An outbreak in slow motion

Not too many infections have crude mortality rates of 50% or more. Those that do generally inspire fear, alarm, and media coverage (see: avian influenza, Ebola). Hence my surprise that the heater-cooler device (HCD)-associated M. chimaera global outbreak has attracted so little attention in clinical, public health and media circles.

Now, over a year since Hugo Sax and his group first described the role of HCDs in invasive M. chimaera infections, this may be about to change. Why? Because today the CDC published (in MMWR) the results of whole genome sequencing from 11 patients and 5 HCDs in Iowa and two centers in Pennsylvania (the Iowa isolates were from our patients and devices). The results confirm what we’ve suspected from the beginning: this is a point source outbreak, and the likely source is the factory in Germany where the HCDs are manufactured. There are now several media outlets that have picked up the story (here's one from NY Times and one from Consumer Reports). 

In response to these findings, both CDC and FDA are making new recommendations for centers that use the implicated HCD (the LivaNova (formerly Sorin) 3T). You can read the details for yourself, but the major new recommendations are for provider and patient notification (not just for centers that have detected cases, but for all that use the devices), and from the FDA, a recommendation to remove any HCDs linked to contamination or clinical cases, and to transition away from use of the 3T model entirely (the alert states that use of 3T units manufactured prior to September 2014 “should be limited to emergent and/or life-threatening situations if no other heater cooler devices are available”). 

The problem is that the 3T has at least 60% of the HCD market, and if all hospitals stopped using them (even just those manufactured prior to September 2014), there wouldn’t be enough other units to fill the void. Also important to note: the FDA alert provides evidence that some 3T’s manufactured after September 2014 have been found to be contaminated with M chimaera. Whether the post-2014 contamination represents point-source contamination or not, it’s a huge problem and calls into question the use of the manufacture date in decision-making.

The bottom line is that the 3T is a proven bio-aerosol generator, and should not be in the same room as the operative field. No amount of focus on cleaning and disinfection, the direction of the exhaust fan, or the results of water cultures (which, as we’ve pointed out, are not actionable) changes that.

Goodbye Triclosan (and Triclocarban)

Back when I was an ID fellow, I completed a national survey (along with Anthony Harris) of the availability of tricolsan and triclocarban containing antibacterial soaps. At the time, the industry wouldn't release the use or sales data we needed to estimate a population risk from these chemicals. We found that 76% of liquid soaps and 29% of bar soaps sold to consumers contained these agents. Fifteen years ago we concluded: "with limited documented benefits and experimental laboratory evidence suggesting possible adverse effects on the emergence of antimicrobial resistance, consumer antibacterial use of this magnitude should be questioned."

Well, patience is a virtue. Today, the FDA issued a rule banning triclosan, triclocarban and 17 other agents in hand soaps and body washes. The ban does not apply to antibacterial soaps used in healthcare settings. In a press release, the FDA stated:

"there isn’t enough science to show that over-the-counter (OTC) antibacterial soaps are better at preventing illness than washing with plain soap and water. To date, the benefits of using antibacterial hand soap haven’t been proven. In addition, the wide use of these products over a long time has raised the question of potential negative effects on your health."

It's nice to see positive change happen in your lifetime. It's also nice not to have to read a soap's ingredients before washing our hands.

The unfolding M. chimaera debacle: June 2016 update

It’s time for some updates about the evolving global outbreak of invasive M. chimaera infections linked to heater-cooler units (HCUs—see prior posts here). Notable developments in June include:

Release of an FDA Safety Alert regarding the Sorin 3T HCU: In this alert, the FDA references the Eurosurveillance study we recently discussed, recognizing the evidence for factory-source contamination of 3T units, stating that “if your facility purchased and used a 3T prior to September 2014, be aware that the units may have been shipped from the factory contaminated with M. chimaera”. FDA now recommends all such facilities (1) inform surgeons about their patients’ infection risk, and (2) “determine a method for patient follow-up and establish patient surveillance” (per CDC recommendations). 

Do you know if your hospital uses the 3T units? If so, are you alerting clinicians and working on a surveillance approach?

Meeting of the FDA Circulatory System Devices panel (June 2-3, 2016): During this meeting, the risks of bio-aerosol generation by HCUs were discussed at length. Slides and other materials from this meeting are here. Although all slide sets are available at this site, a quick 24-hour summary is here. Here are a few of my own random observations from this meeting:

• Awareness of this issue is still very limited, a point made by several panel members who should have already heard about fatal infections linked to HCU bio-aerosol generation. Broader notification is needed.
• HCU models differ dramatically in their design, and in their risk for production of aerosols (for example, the range of air movement by the HCU fans is an astonishing 20->700 cubic feet of air per minute, and the location and containment of the water source also varies). 
• Routine culturing of HCU water for mycobacterial contamination isn't particularly useful and will likely not be recommended outside of outbreaks or clusters of infection. Only a small number of labs can do the cultures properly, negative results can be falsely reassuring, and the cultures take 8 weeks to return. Our own experience confirms this--we've had consecutive samples from the same unit yield different results, as have others. However, routine bacterial cultures ("heterotrophic counts") will continue to be recommended as a monitor for effectiveness of disinfection.
• No obvious near-term solution is evident. Replacement or recall of all 3T units is not possible given that it has 60% market share, and the panel felt that removal of the HCUs from the OR is not practical (despite the fact that some EU countries have done so). A rapidly-implementable engineering solution is desperately needed.

Thus there are undoubtedly many M. chimaera-contaminated 3T units being operated inside ORs, which really is an untenable situation. If your hospital can’t engineer a solution to remove this device from the OR (or otherwise separate the 3T HCU exhaust air from OR air), then you should seek to replace them with other makes/models not linked to this global outbreak. 

Publication of the first US case series of invasive M. chimaera infections. Three cases have been reported from Mayo Clinic, preprint available from OFID here. The cases have similar clinical presentations to those reported already from Europe, and larger case series are undoubtedly to follow. Notably, two of the three patients in the Mayo series died, and the third (a 66 year old with aortic graft infection) is being treated medically due to the risk of graft replacement.

Based upon what I’ve heard from other clinicians caring for these patients, I propose this as an open question: once a patient has a device-associated invasive/systemic infection due to M. chimaera, is cure possible? Given the very long incubation period for this syndrome, this question is not currently answerable. The criteria for cure would require 24+ months without symptoms (and with negative cultures), after device replacement and 18 months of therapy. Stay tuned.

Image: The Chimaera of Arezzo

Finally, the outbreak of meetings!

We’ve done a lot of blogging about the insidious M. chimaera outbreak linked to heater-cooler units (HCUs). Still, the general awareness of this problem lags, despite the fact that an untold number of HCUs are affected, and an unknown number of people are suffering with an undiagnosed granulomatous inflammatory process that has a crude mortality rate in excess of 50%. We heard excellent talks about the issue at SHEA 2016 from Emily Cooper at Wellspan (10 cases, 6 deaths), from Dr. Ray Chinn in the “Challenging Cases in Infection Prevention” session, and I gave a late-breaker on Friday evening (slides to follow in an upcoming post). By the way, SHEA 2016 was EXCELLENT, and the slide image above is from Bob Weinstein’s talk in the SHEA/CDC Training Course. 

Well, the FDA is hosting a meeting on this problem, details of which can be found here. I will be presenting about our experience at Iowa, but others with more expertise will be there as well, from US and Europe. I’m hoping to come away with a better sense of the way forward, which in my view must address (1) better case finding: improved clinician awareness via national patient and provider notifications, so that clinicians everywhere recognize exposure to cardiopulmonary bypass as a risk factor for disseminated MAC infection among patients with implants (valves, grafts), and creative approaches to identify potential cases who currently carry other diagnoses (e.g. sarcoidosis); (2) improved management of existing cases: we desperately need more clinical information about management approaches and outcomes, to help guide decision making for patients and their physicians; and (3) prevention of additional cases: the HCU has been revealed to be a bioaerosol generator that is too risky to share air with an open chest—the make/model implicated in this particular outbreak must obviously be removed from ORs, and other devices that include fans and water sources should also be scrutinized for the risk they may pose.

Insidious

This term, defined by Merriam-Webster as “causing harm in a way that is gradual or not easily noticed”, keeps occurring to me as we continue our investigation and response to a case of M. chimaera infection. Our early efforts to address the “not easily noticed” part of this problem is starting to bear fruit, with some increased media attention and an excellent piece by Maryn McKenna.

In this post I want to raise three questions about this situation (note that I say “raise”, not answer):

1. Why M. chimaera?

Why is this particular, uncommon species from within Mycobacterium avium complex (MAC) causing infections in multiple countries in Europe and multiple states in the U.S.? If the cause of this outbreak were simply a faulty heater-cooler unit (HCU) design that allows whatever water is placed in the device to be aerosolized, one would expect a greater variety of environmental flora to be implicated (other MAC species, environmental Gram negatives, etc.). And indeed, there has been concern regarding a link with some of the rapidly-growing mycobacteria (e.g. M. abscessus), that are often found in the hospital tap water used to fill the HCUs (until more recent guidance to use sterile or filtered water). However, the consistent finding of M. chimaera from patients exposed to HCUs suggests a “point-source”. Molecular typing or genome sequencing will be needed to confirm this, and I know some of this work has been done—I hope the results are published soon. It is extremely important to understand this, because a point source implies that the HCUs may already be contaminated when shipped to hospitals. The units are tested prior to shipping, so they do get filled with water at the factory, and the recent FDA warning letter suggests that the tests used by the company to monitor their disinfection and drying process at the factory are “inadequate”. If an organism like M. chimaera has already colonized the HCU (and formed a biofilm), good luck disinfecting it.

2. When should patients be notified as part of a look-back or case-finding investigation?

There are several hospitals across the U.S. that are working with public health officials (state or CDC) to respond to the identification of one or more M. chimaera infections. Obviously, notifying every patient who has undergone bypass for the past four years is a huge endeavor: resource intensive, generating bad press and patient anxiety. Undoubtedly there are hospitals that have decided not to do patient notification (which is why you’ve not heard about them).

So let me review our thinking on this. One of the first steps of any outbreak or exposure investigation is to do additional case-finding, without which it is impossible to understand the extent of the problem, and impossible to provide either preventive or therapeutic care to the exposed or infected. In some outbreaks, case-finding can be limited to record reviews because the infection essentially always comes to medical attention (e.g. MRSA bacteremia), or because it resolves without treatment if it doesn’t come to medical attention. For the reasons outlined by Mike, there is no way to know how many M. chimaera infections have occurred without doing notification—of both patients and providers. Thus once we learned about a case, we felt the only ethical option was to proceed with an extensive patient notification (in addition to the other case-finding using lab and patient records). If even a single exposed patient is being bounced from one specialist to another with prolonged FUO because nobody has reason to do mycobacterial blood cultures in someone with an intact immune system, we need to identify that person in order to provide therapy.

A counterargument would be that a nationwide notification should be performed, rather than these piecemeal notifications from individual centers that happen to find a case—however, it is not clear to me how that could be done, logistically, and we’ve learned in the past few days that the notifications from CDC and FDA in October of last year were insufficient at increasing awareness of the problem.

3. What should FDA be doing?

Note that I say FDA, not CDC—because CDC has no enforcement function. The agency that needs to step up aggressively to address this problem is FDA. As outlined here, they’ve already informed the manufacturer that they will block the shipment of new units to the U.S. until this problem is addressed. However, depending upon the answer to question 1 above, we are still left with 60-80% of all HCUs in US hospitals at risk for aerosolizing M. chimaera, with no way to know whether current cleaning and disinfection protocols are effective. The approach we’ve taken (to move the units outside the OR) is not feasible for many hospitals due to the requirement that the unit be within 5 meters of the patient. Likewise, it isn’t feasible to ban the existing units, as the supply of other HCUs is not sufficient and you can’t just stop doing heart surgery. The Sax group referenced construction of a containment unit for the HCUs that exhausted through a HEPA filter, but it isn’t known how that might impact the performance of the HCU. Other engineering solutions must be available, something that can be mass-produced and used to modify the existing units so that the exhaust is safe. In the era of 3-D printers and such, someone must be able to figure this out quickly!

$1.2 billion Requested for Antibiotic Resistance!

You don't tug on superman's cape
You don't spit into the wind
You don't pull the mask off the old lone ranger
And you don't mess around with Jim

-Jim Croce

Most days, controlling the spread of antibiotic-resistant bacteria in hospitals feels like fighting with one hand tied behind our backs, or spitting into the wind or...  For example, we have very little control over whether patients are colonized or infected with antibiotic resistant bacteria on admission. It's not like we can move a hospital from the high-prevalence East Coast to the low prevalence Upper Midwest. And once resistant bacteria become endemic in our region/hospitals, we have few reliable evidence-based interventions to prevent patient-to-patient transmission.

So, it's with some trepidation that I began reading the President's proposal to provide extra funds to tackle antibacterial resistance. Would there be any funds for infection prevention? When discussing past initiatives, we've remarked on how little attention is given to infection control programs and research. This time, however, things are looking better.

Here's how the $1.2 billion will be distributed under the current plan:

• $650 million to the NIH and the Biomedical Advanced Research and Development Authority to expand development of antibacterial drugs and diagnostics
• $280 million for CDC-led efforts to curb overprescribing of antibiotics and track outbreaks of drug-resistant infections
• $47 million would go to FDA to evaluate new drugs and monitor livestock antibiotics use
• $77 million to USDA to help develop alternatives to the antibiotics used in farm animals
• $75 million to DoD and $85 million to VHA to focus on reducing antibiotic-resistent infections in health care settings 

This is a well thought-out list and is very close to how I would wish to distribute the resources. I would perhaps request a bit more for CDC to study HAI prevention interventions in addition to stewardship efforts; however, this extra-funding, while long overdue, is on target. I'm also encouraged that the President is asking for increased funds and not reducing other critical research in infectious diseases like HIV, TB and malaria. Let's just hope Congress can approve this request and it's renewed annually. It will be nice to get back to work preventing HAI - this time with two hands and a mask to keep the spit off our faces.

Another kibosh

Increasingly, my work life seems to revolve around C. diff. Yesterday I performed three fecal transplants. All were elderly patients who had been suffering with recurrent C. difficile for many months. Using stool from OpenBiome's stool bank greatly simplified my job and made the entire process much easier for the patients. Since OpenBiome's donors are extensively screened, the patients did not have to identify a donor and bear the unreimbursed costs of donor screening. Family members of all three patients commented on the ease of the process, and were quite happy with not having to identify a donor. The daughter of one patient who been transplanted previously with a directed donor, specifically commented on her preference for using a standard donor. And as always, the patients and family members were incredibly grateful and very happy to think about life without vancomycin. I left clinic feeling as though I had made a real difference by providing these patients a therapy that still is unfortunately relatively rare. One of the patients yesterday had to travel three hours to see me for this very simple, yet highly effective treatment.

Last night, on the way home, one of our infectious diseases fellows called me to discuss fecal transplant for a critically ill patient in the ICU who was failing all the drugs we have available to treat C. difficle. I happily told him that fecal transplant should not be a problem as we have frozen stool now available in the pharmacy.

This morning I spoke by phone with a woman whose mother is hospitalized two hours away after having multiple recurrences of C. difficile regarding coming to Richmond for transplant. And a patient that I transplanted a few weeks ago (the first patient I transplanted with donor stool from OpenBiome) called to tell me how well he was doing.

It seemed as though the whole fecal transplant process was finally working very smoothly. But as I went to bed last night, I took a final look at my phone and saw an email from a colleague with a link to new information from the FDA on fecal transplant. Those of you who follow this blog may recall that the FDA had previously proposed that all fecal transplants would require an IND number; however, this requirement was later relaxed. I was stunned by the FDA's proposed new rule. Since the FDA seems to write in a different language, I will paste their verbiage here:

After publication of the July 2013 Guidance, FDA has continued to review this area and is clarifying its enforcement policy.  FDA intends to exercise this discretion on an interim basis, provided that:

1. The licensed health care provider treating the patient obtains adequate informed consent from the patient or his or her legally authorized representative for the use of FMT products.  The informed consent should include, at a minimum, a statement that the use of FMT products to treat C. difficile is investigational and a discussion of its potential risks.
2. The FMT product is obtained from a donor known to either the patient or the treating licensed health care provider. 
3. The stool donor and stool are qualified by screening and testing performed under the direction of the licensed health care provider for the purpose of providing the FMT product to treat his or her patient.  

FDA does not intend to exercise enforcement discretion for the use of an FMT product when the FMT product is manufactured from the stool of a donor who is not known by either the patient or the licensed health care provider treating the patient, or when the donor and donor stool are not qualified under the direction of the treating licensed health care provider. 

So it seems that the FDA is not happy with the concept of banked stool from standard donors and would prefer directed donors. If I test a donor once for infections and that donor is known to the patient, I don't need an IND. But, if I obtain the stool from a stool bank that has a small number of highly selected donors that are tested serially every 60 days, and the stool is quarantined to avoid the problem of an infected donor in a seronegative window period, I need an IND? The blood bankers actually discourage the use of directed donors as the directed donor may be less likely to disclose risk factors for infectious diseases. There is no reason to think that would be different here.

I called the number on the FDA's announcement. The person I talked to was polite but I felt as if I was talking to someone in a parallel universe. After 10 minutes, I didn't feel like I had any better understanding of the issue. She told me that there were no data that fecal transplant is effective for C. difficile. Really? I reminded her that the randomized controlled trial published in the New England Journal was stopped early because it worked so well. She could not tell me whether I could even get an IND if I was using product from a stool bank, though later implied it could only be used in a clinical trial. She transferred me to "Manufacturing" and felt sure they could help me. The person in Manufacturing was not even aware of the announcement and said that I need to talk to someone in "Vaccines." Between this issue and the IV zanamivir issue, I have come to the conclusion that the FDA is so isolated and so sucked into the parallel universe of its bureaucracy that's it's lost touch with its mission.

While I might not be able to understand what the FDA is saying, here is what I do know: recurrent C. difficile is a terrible illness that is becoming increasingly common. In a subset of patients, antibiotics are not curative. It destroys quality of life, and if untreated in the elderly leads to wasting and ultimately death. A simple treatment is highly effective in curing the infection. And a group of really bright students in Boston found a creative solution to make stool transplants readily available and quite safe for patients. But a behemoth bureaucracy chooses to stand in the way.

There's got to be a better way...

There are reports from across the country regarding severe influenza in young people. In addition to mechanical ventilation, many are requiring ECMO. Given the severity of illness and the presence of multiple organ dysfunction, relying on an oral antiviral for influenza therapy seems unwise. However, at this point, the only option for intravenous therapy is IV zanamivir, which is not approved by the FDA, but available on a compassionate use basis.

I recently had the misfortune of experiencing the compassionate use process. During my last stint on the Infectious Diseases consult service we were crazy busy, and on a Friday morning, with my fellow in clinic and unavailable, and with eight new consults to see, I was asked to see a patient on ECMO for severe influenza. I did a quick Google search to see how I could obtain IV zanamivir and learned that I needed to contact the drug manufacturer, the FDA and my IRB. I soon learned there were numerous forms to complete, almost all of which required me to record the same information over and over. From start to finish it took approximately 4 hours and the best word to describe the situation was kafkaesque. Some of the forms had pages of instructions, and after reading these instructions I still had no idea as to how to complete them. I finally called the FDA and said, "Just tell me which boxes to check." Is there anyone who thinks that physicians have 4 hours to spend filling out forms to get one patient one drug? I made the mistake of including the patient's initials on one form and the drug company called me to say that they would have to destroy the document and I would need to re-do it and re-send. Maybe I'm just a simpleton, but couldn't there be a website where information is entered once and then routed to the appropriate agencies? I'm sure we could leverage the technology to include the patient initials on the FDA's but not the company's forms. Over the ensuing weeks, I have spent several additional hours submitting more documents to the FDA, the drug company and the IRB. All of this makes me wonder how many patients don't receive treatment with potentially lifesaving drugs because the process is so painful, duplicative, time intensive and byzantine.

At dinner a few nights ago, my wife (also a physician) and I were lamenting about how much each of our days is filled with activities that don't add value to the care of patients. Every time I watch "House MD" I am immediately struck by what the physicians in the hospital are doing. They are either interacting with patients or discussing cases with each other. Those activities are the joy of medicine. But it seems that with every passing year, we do less true patient care as we heap on more nonvalue added activities. Unfortunately, twenty-five years into this career, I frequently find myself thinking, I didn't sign up for this!  

Graphic: Drawception.com

A pleasant surprise....

Yesterday, the FDA quietly posted an announcement regarding the requirement for submitting an investigational new drug (IND) application by physicians who perform fecal transplantation. In part, it says:

Some health care providers have stated that applying IND requirements will make FMT unavailable and have suggested that an alternative regulatory approach is needed to ensure the widespread availability of FMT for individuals with C. difficile infection unresponsive to standard therapies. 

The agency acknowledges these concerns and intends to exercise enforcement discretion regarding the IND requirements for the use of FMT to treat C. difficile infection not responding to standard therapies provided the treating physician obtains adequate informed consent from the patient or his or her legally authorized representative for the use of FMT products. Informed consent should include at a minimum, a statement that the use of FMT products to treat C. difficile is investigational and a discussion of its potential risks. 

FDA intends to exercise this discretion while the agency develops appropriate policies for the study and use of FMT products under IND. The agency intends to issue guidance reflecting the agency’s intention to exercise enforcement discretion.

During this time FDA strongly encourages compliance with the IND regulations, and stands ready to work with sponsors who are interested in conducting clinical trials.

I've read this a couple of times, and I'm not sure exactly what this means. Can fecal transplantation now be performed without an IND as long as there is informed consent? It sounds as though further information is forthcoming. Nonetheless, it appears to be a step in the right direction. Kudos to the patients and their families for making their voices heard. Yesterday, one of my patients spoke about her experience here:

NBC12.com - Richmond, VA News

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.

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!

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

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

Were bean sprouts the vehicle for E. coli O104:H4?

Some new developments today in the enormous enterohemorrhagic E. coli (EHEC) outbreak in Germany, an outbreak that has sickened at least 1600, caused over 600 cases of hemolytic uremic syndrome (HUS), and killed 22 so far. Daily updates can be found at the European CDC site, here.

Eli has blogged several times about the FDA Food Safety Modernization Act, which was passed several months ago. That law will do little to protect U.S. consumers from foodborne illness, however, if the FDA is not provided sufficient funding to implement it. Perhaps they should serve a delicious bean sprout salad at the next House Appropriations subcommittee meeting--we'll find out if our representatives are confident enough in U.S. food safety systems to eat it.

FDA Warns: OTC products caught making false MRSA claims

Today, I was off searching the interweb for news at sites not named The New York Times, when I came across this piece in the LA Times. Apparently, the FDA has issued four warning letters to companies making false claims that their products prevent MRSA infection.  These products, which include some 'natural' hand sanitizers, had little data to back up these claims.  The companies/products include:

• Tec Laboratories for Staphaseptic First Aid Antiseptic/Pain Relieving Gel;
• JD Nelson and Associates for Safe4Hours Hand Sanitizing Lotion and Safe4Hours First Aid Antiseptic Skin Protectant;
• Dr. G.H. Tichenor Antiseptic Co. for Dr. Tichenor’s Antiseptic Gel;
• Oh So Clean, Inc dba CleanWell Company for CleanWell All-Natural Foaming Hand Sanitizer, CleanWell All-Natural Hand Sanitizer, CleanWell All-Natural Hand Sanitizing Wipes, and CleanWell All-Natural Antibacterial Foaming Handsoap

My recommendation:  stick with alcohol hand rub or just plain-olde soap-n-water (TM)

Source: FDA News Release 4/20

80% of antibiotics given in US go to animals

Just catching up on things after my long winter nap...  Three weeks ago, FDA reported that 29 millions pounds of antibiotics were used in livestock production in the US.  How does that compare to human use?  A new estimate for human use is 7 million pounds.  Thus, almost 80% of antibiotic use is in food production.  One caveat, it appears this estimate was derived from IMS sales data for selected antibacterial drugs and I'm not sure how accurate those figures are. Early estimates were closer to 70%.

With all of the antibiotic stewardship efforts both in hospital and through education of primary care physicians and patients, you wonder how effective these efforts could possibly be?  If by magic, we could reduce antibiotic exposure in human populations by 50% that would still leave 90% of the actual antibiotic exposure burden untouched.  The funny thing is, bacteria don't care if the antibiotic they are exposed to was ingested by a human or an animal...

link: Maryn McKenna Superbug Blog

Deadly Medicine

The January issue of Vanity Fair has a very interesting investigative piece entitled Deadly Medicine (free full text here) by Donald Bartlett and James Steele, which explores the globalization of the pharmaceutical industry and the effect that has had on the drug approval process. The majority of data used in the new drug approval process now comes from other countries where regulatory oversight is scant. Moreover, they describe co-opting of the FDA by industry. In some countries, doctors enrolling patients in clinical trials can earn 25-fold more money from enrolling one patient than from their monthly salary. This creates huge conflicts of interest. And then there is the exploitation of patients who may not even understand the trial they have been enrolled in and the risks they are bearing. It's a sobering and scary piece, but well worth reading.

Listeria: Safety-based date labels, cheese and the FDA

As I've written before, I spent several years on the USDA's National Advisory Committee on Microbiological Criteria For Foods (NACMCF).  We spent several years writing scientific briefs on a variety of topics. During 2002-2004, I worked on a subcommittee looking at "Criteria for Refrigerated Shelf-life Based on Safety."  For someone who didn't spend 100% of my time on food-safety issues, I was initially surprised that the dates on foods were not at all related to safety.  Dates on that yogurt you are about to eat are based on palatability, FYI.

The document we produced and then published in 2005 in the Journal of Food Protection was predominately a Listeria control document even though we considered four psychrotrophic pathogens: L. monocytogenes, nonproteolytic C. botulinum, Y. enterocolitica, and B. cereus. The hope was that a safety-date on refrigerated foods, when combined with education about proper storage and handling of these foods, could reduce the health risk in the very young, very old, immunocompromised and pregnant women, who are at increased risk for miscarriages and stillbirths after Listeria infection.  Of course, any safety-based date label would have little impact if the food is highly contaminated during production. 

One thing I noticed serving on NACMCF was the hard work and honest efforts of the others on the committee. Even though some members worked for industry, some worked for the government and some had worked for both, they all tried hard to produce a good document. There was no evidence of some conspiracy to harm the public.  Outbreaks of foodborne illness are bad for everybody. Producers looked to government to set standards and then helped determine the best ways to meet those standards.

With that background, I was shocked to read recently in the NY Times about an artisanal cheese producer from Washington state who was defying a recall order from the FDA. Her cheeses were found to be contaminated with Listeria.  She and others are claiming that the FDA is going after the little producers - a David vs Goliath story.  Senators and others are rallying to modify the food safety bill in the Senate that I blogged about last week, in an effort to exempt these types of small producers.  They suggest that the real risk is in the big producers since they make the most foods, but I think they are making a very poor decision.  If you had the choice to buy cheese that was subject to regulation and unlikely to be contaminated or some cheese that wasn't tested for safety, which would you buy?  I agree with William Marler, a Seattle food safety lawyer, who said he just doesn't "know how they make the leap from the government trying to do the right thing for public health to ‘they’re food Nazis in the pocket of big agribusiness.’ ”

What if we had that situation in HAI prevention? What if big hospitals had to publicly report CLABSIs and follow Joint Commission standards and small hospitals got a free pass? Wouldn't that be the quickest path for bankruptcy for small hospitals? It would be hard to imagine small hospitals claiming that they only take care of a few patients so a few excess deaths don't matter, but that is exactly what the small food producers are claiming in the NY Times article.

Falsum in uno, falsum in omnibus
It seems that we currently live under a logical fallacy, where the government is evil and people claim that the government is bad at everything. Sure, government has its faults and could improve its efficiency, but when we get to a point where we are saying that small food producers shouldn't have to be regulated and thus produce safe food, we have gone too far. I would love to support local producers and serve fresh produce in my home, but I won't do it if they get a free pass on safety.  I hope they can work out a compromise where the FDA and small producers can work together.

NY Times article: Small Cheesemaker Defies F.D.A. Over Recall - November 19, 2010

Food Safety Modernization Act

Senator Durbin (D IL)

Not hospital infection prevention, but still infection prevention.  I won't go into too much detail, but the Senate may "pass" the FSMA - S. 510 tonight - this would change how the FDA regulates what it regulates, which is to say, not all foods.  You can read Michael Pollen's take on the bill here.  From what I gather, this won't impact USDA, CDC, and NOAA's NMFS etc.  Will be interesting to see what happens and also how the 'spinmeisters' treat this.  There has been surprisingly little mentioned about this given how important food safety is.

FDA releases a "Dear ICP" letter for positive displacement needleless connectors

Similar to a "Dear Doctor" letter, the FDA just sent out a "Letter to Infection Control Practitioners Regarding Positive Displacement Needleless Connectors" and addressed it to "Dear Infection Control Professional." My first thought was that there are no more ICPs, so someone should alert the FDA.

On a serious note, the FDA is requiring nine companies to conduct postmarketing surveillance of positive displacement needleless connectors as they have been associated with higher CLABSI rates. However, while the FDA is not recommending changing the use of these devices, they refer people to the SHEA/IDSA HAI Prevention Compendium. Since the Compendium states to "not routinely use positive‐pressure needleless connectors with mechanical valves before a thorough assessment of risks, benefits, and education regarding proper use," it appears that FDA has taken a risk-averse stance. The studies, which are expected to take up to 3 years, have to answer the following two questions:

1) What is the rate of bloodstream infections for subjects receiving your positive displacement connector for central line access and is it statistically non-inferior to the rates seen in subjects receiving other needleless connectors (e.g. negative, neutral, or split-septum connectors) for central line access, given comparable patient populations?

2) Are there patient demographics, comorbidities/severity of illness, or device cleaning practices for which placement of your positive displacement connector for central line access increases subjects’ risk of bloodstream infections compared with other needleless connectors?

Full FDA letter is here.
SHEA/IDSA HAI Prevention Compendium
Image from Edgar K. Infect Control Hosp Epidemiol, April 2009