Progress on HAI progress: CDC portals and data

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

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

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

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

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

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

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

Show me the data!

The following post is from Scott Fridkin, MD, about the new public availability of NHSN antibiotic resistance data:

Finally, some NHSN antibiotic resistance (AR) data for easy access to all! 

Use the HAI Antibiotic Resistance Patient-Safety Atlas to get metrics of AR for the U.S., your region, or your state. It’s currently limited to NHSN defined HAIs, and aggregate measures; but it is dynamic and will grow in size and functionality. Hopefully this will help public health, the public, providers, and researchers to improve patient care. 

Given the public health priority of preventing antibiotic resistance in healthcare, even before the National Action Plan to Combat Antibiotic Resistance was in place, there was a recognition by CDC that it was imperative to make HAI data reported to CDC more accessible to the public, including the public health community, consumers, the press, and industry partners. In addition, academic researchers could benefit from easier access to generate specific hypotheses to test with more definitive research.

Toward this end, CDC finally has expedited the availability of antibiotic resistance data to allow for more time-sensitive evaluations independent of publishing timelines, to allow diverse approaches to ecologic assessments such as geographic comparisons, and to allow evaluation of subsets of data not previously explored in-depth. This month CDC launched the first version of the HAI Antibiotic Resistance Patient Safety Atlas:

As CDC’s National Healthcare Safety Network has migrated from a sentinel surveillance program to a national performance measurement system, the number of facilities reporting has surpassed 4,000 for acute care hospitals, and 15,000 when including dialysis facilities, long term care, inpatient rehabilitation, and long term acute care. The “events” reported into the system have skyrocketed as well. When you consider that the antibiotic resistance data can include up to four pathogens per infection, there is a huge amount of antibiotic resistance data that rarely sees the light of day. In fact, historically all of the antibiotic resistance data reported to NHSN have been released mostly as peer reviewed papers, with very two-dimensional views of the data. This model provided very limited access to the data, diminished relevance when publication lagged several years behind the reporting year, and limited amounts of data presented given the constraints of the paper-based publication model. Although this first version of the Atlas is fairly limited in one’s ability to create customizable queries, it does allow for temporal and geographic evaluation of trends at a superficial level. For now, the identities of facilities are protected and the data are presented at only the national or state level. However, in future iterations more national customized queries will be possible, and perhaps more granular geographic divisions. For now, I urge anyone to access the maps and query functions and let CDC know how to make the site more useful to your professional endeavors.

Exactly how useful these data will be to the public, press, public health, and most importantly patients – is still uncertain. It is a starting point for improved access, transparency, and innovation to advance antibiotic resistance infection prevention – I hope the users of this Atlas can help us make it better over time.

Our slow motion pandemic

    “We keep fantasizing about what will be the next biothreat, the next pandemic. It’s actually already here! We’re going to save our grandparents with triple bypass, but they’re going to die from pneumonia, because we will not have the right antibiotics to save them.”

Dr. Joanne Liu, International President of MSF, on Here’s the Thing.

Today the CDC releases it’s latest edition of Vital Signs, which is dedicated to the problem of antibiotic resistance (AR) among healthcare-associated pathogens. Using data from NHSN, CDC investigators estimate that the likelihood an HAI is caused by a targeted AR pathogen is one in seven in acute care facilities, and one in four in long term acute care.

There's good news in the report—the figure below shows impressive progress in reducing CLABSI rates, and to a lesser extent SSI and C. difficile. CAUTI, though, is a mixed bag (pun intended), and Mike’s covered this ground before. For reasons that Eli and our colleague Dan Livorsi outline here, it’s a shame that CAUTI has become such a prevention focus. Ironically, an unhealthy focus on CAUTI can drive testing and treatment practices that can result in antibiotic overuse, worsening the AR epidemic.

Today the CDC is also releasing the “AR Patient Safety Atlas”, a new web app with interactive data on HAIs caused by AR bacteria. I am about to post a more detailed item from Scott Fridkin about this exciting new development. Stay tuned!

Humans vs bugs

Click here to see a really cool animated infographic on antibiotic development and resistance.

When antibiotics don't work any more: Maryn McKenna's TED Talk

Maryn McKenna is a public health journalist whose stories, books and posts have been important for explaining antibiotic resistance to those not already immersed in its study. Her TED talk from last spring just became available - well worth the listen. If you want to read more, head over to her 'new' blog at National Geographic: Phenomena: Germination.

WHO: Antimicrobial Resistance

Last week the WHO released a report covering global surveillance for antimicrobial resistant bacterial pathogens. The report starts off by highlighting the major gaps in knowledge about the magnitude of the MDR-bacterial problem and suggests that the post-antibiotic era is a very real threat. While the levels of resistance in the report are very alarming, the authors also note that worldwide surveillance lacks coordination, so it's likely we're only seeing the very tip of the iceberg.  One interesting aspect of Dr. Fukuda's introduction was his acknowledgment that TB, malaria and HIV have much better surveillance systems and should serve as models for MDR-bacterial surveillance.

The report focuses on "nine" bacteria-drug combinations: E coli vs 3rd gen. cephalosporins and fluoroquinolones,  K. pneumoniae vs 3rd gen. cephalosporins and carbapenems, MRSA, S. pneumoniae vs. penicillin, nontyphoidal Salmonella and Shigella vs. fluoroquinolones and N. gonorrhoea vs. 3rd gen. cephalosporins.

I think the take home point is summed up in the reports Figure 1, which I've pasted below.  No new antibiotic classes since 1987. We can safely say that the bacteria didn't take a 30-year break while we rested on the laurels of the prior generation(s).

The report is 232 pages long, so you have two options if you want to learn more: (1) Head over to the WHO website and read the whole thing or (2) Listen to my 15-minute interview on Iowa Public Radio from last week. Just click on the audio player below or head over to IPR's page and listen there.



For additional reading on the US burden of antimicrobial resistant bacteria:

1) Sievert DM et al. ICHE January 2013 (2009-2010 NHSN Summary)

2) CDC 2013 Antibiotic Resistance Threats Report

Antibiotic Resistance - A Global Problem

Today, The Lancet Infectious Diseases Commission on Antibiotic Resistance led by Otto Cars from the Swedish Institute for Communicable Disease Control has published "Antibiotic resistance—the need for global solutions." The stated goal of this 42-page tour-de-force is to "explore why antibiotic resistance has become such a problem worldwide, and, most importantly, propose solutions to avert the impending crisis."  The Commission is broken down into nine parts with each group of authors responsible for their individual sections. I've pasted the table of contents to the right (click to enlarge). The document discusses antimicrobial use in humans and animals including stewardship, improved diagnostics (hopefully Dan will comment on part 3), novel therapeutics and antibacterial drug discovery.

The Commission is accompanied by 7 commentaries from the global community, which are each worth a read. All articles are free to access once you set up a username and password.

These documents are largely focused on antibacterial use and development, which are incredibly important global problems that will require collaborative responses at the local, national and international level.

But much like the recent Frontline documentary that, as Dan mentioned, did not have "enough discussion of the hard work of basic infection prevention," infection control is only briefly mentioned in the main document. (Section 2, page 7) You can get the sense of the Commission's approach with this quote: "From a resistance perspective, prevention reduces antibiotic use and the spread of resistant bacteria; however, prevention is not the main strategy to control resistance because antibiotic use also needs to be controlled."

Of course, "benchmarking (open comparison of health-care facilities) of frequencies of health-care-associated infections is useful." Yet public reporting is only useful as far as we have effective methods to prevent the reported infections.

Despite these minor quibbles, this is an incredibly timely and tremendously useful report. The authors and the Journal should be congratulated. Let's hope it moves the needle towards more recognition and funding for antimicrobial discovery, antibiotic stewardship, and perhaps... infection prevention?

Further thoughts on CRE: "Once in A Lifetime" addition

"You may ask yourself, well, how did I get here?" - the Talking Heads

It's been a busy week in antibiotic resistance. From Tuesday's MMWR early release identifying terrifyingly large increases in CRE until today, there has been non-stop media coverage.  This morning, I had a long discussion with a colleague about CRE and it got me thinking about how we got to this point. As Maryn McKenna so astutely said this week: "it will be interesting to see whether the news sinks in this time." So, how did we get here?

1981: What we now call AIDS was recognized as a clinical syndrome. Thus began the cascade of  infectious diseases research towards a full-scale and massively-funded response to the AIDS crisis. This has been an incredibly successful, if not yet complete effort. At the 2011 IDSA meeting, Cornell's Trip Gulick said that we now have 10,000 possible combinations of antiviral therapy agents for HIV. Thirty years after the virus was discovered in 1983, the progress has just been incredible. Sure, we've not yet achieved a significant number of cures and an effective vaccine remains just out of reach, but if you'd asked most of us in 1990 if we'd wanted to switch places with 2013, we would have said yes in a heartbeat.

2013: Most ID research efforts still target HIV and other viral pathogens. As we published last year, 2009 NIAID funding for HIV was $1.3 billion, while funding for all ESCKAPE pathogens was around $49 million. When we reported this disparity, it seemed quite obvious that we needed to fund more research of antibacterial resistant pathogens. However, nothing is ever that easy. One of the peer-reviewers of our paper made the excellent point that the "historically poor funding for antimicrobial resistance over the years along with the exit of pharma from the field has led to a lack of significant infrastructure. There may not be enough productive labs to send more money to at this point." So, even if the US wanted to fund more research, it may take time to train or retrain investigators to undertake the relevant research.
___

Now that I've shared some brief thoughts on why we are where we are, I have some further thoughts on where we should go. First, as I said earlier this week, we need a national response to CRE and antimicrobial resistance in general. This response needs to be horizontal in approach, as Mike Edmond and Dick Wenzel recommended several years ago. For it is quite clear that if we follow the vertical approach recommended by the CDC and others, swab for CRE and isolate, that this will bankrupt hospitals and ultimately fail.

This surveillance approach will bankrupt us, because CRE isn't the only "nightmare" in our hospitals. Back in 2010, when Dan was discussing MRSA on NPR, he said so eloquently: "MRSA is not the only bad bug out there. It's just the most famous." And along with MRSA, we have VRE and ESBL and C. difficile and Acinetobacter and MDR-Pseudomonas. You see, we might not be able to take this single-hospital outbreak approach and extrapolate it to the entire country and 10+ pathogens. And if there is one lesson we should be taking away from the NIH CRE outbreak it's not that new-fangled whole genome sequencing stopped the outbreak (because it didn't), it's that the outbreak spread and killed many patients despite herculean efforts to detect and eliminate it. Furthermore, if we target MRSA like many hospitals are now doing with chlorhexidine (CHG) baths, this approach could select for Gram-negative bacteria like CRE.

My recommendations:
(1) Invest significantly in antimicrobial discovery. Apart from the need for new treatment options, optimal control of resistant pathogens may depend on availability of effective antibiotics.
(2) Invest in studies to improve compliance with hand hygiene – only 4 studies on this topic since 1980 per a recent Cochrane Review. Compliance is terrible, but currently the approach is to blame healthcare workers and not figure out how to help them easily clean their hands.
(3) Study universal gowning and gloving (several studies are ongoing). Dentists wear gloves with every patient, why not doctors?
(4) Undertake studies to further optimize environmental source control
(5) Actually study antimicrobial stewardship. Stop yelling at patients and clinicians to not use antimicrobials. Actually fund studies that use advertising and other other messaging techniques that have a chance to be effective.

Oh, and no more ridiculous hand hygiene song and dance videos...unless they include folks like the Talking Heads...

What does 'antibiotic resistance' mean to patients?

We've all heard a patient or family member claim that "they've become resistant to an antibiotic." Clinicians and public health campaigns often attempt to communicate the importance of appropriate antibiotic use, yet how patients interpret the concept of 'antibiotic resistance' may impede their best efforts. Thus, could patient misunderstanding hinder antibiotic stewardship efforts?

In July's JGIM (abstract free here), Lucy Brookes-Howell and colleagues from nine European countries completed semi-structured interviews of 121 patients with a recent lower respiratory tract infection, in order to determine their understanding of 'antibiotic resistance'. The most common theme that emerged from this study was that patients conceptualized antibiotic resistance as being 'the resistant human body' with 43 of 121 expressing this idea. Only 28 patients correctly understood that resistance was a property of the bacteria. Thus, substantial confusion was present in the majority of patients.

With almost two-thirds of patients not understanding the basics of antibiotic resistance, it is unclear if current public health campaigns that suggest that individual misuse promotes resistance can ever be effective. The authors of this study correctly wonder whether a community focus might be a better approach and also mention that using terms like 'superbug' might improve patient understanding. Maryn McKenna might be onto something...

Image source: (here)

Addendum: Really nice editorial by Timothy Edgar accompanies the study.

Bacterial Fitness and Antimicrobial Resistance

I just posted about how little we understand the rise and fall of MRSA. As a follow-on, read this recently published work from Denmark—which investigates the relative “fitness” of different S. aureus isolates within clonal complex 8 (using older terminology, phage type 83A). As might be expected, the more resistant strains were relatively less “fit”, and in the absence of antimicrobials were "out-competed" by the more susceptible strains. The authors suggest that one explanation for the waning of Denmark’s MRSA epidemic was the bacterial fitness cost of maintaining resistance in the absence of antimicrobial pressure.

We often discuss the transmission and spread of resistant bacteria on this blog, but we rarely discuss the downside, from the bacteria’s standpoint, of maintaining multiple drug-resistance mechanisms. This concept is quite old, and fairly intuitive. Wearing 30 pounds of body armor and lugging an 80-pound rucksack might favor the survival of a soldier in combat, but if I wore this gear for my daily walk to work (through non-hostile territory), I might not make it to my office. See this Nature Blog post from 2010 for a great general discussion of this topic.

Illustration by Don Smith

When antibiograms mislead

Whether in our coat pocket or e-device, most of us carry an antibiogram whenever we are seeing patients. The antibiogram is meant to help guide empiric antimicrobial therapy, and usually provides “percent susceptible” for most common bug/drug combinations. However, too many antibiogram users do not understand the limitations of using these aggregate data to treat individual patients. Most understand that hospital-wide antibiograms aren’t applicable across every unit, and formulating unit-specific antibiograms is now common practice.

A more concerning issue, though, is that current antibiogram guidelines recommend including only the first isolate of a given species from each patient, excluding subsequent isolates. While this approach prevents a single patient from having undue influence on the aggregate data, it has the effect of ignoring the risk of emerging resistance during prolonged hospitalizations. In this month’s issue of ICHE, Duke investigators demonstrate the consequences that this approach may have. Read this study for yourself, but the short version: antibiograms lose their predictive utility for Pseudomonas aeruginosa susceptibility by about day 10 of hospitalization for most important anti-pseudomonal agents.

Antibiotics are dangerous

A study in this week’s NEJM is getting a lot of media attention, reporting that azithromycin use is associated with an increased risk for cardiovascular death--especially among those with underlying cardiac risk factors.  The increased risk found in this large retrospective cohort study (performed with a big ole’ Medicaid database) was relative to amoxicillin, and was no different than the risk of cardiovascular death among levofloxacin recipients. 

Now, we can quibble about the study design, and about the small absolute risk found (this NY Times article provides some sample quibbling), but to me the larger point to make (again) is this: ANTIBIOTICS ARE UNSAFE.  They can be lifesaving, to be sure, but they carry risks for all manner of adverse reactions, including life-threatening allergic reactions, organ failure, C. difficile disease, cardiovascular death, emergence of multiple drug resistance, etc., etc. 

I don’t prescribe chemotherapy for treatment of cancer. There are many reasons for this, not least of which is that I am not an oncologist, but one is certainly the widely acknowledged toxicity of chemotherapeutic agents. Somehow, though, antibiotics have developed a different reputation--as generally safe, well-tolerated, with few downsides. Why else would they be so widely prescribed to patients who don’t need them, or made available over-the-counter in some locales, or allowed to enter our food supply?  As John Bartlett points out in the Times piece:

“We use azithromycin for an awful lot of things, and we abuse it terribly,” Dr. Bartlett said. “It’s very convenient. Patients love it. ‘Give me the Z-Pak.’ For most of where we use it, probably the best option is not to give an antibiotic, quite frankly.”

Perhaps spurring stewardship efforts requires striking more fear into the hearts of antibiotic prescribers.  Those who understand the many downsides of antibiotic use will be much more parsimonious about their use.

Detecting antibiotic resistance is hard!

Eli linked me to this recent Nature commentary on the limitations of current screening tests for certain antibiotic resistant gram-negatives (those that carry carbapenemases). Because the resistance mechanisms for gram-negative bacteria are so complex and varied, resistance detection in the clinical microbiology laboratory has become a huge challenge. Furthermore, even if tests perform well to detect a specific single mechanism of resistance, what about bugs that use combinations of mechanisms? Consider how complicated it turned out to be to refine molecular methods for that comparatively simple organism, MRSA....emergence of empty cassette variants that result in false positives, divergent mecA genes that result in false negatives, and on and on we will go.  Multiply that complexity by a thousand fold for gram-negatives.


What this means is that every clinical microbiology laboratory needs a smart, well-trained clinical microbiologist--to optimize testing strategies, to understand the limitations of currently available methods, and to anticipate and detect problems with shiny new methods.  As the authors of the Nature commentary point out, too many hospitals are trying to cut costs in their microbiology laboratories, including being unwilling to staff them appropriately.  I was asked to talk at SHEA on molecular testing and infection prevention, and covered some of these issues (see below).
SHEA 2012 Diekema

Loophole Found in FDA Antibiotic Restriction Rule

Last week, Dan posted on the new FDA rule requiring prescriptions for antibiotics in farm animals. This rule is potentially significant since 80% of antibiotics in the US are used in animals, as mentioned in the referenced NYT article. Now an astute reading by Tom Philpott at Mother Jones picks out a potential loophole in the new FDA rule. 

Here is the quote from the NYT's article as I read it: "Michael Taylor, the F.D.A.’s deputy commissioner for food, predicted that the new restrictions would save lives because farmers would have to convince a veterinarian that their animals were either sick or at risk of getting a specific illness."

and...

Here is the quote as Tom Philpott read it: "Michael Taylor, the F.D.A.’s deputy commissioner for food, predicted that the new restrictions would save lives because farmers would have to convince a veterinarian that their animals were either sick or at risk of getting a specific illness."

That does seem like a pretty big loophole.  If pediatricians used the "at risk" determination for prescribing antibiotics, I think my kids would have been on them 24-7. You can read his full interpretation over at Mother Jones. As Dan mentioned last week, only time will tell. Since Mike Taylor said "we’re confident that it will result in significant reductions in agricultural antibiotic use," we probably should wait a bit before all becoming vegetarians.

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

US District Court Judge Orders FDA to take Action on Antibiotics in Animal Feed

In a story Maryn McKenna broke last night, Judge Theodore Katz of the Southern District of New York (largely NYC) has ordered the FDA to take action on it's 1977 finding that antibiotics in animal feed impact resistance in human populations. For 35 years, various interests have blocked further efforts to limit 'growth promoting' antibiotics in feed. This lawsuit, brought by Natural Resources Defense Council with the Center for Science in the Public Interest, Food Animal Concerns Trust, Union of Concerned Scientists, and Public Citizen, sought to restart the evaluation process and move away from the current voluntary participation supported by FDA.

All right, nothing more here. Head on over to Maryn McKenna's SuperBug post to get the rest of the story. She's also provided links to her prior posts on the topic. Awesome!

Silver lining in rising MDR-N. gonorrhoeae?

We've written about poor funding for MDR-bacterial prevention studies and antimicrobial discovery. In fact, our NIH funding paper with Dan Kwon and Marin Schweizer looking at NIAID support for ESCKAPE-pathogen studies was just published in ARIC. It's a major problem, as there has been almost no governmental or private funding for antibacterial discovery in decades. Don't even get me started on funding for infection prevention studies. Only 4 good studies on hand-hygiene improvement since the 1950's, seriously?

With that background, I read with interest Gail Bolan's (CDC) editorial in this past week's NEJM.  In it she sounds the alarm for resistance in gonococcus based on a recent 17-fold rise in 3rd-generation cephalosporin resistance (cefixime) from 0.1% to 1.7% with higher rates in Western states. (See graph above) This rise in cephalosporin resistance follows sulfa resistance in the 1940s, PCN and TCN resistance in the 1980s, and fluoroquinolone resistance by 2007.

An interesting fact shared in the article is that when resistance to a particular drug class reaches 5%, the CDC's Gonococcal Isolate Surveillance Project(GISP) changes treatment recommendations to a new class of antibiotics. Sadly, only third-generation cephalosporins are left. I wonder if this class switch at 5% is contributing to the rise in resistance?  That question will remain unanswered - no funding. Also, imagine having a 5% threshold in hospitalized patients.  We would have run out of choices years ago!

So what is the silver lining in all of this?  I have a suspicion that politicians and others might be motivated by an STD with an annual incidence of 600,000 in the US. I'm not saying that politicians are at higher risk for STDs, no judging, but STDs put many people at risk, so there will be pressure to respond to this.  The silver lining is that antibacterials designed or discovered that are effective in treating GC will likely have efficacy for other MDR-bacteria, such as Acinetobacter. 

Thus, when Bolan and colleagues suggest that "the immediate priority is replenishing the drug pipeline to treat gonococcal infections," I have hope that people will listen.  There are few grassroots organizations fighting for antibiotic discovery, but there may be soon.  I hope so; our hospitalized patients are counting on it.

Orphan-drug funding crowding out antibiotic discovery?

There's an interesting story today by AP Health writer Matthew Perrone that delves into reasons why little is spent on antimicrobial drug discovery in the US.  His hypothesis is that funding for orphan drugs is crowding out antibiotic drug discovery in the private sector, forcing the US Government into action.  The evidence offered is compelling, including the fact that 11 of the 30 new drugs approved last year were for rare medical conditions, the highest level since FDA incentives began about 30 years ago. These incentives include extra patent protections, higher pricing and a streamlined FDA review. The results speak for themselves: the first new SLE therapy in 50 years and first new Hodgkin's therapy in 30 years.

However, the evidence that this is actually spurring US-government funded antimicrobial drug discovery is weak.  We're offered the somewhat misleading fact that "since 2006, government spending on research for familiar diseases like staph infections, smallpox** and botulism** has increased more than 660 percent, from $54 million to $415 million last year." OK...so what does this have to do with antimicrobial discovery?

To further highlight the dearth of investment in antibiotic discovery, we have this quote from Dr. Anthony Fauci: "We have pushed the envelope more toward diminishing the risk for companies so that they'll be more interested in getting involved with us and developing things like vaccines and antivirals." To be fair, he cold be talking about the mythical Staph vaccine. But seriously, whatever happened to "eschew obfuscation, espouse elucidation"?

The rest of the article highlights new investment in therapies for tularemia and agents of bioterror and new flu-vaccine manufacturing techniques. I had my hopes up for a minute.

**Note: There are on average 110 cases of botulism in the US every year and zero cases of smallpox.  This compares to 19,000 DEATHS from MRSA per year, which would be at least twice that high if we included MSSA. Familar does not equal common.

Source: Matthew Perrone, SFGate (AP) 1/25/2012

Antibiotic-free pork ≠ #MRSA-free pork

Ashley O'Brien in Tara Smith's UI lab has a new study out in PLoS ONE looking at MSSA and MRSA in fresh retail pork samples.  Tara has a comprehensive blog post covering this study and their prior work leading up to this paper, so check it out if you want a lot of the details.

Briefly, they collected 395 samples from 36 stores in IA, MN and NJ. 300 samples were from "conventional" pork and 95 were from pork labeled "raised without antibiotics."  S. aureus was found in 67% of conventional samples and 57% of antibiotic-free samples, while 6.3% of conventional pork and 7.4% of antibiotic-free pork were contaminated with MRSA.

This is a relatively small study, so it likely should be repeated.  Also, as Tara mentioned in her post, in the states included in this study, very few USDA-certified organic products were available unfrozen, and they targeted sampling of fresh meats.  It is hard to speculate why MSSA and MRSA didn't differ significantly between the types of pork, but contamination during processing or at retail is certainly possible.  Could it be that conventional and antibiotic-free pigs are raised in close proximity?

O'Brien AM et al. PLoS ONE January 2012

Tragedy of the commons: Antibiotics in Agriculture

@marynmck broke the story right before Christmas that FDA had silently posted that they are backing-off of their long-held (1977) plan to limit overuse of agricultural antibiotics. Instead of formal bans and policy change the FDA now hopes to “focus its efforts for now on the potential for voluntary reform and the promotion of the judicious use of antimicrobials in the interest of public health.”

So here is the current US policy for protecting a critical and diminishing resource for public health:  Please Please Please don't use antibiotics!  Please?  How about if I'm nice? No? Pretty Please. Sugar on top?  Perhaps we should call this the "Don't let the Pigeon Drive the Bus Policy."  I guess it kinda worked in the book. Kinda.

So after burying the bad news on a Thursday before a major holiday weekend, the FDA posted some sort of half-good news right after the new year. You guys excited?  So what was the good news?  They will limit cephalosporins (woo woo) but with so many loopholes and restrictions that it won't matter much. Today, a NYT Editorial in frustration pointed out that FDA "will ban the injection of the antibiotics into chicken eggs and halt the practice of giving large, sustained doses to cattle and pigs. But it still allows widespread use in animals like rabbits and ducks, and veterinarians will still be able to use the drugs in ways not specifically approved by the FDA."

We've written about this issue many times before.  It's amazing that we continue to squander critical antibiotics in animal populations, while at the same time barely funding efforts to develop new antibiotics or new infection prevention strategies. The NYT stated today that "it’s time for the FDA to consider the public’s health as carefully as it considers the interests of intensive agriculture and pharmaceutical companies." Hear Hear.

Sources:

1) Maryn McKenna, Superbug Blog 12/23/2011
2) NYT Editorial "FDA Creeps Forward" 1/11/2012