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.

MRSA active surveillance: It just doesn't make sense

A study in the June issue of Infection Control and Hospital Epidemiology takes a look at staphylococcal colonization in healthcare workers. Over 250 HCWs were cultured and nearly half (44%) were colonized with S. aureus. MRSA colonization was found in 7% overall and was highest in nurses (10.5%). If the findings of this study are generalizable to other hospitals, this study has two important implications. First, given that nearly half of HCWs were colonized with S. aureus, hand hygiene practiced at very high levels of compliance is warranted. It seems that in the hysteria surrounding MRSA it's been forgotten that MSSA is also a pathogen. Second, why should hospitals engage in active detection and isolation (ADI) when non-patients are a significant reservoir for MRSA in the hospital setting? For those who continue to truly believe in ADI it seems that to me that their logic should dictate that MRSA colonized HCWs be removed from practice. And then there are visitors who may be colonized. The solution there could be to ban all visitors to the hospital. Of course, all of this assumes that the ADI zealots are driven by logic. Here's my recommendation: let's stop focusing on who has what organism (see Eli's posting from a few days ago), and just get everyone to wash their hands before and after every patient contact. The key word here is every. And maybe if that happened, we wouldn't need contact precautions any more. Now here's an interesting thought experiment: what could we do with all the money that's been spent on MRSA surveillance cultures over the last 5 years?

What if all S. aureus was MRSA?

We spend so much time discussing MRSA. We debate, we mandate, and we worry. Frankly, I'm getting tired of it. I'm far more worried about MDR-Gram negatives and all that oil spilling into the Gulf. So, while I was at the Orioles game today with my son, my mind drifted into an absurd thought experiment. To be clear, I'm a big baseball fan and I was trying to pay attention, it was just really boring until the O's scored 5 runs in the 8th, including a grand slam, to win it 6-5.

So as my mind drifted like the (three!) dingers Millwood was allowing, I thought: What if I could magically turn all S. aureus into MRSA? Now, I could have easily dreamed that all S. aureus would become penicillin sensitive, but I prefer to dream possibilities. What would this counterfactual world look like and why would I have such a thought? Would the world end? No. I know MRSA is the SUPERBUG, but I suspect the world would look as it does, but with a few differences; some good and some bad.

Now we all "know" that MRSA is more virulent than MSSA and leads to higher rates of mortality. Do we? I was a co-author on a meta-analysis, one that you must be required to reference if you publish on MRSA, since it's been cited >500 times. We found that MRSA bacteremia was associated with twice the odds of death compared to MSSA. I don't believe it. Never did. It's not that I don't think it was a great study; it was and is. It's just that since (fortunately) you can't randomly infect patients with MRSA or MSSA, you can never really study the clinical impact of MRSA. Since MRSA patients are sicker at baseline, before they even get infected, and vancomycin is a poor antibiotic, it is likely that MRSA just appears more virulent. If you give patients with MSSA vancomycin, they would do as poorly as those who were infected with MRSA.

Another reason that I'm not worried about an all MRSA world is that we have plenty of treatment options for MRSA unlike MDR-GNR. More are likely in the pipeline. The one downside I think of an all MRSA world is that it would be more expensive to treat infections since many of the treatment options would be more expensive. We would also have new abbreviations to learn: LRSA or DRSA (linezolid or daptomycin), etc. Yes, I know VRSA.

So far, I suspect I've put you to sleep, much like I was during the first seven innings of today's game. But here's my point. There would be a very important upside to this all methicillin resistant, Staphylococcus aureus world. It would mean that hospital epidemiologists and clinicians, patients and societies and legislators and journalists and everybody...could stop worrying about MRSA and start worrying about plain old S. aureus. What? Yes! We could isolate, treat, worry about, write about, legislate and actually deal with all patients with Staph aureus the same way. Since all S. aureus would be "the same" - which it really is, we've just forgotten that MSSA and PCN-sensitive SA are so deadly.

So there you have it. We could look to prevent ALL Staph infections, not just MRSA ones, since they would all be MRSA in this new world. And since MRSA is likely not worse than MSSA, no one would be worse off and I suspect many would be better off because we could target for prevention the 99% or 70% or 50% of infections caused by S. aureus that we currently ignore. And better yet, we could do this now. We don't have to wait for this 100% MRSA world. We could stop this MRSA insanity and actually target all S. aureus infections, or dare I dream, all hospital pathogens: resistant or sensitive, Gram-positive or Gram-negative (or C. diff). Alas...

Go Orioles. (Who says a guy can't dream...)