Thursday, August 12, 2010

Why are we colonized with Staphylococcus aureus?

A truly successful parasite is commensal, living in amity with its host, or even giving it positive advantages...A parasite that regularly and inevitably kills its host cannot survive long, in the evolutionary sense, unless it multiplies with tremendous rapidity....It is not pro-survival.

Who said that? I will post the answer tomorrow. You can guess by posting a comment or since you're all busy stamping out hospital infections, you can just google it.

I've been thinking a lot about S. aureus recently for some reason. By recently, I mean spring 2009 when I attended a S. aureus conference in St. Augustine and had the chance to speak with Chip Chambers and Heiman Wertheim, among others. The question was and is, why are 30% of us colonized with S. aureus and what possible survival advantage could there be for this colonization status. Sure there are downsides - carriers are more likely to be infected with S. aureus, but are the costs outweighed by the benefits? Does S. aureus colonization prevent colonization and infection with other pathogens? Perhaps even S. aureus colonization prevents the morbidity and mortality associated with S. aureus infection. What? Did I just say that?

A few years ago (2004), before this blog was started so it's fair game, Prof. Wertheim and colleagues published an interesting study in the Lancet. I will just post the findings from the paper's abstract:

Nosocomial S aureus bacteraemia was three times more frequent in S aureus carriers (40/3420, 1.2%) than in non-carriers (41/10588, 0.4%; relative risk 3.0, 95% CI 2.0-4.7). However, in bacteraemic patients, all-cause mortality was significantly higher in non-carriers (19/41, 46%) than in carriers (seven/40, 18%, p=0.005). Additionally, S aureus bacteraemia-related death was significantly higher in non-carriers than in carriers (13/41 [32%] vs three/40 [8%], p=0.006).

Pretty cool. S. aureus carriers were 3 times more likely to have a nosocomial S. aureus bacteremia as non-carriers, but had one-quarter the risk of death from S. aureus bacteremia. So, if you are a S. aureus carrier you have a 3/3420 or 0.000877 chance of death from S. aureus. If you're a non-carrier you have a 13/10588 or 0.001228 chance of death. Yes, I know, sig figs. Amazingly, being colonized, while increasing the risk of infection, drastically cuts the risk of death such that colonized patients are 30% LESS likely to die. Is this enough to explain why 30% of us are colonized? Obviously not, it's just one paper. Their work and other's since has studied factors associated with colonization, but there is more work to do.

I guess, my question is, what if all of the efforts at decolonization actually increased the mortality in the patients we are trying to benefit? Surely, that would be measured in the intervention trials or at least the meta-analyses, or would it? If you don't think of the question, you might not find the answer.

Wertheim 2004 Lancet Paper

Update:  Answer to the question above:  Mr. Spock, Star Trek II.
I found this quote at the beginning of Janice Moore's excellent book "Parasites and the Behavior of Animals"  Thanks to Dave Smith for recommending the book to me many years ago and also for inviting me to the St. Augustine S. aureus conference.

5 comments:

  1. 2 thoughts:

    1. Does every observed phenomenon have to have a survival advantage? Is everything really so determined? Also, why should we assume that the current state of affairs with respect to any biological observation reflects a final state in which evolution has finished eliminating traits from the population? Put another way, maybe in 1000 years staph aureus colonization will be less frequent due to some disadvantage and we just need to be patient to let selection do its thang.
    2. Colonization with pneumococcus can result in serologic responses, and it is conceivable that those with disease (or with more severe disease) from a commensal either 1) cannot mount a response or 2) have not had time to mount one (in other words, colonization proceeded to disease too quickly). I wonder if the same thing happends with staph.

    A research question: does being colonized with a strain of Staph protect against a distinct non-colonizing strain?

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  2. Good questions. I have some thoughts.

    1) I would expect that over time, traits should at least have no negative effect, especially after many 1000's of years. There is no reason to suspect that the S. aureus and human relationship is new. If colonization does provide a survival advantage, I would expect it to increase in 1000's of years not decrease.

    2. I think for uncolonized, the response might be too slow, ie colonization would proceed to disease too quickly.

    As far as your question, I think the general belief is that there is a close relationship between the colonizing strain and the person. If you decolonize someone and then expose them to numerous random strains, they generally select or get recolonized with their old strain. Also, Mike posted back in May about the Nature paper showing S. epi colonization blocking S. aureus colonization.

    My last thought is that the advantage of S. aureus colonization may even be something really unthinkable. What if it, by its location, improved smell and helped you select a better mate?

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  3. In skimming, I can't find any mention that the physicians providing care were blinded to carrier status. Is it possible that there's a component of bias at play? If physicians are aware that a patient is colonized with S. aureus, do they recognize signs of bacteremia or other infection earlier? Do they culture earlier? Do they start therapy earlier? Do they provide better empiric therapy because they suspect S. aureus is the pathogen?

    Regardless of potential bias, those were very interesting results. It would be nice to see work done, however, with physicians blinded to carrier status. Perhaps by treating all patients as carriers, gathering outcome data prospectively, then examining the nasal swab culture results retrospectively?

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  4. Good points. Although from Marin Schweizer's excellent new study in PLoS One, it doesn't appear that specific knowledge is of much help with S. aureus. Her study found that there was little benefit in up front empiric therapy for S. aureus. Definitive therapy is another matter, but by then clinical culture results are known and initial colonization status shouldn't impact response to clinical cultures.

    link to her paper:
    http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0011432

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  5. For everyone's information: the doctors were not aware of the patient's colonization status. So no bias in that sense. We are trying to confirm these study's findings in a new study. Data expected in 2011

    Best wishes
    Heiman

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