Monday, February 28, 2011

Low hanging fruit: making antibiotic treatment of skin infections less awful

I recently posted about withholding antibiotics after drainage of uncomplicated purulent skin infections. The group at Denver Health now points to another opportunity for antimicrobial stewardship when treating skin or soft tissue infections (SSTI). Believe it or not, patients admitted with SSTI do not all require treatment with vancopime (or its close relative vancopiptaz (piptamycin?)). These investigators implemented a clinical practice guideline to standardize and simplify the management of patients hospitalized with cellulitis and/or skin abscess. The guideline encouraged more judicious use of testing and imaging, avoidance of broad spectrum gram negative and anaerobic coverage, and shorter courses of therapy with earlier IV to oral transition. You can read the details here, but the guideline resulted in improvement in all areas, significant reductions in use of broad spectrum antibiotics, and no difference in clinical failure rates. The study was single center and quasi-experimental, but clearly points out an area ripe for drastic improvement in most hospitals.

The accompanying editorial by Brad Spellberg is also well worth reading, and locates the cloud in this silver lining: even after the intervention, over one-third of the patients were receiving broad spectrum gram negative active agents and almost half were still receiving broad spectrum anaerobic coverage. And yes, the investigators did exclude those patients who had complicating features (e.g. diabetes, recurrence, fasciitis, etc.) that may have justified such broad spectrum therapy. So even though the intervention was a partial success, challenges to optimizing therapy for SSTI remain.

Saturday, February 26, 2011

Maryland report on hospital associated complications: Don't waste your time reading it

This week, NPR and the Washington Post ran stories on a new report on healthcare associated complications in Maryland. The report can be viewed here. Based on the results of the report, nine hospitals are required to pay penalties due to higher than average rates of complications. Eleven of the report's 49 indicators are infectious complications, such as infection related to central venous catheters. However, what is most important to know is that the source of the data for the report is administrative claims (ICD-9 codes which were developed for billing purposes). We've blogged before about how notoriously inaccurate these codes are for determining whether patients experienced healthcare associated infections. This is because case ascertainment is performed by abstractors with little medical training using case definitions that were not designed for surveillance purposes. Last year, Pennsylvania, the state with the most comprehensive mandatory reporting program for healthcare associated infections in the country, abandoned use of administrative claims data and required that all hospitals use CDC surveillance methodology. Particularly when hospitals are going to be punished by fines and bad publicity, valid methods must be used. I noted in the report that there were 431 cases of "moderate infectious," at a cost of over $6 million. What in the world is "moderate infectious"? I don't think you could find an infectious disease doctor anywhere who could tell you what that is because there is no such thing. Those of us who work in hospital epidemiology understand the need for public reporting because our society values transparency and accountability. We get it. But public reporting is a two-way street that requires a commitment on the part of public agencies to insure that the data generated are obtained via state-of-the-art methods and risk adjusted in order to produce the most valid reports for the public. In other words, it's about playing fairly.

Friday, February 25, 2011

Obit: Dr. Edwin D. Kilbourne

Dr. Kilbourne, source: NYT
Edwin Kilbourne MD, who was a graduate of Cornell Medical College and an accomplished influenza researcher, died earlier this week at the age of 90.  He was most widely known for his involvement in the swine flu epidemic of 1976. There is a nice obituary in today's NY Times.

Thursday, February 24, 2011

Bad Science (part 2)

I just finished reading Ben Goldacre's book, Bad Science, and I highly recommend it. About a month ago, I posted about Dr. Goldacre, a British psychiatrist, and included his excellent, humorous video on the placebo effect. I liked it so much that I bought his book. He has an amazing ability to explain epidemiologic concepts and critical analysis to the general public. The book gives many interesting examples of problems with scientific papers and the problems with how the media translates them (often incorrectly).

Here's another video of him addressing a non-medical audience on evidence-based medicine. If only I could be this entertaining when I lecture!

Ben Goldacre Talks Bad Science from PopTech on Vimeo.

Dallas in April!

What could be better? Don’t miss the next SHEA pre-registration deadline! If you haven’t yet registered, you will save $50 by registering before February 28th.

Wednesday, February 23, 2011

VRE Forever!

Without despair we will share
And the joys of caring will not be replaced
What has been must never end
And with the strength we have won't be erased
When the truths of love are planted firm, they won't be hard to find
And the words of love I speak to you will echo in my mind

I believe when I fall in love with you
It will be forever
I believe when I fall in love this time
It will be forever

Stevie Wonder  -  I Believe (When I Fall in Love It Will Be Forever), 1972

One of the most consistent obstacles to halting the spread of MDROs in hospitals is the ability for the organisms to persist in the environment.  Nosocomial outbreak pathogens such as MDR-Acinetobacter baumannii have been shown to persist for up to a year in vitro. Vancomycin-resistant Enterococcus faecium (VREFm) has been shown to persist for up to 4 months.  Now a new letter to the editor in the March issue of Journal of Hospital Infection suggests that we may have underestimated VREFm.

Researchers at the University Medical Centre Utrecht took an outbreak CC17 VREFm strain and a non-outbreak but concurrently isolated non-CC17 VREFm strain recovered during a year 2000 outbreak and placed 1ml at 10^9 cfu/ml of each strain in 104 bottles to dry. They then tested for recovery weekly and then quarterly.  I have pasted the survival curve below.  Survival for both strains was gradual to 10^4 at 9 months and 10^2 during the next 30 months.  Out to week 170-194 between 1-7 colonies were detected. Thus, these strains survived almost 4 years!!!

Certainly gives you something to think about.  Just another reason to love the enterococcus and Stevie Wonder - the pride of Saginaw, Michigan.


Will this contraption work?

One of the biggest obstacles to the accurate diagnosis of pneumonia is determining whether an expectorated sample is representative of the upper airway/oral cavity (representing colonization or, at most, tracheobronchitis) or the lower respiratory tract (representing a true pathogen).

A group from the Georgia Institute of Technology recently developed a gadget they claim can separate lower respiratory from upper respiratory aerosols. The report can be found here, in the Journal of Medical Devices.

Just drain it

Check out this article from Hopkins on treatment of uncomplicated skin and soft tissue infections (SSTI) due to MRSA…..more evidence that antibiotic therapy makes very little difference in outcome. A previous large observational study of antibiotic treatment for MRSA SSTI demonstrated a benefit to receiving an “active” antimicrobial agent, but the response rate for the group who didn’t receive active therapy was still 87% (versus 95% in the active antibiotic group).

This new randomized controlled trial was smaller, confined to children, and showed no difference in outcome between those children treated with cephalexin versus clindamycin for MRSA SSTI. Although when the investigators looked at subgroups, they did find some slight evidence for a short-term benefit:


For the subset of subjects for whom an organism was isolated from the initial wound culture and susceptibility data were known (183), 2% (2 of 111) of those who received an antibiotic with in vitro activity against the isolate versus 10% (7 of 72) of those who received an inactive antibiotic had worsened by the 48-to-72– hour visit (P=0.02).

Treatment of uncomplicated MRSA SSTI now involves a balance between the benefits of avoiding antimicrobial therapy (individual and societal) and what appears to be a very small risk for slower response to therapy. There is also the issue of whether receipt of an “inactive” antibiotic (e.g. cephalexin for MRSA) is the same thing as receiving no antibiotic (or placebo). Another recent study of managing pediatric SSTI suggests that it is.

The bottom line? Avoid antibiotic therapy in the management of purulent (i.e. drainable) uncomplicated SSTI. Incision and drainage, and good wound care, should suffice.

And as long as we’re talking about good antimicrobial stewardship, go read this JAMA piece by Jim Hughes on preserving the power of antimicrobials….

Tuesday, February 22, 2011

Collateral Damage

Source: Doonesbury by Gary Trudeau


"[T]here are known knowns; there are things we know we know. We also know there are known unknowns; that is to say we know there are some things we do not know. But there are also unknown unknowns – the ones we don't know we don't know."
-Donald Rumsfeld 

This comic was circulated today via a hospital epidemiology email list, so I had to post it here. We keep no secrets.  I don't know why I included the quote above, other than when I think of collateral damage, he comes to mind. In infection prevention, I think there are a lot of unknown unknowns masquerading as known knowns, but that is another post for another day...

Pandemic Flu: Hit hard, but should we hit early?

Image courtesy of CU Boulder Applied Math
Mathematical Biology Group
When a new pandemic flu strain emerges, as happened in Mexico in 2009, public health interventions such as social distancing are often implemented in the hope of reducing transmission. It is often assumed that the more measures that can be implemented early in the epidemic, the better. However, social distancing policies, while sounding simple, are very costly and typically of finite duration.  It is also unclear, what the policy 'objectives' of the intervention should be. Is the aim to reduce total morbidity/mortality or is it to reduce peak prevalence? How are these aims to be balanced against the societal impact of the interventions? Heady questions indeed.  Fortunately, a new paper in PLoS Computational Biology by Deirdre Hollingsworth and colleagues (including Roy Anderson) poses many of these questions and attempts to explore the intertwined policy objectives of various pandemic flu mitigation strategies.

Using a mathematical model (deterministic SIR model) and assuming a mean infectious period of 2.6 days, an Ro=1.8 and a population size of 58 million (the population of the island of Great Britain), the authors estimated the impact of social distancing interventions on influenza dynamics. They looked at a three possible durations of the intervention: (1) indefinite (2) 12 weeks - the current US policy maximum and (3) until a pandemic vaccine becomes available at 6 months. The also incorporated the use of a limited stockpile of antiviral drugs to limit disease severity and reduce transmission and also looked at the utilization of a partially protective pre-pandemic vaccine during the first 6 months of the pandemic.

What did they find? Well, it is pretty messy, like the truth typically is. One finding that sticks out is that in long-term interventions, there is very little disease incidence before week five, so there is little overall benefit from starting social distancing policies too early. The authors estimate that a few weeks delay in implementing a long-term intervention may result in a higher peak prevalence, but a considerably shorter duration of the epidemic.

What about short-term (12-week) interventions, such as those recommended by the current US pandemic plan? In this scenario, strategies that might contain an epidemic size below a certain level would not be the same ones that could limit peak prevalence. In these scenarios there would be a second peak after the intervention is lifted and they may even result in almost no change in overall epidemic size. For these "short" duration interventions there are no easy answers. For example, if the social distancing intervention is 33% effective in reducing transmission and is started at week 5, it might minimize peak prevalence. However, the same intervention with 22% effectiveness and similar timing would be expected to minimize the epidemic size.

The authors describe and discuss various other scenarios and provide a multitude of estimates for what the effects might be.  However, I think their key contribution is to force us to confront very important policy questions head on.  We need to have discussions about what our policy objectives should be in a pandemic.  Should we aim to limit the total number of cases or should we care about the peak size of the pandemic when our hospital and other public health services are stretched to the limit?  Maybe we should just want the epidemic to end as quickly as possible, so that society can get back to the new normal? We should probably have these discussions before the next pandemic, so we can design the optimal policy to achieve our goal(s). 

Hollingsworth et al. PLoS Computational Biology February 2011

Sunday, February 20, 2011

Amazing images

HIV in 3D
Here's a really cool slide show: the 15 best submissions to the International Science and Engineering Visualization Challenge published by Science.

Saturday, February 19, 2011

I'm still in scrubs...

There's a new paper in the Journal of Hospital Medicine that takes a look at one of my favorite topics, the role of the white coat in the transmission of nosocomial infections and the impact of bare below the elbows.

Investigators at Denver Health performed a randomized, controlled trial to assess the degree of bacterial colonization and contamination by MRSA on work clothes. The participants were 100 physicians (residents and attendings) on the internal medicine service who were randomized to wear either their personal white coat (subjects were not given prior notification to avoid laundering for the purpose of the study) or a freshly laundered short-sleeved uniform. After eight hours at work, the coats and uniforms were cultured at designated sites using RODAC plates.

The main findings of the study were:

  • No difference in overall bacterial counts between the white coats and the uniforms
  • No difference in MRSA contamination (16% for white coats vs. 20% for uniforms, p=0.6)

There are a number of potentially confounding issues for which we don't have information:
  • What is the prevalence of MRSA infection and colonization among internal medicine service patients at this hospital?
  • Does the hospital have a MRSA active detection and isolation program for MRSA?
  • Are patients with MRSA placed in contact precautions? If so, what is the compliance with contact precautions?
  • Are the white coats hospital issued (thereby implying a uniform fabric) or purchased by physicians (implying various types of fabric) and of what type of fabric were the uniforms constructed? Previous studies have shown that duration of contamination by important pathogens can vary with the type of fabric.

Also, were there any differences after randomization between those who wore the white coats vs. those who wore the uniforms? More importantly, I think the biggest concern with the study is that it's relatively small, from a single service in a single hospital, making external validity questionable. And MRSA is only one of several important pathogens that need consideration.   

One of the most important issues in hospital infection prevention today is the role of clothing in the transmission of nosocomial pathogens. This not only impacts the issue of whether healthcare workers should wear neckties and white coats, but also has an impact on whether contact precautions should continue. It's important to note that the entire rationale for plastic gowns in contact precautions is the assumption that contaminated clothing can transmit pathogens to patients. If that's not true we sure could save the planet from a huge amount of disposable plastic and healthcare workers a lot of grief. We desperately need a funded, large, multicenter, well designed trial to answer the questions once and for all as to whether we go bare below the elbows or kill contact precautions.

While I think the authors of this study should be commended for addressing an important topic, I don't think many people will be swayed by its results. Those believers in the white coat will find the results reassuring and the pro-bare-below-the-elbows crowd will focus on the external validity of the study. 

Friday, February 18, 2011

Why are parents anti-vaccine?

Just a quick post from the road. My friend Anna Reisman has a nice post on Slate reviewing Seth Mnookin's new book The Panic Virus: A True Story of Medicine, Science and Fear. enjoy

Monday, February 14, 2011

More Chlorhexidine Love

Just in time for Valentine’s Day, another study extols the benefits of the compound we all love, chlorhexidine (CHG). We’ve posted before about the many uses of CHG, including its use as “source control” (bathing patients to reduce bacterial burden, to decrease both transmission and infection risk). The data on source control have to this point been from ICU settings (and, to be fair, not all the data suggest effectiveness, and concerns regarding CHG resistance are valid).

Now, the Rhode Island group has examined the impact of CHG bathing on general wards as well. Using a quasi-experimental study design, the investigators performed daily soap and water bathing of all patients on four general medical wards for one year, and then used daily CHG bathing for the next year (13 months, actually). The composite rate of MRSA and VRE healthcare associated infections (HAIs) was reduced by 64% during the intervention period. Interestingly, nearly the entire difference in infection rates was accounted for by UTIs (10 in the pre- vs. 2 in the post-intervention period). Nosocomial bloodstream infection rates were exactly the same pre and post (5 MRSA and 1 VRE BSI during each time period). Clostridium difficile incidence was unchanged over the time course of the study, serving as a nonequivalent dependent variable (to assess for confounders that might be associated with a general decline in HAI rates).

Given the quasi-experimental design, small size (few HAI events), lack of a concurrent control group, etc., these data require confirmation from a larger controlled trial. I also think the study would be more persuasive if the effect was seen across all body sites, rather than UTI alone. Enough of this unromantic nitpicking—go out and buy your valentine a big bottle of CHG!

SUPERBUG - now in paperback

We've posted several times (here and here) on Maryn McKenna's homage to MRSA.  Head on over to Maryn's Wired Science Superbug blog to hear more about the book.  It's too bad that there is a new C. difficile PCR out. Now the world is conspiring to turn C. diff into the new superbug leaving poor old MRSA in the dust.  I have a sneaking feeling that MRSA doesn't read the news though, so I would imagine that it won't change its behavior too much.

Thursday, February 10, 2011

WHO update: no antibiotics and new H5N1 death

There is an article in the February 2011 Bulletin of the World Health Organization that outlines the reasons behind the shrinking antibiotic pipeline even in the setting of emerging antimicrobial resistant pathogens.  The range of reasons offered goes from the biological (the low hanging fruit has been picked) to the economic (why invest in meds that will only be taken for 7 days).  The article does offer hope in both cases by describing recent discoveries and offering potential incentive arrangements that could encourage antibiotic development and proper use.

Bulletin of the WHO (February 2011)  html or pdf

Note: World Health Day on April 7th is devoted to raising awareness around the issue of antimicrobial resistance. Although, when you read the description of World Health Day, it only talks about HIV, TB and malaria.  I wonder what it will take for the ID folk to mention a bacteria?

Finally, the WHO has announced a confirmed H5N1 related death in a 5-year old Cambodian girl. This is the first reported mortality due to avain flu since early 2010. The girl had been exposed to sick poultry during the 7-days prior to disease onset. The influenza clock keeps ticking.

Monday, February 7, 2011

Flu vaccine breakthrough

Influenza virus, A/Hong Kong/1/68
Yesterday, when commenting on Bill Gates' vaccine efforts, I wrote that a key breakthrough might be "an influenza vaccine that targets a conserved region of the virus, which would eliminate the need for costly annual vaccinations."  As if on cue...

The Guardian reports of an influenza vaccine breakthrough out of Oxford University. The new vaccine, developed by Dr Sarah Gilbert's team, targets proteins inside the flu virus that are common across all strains. The two proteins, Nucleoprotein and matrix protein 1, are more than 90% conserved across all influenza A strains and less liable to change over time.

In their initial human trial of 11 healthy vaccinated people and 11 non-vaccinated people, they exposed them to what I think is A/Wisconsin/67/2005 (H3N2). Fewer vaccinated people got the flu and vaccinated people had more T-cells and more activated T-cells. We will have to wait a bit for more details, since they have just submitted the paper for publication. Interesting that the Guardian is reporting this before a a medical journal. Given how dysfunctional the peer-review process is these days (STAR-ICU trial anyone?), I don't blame them for communicating the results in this time-efficient manner.

You can read about the initial vaccine creation and phase 1 safety trial of the Modified Vaccinia virus Ankara vector encoding nucleoprotein and matrix protein 1 in the January 1st CID.

Guardian article by Alok Jha

Berthoud et al Clin Infect Dis, January 1, 2011

Bill Gates pledges $10 billion to vaccinate children

Source: Gizmodo.com
Bill Gates spoke with Sanjay Gupta (CNN) recently and is pledging $10 billion over 10 years to vaccinate children worldwide.  Gates' plan:

"Over this decade, we believe unbelievable progress can be made, in both inventing new vaccines and making sure they get out to all the children who need them. We could cut the number of children who die every year from about 9 million to half of that, if we have success on it. We have to do three things in parallel: Eradicate the few that fit that profile -- ringworm and polio; get the coverage up for the vaccines we have; and then invent the vaccines -- and we only need about six or seven more -- and then you would have all the tools to reduce childhood death, reduce population growth, and everything -- the stability, the environment -- benefits from that."

My favorite quote (the counterfactual):  "In fact, it is so simple, people often forget what a big deal this is. The 2 million people that would have died from smallpox now don't think, 'Wow, I'm alive today because of vaccinations,' but that's the case."

It will be interesting to see if this effort can lead to 6 or 7 new vaccines.  A key one would be an influenza vaccine that targets a conserved region of the virus, which would eliminate the need for costly annual vaccinations.  I think we will also need a similar effort to identify new antibacterials before too long.

Full transcript and video of Bill Gates interview (CNN.com)

h/t gizmodo

Sunday, February 6, 2011

Cholera in New York City

I know it isn't Friday, but strictly speaking this is a fecal-oral post and not just a feces post.  Three cases of cholera were recently confirmed in NYC residents returning from a Dominican Republic wedding.  NYC typically sees 1 case/year of confirmed cholera.  All three people fully recovered without hospitalization, so no hospital infection prevention issues in this incident.  Even if a patient was admitted, transmission in hospital would be extremely unlikely.  Even then, something to be aware of.

Link:  NY Times story 2/5/2011

Misguided mandates

Photo: New York Times
The Bangor Daily News is reporting that a bill being considered by the Maine legislature would mandate MRSA screening of high risk patients admitted to hospitals. I won't rehash all the writing we have done on active surveillance for MRSA, but you can see those posts here. So MRSA exceptionalism lives on, and more money will pour into the coffers of companies that produce MRSA test kits.

Another use for the checklist

A press report from the Society of Critical Care Medicine Meeting outlines a study with a simple, novel intervention to improve hand hygiene compliance. In this study, investigators in a surgical/trauma ICU added a question to their daily care checklist: Has anyone seen anyone else touch the patient without washing their hands in the past 24 hours? If the answer is yes, the name of the offender is recorded. The result of this simple intervention was improved hand hygiene compliance from 69% to 89%. Though there isn't much detail about the study given in the report, one could envision how this would integrate front-line providers into a continuous vigilance that could be quite powerful. One downside is that this would likely not work well outside the critical care setting.

Saturday, February 5, 2011

Wash 'em

Here's a new hand hygiene video, which comes from Thomas Jefferson University Hospital.



Sure beats $1,000 fines!

Click here to read more about the hospital's hand hygiene efforts.

Friday, February 4, 2011

Another Friday, another feces post...

Recurrent Clostridium difficile disease is a huge problem—a nightmare for patients, and a recalcitrant challenge for clinicians and infection preventionists. So this week’s New England Journal of Medicine brings good news about fidaxomicin*, a new nonabsorbable macrocyclic antibiotic active against C. difficile. In a head-to-head trial with vancomycin, cure rates were equivalent but recurrence rates were significantly lower for fidaxomicin (15% versus 25% for vancomycin, in the modified intent-to-treat groups). Unfortunately, this difference held only for non-NAP1 strains. For the nasty, hypervirulent NAP1/BI strain, recurrence rates were 24% in both groups—meaning that for the majority (64%) of patients with other strain types, the difference in recurrence rates between fidaxomicin and vancomycin was even greater (7.8% vs. 25.5%).

Why? Fidaxomicin is more active against C. difficile (bactericidal rather than bacteriostatic), has a longer post-antibiotic effect, and is slightly narrower in spectrum than vancomycin. So it probably kills C. difficile better, for longer, and without as much disruption of the rest of the colonic flora. Further studies will be needed to investigate this further, and to determine why this effect is not seen with the NAP1/BI strain.

The accompanying editorial by Dr. Herbert DuPont is well worth reading, and raises questions about whether our initial therapy for C. difficile is too short in duration (in this study, 10 day treatment courses were used), and whether we’ll eventually be using a combination of antibiotics and immunotherapy to effectively treat and prevent C. difficile recurrences. That is, if stool transplants haven’t become the treatment of choice by then.


*This drug is made by Optimer Pharmaceuticals, and all of the authors have listed disclosures at the end of the article—three of the authors are Optimer employees

Wednesday, February 2, 2011

Extreme infection prevention

The new "didn't wash hands!"
There are differences of opinion on how to motivate healthcare workers to comply with infection prevention measures. Some hospitals favor carrots. Others prefer sticks. And then there's the University of Pittsburgh Medical Center's Rambo approach. As reported in the Pittsburgh Post-Gazette, the hospital has implemented a new policy to improve handwashing compliance. Attending physicians who fail to wash their hands are fined $1000, residents and fellows $250, and all others will be sent home. It makes the old Far Side cartoon with an alarm and sign (didn't wash hands!) seem quaint.

This approach worries me. It's punitive and adversarial, and in the end, may damage the trusting relationship between hospital epidemiology and healthcare workers that I think is needed for effective infection control. Other hospitals have had successes in improving hand hygiene compliance without resorting to such extreme measures. It's really quite rare for a healthcare worker to refuse to wash when confonted, and offenders can still be held accountable. It makes me wonder how bad hand hygiene compliance must have been to drive this approach.

Well, I sure hope this strategy works, since I shudder to think what could be next. Public stocks? Caning? Finger amputations?

Oh, one last question:  who gets the money?

Tuesday, February 1, 2011

Sterile gloves for drawing blood cultures?

Photo: RightHealth.com
A new study in the Annals of Internal Medicine evaluated whether blood culture contamination could be reduced if the phlebotomist wore sterile gloves. The study was performed in a 1600-bed Korean teaching hospital where all blood cultures are drawn by interns. The design was a cluster randomized crossover trial. Over 10,500 blood cultures were evaluated, and a contaminant was defined when only 1 of 2 of more blood culture sets were positive for skin flora (which in this study included enterococci).

The authors found a reduction in contaminated cultures from 1.1% to 0.6% (OR 0.57, p 0.009) with sterile gloves.

It's worth pointing out that cultures drawn through lines were excluded, as were cultures obtained in the Emergency Department (an area of high contamination rates in some hospitals), pediatrics wards and surgical wards. In addition, povidone-iodine was used as the skin disinfectant.

When I was a resident, all blood cultures were drawn by housestaff and I proudly recall that I never had a contaminated blood culture (and I did wear sterile gloves). But we had a vested interest in avoiding contaminants, as it would mean drawing more cultures and potentially extending the patient's hospital stay, all of which meant more work for us.

Guideline fail?

What if adherence to a guideline was associated with worse outcomes? How much independent validation of guideline recommendations should occur? Is it realistic to expect guidelines to be subjected to “real-world” testing prior to adoption?

If these questions intrigue you, you’ll be interested in a Pfizer-pfunded four-center performance improvement initiative that included education around the ATS-IDSA pneumonia guidelines and a prospective assessment of outcomes. As the authors report in Lancet Infectious Diseases this week, patients who received “guideline compliant” empiric therapy were more likely to be dead at 28 days than were those who received “guideline non-compliant” therapy.

Before you submit your resignations to IDSA and ATS, you should know that there were plenty of problems with this observational study—most of them are well-summarized in an accompanying editorial. The failure of the authors to consider appropriate de-escalation of therapy in their determination of guideline compliance is an especially big problem, given that antibiotic overuse has been linked to increased mortality in the ICU.

Despite the limitations, I think this study raises important questions about guideline-driven approaches to complex infections. It is interesting, for example, that guideline non-compliant empiric therapy was equally or even more likely to cover the eventually-isolated pathogen than was compliant therapy (85% vs. 81% of the time, respectively).