Antibiotic resistance: myths and misunderstandings

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A pig flying at the Minnesota state fair. Picture by TCS.

I’ve been involved in a few discussions of late on science-based sites around yon web on antibiotic resistance and agriculture–specifically, the campaign to get fast food giant Subway to stop using meat raised on antibiotics, and a graphic by CommonGround using Animal Health Institute data, suggesting that agricultural animals aren’t an important source of resistant bacteria. Discussing these topics has shown me there’s a lot of misunderstanding of issues in antibiotic resistance, even among those who consider themselves pretty science-savvy.

I think this is partly an issue of, perhaps, hating to agree with one’s “enemy.” Vani Hari, the “Food Babe,” recently also plugged the Subway campaign, perhaps making skeptics now skeptical of the issue of antibiotics and agriculture? Believe me, I am the farthest thing from a “Food Babe” fan and have criticized her many times on my Facebook page, but unlike her ill-advised and unscientific campaigns against things like fake pumpkin flavoring in coffee or “yoga mat” chemicals in Subway bread, this is one issue that actually has scientific support–stopped clocks and all that. Nevertheless, I think some people get bogged down in a lot of exaggeration or misinformation on the topic.

So, some thoughts. Please note that in many cases, my comments will be an over-simplification of a more complex problem, but I’ll try to include nuance when I can (without completely clouding the issue).

First–why is antibiotic resistance an issue?

Since the development of penicillin, we have been in an ongoing “war” with the bacteria that make us ill. Almost as quickly as antibiotics are used, bacteria are capable of developing or acquiring resistance to them. These resistance genes are often present on transmissible pieces of DNA–plasmids, transposons, phage–which allow them to move between bacterial cells, even those of completely different species, and spread that resistance. So, once it emerges, resistance is very difficult to keep under control. As such, much better to work to prevent this emergence, and to provide conditions where resistant bacteria don’t encounter selection pressures to maintain resistance genes (1).

In our 75-ish years of using antibiotics to treat infections, we’ve increasingly found ourselves losing this war. As bacterial species have evolved resistance to our drugs, we keep coming back with either brand-new drugs in different classes of antibiotics, or we’ve made slight tweaks to existing drugs so that they can escape the mechanisms bacteria use to get around them. And they’re killing us. In the US alone, antibiotic-resistant infections cause about 2 million infections per year, and about 23,000 deaths due to these infections–plus tens of thousands of additional deaths from diseases that are complicated by antibiotic-resistant infections. They cost at least $20 billion per year.

But we’re running out of these drugs. And where do the vast majority come from in any case? Other microbes–fungi, other bacterial species–so in some cases, that means there are also pre-existing resistance mechanisms to even new drugs, just waiting to spread. It’s so bad right now that even the WHO has sounded the alarm, warning of the potential for a “post-antibiotic era.”

This is some serious shit.

Where does resistance come from?

Resistant bacteria can be bred anytime an antibiotic is used. As such, researchers in the field tend to focus on two large areas: use of antibiotics in human medicine, and in animal husbandry. Human medicine is probably pretty obvious: humans get drugs to treat infections in hospital and outpatient settings, and in some cases, to protect against infection if a person is exposed to an organism–think of all the prophylactic doses of ciprofloxacin given out after the 2001 anthrax attacks, for example.

In human medicine, there is still much debate about 1) the proper dosing of many types of antibiotics–what is the optimal length of time to take them to ensure a cure, but also reduce the chance of incubating resistant organisms? This is an active area of research; and 2) when it is proper to prescribe antibiotics, period. For instance, ear infections. These cause many sleepless nights for parents, a lot of time off work and school, and many trips to clinics to get checked out. But do all kids who have an ear infection need antibiotics? Probably not. A recent study found that “watchful waiting” as an alternative to immediate prescription of antibiotics worked about as well as drug treatment for nonsevere ear infections in children–one data point among many that antibiotics are probably over-used in human medicine, and particularly for children. So this is one big area of interest and research (among many in human health) when it comes to trying to curb antibiotic use and employ the best practices of “judicious use” of antibiotics.

Another big area of use is agriculture (2). Just as in humans, antibiotics in ag can be used for treatment of sick animals, which is completely justifiable and accepted–but there are many divergences as well. For one, animals are often treated as a herd–if a certain threshold of animals in a population become ill, all will be treated in order to prevent an even worse outbreak of disease in a herd. Two, antibiotics can be, and frequently are, used prophylactically, before any disease is present–for example, at times when the producer historically has seen disease outbreaks in the herd, such as when animals are moved from one place to another (moving baby pigs from a nursery facility to a grower farm, as one example). Third, they can be used for growth promotion purposes–to make animals fatten up to market weight more quickly.  The latter is, by far, the most contentious use, and the “low hanging fruit” that is often targeted for elimination.

From practically the beginning of this practice, there were people who spoke out against it, suggesting it was a bad idea, and that the use of these antibiotics in agriculture could lead to resistance which could affect human health. A pair of publications by Stuart Levy et al. in 1976 demonstrated this was more than a theoretical concern, and that antibiotic-resistant E. coli were indeed generated on farms using antibiotics, and transferred to farmers working there. Since this time, literally thousands of publications on this topic have demonstrated the same thing, examining different exposures, antibiotics, and bacterial species. There’s no doubt, scientifically, that use of antibiotics in agriculture causes the evolution and spread of resistance into human populations.

Why care about antibiotic use in agriculture?

A quick clarification that’s a common point of confusion–I’m not discussing antibiotic *residues* in meat products as a result of antibiotic use in ag (see, for example, the infographic linked above). In theory, antibiotic residues should not be an issue, because all drugs have a withdrawal period that farmers are supposed to adhere to prior to sending animals off to slaughter. These guidelines were developed so that antibiotics will not show up in an animal’s meat or milk. The real issue of concern for public health are the resistant bacteria, which *can* be transmitted via these routes.

Agriculture comes up many times for a few reasons. First, because people have the potential to be exposed to antibiotic-resistant bacteria that originate on farms via food products that they eat or handle. Everybody eats, and even vegetarians aren’t completely protected from antibiotic use on farms (I’ll get into this below). So even if you’re far removed from farmland, you may be exposed to bacteria incubating there via your turkey dinner or hamburger.

Second, because the vast majority of antibiotic use, by weight, occurs on farms–and many of these are the very same antibiotics used in human medicine (penicillins, tetracyclines, macrolides). It’s historically been very difficult to get good numbers on this use, so you may have seen numbers as high as 80% of all antibiotic use in the U.S. occurs on farms. A better number is probably 70% (described here by Politifact), which excludes a type of antibiotic called ionophores–these aren’t used in human medicine (3). So a great deal of selection for resistance is taking place on farms, but has the potential to spread into households across the country–and almost certainly has. Recent studies have demonstrated also that resistant infections transmitted through food don’t always stay in your gut–they can also cause serious urinary tract infections and even sepsis. Studies from my lab and others (4) examining S. aureus have identified livestock as a reservoir for various types of this bacterium–including methicillin-resistant subtypes.

How does antibiotic resistance spread?

In sum–in a lot of different ways. Resistant bacteria, and/or their resistance genes, can enter our environment–our water, our air, our homes via meat products, our schools via asymptomatic colonization of students and teachers–just about anywhere bacteria can go, resistance genes will tag along. Kalliopi Monoyios created this schematic for the above-mentioned paper I wrote earlier this year on livestock-associated Staphyloccocus aureus and its spread, but it really holds for just about any antibiotic-resistant bacterium out there:

And as I noted above, once it’s out there, it’s hard to put the genie back in the bottle. And it can spread in such a multitude of different ways that it complicates tracking of these organisms, and makes it practically impossible to trace farm-origin bacteria back to their host animals. Instead, we have to rely on studies of meat, farmers, water, soil, air, and people living near farms in order to make connections back to these animals.

And this is where even vegetarians aren’t “safe” from these organisms. What happens to much of the manure generated on industrial farms? It’s used as fertilizer on crops, bringing resistant bacteria and resistance genes along with it, as well as into our air when manure is aerosolized (as it is in some, but not all, crop applications) and into our soil and water–and as noted below, antibiotics themselves can also be used in horticulture as well.

So isn’t something being done about this? Why are we bothering with this anymore?

Kind of, but it’s not enough. Scientists and advocates have been trying to do something about this topic since at least 1969, when the UK’s Swann report on the use of Antibiotics in Animal Husbandry and Veterinary Medicine was released. As noted here:

One of its recommendations was that the only antimicrobials that should be permitted as growth promotants in animals were those that were not depended on for therapy in humans or whose use was not likely to lead to resistance to antimicrobials that were important for treating humans.

And some baby steps have been made previously, restricting use of some important types of antibiotics. More recently in the U.S., Federal Guidelines 209 and 213 were adopted in order to reduce the use of what have been deemed “medically-important” antibiotics in the livestock industry. These are a good step forward, but truthfully are only baby steps. They apply only to the use of growth-promotant antibiotics (those for “production use” as noted in the documents), and not other uses including prophylaxis. There also is no mechanism for monitoring or policing individuals who may continue to use these in violation of the guidelines–they have “no teeth.” As such, there’s concern that use for growth promotion will merely be re-labeled as use for prophylaxis.

Further, even now, we still have no data on the breakdown of antibiotic use in different species. We know over 32 million pounds were used in livestock in 2013, but with no clue how much of that was in pigs versus cattle, etc.

We do know that animals can be raised using lower levels of antibiotics. The European Union has not allowed growth promotant antibiotics since 2006. You’ll read different reports of how successful that has been (or not); this NPR article has a balanced review. What’s pretty well agreed-upon is that, to make such a ban successful, you need good regulation and a change in farming practices. Neither of these will be in place in the U.S. when the new guidance mechanisms go into place next year–so will this really benefit public health? Uncertain. We need more.

So this brings me back to Subway (and McDonald’s, and Chipotle, and other giants that have pledged to reduce use of antibiotics in the animals they buy). Whatever large companies do, consumers are demonstrating that they hold cards to push this issue forward–much faster than the FDA has been able to do (remember, it took them 40 freaking years just to get these voluntary guidelines in place). Buying USDA-certified organic or meat labeled “raised without antibiotics” is no 100% guarantee that you’ll have antibiotic-resistant-bacteria-free meat products, unfortunately, because contamination can be introduced during slaughter, packing, or handling–but in on-farm studies of animals, farmers, and farm environment, studies have typically found reduced levels of antibiotic-resistant bacteria on organic/antibiotic-free farms than their “conventional” counterparts (one example here, looking at farms that were transitioning to organic poultry farming).

Nothing is perfect, and biology is messy. Sometimes reducing antibiotic use takes a long time to have an impact, because resistance genes aren’t always quickly lost from a population even when the antibiotics have been removed. Sometimes a change may be seen in the bacteria animals are carrying, but it takes longer for human bacterial populations to change. No one is expecting miracles, or a move to more animals raised antibiotic-free to be a cure-all. And it’s not possible to raise every animal as antibiotic-free in any case; sick animals need to be treated, and even on antibiotic-free farms, there is often some low level of antibiotic use for therapeutic purposes. (These treated animals are then supposed to be marked and cannot be sold as “antibiotic-free”). But reducing the levels of unnecessary antibiotics in animal husbandry, in conjunction with programs promoting judicious use of antibiotics in human health, is a necessary step. We’ve waited too long already to take it.

Footnotes:

(1) Though we know that, in some cases, resistance genes can remain in a population even in the absence of direct selection pressures–or they may be on a cassette with other resistance genes, so by using any one of those selective agents, you’re selecting for maintenance of the entire cassette.

(2) I’ve chosen to focus on use in humans & animal husbandry, but antibiotics are also used in companion animal veterinary medicine and even for aquaculture and horticulture (such as for prevention of disease in fruit trees). The use in these fields is considerably smaller than in human medicine and livestock, but these are also active areas of research and investigation.

(3) This doesn’t necessarily mean they don’t lead to resistance, though. In theory, ionophores can act just like other antibiotics and co-select for resistance genes to other, human-use antibiotics, so their use may still contribute to the antibiotic resistance problem. Studies from my lab and others have shown that the use of zinc, for instance–an antimicrobial metal used as a dietary supplement on some pig farms, can co-select for antibiotic resistance. In our case, for methicillin-resistant S. aureus.

(4) See many more of my publications here, or a Nature profile about some of my work here.

 

The human origins of “pig” Staph ST398

I recently gave a talk to a group here in Iowa City, emphasizing just how frequently we share microbes. It was a noontime talk over a nice lunch, and of course I discussed how basically we humans are hosts to all kinds of organisms, and analysis of our “extended microbiome” shows that we share not only with each other, but also with a large number of other species. We certainly do this with my particular organism of interest, Staphylococcus aureus. There are many reports in the literature showing where humans have apparently spread their strains of S. aureus to their pets (dogs, cats, hamsters)–and sometimes the pets have been nice enough to share it right back. My own research looks at S. aureus in pigs and the humans who care for them, and many studies have shown that a “pig” type of MRSA, dubbed sequence type 398 (ST398), can be transmitted from pig carriers to their human caretakers. The assumption has been that this is truly a “pig” strain, originating in swine, and has spread to humans (and other animals, including cattle, poultry, dogs and horses) from pig hosts, either directly or indirectly via contaminated meat products.

According to a new study (open access in mBio), it seems that there has been more sharing of ST398 than we’d realized. Led by Lance Price at TGEN (full disclosure–I’m a coauthor on the paper), his group analyzed 89 ST398 isolates from China, Europe, and North America, including isolates from humans and animals as well as both methicillin-susceptible and -resistant strains. Using whole genomic sequence typing, the evolutionary history of these isolates was reconstructed.

The findings throw the ST398 story a bit on its head. Instead of being a true pig strain, ST398 appears to have originated as a methicillin-susceptible human strain which was transferred into the pig population, picked up antibiotic resistance genes (including resistance to methicillin and tetracyclines), and then has been passed back to farmers as more resistant organisms. Some prophages were also gained or lost along the way, probably due to selection by host factors.

This also suggests that there is still likely a low level of “native human” ST398 circulating in people. There have been a few case reports of ST398 colonization and/or infection in people without any known livestock contact. Some of these have been resistant to methicillin and/or tetracycline, which are more frequently associated with livestock-adapted strains. Are these truly “human” strains which aren’t involved in livestock at all, or are these ST398 findings in people lacking livestock contact still due to some livestock exposure along the chain of transmission (farmer neighbors? Transmission via food?) We still don’t know, but carrying out more of this WGST will give us better targets in order to be able to differentiate true “human” ST398 strains from those that have been hanging out in animals, and then transmitted back to people.

Now, for long-time science blog readers, this story may sound a bit familiar. Indeed, it looks like ST398 has taken a very similar path to that of another animal-associated S. aureus strain, ST5. As Ed Yong described back in 2009, humans are also the ultimate origin of a “chicken” type of S. aureus ST5, which spread around the world in broiler chicken flocks. In Ed’s article, the first author of the chicken ST5 paper, Bethan Lowder, notes that the change in chicken farming from small farms to multinational corporations likely aided the spread of this organism–and the exact same thing has happened with pig farming.

One difference between the two is that ST5 causes disease in chickens, whereas ST398 seems to be a very rare cause of illness in pigs. This is likely one reason that ST398 in pigs went undetected until relatively recently–it’s simply not much of an economic issue for pig producers, whereas in chickens, S. aureus can cause several nasty diseases (such as bumblefoot and BCO) leading to animal loss (and thus, less money for the farmer).

So, where do we go from here? Clearly studies like this show the utility of using WGST to examine the evolution and spread of these strains. If you look at how spa types are distributed throughout the tree, you can see that those alone don’t tell you much about where the strain came from, or if it’s fully “human” or a pig-adapted lineage. Ideally, a set of simple markers could be found to distinguish ancestral human strains from livestock strains (as methicillin-sensitive ST398 can also be found in pigs, so methicillin resistance alone isn’t enough of an indicator that it’s a “pig” strain). We’ll be working on this in ST398 and other strains we see being shared between animals and humans, in order to better understand this generous sharing we’re doing amongst species.

Reference:

Lance B. Price, Marc Stegger, Henrik Hasman, Maliha Aziz, Jesper Larsen, Paal Skytt Andersen, Talima Pearson, Andrew E. Waters, Jeffrey T. Foster, James Schupp, John Gillece, Elizabeth Driebe, Cindy M. Liua, Burkhard Springer, Irena Zdovc, Antonio Battisti, Alessia Franco, Jacek Żmudzki, Stefan Schwarz, Patrick Butayej, Eric Jouy, Constanca Pomba, M. Concepción Porrero, Raymond Ruimy, Tara C. Smith, D. Ashley Robinson, J. Scott Weese, Carmen Sofia Arriola, Fangyou Yu, Frederic Laurent, Paul Keima,, Robert Skov, & Frank M. Aarestrup (2012). Staphylococcus aureus CC398: Host Adaptation and Emergence of Methicillin Resistance in Livestock mBio, 3 (1), 305-311 : 10.1128/mBio.00305-11

MRSA in pork products: does the “antibiotic-free” label make a difference?

Back in November, I blogged about one of our studies, examining methicillin-resistant Staphylococcus aureus (MRSA) in Iowa meat products. In that post, I mentioned that it was one of two studies we’d finished on the subject. Well, today the second study is out in PLoS ONE (freely available to all). In this study, we focused only on pork products, and included 395 samples from Iowa, Minnesota, and New Jersey. We also looked at not only conventional meats, but also “alternative” meat products. Most of the latter were products labeled “raised without antibiotics” or “raised without antibiotic growth promotants”–in the markets we tested, very few USDA-certified organic products were available unfrozen, and we were looking for fresh meat products.

In our previous paper, we found MRSA on 1.2% of 165 meat samples. In the current study, we found a higher prevalence–6.6% of 395 samples were contaminated with MRSA. (More about the differences in methods between our two studies later). Interestingly, we didn’t find a statistically significant difference in MRSA prevalence on conventional versus alternative pork products–a finding that surprised me, as it contradicts what we’ve found to date looking at the sources of this meat–conventional versus “alternative” pig farms. Other groups have also found differences on-farm versus on-meat: a 2011 study looking at feedlot cattle didn’t find any MRSA in animal samples, though the same group found MRSA in beef products. So, our disparate findings between farms and meat samples are not unheard-of. However, even though our sample size was larger than other U.S. studies to date, it was still fairly small overall–300 conventional and 95 alternative pork samples over a 4-week sampling period from 3 states, so larger multi-state studies are needed to further examine this angle.

It also suggests that we need processing plants and packing companies to work with us to determine where products are being contaminated–because while there may be arguments about the public health importance of MRSA on meats (or lack thereof), it’s very likely that if S. aureus are ending up on meat products, other pathogens are as well.

What does the molecular typing tell us, speaking of contamination source? We carried out analyses on all the MRSA and found that the most common type of MRSA was ST398, the “livestock” strain that we previously found on pig farms in the U.S. We also found two “human” types were common: USA300 (a “community-associated” strain) and USA100 (typically considered a “hospital-associated” strain). In the simplest analysis of these findings, these molecular types (a combination of “human” and “pig” strains) suggests that MRSA on raw pork products may be coming both from farms and from food handlers. However, in real life, it’s not quite so straightforward. USA100 types have also been found in live pigs. So has USA300. As such, the source of contamination and relative contributions of live pigs versus human meat handlers currently isn’t certain.

Within the MRSA strains, we found high levels of antibiotic resistance, similar to what was reported in the recent Waters et al. study. In ours, 76.9% were resistant to two or more antibiotics and 38.5% were resistant to three or more antibiotics tested. (I’ll note that we only had funding to test the MRSA–we weren’t able to do these tests on all the methiciin-susceptible strains).

Did MRSA prevalence increase in the period between our first study (spring 2009) and this one (late summer/fall 2010)? I doubt it. For this paper, we used a different sampling method, adding the samples to a sterile stomacher bag so that the entire sample was immersed in the culture medium; for the first paper we used external swabbing and so likely didn’t capture as many bacteria. This current study more likely represents the “true” MRSA prevalence. But–all isolates were only called as positive/negative, and we didn’t measure the number of bacteria on each piece of meat. So, there theoretically could have been just a few colonies of MRSA on the entire piece of meat, and that would have been called a positive sample, while another meat product covered with hundreds of MRSA would have been put in the same category. Therefore, more subtle differences may exist that we didn’t pick up in this study, but we will examine in other ongoing studies.

So–what’s the take-home here? Don’t assume that any meat product is contamination-free, and always use good food handling/cooking practices when dealing with raw meats. As far as the titular question, well, we’re still hashing that one out.

References

Hanson et al. Prevalence of Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) on retail meat in Iowa.

Waters et al. Multidrug-Resistant Staphylococcus aureus in US Meat and Poultry.

O’Brien et al. MRSA in conventional and alternative retail pork products.

Lin et al. Evidence of multiple virulence subtypes in nosocomial and community-associated MRSA genotypes in companion animals from the upper midwestern and northeastern United States.

Weese et al. The Prevalence of Methicillin-Resistant Staphylococcus aureus Colonization in Feedlot Cattle.

Weese et al. Detection and quantification of methicillin-resistant Staphylococcus aureus (MRSA) clones in retail meat products.

MRSA found in Iowa meat

I’ve blogged previously on a few U.S. studies which investigated methicillin-resistant Staphylococcus aureus in raw meat products (including chicken, beef, turkey, and pork). This isn’t just a casual observation as one who eats food–I follow this area closely as we also have done our own pair of food sampling investigations here in Iowa, and will be doing a much larger, USDA-funded investigation of the issue over the next 5 years.

Let me sum up where the field currently stands. There have been a number of studies looking at S. aureus on raw meat products, carried out both here in North American and in Europe. In a study from the Netherlands, a large percentage of samples were found to harbor MRSA (11.9% overall, but it varied by meat type–35.3% of turkey samples were positive, for example). Most of there were a type called ST398, the “livestock” strain. This was also found in one Canadian study (5.5% MRSA prevalence, and 32% of those were ST398), but no ST398 were found in a second study by the same group.

Here in the US, prevalence has found to be lower than in that Dutch study (from no MRSA found, up to 5% of samples positive). Furthermore, in the previously-published studies, no MRSA ST398 was found in samples of US meat, though this paper did find plenty of methicillin-sensitive S. aureus (MSSA) ST398 strains. Instead, most of the MRSA isolates have been seemingly “human” MRSA types, like USA100 (a common hospital-associated strain) and USA300 (a leading community-acquired strain).

Why am I rehashing all of this? We have a new paper out examining S. aureus in Iowa meats–and did find for the first time MRSA ST398, as well as MRSA USA300 and MSSA strains including both presumptive “human” and “animal” types. This was just a pilot study and numbers are still fairly small, but enough to say that yes, this is here in the heart of flyover country as well as in the other areas already examined.

As I mentioned, this is one of two studies we’ve completed examining MRSA on meat; the other is still under review and much more controversial, but I will share that as soon as I’m able. And with the USDA grant, we’ll be working on better understanding the role that contaminated meats play in the epidemiology and transmission of S. aureus for the next several years, so expect to see more posts on this topic…

References

Hanson et al. Prevalence of Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) on retail meat in Iowa. J Infect Public Health. 2011 Sep;4(4):169-74. Link.

Waters et al. Multidrug-Resistant Staphylococcus aureus in US Meat and Poultry . Clin Infect Dis. 2011 May;52(10):1227-30. Link.

Weese et al. Methicillin-resistant Staphylococcus aureus (MRSA) contamination of retail pork. Can Vet J. 2010 July; 51(7): 749-752. Link.

De Boer et al. Prevalence of methicillin-resistant Staphylococcus aureus in meat. Int J Food Microbiol. 2009 Aug 31;134(1-2):52-6. Link.

Pu et al. Isolation and characterization of methicillin-resistant Staphylococcus aureus strains from Louisiana retail meats. Appl Environ Microbiol. 2009 Jan;75(1):265-7. Link.

Bhargava et al. Methicillin-resistant Staphylococcus aureus in retail meat, Detroit, Michigan, USA. Emerg Infect Dis. 2011 Jun;17(6):1135-7. Link.

It’s not a freaking spider bite

Over at White Coat Underground, Pal has the post that I’ve been meaning to write. Earlier this summer, a family member posted on Facebook that a friend of her daughter was nursing a “nasty spider bite” that she got while camping in Michigan. Her post claimed it was a Brown Recluse bite. Being my usually buttinski self, I posted and told her that it was really, really unlikely to be a brown recluse bite, and that the friend-of-the-daughter-of-the-relative should hie thee to her physician and get the “bite” checked out. I told her that rather than a spider bite, it could be a Staph infection and may require antibiotics.

Now, I should note that few people in my family really “get” just what it is that I do, and even fewer of them realize that I spend my days researching bacterial infections, and that Staph in particular is my specialty. So I didn’t take it personally when she pooh-poohed my suggestion and told me I had no idea what I was talking about, and that FOTDOTR’s doctor had already seen the bite and proclaimed it to be due to a brown recluse. Okay, whatever, northern Michigan is completely the wrong place to get a bite from one of these critters and many research papers say the same thing–that “spider bites” usually aren’t bites at all. I pointed this out (and linked some Google images of supposed spider bites in comparison to Staph infection images) and then left the conversation.

A day later, relative posted an update in the thread–FOTDOTR ended up going back to the doctor as the “bite” was getting worse. As I suspected, she had now officially been diagnosed with a staph infection–and yet they were still trying to determine “what kind of spider bit her.” A few hours later, relative asked “What is MRSA? FOTDOTR was just diagnosed with that from the spider bite.”

This is when I started pulling out my hair, since I’d linked info about MRSA several days prior by this point. There was no spider bite, damn it!

Anyway, FOTDOTR got treatment (though relative probably still believes it’s from a spider bite) and I know at least a few people on the thread now may at least think “staph” when someone says “spider bite”–so overall, a good ending.

Pal notes:

Despite this widespread belief, most “spider bites” in my part of the country [Michigan, ahem–TS] aren’t caused by spiders, and probably aren’t bites at all. (The feared “brown recluse” does not live naturally in my part of the country, although importations have been reported. They do not generally survive through the winter.) The distinction is important for a few reasons. First, many of us are guilty of wanton arachnicide propelled by our unwarranted fears. Second, many “bites” are probably bacterial infections and should be treated properly. Finally, there’s my own bias that we shouldn’t assume things that aren’t so.

Indeed.

When is MRSA not MRSA?

…when it contains a weird gene conferring methicillin resistance that many tests miss.

Methicillin-resistant Staphylococcus aureus (MRSA) has become a big issue in the past 15 years or so, as it turned up outside of its old haunts (typically hospitals and other medical facilities) and started causing infections–sometimes very serious–in people who haven’t been in a hospital before. Typically MRSA is diagnosed using basic old-school microbiology techniques: growing the bacteria on an agar plate, and then testing to see what antibiotics it’s resistant to. This can be done in a number of ways–sometimes you can put a little paper disc containing antibiotics right onto a plate where you’ve already spread out a bacterial solution and see which discs inhibit growth, or sometimes you can grow the bacteria in a plate with increasing concentrations of antibiotics, to see when the drugs are high enough to stop growth. Both look at the phenotype of these bacteria–the proteins they’re expressing which lead to the bacteria’s drug resistance.

However, these culture-based methods are slow–they can take days between when the patient first is seen by a doctor and the time the results come back from the clinical lab. For this reason, increasingly labs are moving to molecular methods, which are much quicker than the culture-based methods. Indeed, detection of the gene responsible for methicillin resistance, mecA, has been the gold standard for *really* identifying MRSA, even beyond phenotypic methods.

A new pair of papers demonstrate the limitations of this reliance. Like many science discoveries, this one started with a “huh, weird” moment. Investigators noticed that a number of their S. aureus samples were categorized as MRSA using the traditional phenotypic methods, but were negative when it came to the mecA DNA test. Genetic analysis showed that these isolates carried a different mecA gene, dubbed mecALGA251. The investigators searched their isolate collection in England, and also worked with collaborators in Scotland and Denmark to search through their banks for additional mecA-negative MRSA, and found almost 70 isolates, including one dating back to 1975. (A second paper by a different group examined two isolates in Ireland).

Now is when it starts to get really interesting. (Continued below)
Continue reading “When is MRSA not MRSA?”

MRSA, Meat, and Motown

It’s been not even a month since the last paper looking at MRSA in meat, and up pops another one. So far here in the US, we’ve seen studies in Rhode Island (no MRSA found); Louisiana (MRSA found in beef and pork, but “human” types: USA100 and USA300); the recent Waters et al study sampling in California, Florida, Illinois, Washington DC, and Arizona, finding similar strains (ST8 and ST5, associated with USA300 and USA100, respectively). Now a new study has collected MRSA samples in Detroit, collecting 289 samples from 30 retail stores in the city.

For this study, they collected only beef, turkey, and chicken–a bit odd, since pork has been the meat product typically linked to MRSA to date. The paper is short on methods so it doesn’t say how the sampling was done, which is a bit frustrating as they found levels of S. aureus that were quite a bit lower than those found in the Waters paper. Unlike the Pu and Waters papers, *all* of the Detroit samples were USA300. No typing data was given for the S. aureus that were susceptible to methicillin.

There’s also something interesting about some of the USA300 isolates–they’re resistant to tetracycline. Resistance to this antibiotic is relatively rare in human S. aureus isolates, but it was found in 3 chicken samples–all a molecular type called t2031. The other isolates were resistant to erythromycin, and one was additionally resistant to ciprofloxacin and levofloxacin, suggesting (like the Waters paper) that multi-resistant S. aureus are present in our meat supply. Unfortunately, there’s no information letting us know whether these positive isolates–especially the unique t2031 strains–were from the same brands of meat product, same stores, etc.

So what’s going on here? The authors suggest that human contamination is probably at play here, and that’s quite possible. No ST398 (“livestock-associated”) MRSA has been found yet in published papers examining U.S. meat, though Waters did find ST398 in their S. aureus which were methicillin-susceptible. That suggests that farm-origin Staph can make it through the processing chain, but is human contamination along the line a bigger issue in the U.S.? This is different than the situation in The Netherlands, where they found ST398 MRSA almost exclusively in the meat products they tested. But–the prevalence of humans carrying MRSA in that country is also much, much lower than it is in the U.S., so it may simply be an issue of relative colonization rates (more MRSA in Dutch animals versus their human population, while we may have more in American humans versus our animals–but additional surveillance would be needed to confirm that).

So what we’re left with here is another piece of the puzzle, but one that unfortunately doesn’t yet add a whole lot to the bigger picture.

Bhargava K, Wang X, Donabedian S, Zervos M, da Rocha L, Zhang Y. (2011). Methicillin-resistant Staphylococcus aureus in Retail Meat, Detroit, Michigan, USA Emerging Infectious Diseases : 10.3201/eid1706.101095

MRSA and bedbugs?

An ahead-of-print paper in Emerging Infectious Diseases is generating some buzz in the mainstream media. While the findings are interesting, I’m honestly not sure how they got published, being so preliminary.

Like many areas, Vancouver, British Columbia has seen a jump in the prevalence of bedbugs. After finding impoverished patients infested with the bugs, researchers decided to collect some and test them for pathogens–specifically, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). So, they tested 5 bugs from 3 patients. That’s it–it doesn’t even appear to be 5 bugs apiece, but just 5 total. And the bugs were simply homogenized and streaked–not an uncommon way to test bugs for microbes, but one that has pretty severe limitations if you’re really looking at transmission via biting.

They did find MRSA (and VRE)–obviously, or it wouldn’t have made news. VRE was isolated from 1 bug each from 2 patients; MRSA was isolated from 3 bedbugs from the remaining patient. At first read, I thought they’d confirmed the MRSA strains were USA300, but they didn’t even do that–all they did was note the antibiotic susceptibility profiles of the isolates were consistent with USA300 (though headlines are already screaming “flesh eating bacteria isolated from bedbugs!” as you can see from the link up top). However, what we don’t know if whether the bedbugs were simply externally contaminated (perhaps from close contact with their human hosts), or if they were actually carrying the organisms in their salivary glands (as has been previously reported for S. aureus). If it’s the latter, an infection risk seems more plausible, although I suppose a bite from an externally-contaminated bedbug could also introduce organisms into an open wound.

Still, the paper is really, really, really sparse on data. I’ll sum up with words expressed in the newspaper story above:

Medical health officer Dr. Reka Gustafson said the St. Paul’s study is so small that no public health warning is necessary. She noted the superbug MRSA can be found on “doctors’ ties” and chairs in public places and that it’s more important to counsel people “to wash their hands thoroughly and use antibiotics wisely.”

Lowe CF, Romney MG (2011). Bedbugs as Vectors for Drug-Resistant Bacteria Emerging Infectious Diseases

Epidemiological studies–why don’t people participate?

Maryn McKenna was awesome enough to take some time out of her vacation to blog about our recent ST398 paper, finding “livestock-associated” S. aureus in a daycare worker. She raised one question I didn’t really address previously, regarding our participation by kids and workers at the facility (eight kids out of 168, and 24 out of 60 staff members).

(Staph screening is very non-invasive, by the way; it effectively involves twirling a long-handled Q-tip inside the front of your nostrils. Kinda makes you wonder why families would not have wanted to participate. On the other hand, since Iowa is the pig-growing capital of the U.S., they may have been motivated not to want to know.)

I thought I’d chat a bit about enrollment for this project, since getting people to participate is one of the most difficult parts of these types of studies. First, there really wasn’t any mention of MRSA and swine for this particular study, so I doubt protecting the pig industry was high on anyone’s list for reasons not to participate. However, anytime we do these type of studies, we’re relying on the generosity of individuals in the community–particularly when we didn’t really have participation incentives, as was the case in this project, which was done on a shoestring budget. (We passed out mini hand sanitizer bottles for adults, and had some little toys for the children).

We ran into several challenges for the research which limited our ability to enroll children. Along with a swab, we also had a questionnaire for parents and employees to fill out (as well as a third questionnaire for the director of the facility). For parents and employees, we asked about exposures: did they spend time in hospitals, around animals, at the gym? Had they recently had an infection? etc. For the directors, we asked about cleaning routines at the facility, as well as facility size (number of children and employees). So it wasn’t only the swabs, but also a decent amount of paperwork to fill out when you include the informed consent forms. We also had to do all of this at the facility; because of the way we were sampling, parents didn’t have a chance to take the questionnaire home to fill it out and then return it. So only parents (and employees) who had some spare time during either child drop-off or pick-up really had the chance to participate.

This particular study also started in roughly March 2009–right around the same time as the emergence of novel H1N1. There was a lot of news about the swabs that were taken to test for flu, which are more invasive than regular Staph swabs, so perhaps many potential participants had the mistaken assumption that the swab collection would be more uncomfortable than it really is. (When we were able to swab the child participants, most of them giggled and said that the swab tickled).

Finally, I should note that this facility was one of the larger ones we sampled, and to do this, my grad student returned several times during the day to try and catch parents during common drop-off/pick-up times (and employees who worked different shifts). However, even with this, we certainly missed a number of children and employees, such as those who were part-time and simply didn’t attend or work the day that we were there. We did have higher participation rates at some of the other facilities.

So, I think timing and misinformation–rather than any kind of fear of finding out things they might not want to know–led to our lower participation rate at this facility.