Mike the Mad Biologist

In the midst of the concern about TEH SWINEY FLOO!, very few people (other than the Mad Biologist), have been discussing the double whammy of influenza followed by bacterial infections. A couple of years ago, I first started describing reports of KPCs:

No, KPC isn’t a new fast food restaurant. It’s short for Klebsiella pneumoniae carbapenemase. The bad news: it’s very hard to treat. The good news: it’s very rare…for now.

Actually, the correct term is KPC-possessing K. pneumoniae [these genes are now showing up in other bacteria], but we’ll just use the slang ‘KPC’–it’s what all the cool microbiologists use (I’ll refer to the carbapenemase gene as the ‘KPC gene’). KPC causes pneumonia, urinary tract infections, and sepsis; the mortality rate from these infections is extremely high.

The KPC gene confers resistance to all cephalosporins and ß-lactam antibiotics: basically, anything named “-cillin”, “-penem”, or “cef-” won’t kill it. Aztreonam doesn’t kill it either. And, of course, it happens to have evolved resistance to most of the other classes of antibiotics, so, like some Acinetobacter, it is only treatable with colistin and tigecycline, which works…except when resistance evolves in the patient, which has been observed multiple times (this is alarming given the relatively few times this therapy has been used).

The KPC gene is found on a highly transmissible plasmid, which means it can be transferred within Klebsiella and can also spread to other Gram-negative bacteria (E. coli, Enterobacter, and others). The good news is that the plasmid is unstable: it doesn’t always manage to wind up in both daughter cells after cell division.

And given that these strains are pan-resistant–not only does the KPC gene provide resistant to all of the derivatives of penicillin, but these strains, and the KPC plasmid, are loaded with other resistance genes–I advocated that this be treated as a serious health threat:

Now is the time to enact national mandatory quarantine and reporting requirements. If KPC becomes prevalent to even a fraction of the extent that MRSA is, we are really in trouble, since MRSA can almost always be treated successfully with vancomycin. KPC is a lot more difficult to treat.

We have a chance to get out in front of a potential public health problem rather than reacting to it once it has already become a severe problem. This one is really scary–if it gets out of control, it will be a lot worse than Acinetobacter ever could be.

Today, in The Wall Street Journal, an op-ed also argues that we need to get out in front of KPC:

Compare this response [to influenza] to the scant media and political attention that have been given to several silent but no less deadly outbreaks of disease in recent years caused by antibiotic-resistant bacteria. Most such outbreaks are treated as the poor stepsisters of pandemic influenza, even while they have killed far more people than swine flu over the same period….

In contrast to the flu, most of these infections receive little or no public attention. The only exception has been methicillin-resistant Staphylococcus aureus (MRSA). This microbe is now receiving significant public attention–but this attention has come some three decades after its spread in the U.S. first began. That delay allowed MRSA to spread uncontrollably, and more than 18,000 people are now estimated to die each year in the U.S. from this bug, according to the Journal of the American Medical Association.

Initially, MRSA was confined to hospital wards and affected primarily the elderly and chronically ill. It therefore remained outside of the headlines and off political agendas. MRSA entered the spotlight only after it began to affect healthy people living outside of hospitals.

But we haven’t learned our lesson:

In the four-month period since it entered the U.S., swine flu has killed 436 people in this country. During this same period, more than 100 people are estimated to have succumbed to carbapenem-resistant Enterobacteriaceae in the New York City area alone, and more have undoubtedly died outside of New York.

Yet the spread of these and other resistant bacteria has met with almost no coordinated effort to fight them in the U.S. Very few resources have been allocated to combat antimicrobial resistance. Last fiscal year, for example, the U.S. government budgeted just $16.9 million for the Centers for Disease Control and Prevention to spend fighting antibiotic resistance, about 1% of the total funding requested for swine flu.

As the authors note, there have been successful prevention–not containment, but prevention–campaigns in Israel and the UK. Yet, outside of New York City, we do nothing. There’s one other point the article doesn’t make: K. pneumoniae cause lung infections.

Why does this matter? Because in 1918, many of the deaths were not directly due to the influenza virus. Instead, they were caused by ‘secondary’ bacterial infections that ordinarily wouldn’t have killed people:

Their findings are striking in the context of modern conceptions of the 1918 pandemic; the great majority of deaths could be attributed to secondary bacterial pneumonia caused by common respiratory pathogens, particularly pneumococci, group A streptococci, and staphylococci, and not to the virus itself. In fact, although evidence of severe viral bronchiolitis was found, often the primary viral insult appeared to be resolving at the time of the secondary infection responsible for the fatality. Their conclusions are strengthened by the remarkable consistency in theme, if not details, displayed across the many studies reviewed and the inclusion in their review of not only gross pathologic findings but blood and lung tissue culture data. In only 4% of the more than 8000 cases reviewed was no bacterial superinfection documented.

The article also reports that K. pneumoniae was implicated in the deaths of these patients (although it was less frequent than the Gram-positives), along with other Gram-negatives, such as E. coli. And if we can’t treat these patients due to antibiotic resistance, the number of deaths which are kicked started by influenza, but utlimately due to bacterial infection, will be higher than anyone is currently thinking about.

Comments

  1. #1 Marcie Hascall Clark
    August 12, 2009

    For the last two years I’ve been getting reports of co-infections which usually start out with MRSA and by the time the person dies they also have MDRAb and Klebsiella, and very often C diff as well.
    Nick Narron died at Jewish Hospital in Louisville Kentucky two years ago this month after successful heart surgery with MRSA, MDRAb, Klebsiella, and an E coli.
    My reports are not official, they are from family members, but lead me to believe that KPC is likely a lot less rare than it appears.

  2. #2 JD
    August 12, 2009

    This must be Obama’s fault via nazibioterrorism health care reform measures. Rush told me so.

  3. #3 Trin Tragula
    August 12, 2009
  4. #4 Adams
    August 12, 2009

    I work at a SNF and there are several patients with KPC. When it first appeared it spread very fast and the facility did multiple room changes for pts to isolate the KPC, even so, it seems to be hopping around to different rooms. I believe the CDC was involved when it first arrived as well. It is also, to my knowledge, contained only to the trach/vent population.

  5. #5 Tom Jenkins
    August 13, 2009

    One must remember that a significant part of the population is uninsured, and we are overestimating the role of doctors in curing bacterial disease. There are many untreated pneumonias, and the body does just fine with an immune system more effective and advanced than most drugs at curing it. The “resistant” strains are easy prey for the a healthy bodies immune system. Bacteria are quite foreign to the body, and most strains do not exists intracellularly like viruses, so the body has a very effective way to treat naturally with antibodies, which are by far superior than small molecule antibiotics. Antibiotics are very effective of course also for non-resistant strains and for treating the elderly, immunocompromised, the severe cases where patients are very sick, or the average hypochondriac. My suspicion is that many infections by even antibiotic resistant strains in healthy people are subclinical or mild and are never even are seen or diagnosed in the hospital setting. We have much more to worry about viral pandemics, bacteria for the most part, are small fry the body can usually handle.

  6. #6 rastabob
    August 13, 2009

    I work in a clinical micro lab in the Midwest – we do a 10 disk Kirby-Bauer test on any suspicious bugs. Most of the resistant bugs are typical ESBL’s, with a few AmpC and K1 resistance patterns thrown in – but – about twice a week we get a super resistant Kleb.pneumo. – (we do a test called the Hodge test, which tests whether the KPC eats up the imipenem.) Anyway – these bugs scare the hell out of Infection Control and the ID docs – for good reason – there are hardly any sensitive drugs left and we are getting more all the time. Forget VRSA – this is the truly scary bug.

  7. #7 Loneviking
    August 16, 2009

    Very good, very timely post. I’m a Resp. Therapist and I see these resistant types of pneumonia. Lately, they have been in conjunction with H1N1, and although rare, they are very serious. Within the last month, I know of three patients who had to be put on life support for several days to treat this type of pneumonia. I know of at least two other patients currently inhouse, who likely will wind up having to be vented as well.
    In addition to this resistant form of pneumonia, there are lots of pneumonia cases going around in the middle of summer–which is quite unusual. Many of these cases are also quite serious, requiring days of hospitilization and antibiotics. Folks need to get the pneumonia vaccine now before the fall flu season hits.

  8. #8 Crustyrusty
    August 17, 2009

    I can’t speak for acute care facilities, but I do have to lay a lot of this on the subacute/rehab/LTC facilities. The last few places I’ve worked had absolutely worthless or nonexistent infection control procedures. The ones who actually tried couldn’t get their collective feces together, and would make people gown and mask for contact iso, and totally ignore the guy with MRSA spewing out his trach. The rehab facility that takes the patient who ought to be on droplet precautions out to the gym fiddle-dee-dee to infect the crap out of the other patients; the family members who don’t bother to wear gloves or gowns into an isolation room; the clinicians who don’t even take the patient to the sink to wash hands after they’ve been to the toilet… I could keep going.

    Then there’s all this about the hand sanitizers. When I was in Micro, we were told that alcohol basically didn’t kill diddly, and that we needed to physically wash our hands to get clean. Now they’re shoving this hand sanitizer thing on us, the clinicians slop some sanitizer on between rooms, and by time they get to the end of the hall, the bugs left on their hands are resisitant to nuclear weapons. Gimme a break.

  9. #9 jc
    August 17, 2009

    These bugs may be resistant to antibiotics, but not silver. Several of my family members were hit by H1N1 recently, along with the associated mucus problems in the lungs that can lead to pneumonia. Colloidal silver knocked out the flu virus within a day or so and kept the lung problem contained. They’re on track to recover within days, not weeks, and without requiring a doctor visit or a course of those nasty antibiotics. There are simple solutions out there. I hope people will find them without going through great suffering.

  10. #10 TikiHeada
    December 27, 2009

    Are phages a promising weapon against these bugs?

  11. #11 FullPPE
    March 27, 2010

    I work at a large LA hospital as an RN had a pt today with KPC and VRE stool. We do have vent pts on the floor but this pt is a walkie talkie on room air. Treatment has included vanco and tobramyacin. Certainly the first time I’ve ever seen contact plus and this bug got my attention I even masked not knowing what it was initially.

  12. #12 jeanne
    November 30, 2010

    I am an RN working in a LTAC and each nurse’s assignment is 7 pts. Trach, vented, multiple organ failure pts many with multiple infections/sepsis and now KPC. The nurse to pt ratio is criminal I think considering the extra time and degree of caution a clinician must take to gown and glove and wash their hands. I think that expecting nurses to care for this many pts can only increase the spread of KPC and destroy not only pts lives, but their visitors and the staff. Hospitals must be made to practice “do no harm” first instead of the “bottom line”.

  13. #13 Jim
    February 9, 2011

    Mike,

    I’ve got info. on new KPC, MBL, ESBL and AmpC diagnostic kits that I suspect may be of interest to you and your readers. I’m concerned about posting since we are obviously a commercial micro. products supplier, and I don’t want anyone to get angry with us. Could you please give me some direction?? Thanks!

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