Saturday, February 6, 2016

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!

Tuesday, February 2, 2016

M. chimaera infections associated with cardiopulmonary bypass

Dan and I have spent numerous hours recently on a particularly difficult infection prevention issue. We recently learned that a patient who underwent cardiothoracic surgery at our hospital developed an infection due to Mycobacterium chimaera. Last year, it was recognized that this organism is associated with heater-cooler devices used in cardiac surgery, and CDC and FDA put out alerts to hospitals in October 2015 regarding appropriate disinfection of these devices.

A paper in Clinical Infectious Diseases last year described an outbreak of these infections in Switzerland. The outbreak investigators determined that the water used in the heater-coolers became contaminated by M. chimaera. This water never comes into physical contact with the patient, but the investigators found that a fan on the heater-cooler unit aerosolized the organism into the air leading to direct contamination of the surgical wound. When the heater-cooler devices were present in the operating room but not turned on, the organism was not aerosolized.

Most of the reported cases have manifested as prosthetic valve endocarditis or vascular graft infections, and there may be involvement of the bone marrow causing cytopenias, as well as splenomegaly. The patients were not immunosuppressed. Often these patients presented with nonlocalizing symptoms, such as fever, mylagias, arthralgias, fatigue and weight loss. The mortality rate is approximately 50%.

Several issues make case finding problematic:
  • The time to diagnosis can be up to four years, as the incubation period for the infection due to this slow-growing mycobacterium is long, and diagnosis is often delayed since the organism isn’t detected in routine cultures.
  • Symptoms of the infection are often nonlocalizing.
  • We rarely order mycobacterial blood cultures in nonimmunosuppressed patients, and these cultures are key to making the diagnosis since most of the patients have infections of endovascular grafts or prosthetic cardiac valves.
  • Given that Iowa is primarily rural, many patients receive their post-operative care by local providers, making it more difficult to identify cases. 
For the reasons above, on the basis of a single case, we have embarked on a four-year look-back of 1,500 patients who underwent procedures utilizing cardiopulmonary bypass at our hospital. These patients are being instructed to call a toll-free number to be screened for symptoms that may be related, and then to undergo further evaluation if needed.

If your hospital performs procedures requiring cardiopulmonary bypass, the most important control measure to prevent infection is to move the heater-cooler devices out of the operating room. Our engineers were able to develop a solution and accomplish this within 24 hours. In addition, ensure that the devices are being disinfected according to manufacturers’ guidelines.

M. chimaera is one of 8 species in the M. avium complex, and was recognized as a a distinct species in 2004. Given the ubiquitous nature of nontuberculous mycobacteria, we suspect that the cases linked to heater-cooler devices reported to date represent only the tip of the iceberg, and it is likely that more hospitals will be facing extensive look-back investigations.

Friday, January 29, 2016

Retractions - One now, perhaps more in the future

We've written before about article retractions and why high-profile journals like NEJM might have the highest retraction indices (figure). Yet, retractions in infection prevention are very infrequent. In fact, the one major retraction we mentioned during 7 years of blogging was not strictly a retraction, but a re-analysis of N-95 vs surgical masks.

Which brings us to a rare retraction in infection prevention, namely this 2014 AJIC study looking at zero fluid displacement intravenous needless connector and CLABSI prevention. As reported this week in Retraction Watch, the study was initially questioned because of a failure to report conflicts of interest but has now been fully retracted by AJIC since an investigation found problems with the "consistency of the statistics over various study periods as well as the methods by which study sites were chosen." Fortunately, since this study was published less than 2-years ago and only cited once, this retractions won't be particularly damaging to the field.

However, with the recent announcement that NIH is providing an additional $100 million for antimicrobial resistance (AMR) along with increases in CDC and industry funding, there are now resources to fund high-impact studies that will appear in high-impact journals. And as if those pressures are not enough, the US Government has been tasked to reduce C. difficile infection by 50%, CRE by 60% and MRSA by 50% by 2020 compared to 2011. With the unprecedented increase in funding combined with difficult to achieve targets, there will be unbelievable pressure to cut corners in study design and analysis and over-promise or over-promote results. This all represents a potential recipe for disaster if our field isn't careful. On the bright side, societies like SHEA have very strict conflict of interest reporting, so we have some checks in place to identify conflicts and bias. Of course, this won't be enough. Be careful out there.

Thursday, January 21, 2016

Measurement fatigue: The backlash



Anyone who’s been in the hospital infection prevention business for any length of time is familiar with a specific form of cognitive dissonance. We believe, on the one hand, that the publicly-reported, metric-focused, pay-for-performance (PFP) environment has brought increased resources to infection prevention and resulted in a real decrease in healthcare-associated infections (HAIs); yet we believe, on the other hand, that these high stakes have led to a number of unintended adverse consequences, including gaming of HAI definitions, an unhealthy focus on measures that may not merit the resources and attention, and have engendered cynicism as it becomes apparent that PFP measures may not correlate with actual quality or value.

Over the past week, I’ve read three pieces that make me wonder if we’re reaching a tipping point, as clinicians begin to push back effectively against the proliferation of “measures”, “metrics”, “performance targets” (whatever you wish to call them), in an attempt to seek a balance between them and the words of Francis Peabody, that “the secret of the care of the patient is in caring for the patient.” I’ve pasted some key quotes below from each of these pieces.

First, an excellent opinion piece from Dr. Robert Wachter in the New York Times:
"All of this began innocently enough. But the measurement fad has spun out of control. There are so many different hospital ratings that more than 1,600 medical centers can now lay claim to being included on a “top 100,” “honor roll,” grade “A” or “best” hospitals list. Burnout rates for doctors top 50 percent, far higher than other professions. A 2013 study found that the electronic health record was a dominant culprit. Another 2013 study found that emergency room doctors clicked a mouse 4,000 times during a 10-hour shift. The computer systems have become the dark force behind quality measures….
....Our businesslike efforts to measure and improve quality are now blocking the altruism, indeed the love, that motivates people to enter the helping professions. While we’re figuring out how to get better, we need to tread more lightly in assessing the work of the professionals who practice in our most human and sacred fields."
"To work in a hospital today is to be constantly preoccupied with money, and one of the more grating features as far as the Sacred Heart hospitalists are concerned has been the administration’s celebration of “skin in the game.” That means creating financial incentives for doctors to hit performance targets — like lowering patient’s length of stay and doing well on patient satisfaction surveys. The phrase entered the Sacred Heart lexicon in 2014, but the underlying concept has spread throughout the profession in recent years…. 
…the increasing focus on metrics like readmission rates and hospital-acquired infections had created more work for hospitalists, who are responsible for a lot of documentation."
"Instead of gaining happiness minutes, clinicians are increasingly experiencing dissatisfaction and burnout as they’re subjected to the time pressures of Taylorism and scientific management in the name of efficiency. We have watched colleagues fleeing to concierge practices, where they have control over their schedules. Others have taken early retirement, unwilling to compromise on what they believe is the time needed to deliver compassionate care. Some have moved into management or consulting positions, where they tell others how to practice while unburdening themselves of their clinical load. Just as Taylor enriched himself by consulting for companies, a growing and lucrative industry has emerged to generate and enforce metrics in medicine. By 2014, the Centers for Medicare and Medicaid Services alone had mandated the use of more than 1000 performance measures. As the Institute of Medicine recently reported, such metrics have proliferated, though many of them have little proven value."
(This last piece probably should have given a shout-out to a piece by Mike that started by similarly invoking Frederick Winslow Taylor.)

Tuesday, January 19, 2016

SHEA Abstract Deadline - January 29, 2016

Good morning!


I'm sure that you all have plenty of time on your hands with Ebola and contact precautions all but eliminated! Nice that most of us infection prevention and control types finally have some valuable time on our hands to do science!

SHEA now accepts abstracts with original data and last year over 200 abstracts were presented in Orlando. (I think it was closer to 250, but I've lost my notes) Anyway, get into your data and start writing - you only have until January 29th!

See you in Atlanta in May!

Sunday, January 17, 2016

Rethinking contact precautions


I'm working on a talk entitled "Rethinking Contact Precautions" for the Winter Course in Infectious Diseases. If you've never been to the Winter Course, it's a great conference in a casual setting with state-of-the-art lectures on a wide variety of ID topics. And there's lots of skiing. This year, we'll be at Big Sky, Montana, February 14-18.

This weekend, I ran across a brand new paper in Infection Control and Hospital Epidemiology on discontinuing contact precautions. This one comes from Roswell Park Cancer Center where active surveillance (weekly perianal cultures) for VRE was discontinued in March 2011. At the same time contact precautions for VRE infection and colonization were also discontinued. The investigators compared VRE bacteremia rates for the 3-year period before and the 3-year period after discontinuing active surveillance and contact precautions. The 6-year period of the study included over 1,300 patients with hematologic malignancies, bone marrow transplant and lymphoma. Over the study period there were no changes in antibiotic utilization, nurse-to-patient ratio, age, gender, underlying malignancies or length of stay. Importantly, via interrupted time series analysis, there was no significant change in the rate of VRE bacteremia (2.32 infections/1,000 patient days before vs. 1.87 after). This is the third published study (see the others here and here) and there are two more studies in abstract form all showing no change in infection rates after contact precautions were discontinued.

I also re-read Kathy Kirkland's thoughtful paper, Taking Off the Gloves: Toward a Less Dogmatic Approach to the Use of Contact Isolation (free full text here). Kathy was way ahead of the curve with her thinking on this topic. Below is a table from her paper that summarizes the likelihood of benefit for contact precautions:























As I thought more about where we are in infection prevention in 2016, it seems to me that contact precautions is a decrepit concept. When introduced 50 years ago, contact precautions made sense. At that time hand hygiene rates were abysmal, alcohol-based handrubs were not available, patients weren't bathed with chlorhexidine, there were few single-bed hospital rooms, and there was no enhanced technology for environmental disinfection.

Putting it all together, there's little evidence that contact precautions are effective in the non-outbreak setting, and we're learning that nothing bad happens when contact precautions are stopped. At the University of Iowa, we're focusing on hand hygiene, stethoscope wipe down and bare below the elbows. And the list of hospitals forgoing the plague doctor suit for MRSA and VRE grows ever longer.

Tuesday, January 12, 2016

Humans vs bugs

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