A Research Agenda for MDRO Prevention

Of course, I don't need to explain the clinical importance of multi-drug resistant bacterial pathogens to readers of this blog. I probably don't need to remind you that "more research is needed" either - that's why we have controversies! But, I should probably point you to five papers recently published in ICHE that outline the future research agenda for MDRO prevention in the US Veterans Health Administration (the VA).

For our non-US readers, the VHA is the largest integrated healthcare system in the United States with over 130 acute care facilities, 1000 outpatient clinics, numerous long-term care facilities and 9 million enrolled patients. The VA has been a leader in medical and health services research for decades and has been well-ahead of the curve in application of interventions to prevent MDRO including its MRSA prevention bundle and antibiotic stewardship initiative.

To continue the VA's success in MDRO prevention and link future research questions to the greatest clinical need, we invited a multidisciplinary group with 37 participants to Iowa City in September 2016. The aim of the panel was to outline the VHA's research agenda for MDRO prevention. Dan Livorsi describes the process we used to identify the domains and research questions in an introductory editorial. The outlined research agenda was broad in scope and included efficacy, effectiveness and implementation questions. In addition, many of these questions are broadly applicable to study in non-VA and non-US hospitals. We are all more alike than different.

Research questions fell into four domains:

1. Transmission dynamics: Resistant pathogens are spread via human hands and environmental surfaces. Disrupting this transmission is essential to controlling MDROs.

2. Antimicrobial stewardship: Strategies to reduce and improve the use of antimicrobials will slow the emergence of resistant pathogens.

3. Microbiome: There may be ways to manipulate or augment the human microbiome to eradicate or prevent colonization with resistant pathogens.

4. Special populations: Strategies need to be tailored to patient populations with distinct underlying conditions and in nontraditional care settings.

All 5 papers are open access. Thanks ICHE!  And thank you to the brilliant group of VA investigators, clinicians and operational partners who traveled to Iowa City and contributed to this effort. We all hope it's helpful.

ICD Coding and MDRO - If you don't bill for it, it doesn't exist

Fact 1: Infectious Disease specialists are among lowest paid physicians in the US

Fact 2: Many infectious diseases, including HAI, are absent from ICD billing codes or are poorly coded, and thus the true population health impact of infections, particularly MDROs, is invisible

Hypothesis: If we could improve ICD codes for infectious diseases, ID salaries would increase and the field could be saved from extinction

Many of us on the blog have lamented about the current state of ID with a particular focus on low relative salaries compared to other medical subspecialties and concerns about the annual fellowship match. If we focus on academic ID, the folks who supposedly will train the next generation, we also need to worry about low levels of NIH funding for anything other than HIV research; a trend that is slowly improving. (Fact 1, above)

Our group has looked at the accuracy of ICD billing codes for both HAI and MRSA and the results are not pretty. Michi Goto completed a systematic review of ICD code accuracy for CDI, SSI, VAP/VAE, CLABSI, CAUTI, post-procedure pneumonia and MRSA. He found that apart from CDI and orthopedic SSI, the codes have poor sensitivity and specificity. Marin Schweizer looked at the validity of the V09 code pre-2008 for MRSA and found it to be a very poor at detecting proven incident MRSA infection. (Fact 2, above)

Since many of those studies were completed, there have been new codes added for CLABSI (October 2011), VAE/VAP (October 2008), MRSA infections (October 2008), and post-procedure pneumonia (October 2012). So there is some hope that HAI and MRSA will become better recognized. But what about MDROs?  Investigators from Wash U (including co-blogger Hilary) just published a research letter in ICHE that calculated the sensitivity of ICD-9 codes for various MDRO at their hospital between 2006 and 2015. The gold-standard was a culture at a sterile site or BAL/brochial wash culture with an MDR-Enterobacteriaceae, Enterococcus spp., Staphylococcus aureus, Pseudomonas aeruginosa, or Acinetobacter spp.

As you can see in their Table 1, apart from MRSA (after 2008 code added) and P. aeruginosa, ICD organism coding had poor sensitivity and MDRO/V09 codes were - terrible. The authors concluded: "ICD-9-CM diagnosis codes cannot be used to estimate the burden of MDRO infections in hospitals."  I think we'd all agree. I would have liked to see more information on the specificity and positive/negative predictive values of individual codes (I understand this was a Research Letter).  I'm not sure what the ultimate solution is, but perhaps SHEA or IDSA (or ASM) could work to update ICD-10 codes and come up with ways to encourage accurate coding for infectious diseases. If we don't make sure infections "exist" in administrative data, the field of infectious diseases might not exist for long.

image source

Effect of Nonpayment for Preventable Infections on SSI Rates Following Orthopedic Procedures

The debate regarding the effect of CMS's 2008 policy denying incremental payment for 8 complications of hospital care, also known as never events, is ongoing. Some studies have identified reductions in CLABSI and CAUTI after the policy was implemented, while others failed to find reductions in CLABSI, CAUTI or VAP, using a different dataset and methodology.  The impact of the nonpayment policy change on orthopedic procedures is less well studied.

Authors Jereen Kwong and colleagues published a study in the July ICHE that examined the effect of the policy on SSI following spine fusion, shoulder and elbow arthrodesis and repair, and spinal refusion procedures, but not hip and knee replacements (since they aren't covered under the policy). To determine the impact, they analyzed 20% of all inpatient discharges among patients ages 60 to 80yo using the HCUP National Inpatient Sample from 2000 to 2013. This is an all-payer sample in that it covers patients where Medicare is the primary payer but also non-Medicare populations.

The authors' primary hypothesis was that if the CMS policy had an impact, we would see larger reductions in SSI rates among Medicare vs control, non-Medicare patients. You can probably sense my concern immediately. How would bundles implemented to reduce SSI only have an effect on Medicare patients? It is unlikely that infection preventionists or clinicians would even have knowledge of their payor status. If non-Medicare controls have had the same exposure, they can't be used as controls!

Without getting into the methods details, the authors were expecting larger changes in SSI rates in the Medicare vs non-Medicare populations and they didn't find significant differences RR=0.9, 95% CI 0.8-1.1)  Looking at their Figure 1 below, we can see that SSI rates were slightly higher in Medicare populations (dashed line) vs non-Medicare populations before and after the non-payment policy went into effect. If I were to do this analysis, I would have looked for a change in intercept and/or slope in the SSI rates before vs after the policy combining both payor populations. Looking at the figure, there doesn't seem to be much change after the policy went into effect in either group. So we can agree with the authors that the policy had limited or no impact on SSI rates, but not for the reasons the authors state.

On the positive side, SSI rates have been declining over the entire 14-year study period - so surgeons and infection prevention folks can pat themselves on the back. Keep on doing whatever you've been doing!

Efficacy versus effectiveness

Take a moment to check out this video from today's NY Times.

If a hand hygiene method demonstrates marginally better reduction in bacterial counts on hands, but is also more complicated and takes longer to complete, should it become the standard?

Related question: does the difference in log10 bacterial counts between 2.58 CFU/ml and 2.88 CFU/ml translate into a greater risk for pathogen transmission in healthcare settings?

I’ll let you ponder the above questions, as I don’t have the answers. One thing I do know: when a hand hygiene paper in Infection Control and Hospital Epidemiology is being covered by the NY Times, we’re winning!

I’ll let Eli and Mike comment on how many of the people depicted in the video are bare below the elbows!

Is it time to ditch CHG bathing in ICUs and get back to basic infection control?

We are at an interesting inflection point in infection control. On the one hand MRSA is in decline and VRE has flat or declining incidence in many national samples. Yet on the other, we have largely pulled back from what is considered traditional infection control practice. It is important for us to understand what may be driving the declines in MRSA (and to a lesser extent VRE) and on what shaky foundation these declines are actually resting.

The recent MRSA decline is due to multiple factors including the underlying epidemiology of the pathogen, host immunity and the emergence of effective antibiotics targeting MRSA that are not named vancomycin (e.g. linezolid, daptomycin, ceftaroline). These factors are intertwined. For example, recent CA-MRSA strains have susceptibility to many existing antibiotics (e.g. clindamycin, tmp-sulfa), which highlights the complexity of the underlying reasons for MRSA's decline. I should also mention the antibiotics CHG and mupirocin here too, but I'll get back to them in a bit.

During the past decade, we've also seen a decline in the importance of basic infection control. Many of you will disagree with this statement but let me explain. The cornerstone of infection control has always been hand hygiene compliance and yet very little "honest" attention is paid to it. There is now so much pressure to report hand hygiene compliance rates greater than 90% that we have hit the target without actually improving compliance. Over and over in studies at hospitals across the US where we've looked, hospitals are reporting compliance rates over 90% and it's actually 40-60%, when we look closely with independent observers. Why does this matter? Because when we believe it's 90%, we ignore it.

On top of our hand hygiene conundrum, contact precautions are no longer favored for MRSA prevention. A bit of history - the second ever post on this Blog back in 2009 was titled: "Why I hate Contact Precautions, vol. 1." So there's not much love here for ye olde CP. Which brings me to the point of this post (finally) - when we no longer have hand hygiene compliance, gowns and gloves and when the foundation of infection control is based on antibiotics like linezolid, CHG and mupirocin, what will we do when the foundation begins to crumble?  Will we even notice the crumbling or will we stick our heads in the sand and ignore it?

Many of the gains in infection control over the past decade have rested on the foundation of CHG bathing. Ignoring for now that CHG might select for Gram-negative pathogens that have fewer effective therapies, CHG use might also select for CHG resistance through efflux pumps coded by qacA/B, which has been associated with MRSA decolonization failures. Yet the long-term (and after a decade, we are getting longish) effects of daily CHG bathing are not well described.

Into this void, David Warren and colleagues just reported in ICHE 8-year trends in the epidemiology of MRSA strains after initiating daily CHG bathing in their SICU. A random sample of 504 MRSA isolates were selected for analysis (63/year). Among all isolates from 2005 (when CHG bathing was implemented) to 2012, 7.1% were qacA/B(+). Somewhat disconcerting was the rise of qacA/B from 6.2% (2005) to 16.9% in both 2009 and 2010. Also concerning was the finding that 25% of qacA/B(+) MRSA isolates were mupirocin resistant. Results stratified by timing of nasal swab collection are in the Figure above. In explaining this increase the authors noted: "qacA/B(+) isolates from 2009 and 2010 were more likely to have ≥1 hospital admissions in the prior year, suggesting a possibility of an expansion of qacA/B(+) MRSA at BJH during this time period, which resulted in qacA/B(+) patients in those years being exposed in prior admissions."

So where do these findings leave us? Yes, more studies, larger studies, bigger and better studies - $6 million dollar man studies. But pending those dream-like studies, can we state at what level of CHG resistance we should ditch universal CHG bathing?  Are we compromising the effectiveness of CHG in preoperative settings like those supported by STOP-SSI? And when can we get back to basic infection control? To my knowledge hand hygiene and gowns/gloves don't drive resistance like CHG. Well, except resistance from my esteemed co-bloggers and colleagues. ¯\_(ツ)_/¯

Stewardship, Stewardship, Stewardship

There has been a plethora of antimicrobial stewardship scholarship published these past few weeks. I'm currently on the inpatient medicine service and have even been harassed by the antimicrobial stewardship team (humor), so I only have a moment to briefly highlight three can't miss articles:

(1) Manisha Juthani-Mehta and co-authors just published an excellent JAMA Viewpoint discussing Antimicrobials at the End of Life.  It is open-access (free), so I hope you have a chance to read it thoroughly, but the main points include:

1. "Evidence-based and goal-directed counseling about infection management at the end of life must be a routine part of advance care planning and treatment discussions between clinicians and patients with advanced illness."
2. "Clinical algorithms aimed at improving antimicrobial stewardship from an infectious disease standpoint must also integrate treatment preferences when applied to patients near the end of life." 
3. "To the extent that inadequate outcome data hinder decision making, researchers should consider whether there is adequate clinical equipoise and need to justify a carefully designed randomized trial comparing symptom control and survival among patients with advanced illness who receive antimicrobials vs high-quality palliative care for suspected infections."

(2) Dan Livorsi and colleagues at the Sidney and Lois Eskenazi Hospital and the Richard Roudebush Veterans Affairs Medical Center in Indianapolis just published an important qualitative study in September's ICHE of factors that influence antibiotic prescribing among inpatient physicians (10 resident and 20 staff physicians). I'm happy to add that Dan Livorsi has just joined our group in Iowa City, where he is helping to jump-start our stewardship programs. Key findings of his study include:

1. "Antibiotic overuse is recognized but generally accepted; 
2. the potential adverse effects of antibiotics have a limited influence on physician decision making;
3. physicians-in-training are strongly influenced by the antibiotic prescribing behavior of their supervising staff physicians; and
4. other physicians’ prescribing decisions are sometimes questioned, but there is limited peer-to-peer feedback or critique."

(3) Nick Daneman and colleagues in Ontario examined antibiotic use and secondary harms in 607 nursing homes housing 110,656 residents in a recent JAMA Internal Medicine. Their findings are quite striking (if not surprising) in that antibiotic use varied from a low of 20.4 antibiotic days to a high of 192.9 antibiotic days per 1000 resident days. Antibiotic-related adverse events were higher in "high-use" nursing homes even among patients who did not receive antibiotics. An interesting finding (for someone in Iowa) was that rural facilities were overrepresented in the highest tertile of antibiotic use (see figure below), but after accounting for other nursing home– and patient-level characteristics, rurality was found to be protective against antibiotic-related harms." Would be interesting to figure out why rurality is associated with higher antibiotic use but fewer harms but my guess is that rural folks are just awesome. Of note, Lona Mody and Chris Crnich published an accompanying editorial that is worth reading.

Lovin' Contact Precautions (this time in nursing homes)

Contact precautions get very little love on our humble blog. So little in fact, that I've taken it upon myself to be the resident contact precautions fanboy. Just today on rounds, I was waxing sentimental about the poor yellow gowns that protect us from horrible pathogens and how we unceremoniously toss them into the trash after wearing them - we never even say goodbye...but I digress

There is a new study in the September ICHE by Mary-Claire Roghmann and colleagues from the University of Maryland and University of Michigan that sought to estimate the transmission of MRSA from nursing home residents to healthcare workers' gowns and gloves based on clinical activity and resident characteristics (i.e. skin integrity or stool incontinence).  They aimed to determine if there were certain situations where wearing gowns/gloves would be most protective of HCW contamination (and thus reduce MRSA transmission).  The logic - if gowns and gloves are contaminated, the underlying hands would be contaminated if gloves/gowns weren't worn and since no one has ever gotten hand hygiene compliance near 90-100% anywhere, including nursing homes, then gowns/gloves result in cleaner hands and less MRSA transmission. I know, much more complicated than a cluster-RCT, but important data...but I digress again...

RESULTS! Overall, they enrolled 401 nursing home residents from 13 facilities including 113 (28%) who were MRSA colonized. 62% were nasally colonized, 9% were colonized at the perianal skin and 28% were colonized at both sites. There were 954 HCW interactions (median 7 per patient) with MRSA+ patients with a median duration of 6 minutes. Overall, gowns were contaminated after 14% of the interactions and gloves were contaminated 24% of the time. Gown/Glove isolates were identical (Spa type) to patient isolates 89% of the time. Overall, the contamination rate ranged from zero to 24% for gowns and 8 to 37% for gloves based on activity. So as far as hand contamination goes, there were no safe interactions and thus, we wouldn't expect activity-based precautions to be effective. (See figure below)  Significant predictors of glove/gown contamination included dressing, transferring, patient hygiene, changing linens and changing diapers.

As far as patient characteristics, stool incontinence did not modify gown/glove contamination with MRSA, but skin breakdown was associated with higher contamination when healthcare workers transferred the patient, changed their diapers and helped dress the patient.

My interpretation of the study is that if we want to limit the substantial transmission of MRSA in nursing homes, we better up our game. And that game should probably include gloves and perhaps gowns for most of the analyzed patient care activities. Unless we can get hand hygiene compliance up to 100%, we better just learn to love the glove.

Give Directly-Observed Hand Hygiene Compliance Monitoring a Chance

As I've said before, "It's amazing how little evidence is required before infection prevention interventions are adopted." This phenomenon is particularly evident in the setting of automated hand hygiene monitoring systems. Few trials have been completed that have assessed the efficacy, effectiveness or cost-effectiveness of these systems, at least as of our recent systematic review.  However, it appears that many facilities are purchasing these systems anyway. Why is this?

It appears that there are two potential limitations of directly-observed hand hygiene monitoring driving the purchase of automated systems: (1) the fear that the Hawthorne effect renders all direct observations invalid and (2) the idea that all hand hygiene opportunities must be counted, i.e. it's unacceptable to sample opportunities. There is a third potential reason for adopting these systems - anecdotal reports that automated systems improve compliance. However, there is little published evidence that compliance increases are sustained and some evidence that automated systems actually decrease compliance.

With the potential limitations of directly observed compliance monitoring in mind, our research group just completed a study published in ICHE that sought to determine if/when the Hawthorne effect appears in hand hygiene observation data. The idea being, if it takes some period of time for HCW to know they are being observed, shorter periods of hand hygiene monitoring could be less susceptible to bias from the Hawthorne effect. After 3,432 hours of observations and 11,444 witnessed opportunities in a multi-center study, we calculated that room-entry compliance increases after 38 minutes and room exit compliance increases after 14 minutes and then again after 50 minutes (Figure below). Thus, it appears that limiting direct observation periods to less than 15 minutes limits the impact of the Hawthorne effect.

The other aim of our study was to determine the number of hand hygiene opportunities that must be observed to have an adequate sample size for comparison. For example, if hand hygiene compliance in your ICU is 80% this month and you would like to get it to 90% next month, you would need to observe 108 opportunities in each month to have enough power to detect a difference. We provide a table (below) so that anyone can quickly determine the number of observations in a month/quarter/year needed to compare time-periods or units/wards or facilities. We hope you find this information useful and that you'll still give directly observed hand hygiene compliance monitoring a chance.

Laundering White Coats - We are asking the wrong question!

There is a very nice survey of bare-below-the-elbows perceptions and practice in this month's ICHE by co-blogger Mike's group. They asked 300 attendees (190 or 63% responded) at medical and surgical grand rounds about their beliefs and behavior concerning wearing white coats, neckties and wristwatches. I've posted the results below. As expected (since Mike has recommended BBE at his hospital since 2009), most thought that white coats were vectors and that not wearing a white coat would not alter patients' perceptions of them. Most did not wear white coats daily, neckties (males only) or wristwatches. Approximately half practiced the bare-below-the-elbows approach.

This all seems great except that it occurred to me that this group, and me and everyone else have asked the wrong questions as far as laundering practices of white coats. We've generally asked if the clinicians washed their coats daily, weekly, monthly, etc., when we should be asking them if they washed their white coats between patients! Asking about daily or monthly! laundering would be like asking about daily or monthly hand hygiene! Of course, this is ridiculous! I bet we could get hand hygiene compliance to 99% if the denominator was days instead of moments. By including a white coat laundering question with a lower bound of daily somehow implies that daily laundering is acceptable. Which it really isn't. Given that 96% of folks in this survey didn't wash their coats daily or every other day, this point is largely moot. Practically, we gotta give white coats the boot!

The In(patients) and Out(patients) of Antimicrobial Stewardship

I've been lucky enough to attend the 4th World HAI Forum on Antimicrobial Resistance this week in Annecy. This morning's excellent session on antimicrobial stewardship was chaired by Stephan Harbarth and Herman Goossens and brought to light many barriers to the wider adoption of stewardship by non-ID physicians. For one, the accuracy and economics of rapid diagnostics and algorithms were identified as a major barrier. In particular the negative predictive value, which would allow primary care physicians to stop (or not start) antibiotics, was suggested as a key target.

Another, brought forth by Kent Sepkowitz, was that the whole enterprise of "stewardship" lacks a main outcome measure or at least has transitioned from Decreasing Antimicrobial Resistance, to decreasing costs, shortening length of stay, educating the next generation of clinicians, and finally easing workload for ID specialists and trainees. He suggested that presenting stewardship as a patient safety issue with a primary target of drug resistance rates in key indicator organisms will bring greater rewards. Tom Gottlieb responded that the burden should be on the others to prove that stewardship doesn't work since antibiotics are such a limited resource. Bob Wachter implied that a key "bias" against stewardship in the US is that compared to the patient safety movement, which targets the individual patient as the beneficiary, stewardship benefits "others." Loreen Herwaldt said that a microbiome outcome could provide an individually-focused patient safety target.

Of course, I can't even begin to transcribe and communicate all of the excellent points made by the attendees. Fortunately, two interesting studies were published in the past 2 weeks that examined the impact of stewardship interventions in the outpatient and inpatient settings.

The first study by Jeffrey Gerber and colleagues in JAMA described an outpatient cluster-randomized trial in 18 pediatric practices. They examined prescriptions for acute respiratory infections 20 months before and 12 months after the intervention, which included one 1-hour on-site clinician education session followed by 1 year of personalized, quarterly audit and feedback of prescribing. Prescription of broad-spectrum antibiotics decreased by 6.7% more in the intervention practices compared to usual practice clinics, while off-guideline prescribing decreased by 10.7% more for pneumonia and 14% more for sinusitis. Evidence supporting the public health benefits (i.e. reduced resistance) of this intervention are not described in the paper.  In fact, the word "resistance" appears only once in the entire article.

The second study by Greg Filice and colleagues at the Minneapolis VA examined the impact of an inpatient computer decision support system for antimicrobials on appropriateness of antimicrobial prescriptions in a retrospective cohort. The system was associated with a higher level of appropriate prescribing, 44% vs 33%. However, the most interesting finding was that the most important factor influencing prescribing was the accuracy of the initial diagnosis.  If the diagnosis was correct, prescribing was appropriate 62% of the time compared to only 11% when the diagnosis was incorrect or uncertain. Thus, unless we can help clinicians with their diagnostic accuracy, we will have a limited impact on antibiotic prescribing.

ok, back to the meeting for me...

Hand Hygiene Causes Obesity

Subtitle: "Or how you can associate almost anything with a weak study design."

One of my favorite epidemiological study designs is the temporal association "ecological" study that attempts to infer causation by showing one exposure increasing and one outcome increasing and then implying that the exposure is causing the outcome. You know, "Hey, they are both going up so one thing causes another." Vaccine use and autism rates anyone?  So, just for fun I've produced the graph above and as you can see, through the efforts of CDC, WHO, VA and many individually hard-working IPs, hospital epidemiologists and clinicians hand hygiene compliance has increased. And as you can also see obesity is also increasing, ergo hand hygiene causes obesity!  Just try to disprove it!

Now, why am I wasting time with such an exercise? Because there is a paper in this June's ICHE that uses a similar study design and comes to an equally incorrect and perhaps dangerous conclusion.  The study used 2008-2011 data from Ontario to compare yearly hand hygiene compliance rates to quarterly MRSA rates and monthly CDI rates. The study found that despite increases in hand hygiene compliance there was little change in MRSA and CDI rates over this period. The author then concluded: "This study supports the emerging evidence that once a threshold level of hand hygiene compliance is achieved, there is very little if any benefit to attempting to achieve higher rates of hand hygiene compliance among healthcare providers."

Well, except that you can't conclude that from such a study design. For one, the author didn't have exposure and outcome from the same time periods. Why would we think average hand hygiene compliance over an entire year would correlate with monthly CDI rates and quarterly MRSA rates?  And how can we not consider other factors at play like the emergence of NAP1 or CA-MRSA during this period? Maybe there's even a Simpson's Paradox here, but that's a topic for another day. Oh, and keep washing your hands. I doubt we've reached a "threshold" of compliance!

Addendum: Probably the biggest flaw in this study is the accuracy of the reported hand hygiene compliance rates. No doubt the rates are lower than reported.

The Environment and HAI – Where does Biological Plausibility Come In?

This May's Infection Control and Hospital Epidemiology (ICHE) contained a randomized trial of copper-coated surfaces in ICU settings which reported a 50-70% reduction in several aggregate outcomes that included hospital-acquired infections and colonization with MRSA and VRE.  In this guest blog post, physician-scientists Dr. Matthias Maiwald from the KK Women’s and Children’s Hospital in Singapore and Dr. Stephan Harbarth from University of Geneva Hospitals in Geneva, Switzerland question the plausibility of these findings and put them in the larger context of what actually causes HAIs.

In 1965, Sir Austin Bradford Hill published a landmark paper, entitled “The Environment and Disease: Association or Causation?” in which he outlined what would become known as the “Bradford Hill Criteria.” The “Hill Criteria” help distinguish association from causation in epidemiological research. One of nine criteria was biological plausibility. Quoting: “It will be helpful if the causation we suspect is biologically plausible. But this is a feature I am convinced we cannot demand. What is biologically plausible depends upon the biological knowledge of the day.” As commented elsewhere, the spirit of this criterion is to check whether the proposed causation violates any of the known laws and facts of science of biology, and as Hill outlines, this depends on currently available knowledge. It is said that Hill did not intend the criteria to be applied rigidly in the sense of a checklist approach; instead, he regarded them as “viewpoints” that would merely help in the assessment.

Fast-forward to the May 2013 Special Topic Issue of ICHE concerning the role of the environment in infection prevention. In the issue’s introduction, Weber and Rutala quote figures from a 1991 article by Weinstein concerning the biologically plausible sources of healthcare-acquired infections (HAIs): “patients’ endogenous flora, 40-60%; cross infection via the hands of personnel, 20-40%; antibiotic-driven changes in flora, 20-25%; and other (including contamination of the environment), 20%.”

In the same issue, an article by Salgado and colleagues caught our attention. This clinical trial compares 614 patients randomly placed into standard ICU rooms or into rooms where 6 frequently-touched items (e.g. bed rails, overbed tables, intravenous poles, etc.) had been replaced with copper alloy surfaces. The measured primary outcomes, according to the paper’s methods, were:
   (a) any HAIs and
   (b) colonization with methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE). Besides HAI and colonization, outcomes presented in the results section included the numbers of patients who had
   (c) both HAI and colonization,
   (d) HAI and/or colonization,
   (e) HAI only but no colonization (i.e. number of patients who had HAI minus the ones who had both HAI and colonization), and
   (f) colonization only but no HAI.

Are you confused? Separate data for outcomes in each trial arm were only reported for (d-f) but not (a-c).

For HAI and/or colonization (d), the article reported what amounted to a 49% reduction in the copper rooms vs. non-copper rooms (21 vs. 41 patients; p=.02), for HAI only (e) a 62% reduction in the copper rooms (10 vs. 26; p=.013), and for colonization only (f), a 67% reduction (4 vs. 12; p=.063, NS). What was was not reported were the numbers of patients with (a) HAI and (b) colonization, listed separately for each trial arm, but the article concluded – in the discussion – that copper surfaces in rooms reduced the risk of HAIs by more than half. Conventional wisdom, however, would suggest that (a) any HAIs and (b) any colonization events, would be the most biologically relevant outcomes, and that it may not be so informative to combine these two events (under d) in the same statistical calculation, because they are biologically very different from each other. So, we extracted the missing numbers from the other numbers presented and arrived at (a) HAIs 17 vs. 29, and (b) colonization, 11 vs. 15 events. Putting these into our statistics calculator, they were – non-significant.

Now, let us revisit possible transmission routes in hospitals. We have: (i) endogenous transmission, from within the patient’s own flora, (ii) exogenous transmission via direct transfer, (e.g. as in handborne without surfaces), and (iii) exogenous transmission via surfaces and secondary transmission from surfaces onto the patients. If we look at (a) HAIs and (b) colonization with MRSA or VRE, then all three pathways can lead to HAIs, while only the two exogenous pathways can lead to colonization. If there is a >50% reduction of HAIs through copper surfaces (pathway iii), this would mean that the overall proportion of transmission from pathways (i) and (ii) plus the proportion of transmission from the remaining non-copper surfaces in the copper-treated rooms among pathway (iii) among all HAIs together would contribute less than 50% to overall HAIs.

The obvious question comes to mind: is that consistent with the known proportions of the different pathways leading to HAIs? The preliminary answer, given the Weinstein data (see above), would be, “given the biological knowledge of the day, apparently not.” It is also noted that the overall numbers of HAI and colonization events in the present article are relatively small.

Finally, anyone of us engaging in research can accidentally have outcomes that are surprising or do not quite add up with existing knowledge in the field. That is, in our opinion, where the intended purpose and scope of a discussion section of an article comes in, and where the Hill Criteria provide important food for thought. As one of us has put forward (Teleclass Feb. 7, 2013) on a different occasion and concerning a different topic, we would welcome the broad application of a check for biological plausibility when findings from clinical trials – and even systematic reviews – are reported. But we are not confident that our voices will be heard.

Image of Sir Austin Bradford Hill, source: toxipedia

PeerJ and Why Giraffes Have Short Necks

Sometimes in life you need a new perspective. In the entirety of my existence, I've always thought of giraffes as having long necks, and I bet many of you did too. But then PeerJ went live today and suddenly my view of giraffes changed.  Instead of long necks, they're more of a medium neck creature. You see, today I discovered that sauropod dinosaurs had necks 15 meters in length or 6x longer than the world record for giraffes.** And as an aside, I learned what anatomic features enabled them to have such long necks.

And it's not just my perspective on neck length that changed today, it's my perspective on open-access publishing.  Until today, if you wanted to publish in an open-access journal, it would be a high-cost affair. For example, publishing in BMC-Infectious Diseases might cost you $2055/article and publishing in PLoS One might cost you $1350/article. Starting today, you can publish your hard-earned research findings in an open-access, advertising free peer-reviewed journal for .... $99.  And that one-time only $99 "membership" will allow you to publish one article a year.  Of course there's a slight catch. Each author has to pay the $99, so if you have 5 authors, it'll cost you $495. If you usually publish with the same author group, that will be a one-time cost.

We've written frequently about the benefits of open-access publishing including increased readership of your papers and the societal benefits of free access to research findings for our tax-paying funders (thank you tax payers!). There are many perceived barriers to open-access, particularly legacy promotion/tenure committees at universities, but these can be overcome. One real barrier has always been cost, but at $99 or even $495 that barrier is slowly going away. What a nice change in perspective!

For more info see Mike Taylor's post in the Guardian Feb 12, 2013

Image source: wikipedia

COI acknowledgement: I'm an Academic Editor at PeerJ (as is Dan). I'm also a section editor at the open-access journal Antimicrobial Resistance and Infection Control, and was recently named Section Editor for SHEA's journal Infection Control and Hospital Epidemiology.

**Yes, I've seen a sauropod skeleton before but I've never thought of giraffes as having short necks. It's the juxtaposition that was refreshing, like open-access next to $99.

HAI Rates are a Red Herring

"Fictional" Hospital CMO: "Why should I care about hand hygiene or environmental cleaning if I have no CLABSI or CAUTI in my hospital?"

Don't take this the wrong way, since I'd never want a patient to develop a CLABSI or VAP, but I think our focus on device infections is actually harming patients in the long run. If we convince ourselves, like that CMO quoted above or QI and patient safety folks, that we can just prevent device infections (never mind define them away) and everything will be fine, we are missing the bigger picture. The bigger picture is antibiotic resistance and I've yet to see any evidence that our antibiograms are improving.

When did hospital epidemiologists forget we were infectious disease physicians?

In September's ICHE Kerri Thom and colleagues in Maryland published a sobering reminder that resistant pathogens are increasing, particularly Gram-negative pathogens. They (COI alert, I'm a co-author) completed an Acinetobacter baumannii prevalence survey of all mechanically ventilated patients in the state of Maryland. They swabbed intubated patients in 40 of 57 hospitals and collected sputum and/or perianal swabs from  92% of all eligible patients in those hospitals.  What they found was staggering.  Fully 34% of patients were colonized or infected with Acinetobacter baumannii with 16% in acute care settings and an astounding 63% in long-term care settings carrying the pathogen. Even more worryingly, many strains were highly drug resistant with 46% of isolates in long-term care described as "extensively drug resistant," meaning there were no effective therapies - polymixin anyone?

Why does this matter?  Resistant pathogens cause untreatable infections and result in terrible situations like patients being removed from organ transplant waiting lists. These pathogens also carry resistance genes and serve as reservoirs for emerging resistance in other pathogens like E. coli. So, while I'm sure these Maryland hospitals all report zero CLABSI or CAUTI, I guarantee that they all have patients infected and dying of Acinetobacter baumannii and other MDR-Gram negative pathogens. Until we make investments in the science behind hand hygiene improvement, environmental cleaning and other methods for transmission prevention and until we invest in antimicrobial discovery, patients will increasingly die of these untreatable infections.

Luckily, when a kidney transplant patient dies of MDR-Acinetobacter sepsis, the hospital CMO can still sleep at night. At least the patient didn't die of a CLABSI.  I'm sure the patient's family will find comfort in that.


red herring image source: misocrazy

Didn't we say not to use ICD-9 codes to track MRSA?

When you're trying to improve epidemiological methods, I guess you have to be patient.  For example, when Yehuda Carmeli and Anthony Harris told us which control group to use when assessing risk factors for antibacterial resistant organisms, it took years for people to regularly follow their advice. However, I'm still a bit surprised when authors and journals keep publishing studies that track MRSA infections using ICD-9 codes. 

A couple years ago, ICHE published our multi-center validation study showing that ICD-9 codes for MRSA have a very poor positive-predictive value: 31%. To quote our conclusion: "In its current state, the ICD-9-CM code V09 is not an accurate predictor of MRSA infection and should not be used to measure rates of MRSA infection." ICHE also published Marin Schweizer and Mike Rubin's excellent editorial summarizing the issues with ICD-9 code based surveillance for MRSA.

So, knowing what we know about recent MRSA trends and considering my feelings about ICD-9 codes and MRSA, I was a bit surprised when the August ICHE included a study suggesting that MRSA was increasing in academic medical centers between 2003 and 2008 and it used ICD-9 codes! Sure, they attempted to adjust for the billing code's limited sensitivity.  Unfortunately, sensitivity isn't the key issue. If you say something is increasing, it's more important to know if what you're counting as an MRSA infection is actually an incident MRSA infection from the index admission, and not an MRSA infection from a prior admission, or even newly detected MRSA colonization. Thus positive predictive value and specificity are more important measures. 

Just remember this when you read stuff on the interweb that says "contrary to data from the CDC" or posts saying MRSA has doubled in 5 years.  Stick with the CDC. Fortunately, most of the best evidence suggests MRSA is in decline...at least for now.

Important note: Our validation study included three hospitals and compared ICD-9 to actual culture data, the gold standard.

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Ridiculous Example: What if we wanted to estimate the proportion of 30th Olympiad attendees who were born in England by randomly sampling people walking around the Olympic stadium. We could use a somewhat sensitive test, "is the person wearing a Union Jack t-shirt", and catch many people born in England, but this would be useless (ie very low positive predictive value) since anyone can buy a shirt. We could also use a more specific test like checking their passport. Thus, ICD-9 codes are a bit like t-shirts, while microbiological culture results as used in accurate MRSA estimates are more like a passport.

800,000 Reasons to Market Your Science

800,000  That's the number of manuscripts in science and engineering published each year.  If you read a paper a day, a noble goal, you could read 0.05% of the published papers.  Imagine if you are a primary care doc who had to keep up in multiple clinical areas or worse yet, a science journalist.  How could you manage?

JournalWatch from qfever.com

Now let's turn that around.  Let's say you're a scientist who has important data you want to share.  How can you make your one very very important manuscript stand out among the 800,000? Your magnum opus represents a mere 0.000125% of all papers published in the last 365 days.  To make you feel better, we could assume equal likelihood that a paper is published on any given day and find that only 2192 papers are published per day. So your paper would represent 0.05% of papers published on the day it appears.  Better act fast since things get worse if you consider a whole week. You get my point.

So why should anyone read your paper? More accurately, how can you convince me to read your paper if I don't even know it exists?  Answer: You have to market it.  Some authors at some institutions who publish in some journals (AJIC not ICHE) are lucky, since someone does the marketing for them.  If you're not so lucky, you and your colleagues have to do the marketing.  If you're looking for the how and why we should market our science, look no further than this month's issue of Nature Materials. It includes an editorial, commentary and interview of Marc Kuchner, astrophysicist and author of a new book titled Marketing for Scientists, each discussing the importance of science marketing.

This isn't just about selling your paper or raising your profile, nor is it limited to increasing your chances of NIH funding, but rather it has very large public health implications.  We have spent years in infection prevention quietly studying methods to prevent the spread of resistant bacterial pathogens and reducing surgical infections with very little notice and certainly very little funding.  By nature we are type-A, quiet and hard working folk, who don't want to rock the boat.  Well, guess what?  It ain't working.

To emphasize our lack of voice...Q: Who are the two most prominent public voices in quality improvement / infection prevention?  A: Peter Pronovost (critical care) and Atul Gawande (surgery).  Thank goodness someone is speaking up!

So what can we do?

1) When you publish a paper on antibacterial resistance or infection prevention, advertise it.  Get on twitter or Facebook. Call your local paper's science reporter if they still have one, work with your hospital or university to do a press release, and demand the journal do a press release (see point #2)

2) Call ICHE and SHEA and insist on a press releases for your paper, even if it's not published in ICHE (joking on that last part). Currently, ICHE does a little monthly email thingy on 1-2 papers - not going to work!  Ask them to emulate what APIC and AJIC do - much better!

3) Call your representative and ask why no one is doing anything about new antibiotics and why there are all these infections without treatment.  Ask them why there is no direct funding from CMS for infection prevention services for acute and long-term care facilities. Use your science to start the conversation - say - "look what I just found!"

4) Start a local chapter of ID physicians, ICPs, microbiologists and others that focus on raising awareness for antibacterial resistance.  Work together to communicate resistance trends in your locality and the findings of your research. (I know I'm dreaming)

5) Get your state and local health departments involved - send them your papers. I bet they know a way to get newspapers interested in resistance.

We aren't just scientists, we are stewards of our science. If you care enough to do the study and publish the paper, you should care 10x more that someone reads and uses your science!

...that's all I got for now, see you on twitter...

(live) image source: http://www.qfever.com/journalwatch.html

Stewardship, stewardship, and more stewardship!

That’s what you’ll find when you read the April issue of ICHE. The entire issue is dedicated to antimicrobial stewardship, and includes several excellent articles. So consider it your Spring Break reading.

There’s even an article from Eli’s old stomping ground, describing what happens when you take an effective antimicrobial stewardship program and flush it (spoiler alert: turns out to be a bad idea). Lest we forget, the Maryland group is still the only one to demonstrate, in a randomized controlled trial, the effectiveness of adding computerized clinical decision support for stewardship efforts. So go back and read that paper too, while you’re at it.

I’ll end with this quote from our friends Arjun Srinivasan and Neil Fishman, from the intro to the special issue:

There has perhaps never been a more critical juncture for antimicrobial stewardship. There is growing interest from key stakeholders—clinicians, healthcare administrators, and policy makers—and a growing body of evidence demonstrating the benefits of stewardship. We now need to harness the interest and the science to move toward making stewardship programs an integral part of all healthcare facilities. Education and messaging will play an important role. For too long, our message on the benefits of stewardship has been too narrowly focused on reducing costs and potentially reducing antibiotic resistance. The former is not compelling to most clinicians, and the latter, while generally accepted, has been difficult to demonstrate clearly since the emergence and spread of resistance is so complicated and multifactorial. Moving forward, we need to emphasize that antibiotic stewardship is, fundamentally, a critical patient safety and public health issue for all healthcare settings that can improve the quality of care.

Photo: Alexander Fleming, from Wikimedia Commons

Economicks is hard!

I had the privilege of training in hospital epidemiology under Dr. Richard Wenzel, and alongside a number of really smart people (including fellow blogger Mike Edmond). We put a lot of time and energy into estimating the impact of HAIs on costs, lengths of hospital stay (LOS), and mortality…and our approach was simple and intuitive. If our HAI cases had a mean cost/LOS/mortality of x, and matched controls had mean cost/LOS/mortality of y, then the attributable cost/LOS/mortality must be x minus y. Right?

Yes, I’m oversimplifying, and I will give us credit for understanding that it was a little more complicated than that. However, at that time we were still trying to convince people that HAIs actually killed people, and that the damage they did was above and beyond that due to the patient’s underlying illness. So if our estimates were on the high side, it seemed OK (at least to me), since the main purpose was to jar people out of their complacency and increase resources for prevention.

The climate has changed. We know a lot more about the complexity of estimating the costs of HAIs (two excellent sources on this are here and here), and we’ve (at long last) succeeded in attracting needed attention to HAI prevention (from the public, from legislators, from the media, even from our hospital administrators!). So it now behooves us to “take it up a notch”, as advocated by Nicholas Graves and colleagues in a recent letter to the editor at ICHE (with response). You can read these at your leisure, but I want to highlight this section of their CID article, which I think is on target:

"The 'HAI costs a lot' approach to influencing decision making has served the infection control community well…..The time has arrived, however, for the methodological advances that have been achieved in this area to be implemented by researchers. Complete economic evaluations that include changes to all costs and health benefits should be performed...

The information used to update these studies should be of high quality and bias free. Inexorable growth in health care costs is forcing decision makers to respond to scarcity and work toward extracting greater value from health care resources….The time when reliable economic arguments will be paramount for obtaining extra resources—and even retaining existing ones—is close. Those working toward reducing the number of HAIs should craft valid economic arguments on the basis of sound methods and use them to build strong and cost-effective infection control programs"

ICHE Special Issue: Antimicrobial Stewardship

Infection Control and Hospital Epidemiology has just announced that it will publish a special issue devoted to antimicrobial stewardship in conjunction with the SHEA spring meeting in Jacksonville, Florida, April 13-16, 2012. 

Topics of interest include:

• Antimicrobial stewardship for special populations, including pediatrics, oncology, hemodialysis, and critical care
• Health outcome and cost effectiveness impact of antimicrobial stewardship
• Use of diagnostic tools and role of microbiology in antimicrobial stewardship
• Effective implementation of programs in community hospitals, long-term care acute care facilities, outpatient settings and non-acute healthcare settings (e.g., dialysis, ambulatory care and ambulatory surgery centers)

Due date: October 1, 2011.

Get writing and submit your paper here.

Call for manuscripts PDF available here.

Good luck!

The new ICHE is here, the new ICHE is here!!!

Congrats to all of the authors who had articles published in this August's ICHE. Now that ICHE has a massive new impact score, I suspect most of them now feel like Navin when he says, "Page 73 - Johnson, Navin R.!  - I'm somebody now! Millions of people look at this book everyday! This is the kind of spontaneous publicity - your name in print - that makes people. I'm in print! Things are going to start happening to me now."  Well, I hope all the things that happen to these fine authors are a little more positive.

Highlights:

Page 737, Boyce, John M et al. looked at the impact of an automated mobile UV-C light unit on environmental contamination in 25 rooms after patient discharge. They report the unit significantly reduced aerobic colony counts and C. difficile spores.

Page 743, Rutala, William A et al. wrote an accompanying editorial that concluded that "there is now ample evidence that no-touch systems such as UV-C light or hydrogen peroxide can reduce environmental contamination...(however) only a single study using a before-after design has been published that demonstrated that such a system can reduce healthcare-associated infections." There we go again, hospital infection prevention: the queen (or king) of intermediate outcomes. Would be pretty cool if there were more independent (federal or foundation) resources to study HAI prevention interventions, such as these.

Page 791, Gupta, Kalpana et al. report the results of a cohort of all patients at the VA Boston Health Care System that had clean or clean-contaminated in 2008-2009 and a nasal MRSA PCR test less than 31 days prior to surgery. 6.6% of the patients were MRSA+ and were at significantly higher risk for postoperative MRSA infections (RR, 8.46; 95% CI, 1.70–42.04). Interestingly, vancomycin prophylaxis was associated with higher SSI risk in those negative for nasal MRSA (RR, 4.34; 95% CI, 2.19–8.57) but not in MRSA+ patients.

Page 818, Tohme, Rania A et al. reviewed hepatitis B vaccination rates and immunity among healthcare students during a 10-year period at Emory University. They report that among 4,075 students, only 60% had documented vaccination and 84% had anti-HBs concentration greater than or equal to 10 mIU/mL. It is interesting that despite CDC and ACIP (1995) recommendations of routine vaccination of children aged 11-12 years, and for all less than 18yo in 1999, the majority of students were only recently vaccinated.

If I left you off this list, sorry! You are still awesome!