment and exclusion of "patient days not at risk in the denominator" would improve the calculation of hospital-onset CDI rates. As you can see by the portion of Table 2 that I pasted below, most of the corrections had minimal impact on the average hospital-onset CDI rates.  However, "exclusion of patient-days not at risk" had a huge impact on the calculated HO-CDI rate. The correct rate after controlling for all factors was 11.6/10,000 patient days; however, excluding auditing or outside labs, or age adjustment had minimal impact, whereas not excluding patient days not at risk from the denominator led to a rate that was 45% lower (6.4/10,000 pt-days).

The reason that eliminating "patient-days not at risk" from the denominator had such a huge impact is that the CDC NHS definition excludes CDI cases that occur in the first three days from the numerator but does not exclude patient-stays less than three days from the denominator. For example, a patient that stays only two days would not be at risk from contributing a HO-CDI case to the numerator but contributes their patient-days to the denominator.

This has several important implications.  One, not removing the patient days not at risk results in reported CDI rates that were much lower than they actually are. This occurs since many if not most patients have stays that are shorter than 4 days.  Second, as the authors state, "HO-CDI rates at hospitals with shorter LOS are biased downward more than the rates at hospitals with longer LOS." It seems to me that this artificially hurts the rates at tertiary-care and academic medical centers more than it would smaller community hospitals. We always hear how academic hospitals are falling behind, but it may have something to do with how rates are calculated, especially if we are including the wrong patient-days in the denominator.  It seems like this would be an easy fix - hospitals could just exclude the first three days from their patient-day calculations.  I hope this happens.

CDI? Think PPI

Following up on last years MMWR that reported that "nearly 75% of all Clostridium difficile infections (CDI) related to U.S. health care have their onset outside of hospitals", CDC researchers have released a new study in JAMA Internal Medicine looking specifically at the epidemiology of community-associated CDI. The study used data from the Emerging Infections Program, which began to actively collect CDI data in 10 states starting in 2009. This report uses data from 984 patients collected over 29 months with true community-onset CDI, as they excluded community-onset, healthcare facility associated infections.

Somewhat surprisingly, 36% of patients had not received antibiotics and 18% had no outpatient health care exposure. Not surprisingly, 31% of those who had not been exposed to antibiotics had been exposed to PPIs.  I highlighted the risk of CDI from PPIs in my ICPIC talk last month when I discussed this meta-analysis by Kwok and colleagues. In this CDC study, those patients lacking significant outpatient healthcare exposure were also more likely to be exposed to infants and household members with active outpatient healthcare exposure suggesting a potential route of transmission. I agree with the authors primary conclusion that a reduction of outpatient PPI use may be necessary to reduce the risk of CDI. As Mike' pointed out four years ago, PPIs are also associated with HAP, VAP, and SBP, so there are many reasons to be concerned about PPIs.

There is an excellent accompanying editorial by some guy named Kent Sepkowitz, who discusses the "PPI-zation" of the US and the difficulties facing any public health initiative targeting PPIs. For one, PPIs are the third most utilized drug in the US and they are addictive since discontinuation is associated with withdrawal symptoms.  For another, unlike antibiotics, PPIs are widely available over the counter and supported by huge advertising campaigns. Looks like PPIs are here to stay...