M. chimaera update

Big Sky, Montana

Dan and I are at the Infectious Diseases Winter Course in Big Sky, Montana. I'm writing this blog post sitting by the fire while he's out hitting the slopes. This morning, Dan gave a talk on the M. chimaera outbreak associated with heater cooler units in an effort to raise awareness among ID clinicians.

While we continue to work on case finding at the University of Iowa, we continue to receive calls from physicians across the country asking for advice. One of the major problems is the paucity of data to guide recommendations for the best approach to outbreak investigation.

We need CDC and FDA to expedite the needed work to answer many questions. At this point, there is no published descriptive epidemiology of the cases in the United States. There's still no information on molecular typing of the patient and environmental isolates to sort out whether this a point source outbreak with contamination occurring during the manufacturing process of the heater cooler devices. Every hospital working on this issue is struggling alone in the dark, while it's becoming increasingly clear that this is an expanding outbreak.

Today we learned that a class action lawsuit has been filed against Sorin, the manufacturer of the implicated devices.

We'll post more on this topic as it unfolds.

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.

Links to key references are below:

• Swiss outbreak investigation (Clinical Infectious Diseases)
• Review article on M. chimaera infections following cardiac surgery (European Heart Journal)
• CDC Guidance
• FDA Alert
• Pennsylvania Department of Health Advisory
• Pennsylvania Outbreak (New York Times)

E is for...Enterovirus 68

Never a dull moment. Just as facilities have begun wrapping up their Ebola preparation plans, there's gathering evidence that several US states may be facing large clusters of acute respiratory illness associated with human enterovirus 68 (EV68).

Last week the Missouri Department of Health released an Alert describing increased cases in St. Louis and an outbreak of over 300 acute respiratory illnesses in a Kansas City pediatric hospital with 15% requiring ICU care. 19 of 22 specimens sent to the CDC from the Kansas City outbreak were positive for EV68. Many St. Louis cases were positive for enterovirus but specific typing is pending. Denver is seeing severe respiratory illness in very young children and children with asthma. Children's Hospital Colorado has treated 900 children and admitted 86 since August 18th, but so far the specific viral pathogen has not been confirmed. CDC reports similar cases have appeared in at least 10 states -- Missouri, Kansas, Illinois, Kentucky, Iowa, Colorado, Ohio, Oklahoma, North Carolina, and Georgia.

There are a few publications over the last 5 years describing EV68 associated outbreaks including an MMWR covering 2008-2010 clusters and individual reports from the EV68 emergence in the Netherlands, and an Indian Health Services (IHS) outbreak in children (both were already covered in MMWR). The Netherlands has seen the majority of cases in September to November (Figure above) with the highest prevalence in patients ages 50-59, while the IHS outbreak occurred in August-September in children with a median age of 4.8 years.

Clinical Findings: Signs and symptoms include cough, tachypnea, hypoxemia, and wheezing, particularly new-onset. In the Arizona IHS outbreak, at least half of the children had infiltrates on CXR and short hospital stays (median 1.5 days). The clinical presentations of the 18 IHS patients are listed in the table below.

Diagnosis: There are commercially available, FDA-approved, multi-pathogen detection systems including Luminex xTAG RVP, Idaho Technologies FilmArray Respiratory Panel. However, these non-specifically identify pathogens as "entero-rhinovirus" or "human rhinovirus/enterovirus." Most facilities can't currently perform enterovirus typing. Identification of EV68 requires partial sequencing of the structural protein genes, VP4-VP2 or VP1.

Treatment: There is no specific treatment for EV68. Care is usually supportive and only a minority of patients require brief hospitalization. Currently, there are no vaccines available.

Infection Prevention: The CDC currently (2007) recommends Standard Precautions for enteroviral infections but recommends "Contact Precautions for diapered or incontinent children for duration of illness and to control institutional outbreaks." However, most of the data that informed these recommendations were not derived from respiratory EV68 outbreaks. Recommendations from Hong Kong are very similar. 

I contacted a hospital epidemiologist in one of the states experiencing an outbreak, who has graciously shared their current protocol. Currently, they use symptoms to drive precautions so their respiratory patients are placed on droplet plus contact isolation for the duration of their hospitalization. In addition, they started their usual winter respiratory visitation restrictions last week so that children under 13 yo cannot visit and increased their focus on year-round routine screening of all visitors/family members for illness. Finally, they noted that this was the earliest they've ever started respiratory visitation restrictions.

Montgomery County is now in the loop!

The next time a contagion sweeps through the NIH Clinical Center, Montgomery County officials will be on it, thanks to a new agreement between NIH, Maryland and Montgomery County. The back-story is that Montgomery County officials were unhappy that they weren’t informed promptly about the deadly KPC outbreak at NIH.

This raises the question of when a hospital should communicate with public health officials (and the public generally) about fairly common SNAFUs. At any given time, 5-10% of hospitals are dealing with clusters or outbreaks of multiple-drug resistant gram negative bacteria (KPCs, ESBLs, MDR-Acinetobacter, etc.), and even more are in the midst of MRSA, VRE, fungal or other outbreaks. The population at risk during these outbreaks is pretty clearly defined, and doesn’t include the general public. General notification can generate media frenzy, free-floating panic and anxiety, and waste precious time and resources for the personnel trying to contain the outbreak (responding to media, doing damage control of various types, etc.). Furthermore, most states don’t include common healthcare associated bacterial pathogens among their legally reportable diseases.

However, as state and local public health officials become increasingly involved in HAI issues, it would be wise to establish explicit criteria for when healthcare facilities should report clusters and outbreaks. Provided they have sufficient funding (which they currently do not!), public health departments should play a critical role in coordinating responses to HAI outbreaks, which often involve multiple healthcare facilities in a region (across the spectrum of acute, long-term, and long-term acute care).

So when do you think a hospital should notify their state and/or local public health department? Two cases of MRSA infection in the NICU? A single serious post-operative Group A strep infection? New introduction of a carbapenemase into the ICU?

Oh, and Happy Thanksgiving!

Riding the epidemic curve to glory, WGS edition

One reassuring lesson all healthcare epidemiologists learn is that every outbreak will, eventually, come to an end. The trick is to prevent outbreaks in the first place, or to recognize them early enough to intervene effectively. Many outbreaks, though, are recognized as they peak and are entering the “downhill” part of the epidemic curve. Any interventions prescribed by erstwhile epidemiologists are then, in retrospect, credited with helping to contain the outbreak (even if said interventions were completely idiotic). This phenomenon was described by Dr. Alexander Langmuir, the father of the CDC’s Epidemic Intelligence Service, as “riding to glory on the downhill slope of the epidemic curve”.

Now we can add the performance of whole-genome sequencing (WGS) to the list of activities that epidemiologists can “ride to glory” as the key to outbreak control. As WGS becomes faster and more affordable, reports have been published in NEJM, Science Translational Medicine and Lancet Infectious Diseases suggesting that WGS can be the key to real-time or “actionable” information to help contain outbreaks (due to MRSA, KPC-producing K. pneumoniae, and MRSA, respectively). As we’ve pointed out previously, though, it isn’t at all clear that WGS was important to real-time outbreak management, or that WGS is ready for prime-time and coming soon to a hospital near you.

Why? For any technology to see widespread adoption in clinical diagnostic laboratories, there must be sufficient automation (including of the analysis and interpretation of the massive amounts of WGS data), and it must provide a substantial advantage over existing testing approaches.

Which brings us to the more important question: given our crude approaches to outbreak control, how does WGS provide any immediate advantage over other same-day typing methods? Does the added discrimination really make a difference in whether we decide to isolate or cohort patient X, decolonize healthcare worker Y, or close unit Z to new admissions? These questions are particularly pertinent when we don’t yet understand the “within host” variation in genotype and how “within” versus “between” host variation can be applied to determine direction of transmission (or even the fact of transmission). Eli recently sent me a link to this interesting discussion of the Lancet ID report, which addresses some of these issues. 

The bottom line is that we have a relatively few crude tools for outbreak response: enhanced basic practices (e.g. hand hygiene, environmental disinfection), active surveillance, isolation, cohorting (of patients and/or HCWs), decolonization of carriers (both HCWs and patients), removal (temporarily or permanently) of HCWs implicated in transmission, closure of units, mitigation of any identified common sources, etc. The level of discrimination provided by WGS is a great research tool, and will undoubtedly help in retrospectively piecing together the most likely outbreak scenarios--but for now I’m not convinced it has much advantage over other typing methods for guiding real-time outbreak investigation and management.

New twist in the outbreak due to contaminated pharmaceuticals

The New York Times is reporting today that another manifestation of the outbreak of fungal central nervous system infections has appeared. Some patients are developing epidural abscesses at the site of the steroid injection. Particularly worrisome is that some of these abscesses have developed while patients are on antifungal therapy.

Meanwhile, the epidemic continues to expand. The CDC is now reporting 395 cases of central nervous system infection, 9 cases of septic arthritis, and 29 deaths across 19 states. In addition, betamethasone and cardioplegia solution from the implicated compounding pharmacy have also grown multiple species of Bacillus in culture.

Lastly, on the weekend before election day, it's hard not to think about politics. And this outbreak highlights the tensions between business and regulatory oversight, a common theme in our political landscape today. This article published in Salon takes a look at that issue with regards to this outbreak.

Whole genome sequencing and infection prevention

While attending a HICPAC meeting this week, I had a chance to chat with David Henderson about the use of whole genome sequencing (WGS) to help investigate an Acinetobacter outbreak at the NIH Clinical Center. I’m sure you’ll hear more about this at IDWeek (yet another reason to attend!). In the meantime you can check out the report in this week’s NEJM describing use of rapid WGS to investigate a NICU MRSA outbreak. My Journal Watch summary is here, if you want an abbreviated version. I’m a little surprised the paper made it into the NEJM, as it isn’t clear how the WGS contributed much to control of this particular outbreak. The work is most useful as an example of how WGS is now rapid and inexpensive enough to contribute to patient care and infection prevention work in real time (rather than only in retrospect, or as a research tool).

However, there are a couple reasons that you won’t see WGS coming to many labs in the near future. First, analysis and interpretation of the enormous amount of resulting data (the entire bacterial genome sequence) is not simple, requiring substantial local expertise. Second, we have a very incomplete understanding of which genetic differences and mutations are clinically important. Until we expand our knowledge base and bring some automation to the analysis and interpretation, bacterial WGS to inform outbreak and transmission investigations will remain limited to a few large centers that have in-house capacity.

Friday afternoon blogging from Deltaville

Greetings from Deltaville, Virginia.  I had hoped to be north of here by now, but apparently boat engines are fickle.  We hope to be off tomorrow, though, and after that my infrequent blogging will become even less frequent, at least until we reach Boston.  I enjoyed seeing fellow blogger Mike Edmond, and look forward to dinner this evening with the Wenzels.

Speaking of Friday afternoons, you know the old saw that hospital outbreaks are always reported or detected on Friday afternoons? Well, according to this study in AJIC, there might be some truth to it!  Here's hoping that your Friday afternoon isn't rudely interrupted with an outbreak, but beware: Monday's are no better.

Can Influenza Outbreaks Be Controlled? Call for Papers

Influenza Research and Treatment is a peer-reviewed, open access journal that has an up-coming special issue on influenza outbreak control. The lead editor is Lewis Radonovich from Gainesville. Submit early and often. After all, Illinois is voting today.

They are looking for manuscripts exploring methods for controlling influenza outbreaks at the population level including TIV or LAIV vaccines, emerging vaccines and new technologies, barriers to or evaluation of vaccine effectiveness, school-located influenza vaccine programs (SLIV), prophylactic pharmaceutical interventions and treatment regimens and non-pharmaceutical interventions.

Important Dates:
Manuscript Due: Friday, 15 June 2012
First Round of Reviews: Friday, 7 September 2012
Publication Date: Friday, 2 November 2012

Source: Influenza Research and Treatment Call for Papers

Set your TIVO: Animal Planet's Killer Outbreaks

A new Animal Planet series called "Killer Outbreaks" starts April 15th.  The 6-episode series features CDC experts and covers Anthrax, E. coli, Hantavirus, Rabies, West Nile, Monkey Pox, Acinetobacter baumannii, Salmonella, Valley Fever, Meningococcal Disease, SARS and MRSA.  It airs each Friday at 10pm ET and 10pm PT. Doesn't get more exciting than that!


CDC Press Release 4/12/2011

MMWR - Field notes from the Minnesota measles outbreak

Dan posted last week on the ongoing measles outbreak in Minnesota and he provided many links to useful resources.  Today the MMWR published a "Notes from the Field" that summarizes the 13 epidemiologically linked cases that have been identified as of April 1.  Five children were too young to receive the MMR. 

Measles in Minnesota

So there is another measles outbreak, this time in Minnesota. Unlike recent experience with mumps, in which outbreaks are associated with vaccine failure (over 60% of cases occurring among recipients of two mumps vaccines), measles outbreaks occur primarily among the unvaccinated, and are sustained by those who reject or avoid the MMR (see prior posts here and here). Of the 13 confirmed Minnesota cases, 5 were too young to be vaccinated, 6 should have been vaccinated but were not, and 2 so far are of unknown vaccine status. Regular updates can be found on the Minnesota Department of Health website. There’s also an interesting article in the Star-Tribune about resistance in the local Somali community to receipt of MMR, out of fears of….you guessed it, autism.

We’ve covered this ground before—go here for our prior posts on the anti-vaccine movement. We recently had some local news coverage of a pediatrician who was declining patients if the parents refused vaccinations. I believe this is a perfectly reasonable position for a pediatrician to take. In fact, if a pediatrician does accept anti-vaccine families, he or she has a duty to warn all the other patients in the practice of the increased risk to infants or immunocompromised children from being in that office waiting room.

LRSA Outbreak II: The sequel

Another linezolid-resistant Staphylococcus aureus (LRSA) outbreak is described in this week’s JAMA. Eli posted a few months ago about the other outbreak, also in Spain, reported in Clinical Infectious Diseases (CID). The similarities between the two outbreaks are stunning, so please just check out Eli’s post for the most important take-home points about cfr-mediated linezolid resistance in staphylococci.

Hey, wait a minute....I think I know why these outbreaks seem so similar. The two papers report on the same outbreak. You wouldn’t know that right off the bat, because neither paper references the other. {see addendum below}

While I applaud the authors for adhering to the least publishable unit (LPU) concept that I hold so dear, I must reluctantly conclude that this is inappropriate. It was an ICU outbreak that involved 12 infections, and the authors should have been able to describe it in one paper. Before I detected the dual publication, I kept looking through the results and figures in the JAMA paper for more detail on some of the microbiology. The reason I didn’t find it was because it was all in the CID paper….

What additional information can we glean from the JAMA paper? In no particular order, we learn that this hospital had an aggressive MRSA active surveillance and decolonization program (but it’s still rife with MRSA and suffered the first big ICU outbreak of LRSA, which definitely proves something about active surveillance, I’m just not sure what); we learn that they did a whole bunch of environmental and hand cultures, only one of which was positive for LRSA (a single environmental culture, but wait, that was also reported in CID); we learn that they recognized the outbreak, did a bunch of stuff we always do when outbreaks occur, the outbreak went away, and no one is quite sure what all happened. Standard issue hospital infection prevention, in other words.

ADDENDUM: On first read I missed the fact that the authors actually did reference the earlier CID report in the JAMA paper--my apologies. I stand by my comment that the outbreak could and should have been reported in full in one manuscript, but at least the careful reader (which clearly doesn't describe me!) should be able to find his/her way to the additional details (mostly micro related) in the CID piece.

Eli's post
JAMA paper
CID paper

What will they think of next?

There's a new iPhone app, Outbreaks Near Me, that allows the user to view maps of occurrences of infectious diseases based on media reports. Users can search by disease or geographic location. This must be a nightmare for germophobes.

Zombie control

In this blog, we focus on controversial prevention issues. About some issues, however, there is no debate. For example, how to control zombie outbreaks. Quick, decisive action is essential. As these authors rightly conclude from their novel mathematical model:

"An outbreak of zombies infecting humans is likely to be disastrous, unless extremely aggressive tactics are employed against the undead."

Now if we only had a rapid screening test…..