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!