Even NFL Stars LOVE Contact Precautions

What do we love most of all on this blog? Yup - contact precautions. Humor!

Well, I do have respect for the utility of gloves in preventing HAIs and MDRO transmission- but I've never been sure of gowns. It's just that they are pretty annoying to don and doff and little evidence supports any additional benefit above wearing just gloves. I mean, if Rob Gronkowski from the almost champion New England Patriots can't even put on a gown correctly, what chance do we mere mortals have, seriously. Maybe that's the reason why the benefits of gowns and gloves for preventing MRSA and VRE are so hard to estimate?

There are many other reasons why the benefits of contact precautions for endemic MDRO are so hard to quantify, of course. In this week's JAMA, Mike Rubin, Matt Samore and Anthony Harris have written a very nice Viewpoint acknowledging the limitations in the current literature.  In addition, they point out why studying infection prevention interventions is so tricky and suggest a path forward. They should be commended for their thoughtfulness and honesty - something those of us (including me) who support other policies with even weaker evidence bases should remember. If Gronk is having trouble with contact precautions, it's OK if some of the rest of us do too.

Antibiotic prophylaxis isn't needed for removal of below the knee orthopedic implants?

Wow, it has been wicked cold this week and it's only going to get colder. It's so cold that I stayed inside and read JAMA RCTs instead of racing to the mall and fighting for discounted gift wrap. Besides adding to my ID knowledge, perhaps this latest polar vortex is also behind the reduced flammability of the ID profession? One can only hope.

The folks that follow me on twitter know the real reason I'm staying current on JAMA studies is that I've recently accepted a position as an Associate Editor for a new JAMA journal called JAMA Network Open. This open-access journal will begin accepting manuscripts in early 2018. Get those fingers typing - one way to protect yourself from frostbite...

In the Boxing Day issue of JAMA there was a very nice multicenter, double-blind RCT comparing surgical site infection rates post removal of below-the-knee orthopedic implants in patients receiving 1g cefazolin vs saline placebo. The 470 randomized patients were from 19 hospitals in the Netherlands and patients were excluded if they had active infection, fistula or were receiving antibiotics. Outcomes followed CDC definitions. Implant removal is considered a clean procedure with expected SSI rates of 2 to 3.3%, so apparently antibiotic prophylaxis isn't indicated; although reported SSI rates have been higher in removal vs implantation procedures, so some recommend prophylaxis.

Spoiler alert: The study was negative. 13.2% of patients in the cefazolin arm and 14.9% in the placebo arm developed SSI, (absolute risk difference, −1.7 [95% CI, −8.0 to 4.6], P = .60). Results below in Table 2. Thus, with a negative study, I headed to the sample size calculations section where the authors stated that they powered the study with an estimated SSI rate of 3.3% in the cefazolin arm and 10% in the placebo arm based on the SSI rates in clean-contamined procedures and recent Dutch retrospective studies, respectively.

Few thoughts. First, this is an underpowered study. It's true that they hit their target sample size, but their estimates were completed using rosy expectations for the benefits of cefazolin and were not selected based on clinically meaningful reductions in SSI. Many might think a 2% absolute reduction in SSI is clinically meaningful. Second, the authors suggest that the high rates of SSI might have resulted from very low thresholds for starting antibiotics if there was "the slightest suspicion of a SSI." Since CDC definitions define SSI based on receipt of antibiotic treatment, this behavior could have biased the rates. Finally, deep SSI rates were 0.4% (1 patient) in the cefazolin group and a far higher 2.9% (7 patients) in the placebo group, (absolute risk difference, −2.5 [95% CI, −5.7 to 0.4]). Since the study was powered for the primary outcome, all SSI, not much was made of the big difference in deep SSI. 

The end result might be disappointing but this is no discredit to the authors and clinicians behind the study - RCTs are very hard to design and implement  - thumbs up for all their efforts. With that said, I would prescribe cefazolin as a peri-operative antibiotic during implant removal below the knee since a 2% absolute reduction in all SSI and a 2.5% reduction in deep SSI are both clinically meaningful benefits. I will then wait for another larger study powered using clinically meaningful SSI targets, including deep SSI.

Diagnostic Stewardship

The following is a guest post from Dr. Dan Morgan, GFOTB (Good Friend Of The Blog):

This week Preeti Malani, Dan Diekema and I wrote a viewpoint in JAMA discussing diagnostic stewardship, or “modifying the process of ordering, performing, and reporting diagnostic tests to improve the treatment of infections and other conditions.” In other words, guiding laboratory ordering to prevent contradictory results and reporting results in a fashion that makes treatment more appropriate. There really are two Criteria for Diagnostic Stewardship modifying laboratory testing:

1) Does it modify the process of ordering, performing and reporting tests? 

2) Does it improve the appropriateness of patient management? 

When I discussed diagnostic stewardship with my non-medical wife, she asked “you mean they don’t do that? Why would they do tests that contradict other results or provide second or third line antibiotic choices?” 

This is why I think diagnostic stewardship has so much potential. It is about making laboratory ordering more rational, which is hard to debate. Although medicine has existed with the idea that doctors knew best how to order and interpret results, we are now seeing they often don’t, as predicted by psychologists Danny Kahneman and Amos Tversky in the 1970s; “Intuitive judgments are liable to similar fallacies in more intricate and less transparent problems.” 

Doctors ordering and interpreting test results are like other people, often irrational. Diagnostic stewardship makes testing more logical to improve patient care. Ultimately this process shouldn’t be limited to urine cultures, blood cultures and C. difficile testing but applied to new molecular detection panels and non-ID tests, like cascading tests for anemia or limiting PSA testing in young and elderly men. And there has been interest in this idea from areas outside of ID. 

The fact that diagnostic stewardship reduces false-positive tests that contribute to publicly reported HAIs means there is likely a lot of incentive to support these processes. But we shouldn’t forget there are important patient benefits too, including avoiding unnecessary antibiotics, avoiding the distraction of misdiagnosis, and improving the ability of HAI rates to truly measure care.

Contact Precautions for Endemic MRSA and VRE

by Andreas Voss and Eli Perencevich

This response to the recent JAMA Viewpoint by Morgan, Wenzel and Bearman is cross-posted on the “Reflections” and “Controversies” blogs. Both blogs were recently ranked "top 10" ID blogs by this recent ICHE study, so we might as well collaborate ;)

During the recent ICPIC 2017 and a pre-meeting think tank, the sense and non-sense of RCTs looking at various infection control measures was a major point of discussion during many sessions. Data from well-designed quasi-experimental studies, epidemiological evidence and logic seems to vanish whenever a new RCT is published, even if the results are not applicable to situations that are non-endemic, have higher or lower compliance with the preventive measures in question, or whether the intended measures were actually applied within the intended patient group. Some studies seem to assume that the transmission during the first days of admission are of no consequence. Others assume that given endemicity and a high patient load, the intended measures such as single-room isolation can’t be applied, even if a patient was randomized to receive those measures.

We do know that Morgan, Wenzel and Bearman are very well aware of the fine differences, but we fear that their cited research along with editorials like their viewpoint will be misinterpreted by many within the infection control community and those adjacent to infection control, such as the nurses, clinicians from other specialties, administrators, guideline makers, and legislators.

Our question would be, how many more RCTs do we need to slice and dice needed infection control measures? We believe that for as long as one can surmise an acceptable level of endemicity, deduce an allowable lack of compliance with the intended infection control measure, as well as justify the impossibility of applying the intended measures to all assigned patients, any infection control measure can be proven “unnecessary” in an RCT (or a poorly designed quasi-experimental study), and later on, in a Cochrane review. Is this what we need?

Let’s be clear about one thing. We believe that good studies in our subspecialty are needed and that evidence should be stronger than opinions. At a time when costs are critically important we need to know what to invest in. Infection control therefore needs to be effective and cost-efficient. Still we can’t help but feel that at present the “scientific pendulum” is swinging in the wrong direction.

At present, MRSA and VRE are endemic in many countries, ESBL is everywhere, and we are at a decisive moment before the same is true for CRE. Consequently, now more than ever, it is of up-most importance that we acknowledge the limitations of the existing RCTs as well as include all other available evidence in our evaluation of infection control measures. If we are forced to ignore strong epidemiological evidence supporting transmission in healthcare settings and methods for halting the spread of MDR-pathogens while waiting for the perfect study, are we really providing the safest care for our patients?

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.

SSI Prevention Bundle in Cardiac, Hip, and Knee Surgery - A Home Run

...and I'm being modest...

As I mentioned yesterday, it's really hard to write a post when you've already written the accompanying editorial. Today, I have a taller task - posting on a study led by two close colleagues (and favorite people), Marin Schweizer and Loreen Herwaldt. (COI alert) Fortunately, JAMA Associate Editor, Preeti Malani, has done the heavy lifting with her excellent editorial.

In today's JAMA, Schweizer and colleagues reported the results of an AHRQ-funded trial examining the benefits of an SSI prevention bundle in orthopedic and cardiac surgery. The bundle was outlined in a meta-analysis they published in BMJ two years ago and included preoperative nasal screening for MRSA/MSSA, mupirocin BID and daily CHG baths for 5 days if screen positive and vancomycin added to perioperative prophylaxis if MRSA positive. The quasi-experimental intervention study took place in 20 US hospitals across 9 states with 39 months of pre-intervention SSI rates and 21 months of rates collected during the intervention period.

Overall, the results are impressive (i.e. not modest). First, there was a 42% reduction in SSIs after the intervention was implemented (see Figure, below), despite modest bundle adherence (39% full adherence, 44% partial adherence).

The key finding for me relates to the number of months where there were ZERO SSIs across all 20 hospitals. Looking at the Figure above, you can see that "the number of months without any complex S aureus SSIs increased from 2 of 39 months (5.1%) to 8 of 22 months (36.4%; P = .006 by Fisher exact test)." Seven times as many zero-months in all 20 hospitals. That's not a modest finding. ;)

Key points from the editorial:

"inclusion of patients undergoing emergency or urgent operations, a population recognized as at high risk for SSI, improves the generalizability of the findings."

"the primary study outcome was limited to complex S aureus SSIs, eliminating much of the subjectivity of infection surveillance. Even though surveillance practices varied among participating hospitals, complicated S aureus SSIs are not clinically subtle and can be identified easily by any surveillance system."

and given the modest adherence to the bundle, "Moving forward, efforts to promote and maintain adherence to prevention protocols will remain important"

"The study’s setting is among its limitations. All 20 study sites were from a single health care system with a well-established quality improvement infrastructure - certain factors in this health care system may differ from other clinical settings, including a below-average baseline infection rate. It remains unclear what challenges and barriers may present as this bundle is implemented at other institutions. Further studies in different settings will offer additional guidance."

and my favorite quote:"Although getting to zero is unlikely to be achievable, efforts that move closer to this elusive goal hold tremendous value for clinicians, hospitals, payers, and, most importantly, patients."

My final thoughts:
This is a wonderful study that took many years of planning, hard work and tremendous collaborators, including HCA and Ed Septimus. Congrats to all involved. Not every study is a grand slam, but we'll take a home run for infection prevention.

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.

Post-exposure Vaccination for Ebola

The ongoing Ebola virus outbreak in West Africa continues to underscore the importance of a strong international public health infrastructure and continued investment in both basic and clinical research targeting infectious pathogens. The first line of defense for infectious diseases, if available, is a safe and effective vaccine. However, approved vaccines do not exist for many pathogens like Ebola, so well-designed personal protective equipment becomes critical. But even the best available PPE can't protect us from sharps injuries. Which brings us to a fascinating case report of post-exposure vaccination of a physician with a needlestick injury obtained while working in an Ebola treatment center in Sierra Leone.

The report by Lilin Lai and colleagues was just published online in JAMA along with a very well-written editorial. The 44-year-old physician from the US was stuck by an 18-guage hollow-bore needle through two layers of gloves after caring for Ebola patients with very high viral loads. Because doffing procedures had to be followed, there was a 10-minute delay in cleaning the wound with bleach, soap/water and CHG. The patient was evacuated and while boarding the jet received an experimental vaccine - a first-generation recombinant vesicular stomatitis virus–based Ebola vaccine (VSVΔG-ZEBOV) - 43 hours post-exposure.

Post-vaccination, he developed fever and malaise but made it safely to the NIH Clinical Center for further care and evaluation. His course was a bit rocky the first few days with fever, lymphopenia and diminished O2-sats but symptoms and signs slowly improved over 3-5 days and he was asymptomatic by day 7. He was discharged to complete the 21-day mandatory isolation-period at home. Ebola virus was never detected.

You can read the full report (free online) if you're interested in the many tables and figures outlining his immune responses. Briefly, the vaccine did elicit a strong innate and virus-specific immune responses. Most importantly (per the editorial) it was "able to induce an IgG antibody response against the Ebola virus glycoprotein at a level that has been associated with protection of nonhuman primates." However, the editorial correctly notes that no definitive conclusions can be drawn since it is unclear if the patient was ever infected with the virus and the adverse events the patient experienced could have been secondary to his concurrent travelers diarrhea.

What is important is that while numerous candidate Ebola vaccines have been shown to effectively prevent transmission in nonhuman-primate models, post-exposure treatments and vaccines have been harder to develop. I wonder if a trial seeking to reduce sharps injuries in Ebola-treatment settings is in the works or if NIH would fund such a trial? Last time I checked, sharps injuries were on the rise, so investment in prevention research remains critical.

image source: wikipedia

Infectious Disease: JAMA Theme Issue

This week's JAMA is a special ID Theme Issue with a publication coinciding with IDWeek 2014. For the infection prevention inclined there is a Viewpoint by Dan Morgan (along with Dan Diekema and Keith Kaye) that asks us to consider contact precautions as secondary/adjunctive measures for MRSA and VRE but suggests that their use is prudent for MDR-GNR. I guess the BUGG study has me convinced that contact isolation works for MRSA, so I'll have to disagree with my esteemed colleagues. There are two important trials of candidate vaccines for avian influenza and an excellent editorial by John Treanor bringing us up to date on pandemic influenza options. There is also a cluster-randomized trial of SDD and SOD from the Netherlands by Marc Bonten's group with an editorial by Kollef and Micek. I'm sure we'll expound on this study more in the future. Besides the CDC's hospital antibiotic use study that I posted on earlier, there is a CDC outbreak investigation describing a 39-patient NDM-E. coli (CRE) outbreak associated with duodenoscopes. In the accompanying editorial, Rutala and Weber ask "whether current US endoscope reprocessing guidelines are adequate to ensure a patient-safe gastrointestinal endoscope."

I would be remiss if I didn't point you to the Editorial by the ID-Issue Editor, Preeti Malani. She did a wonderful job pulling this issue together and in her editorial outlines the many broad threats to human health that we still face from infectious diseases. In particular she highlights the "worldwide, major disparities (that) cause many individuals to lack access to clean water, safe food, and fundamental elements of infection prevention, such as hand hygiene and basic sanitation." She also worked closely with Cassio Lynm, the medical illustrator who created the cover image (above). Clouds ominously bring forth climate change as the sea harbors new pathogens and threatens those sequestered safely on shore. And the one barrier we have against the multitude of threats? Contact (and droplet) precautions. I couldn't agree more.

Antibiotic Use is Common in Hospitalized Patients

Even with Ebola and Enterovirus D68 on their plate, CDC still finds the time to do one of their day jobs - antimicrobial stewardship. In today's JAMA Infectious Diseases issue, Shelley Magill and her CDC EIP colleagues published (open access) a point-prevelance survey of antimicrobial use in acute care hospitals. The one-day survey included 11,282 randomly-selected patients from 183 hospitals in the 10 EIP states. In addition to recording which antibiotics the patient received, they also determined the rationale for use: treatment of infection (including empiric therapy), surgical prophylaxis, medical prophylaxis, a noninfection-related reason, or unknown.

Approximately 52% of patients received antibiotics that day or the day before. 58% of patients in ICUs vs 49% in other locations received antibiotics. Of those on antibiotics, half received one antibiotic, while the remaining 50% received two or more antibiotics. This seems like an obvious target for stewardship efforts. Encouragingly, 97% of the patients had a documented reason for receiving the antimicrobial: 76% for treatment of infection, 19% for surgical prophylaxis, and 7% for medical prophylaxis. The majority of patients treated had either a lower respiratory tract infection (34%), UTI (17%), skin/soft-tissue infection (15%) or GI infection (11%). I've included Table 3 below that highlights frequently used antibiotics for community vs health care facility-onset infections.

Overall a nice study and one that adds to the growing body of literature quantifying the rate of antimicrobials used clinically. The take home messages are a bit harder to identify. It would have been nice to follow these patients longer and capture their microbiology results to determine the proportion treated appropriately. It is also harder to make sweeping generalizations about antibiotic use in acute-care settings because the patients are very sick and could benefit from antibiotic treatment. If this were the outpatient setting, calls for improved use would be easier to make. Although, it does seems like we use too much vancomycin and pip-tazo in hospitals.

THIS...is what we need more of

A little late on this post, but summer.

There's a new randomized trial published in JAMA that evaluates the efficacy of post-cholecystectomy antibiotics in patients presenting with mild/moderate acute calculous cholecystitis. Upon diagnosis, all patient received amoxicillin+clavulanic acid three times a day pre-operatively and once during surgery. This open-label trial compared patients randomized to 5 days of post-operative antibiotics with the same antibiotic regimen vs. no post-operative antibiotics.  Patients were followed up to four weeks post-operatively for SSI and other infections. In the 414 patients, the infection rate was 15% (31/207) in the post-operative antibiotic group and 17% (35/207) in the no-antibiotic group, in the intention-to-treat analysis. The absolute risk difference was small (+/- 2.0%) and the 95% CI for the difference included zero for all key outcomes in the intention-to-treat analysis including superficial, deep and organ space infections. (Table 3 below)

The study appears to have high internal validity and randomization looks adequate. However, the lack of placebo and a relatively large non-inferiority outcome threshold (11%) are potential limitations. Of course, the study was also limited to amox-clav and perhaps some would favor testing other antibiotic regimens. However, the lack of true difference will hopefully lead to further validation studies or adoption of a no post-operative antibiotic recommendation for this surgical procedure. This study and hopefully more like it are exactly what we need in order to reduce antibiotic exposure in hospitals and subsequent selection of antimicrobial resistant pathogens, including C. difficile. It's great to see important antimicrobial stewardship questions asked and answered.

1955 - Dawn of the Antibiotic Era and Lessons for the Future

It's easy to fall into despair when pondering the decades long rise of antibiotic-resistant bacterial pathogens and the simultaneous decline in funding for antibacterial discovery, surveillance systems and infection prevention. But this wasn't always the case.  Back before 1969 when it may or may not have been said that "It is time to close the book on infectious diseases, and declare the war against pestilence won," clinicians appreciated antibiotics and even understood the idea of antimicrobial stewardship.

A case in point is this 1955 article in JAMA by GE Burch titled "Cardiology for General Practitioners." After pointing out that the first therapy mentioned by Dr. Burch was antibiotics, I would like to call your attention to a few of his thoughts:

"The most important single therapeutic development in the field of cardiology has been the advent of antibiotics. These drugs have not only made it possible to convert almost all fatal diseases, such as bacterial endocarditis and endarteritis, to almost nonfatal ones but have played an important role in control of infections in all cardiovascular disease states. Until the introduction of these drugs, the physician was often able to manage satisfactorily the cardiac disturbances, such as congestive failure, only to have the patient die of bronchopneumonia or urinary tract infection. The fear of secondary infection as a threat to life was constantly present, and the more chronic or prolonged the illness and the older or more debilitated the patient, the greater was the chance for infection. Once it developed, the physician was virtually helpless, despite the many therapeutic rituals used. Most physicians well remember the preantibiotic era."

and the homage to stewardship:
"It is not necessary, or even advisable, however, to administer those of the so-called broad spectrum type to all patients with cardiovascular disease, without regard for the specific problem."

---
After reading Dr. Burch's review I'm convinced that our current situation has several potentially modifiable causes: (1) a lack of understanding of how critical effective antimicrobials are to the practice of modern medicine, (2) a failure to include clinical judgment when selecting antimicrobials and finally (3) a pre-antibiotic era that has been completely lost to history. Addressing all of these will be required if we are to avert a post-antibiotic future.

JAMA Infectious Diseases Theme Issue: Deadline April 15, 2014

Just in time for the holidays, Santa has left a gift for ID folks under the tree. I'm not talking about the recent action by FDA to ask the livestock industry to stop using antibiotics for growth promotion, nor am I talking about the FDA's proposed rule to "require manufacturers to provide more substantial data to demonstrate the safety and effectiveness of antibacterial soaps (that contain triclosan or triclocarban)."  While I'm very excited about those developments, I'm pretty sure Santa doesn't work at the FDA.

What I am attempting to highlight is JAMA's ID theme issue planned for October 2014. I offer a few select quotes from the call for papers written by Preeti Malani and Michael Berkwits:

"Ironically, while advances in public health have been driven historically by management of infections, the body of evidence that guides contemporary practice in infectious diseases remains relatively limited."

"Clinical trials rarely can fill a journal issue, and important clinical questions far exceed the number of trials that can be planned, so we invite authors to submit research with other designs and approaches."

"Studies that present new information relevant to optimizing treatment strategies and prevention efforts, and those that enhance the understanding of quality-of-life and economic consequences of infection are also of interest."

Let's hope this theme issue has some new science in the fields of infection prevention, antibacterial resistance and stewardship. Deadline April 15th!

A good time to ditch contact precautions?

I get that no one likes to don gowns and gloves before seeing patients, particularly ID consultants who see a large number of patients colonized/infected with MDROs. I understand that touching is important for healing and that somehow wearing gloves impedes the healing touch. I even see why some still think that contact precautions place patients at greater risk for medical errors, even if the data supporting that contention is lacking. What I don't get is why infection prevention folks are pillorying one of the most effective methods we have in MDRO transmission prevention right when we need it the most.

My thoughts:
1) MDRO rates, particularly for Gram-negative pathogens like CRE and Acinetobacter are increasing
2) We have no antibiotics in our quiver, so prevention is our only hope for a decade+
3) Most prior room occupant studies are flawed and when proper methods are used, prior room occupants are not a risk factor - thus the environment isn't the only answer.
4) Hand hygiene compliance is only 60% - I know some are claiming 90%+ on their reports, but it's simply not true.
5) Gloves are massively effective in reducing the burden of organisms on hands and CP have now been shown to be effective in an RCT - (if you can look past the JAMA trial nihilists)

Which brings me to the table below modified from a study we completed a few years ago. You'll notice the red circle highlighting the per room entry contamination rate of healthcare workers hands with A. baumannii when hand hygiene compliance is 60%. The green circle highlights the contamination rate when gloves are worn with the 90% compliance achieved in the BUGG study (even ignoring that universal CP is associated with higher HH compliance).  You can see that when a healthcare worker enters an A. baumannii+ patient's room, 15% of the time they will leave the room with A. baumannii on their hands. If the hospital practices universal CP, it will be 3% of the time.

So, I get why people hate contact precautions, particularly ID-trained hospital epidemiologists. I just don't get the delight with which they limit their use given that CP are supported by the strongest evidence that our dismal science can muster. I suspect, again, that I won't have to live that long to witness their regret.

I hope I live long enough

Mike has had his say regarding universal gloves and gowns. I'm a huge fan of Mike's push for horizontal interventions like hand hygiene, but I was surprised when I read that he is pushing universal chlorhexidine bathing in his hospital. I will keep this post short so you can quickly move down to read his post, but I have a couple comments. First - chlorhexidine is an "antibiotic" and resistance already exists.  Second, if there is one thing we know about overuse (i.e. universal use) of antibiotics is that it leads to resistance. Third, I know that CHG is fashionable (like antibiotic cycling once was) and you can't fight fashion. Finally, if we really want clean hands, when you add the BUGG study's gloving+hand-hygiene compliance this would equal ~95% hand cleanliness.

In the meantime, I will sit on the sidelines and wait for CHG resistance to rise and the many MDR-acinetobacter and other GNR outbreaks that will occur secondary to it's overuse. Despite the title of my post, I suspect I won't have to wait too long.

Addendum: looking through the twitter chatter after the BUGG study was released, I noticed a disturbing trend of HCW complaining more about the burden of wearing contact precautions than the burden of HAI.

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...

"Nightmare" on Hospital Street

Not sure how we missed last week's JAMA medical news piece featuring our very own co-blogger Dan, but I suspect we might have been distracted by something pretty terrible. The article highlights the rise of carbepenem (CRE) and 3rd-generation cephalosporin-resistant Klebsiella pneumonia strains originally described in ICHE by Braykov et al. The CDC's Arjun Srinivasan emphasized that these strains are almost exclusively hospital-associated and now is the time for hospitals to implement the latest CRE recommendations from the CDC 2012 toolkit.

Dan "emphasized the importance of infection control basics such as ensuring a high rate of hand hygiene adherence among staff and making sure that surfaces and equipment are properly disinfected."  And said "If you don't shore up those things, screening [for CRE] isn't going to help."

I'll just paste in my favorite section: "An additional problem is the piecemeal approach to tracking these infections. Only 6 states require facilities to report CRE cases. “We need a more coordinated response,” Diekema said. He explained that the CDC is doing as much as it can with the resources it has, but underfunding of public health at the national and state levels makes it difficult to mount a more coordinated national effort to contain the spread of these infections. More research is also needed on the best strategies for environmental disinfection, ensuring adherence to hand hygiene and other measures that would prevent the spread of health care–acquired infections."

CRE isn't just a nightmare, it's a recurring nightmare. And just like the nine Nightmare on Elm Street films, it'll get worse over time. Especially if we continue with the current "piecemeal approach" prevention plan.

Source: Bridget Kuehn, JAMA 4/27/2013
Image source: wikipedia

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Another Staph aureus vaccine failure

The April 3rd JAMA contains the results of a wonderfully designed and executed study by Fowler and colleagues assessing the benefits of a novel (V710) vaccine targeting S. aureus infection in cardiothoracic surgery. The study was negative (i.e. the vaccine didn't work) and highlights how little we know in 2013 about how humoral immunity works for this important human commensal. But first the study and results...

Among 8031 patients entered into the study, the vaccine was given between 14 and 60 days pre-op to 3981 randomly-selected patients prior to surgery while 3982 received saline placebo. The study was powered to detect a 20% reduction in S. aureus bacteremia or deep surgical site infection through 90-days post-op. Secondary outcomes were any invasive S. aureus infection. Three interim analyses were planned but the data monitoring committee terminated the study after the second interim analysis. Thus, only around ~5100 patients completed the full study with 90-day endpoints. Of note, 67% were male, 24% had diabetes, 18% were S. aureus colonized and 2% were MRSA colonized. Randomization appears excellent.

As I suggested, the results are sobering. The primary outcome (deep SSI or bacteremia) occurred in 2.6% of vaccinated patients and 3.2% of controls, p=0.58. There were more adverse events at 14 days in the vaccinated group (31% vs 22% ) and a greater incidence of multiorgan failure. Depressingly, there was far higher mortality secondary to S. aureus infection in the vaccinated group, 23 vs 4.2 per 100 person-years. The overall comparison between vaccinated and unvaccinated for S. aureus related outcomes is striking and humbling. I've pasted Table 4 from the study below, for your review (click on it to enlarge).

The authors of the study point out that their study isn't the first to find worse outcomes in a vaccinated group and also that MRSA infections were more common in the vaccinated arm of the trial. But I don't buy their suggestion that MRSA was a significant contributor to the poorer S. aureus related outcomes in the vaccinated group. There just wasn't enough MRSA disparity between the vaccinated and control groups. I wonder if part of the answer to higher mortality in the vaccinated group could be explained by this old paper by Heiman Wertheim and colleagues that I discussed several years ago. Wertheim report significantly lower mortality among S. aureus carriers vs. non-carriers. Could the vaccine be upsetting the delicate protective effect of pre-existing S. aureus colonization?

There is an excellent accompanying editorial by Preeti Malani and I urge you to read it. She does a wonderful job putting this study in historical context and pointing a path forward for HAI prevention research. The money quote from her editorial is: "Ultimately, the results of the study by Fowler et al say more about the need to rigorously study infection prevention in general than about S aureus per se." I couldn't agree more.

Image source: Vance Fowler, MD MHS from Duke

Value versus return on investment

The Viewpoint piece in today’s JAMA is a helpful reminder to step back and ask why we often apply a different standard to prevention programs (will they save more money than they cost?) than we do to other healthcare expenditures. I’ll paste an excerpt below, but you can read the whole thing here.

“Clinicians and policy makers should not apply one standard when tacitly continuing the status quo and a different standard when evaluating innovative programs that might be implemented. It certainly does not make sense to use one criterion—Are there clinical benefits?—for coverage decisions for treatments and a different criterion—Are health care savings greater than program costs?—for preventive services..”

More antibiotics NOT more better in sepsis

There is a meme in antibiotic therapy for all infectious disease clinical syndromes that earlier and more antibiotics lead to lower mortality. I'm not sure that this meme is supported by data from good studies, but it has been so effectively spread through the establishment that its very existence goes unnoticed (check this abstract's first sentence). I think this unproven belief threatens effective antimicrobial stewardship and is partially responsible for the emergence of antimicrobial resistant organisms, but I digress...

Published online in JAMA this week is a randomized trial of dual antibiotic vs monotherapy in sepsis funded through the German Sepsis Research Network (SepNet). The 2.5 year study in 44 German ICUs compared meropenem monotherapy (n=298) with meropenem+moxifloxacin (n=278) in patients with sepsis or septic shock. Patients were treated for 7 to 14 days or until discharge or death and duration was informed by a procalcitonin-guided treatment protocol on study days 7 and 10. The primary outcome was mean of daily total Sequential Organ Failure Assessment (SOFA) scores over 14-days with similar scores in both monotherapy (7.9 points) and dual therapy (8.3 points) patients, p=0.36. 28-day mortality was 22% in the mero and 24% in mero+moxi patients (p=0.58) and 90-day mortality was 32% in the mero and 35% in the mero+moxi patients (p=0.43).

Groups were similar and infections were predominately pneumonia, intra-abdominal and GU. Blood cultures were positive in 33% of patients with Escherichia coli and MSSA being the most commonly isolated, while 18 had MRSA from any source. 100% of cultures tested were susceptible to the mero+moxi combination while 94% of specimens were susceptible to meropenem monotherapy.

This is an important study and one that should make us question current empiric therapy dogma. However, it doesn't answer the question whether antibiotics overall made a difference and whether other therapeutic options including source control might be more important.  It's nice to see clinical ID slowly emerge into the modern evidence-based medicine era even if so few studies are completed in the US.

image source: http://abacaxihortela.blogspot.com/2011/09/only-1.html