All About MRSA – PediaCast 328

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Dr Sheldon Kaplan (from Texas Children’s Hospital) and Dr Bill Barson join Dr Mike in the PediaCast Studio to talk about Methicillin-resistant Staphylococcus aureus (MRSA). We discuss the emergence of this pathogen, typical disease symptoms, diagnosis and treatment strategies in light of antibiotic resistance. We also cover recurrent MRSA infections and ways to prevent them. We hope you can join us!

TOPICS

  • Methicillin-resistant Staphylococcus aureus
  • MRSA
  • Preventing Recurrent Infections
  • Antibiotic Resistance

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Transcription

Announcer 1: This is PediaCast.

[Music]

Announcer 2: Welcome to PediaCast, a pediatric podcast for parents. And now, direct from the campus of Nationwide Children's, here is your host, Dr. Mike.

Dr. Mike Patrick: Hello, everyone and welcome once again to PediaCast. It's a pediatric podcast for moms and dads. This is Dr. Mike coming to you from the campus of Nationwide Children's Hospital in Columbus, Ohio. It is Episode 328 for October 7th, 2015. We're calling this one "All About MRSA".

I want to welcome everyone to the program.

So those of you who are regular listeners know that we basically produce three types of shows for our parent audience, in addition to our CME episodes for providers which you can find at PediaCastCME.org. We have our News Parents Can Use programs. In those, we dig through the latest pediatric journals. We choose some articles, explain the science in hopefully easy-to-understand terms. But we try not to dumb down the science either, and we try to put a practical spin on the information for parents and families.

Then, we have our episodes with the answers to listener questions, like the one we released a few weeks ago, which included the answers to questions on scabies, laughing gas and spinach popsicles. Now, I know it's a strange mix of topics but look folks, you're the one who asked the questions.

Then, we have our nuts and bolts episodes where we dive a bit deeper into a specific one topic for the entire show with the pediatric expert or two joining me in the studio, so we can explain the science but still keep in terms mom and dads can understand.

Sometimes, this topical discussions sort of take on a life of their own and recruit lots and lots of listeners over a long period of time, because they're topics which affect many children and teenagers and families in one way or another.

0:02:08

I think we have one of those topics today, one that's going to be downloaded and remain popular for quite awhile, because methicillin-resistant staphylococcus aureus and I know it's a mouthful, also known as MRSA, it's one of those infections you've probably heard of or dealt with in your own family. If you haven't heard of it before, you'll likely will at some point in the future. When you do, just keep in the back of your mind, when you need to know more about it, just do a Google search for MRSA and PediaCast, and you can come back here and refresh yourself with another listen.

So MRSA is a type of staph infection. It's on that's really a product of our success in treating bacterial infections with antibiotics. As Dr. Ian Malcolm proclaimed in the original Jurassic Park movie, "Life finds a way," and that's what many bacteria have done in the face of antibiotic bombardment. They find a way.

In the case of community-acquired MRSA, the staph infection frequently shows up as a skin infection, often starting as a red bump, sometimes mistaken for a spider bite, and then it quickly leads to abscess formation.

So we'll talk about how the bacteria that causes MRSA emerge, what symptoms and dangers it poses, how it's diagnosed and treated. And we'll go into the science of antibiotics a bit with some explanations of how they work at the cellular level. You might feel like you're back at high school biology class, but don't worry, we'll explain things as we go.

We have two fantastic studio guests this week to help me with the explaining. Dr. Sheldon Kahn is Chief of Infectious Disease at Texas Children's Hospital. He joins me today, and it's an honor and really quite exciting having him here with us.

We also have an infectious disease expert from Nationwide Children's along for the ride — Dr. Bill Barson. We'll make formal introductions in a moment.

First though, I do want to remind you, PediaCast is your show, So if there's a topic you'd like us to talk about, you have a question for me, it's really easy to get in touch. Just head over to PediaCast.org and click on the Contact link.

0:04:09

Also, I want to remind you, the information presented in PediaCast is for general educational purposes only. We do not diagnose medical conditions or formulate treatment plans for specific individuals. So, if you're concerned about your child's <

health, make sure you call your doctor and arrange a face-to-face interview and hands-on physical examination. Also, your use of this audio program is subject to the PediaCast Terms of Use agreement and you can find that at PediaCast.org.

All right, let's take a quick break, we'll get our guests settled in to the studio and talk about MRSA. That's coming up right after this.

[Music]

Dr. Mike Patrick: All right, we are back.

Dr. Sheldon Kaplan joins me in the PediaCast studio to talk about Methicillin-resistant Staphylococcus aureus, also known as MRSA or M-R-S-A. Dr. Kaplan is Chief of Infectious Disease at Texas Children's Hospital and a professor of Pediatrics at Baylor College of Medicine. His research focuses on infections in children caused by Streptococcus pneumoniae, and Staphylococcus aureus, including the evaluation of new antibiotics for children with infections caused by antibiotic-resistant bacteria.

It's truly an honor having Dr. Kaplan with us in the studio. So let's give a warm PediaCast welcome to Dr. Sheldon Kaplan. Thanks for joining us today.

Dr. Sheldon Kaplan: Thank you, Mike. It's a real pleasure to be here this morning.

Dr. Mike Patrick: Great. Good to see you in the Buckeye State.

0:06:02

We have another guest in the studio, one who's a little closer to home. Dr. Bill Barson is an infectious disease specialist and program director of the Infectious Disease Fellowship Program here at Nationwide Children's Hospital. He's also Professor Emeritus of Pediatrics at the Ohio State University College of Medicine, and we appreciate you joining us today as well.

Dr. Bill Branson: Thank you, Mike.

Dr. Mike Patrick: Really appreciate both of you stopping by.

So Dr. Kaplan, let's just start with the brief definition. What is meant really by the term MRSA?

Dr. Sheldon Kaplan: So MRSA means that the Staph aureus bacteria — which, as you already mentioned, is the most common cause of typical skin and soft tissue infections in children — is resistant to this antibiotic class called methicillin, which is also very similar to an antibiotic that we would normally use, nafcillin or oxacillin. Nafcillin is no longer around. It's an older antibiotic that was perhaps first developed in the late 1950s, early 1960s to combat resistance to penicillin which rapidly developed among Staph aureus organisms.

It's a type of antibiotic that's structured to be resistant to the enzymes that staph aureus can make to break down penicillin.

Dr. Mike Patrick: Sure. We can kind of divide these MRSA Staph infections into community-acquired infections and healthcare-associated infections. What's the difference between those two?

Dr. Sheldon Kaplan: It simply means that where the organism was probably first encountered and where the infection first started in terms of did they start in the hospital? The organism was picked up in the hospital following admission to a hospital or even just being associated with some sort of healthcare environment.

So we also see kids who have so-called community onset healthcare-associated infections. So these are kids who have underlying conditions, are seen frequently in the hospital but they have their initial onset of infection in the community.

0:08:10

In contrast, the kids who have so-called community-associated or community onset Staph aureus, these are otherwise healthy, normal kids, never been in the hospital. They don't have an underlying condition which leads them to be around healthcare professionals frequently, and they have an MRSA-isolate which really was described at some point actually in the 1970s.

And in going back, I actually found a series from Nationwide Children's Hospital of kids who had Staph aureus that was methicillin-resistant, never been in the hospital, had no underlying condition and yet they had an MRSA.

So this probably had been going on for some period of time but it really exploded in the late 1990s with various reports and really around the country now, these community MRSA isolates are pretty common.

Dr. Mike Patrick: Is there any difference between the community ones and the healthcare-associated ones in terms of the bacteria itself? Or is it really just where you come into contact with it?

Dr. Sheldon Kaplan: Well, there used to be a fairly good distinction, at least from a molecular standpoint, between hospital-acquired and community-acquired Staph aureus isolates that are methicillin-resistant. But over time, there seems to have been actually some movement of these community strains into the hospital. So you can do these fancy molecular tests and say, "Well, this is the so-called pattern that's classically associated with the community, but now it can cause hospital-acquired infections."

Typically, the community MRSA isolate has a particular molecular pattern. It's called USA 300, when you do this electrophoresis type gels. And it is carrying a methicillin-resistant gene in the package that's called the Staphylococcal cassette chromosome type IV. That's the typical community MRSA isolate.

It's usually susceptible to many other antibiotics including one we use very frequently called clindamycin to treat these community MRSA infections.

0:10:39

In contrast, the hospital-acquired MRSA isolates are non-USA300, so called genotypes. They may carry genes that are associated with antibiotics resistance to some of these other common antibiotics including clindamycin. But now, this USA300 isolate is moved into the hospital, so we really have a hard time distinguishing the two.

Dr. Mike Patrick: How common are these infections?

Dr. Sheldon Kaplan: Well, it depends in where you live, but in most parts of the United States, I would say the community MRSA account for maybe 25% to over 50% of simple skin and soft tissue infections that are acquired in the community.

Now, in our neck of the woods, we had reached perhaps 70% of the community Staph aureus isolates being methicillin-resistant. But this peaks in about 2007, 2008 and this has now come down to closer to 50% of our community isolates now are methicillin-resistant.

Dr. Mike Patrick: Dr. Barson?

Dr. Bill Branson: Mike, I just want to mention, here in Columbus, our rate of MRSA is about 43% to 47%, so it's a little bit less than what Sheldon mentioned of the 50/50. But that's probably a good thing to remember from the standpoint of the community, that about 50% are susceptible and 30% are resistant.

Dr. Mike Patrick: In terms of becoming infected with this — because a lot of people may have been a carrier, and it's in their nose or just kind of hanging out on their skin — what are some risk factors for it actually becoming a problem?

0:12:17

Dr. Bill Branson: Well, if the child has underlying co-morbidity. So if they have underlying health problems, neurological problems, renal problems, diabetes, surgical problems, they have an increased risk for infection. Again, Sheldon mentioned, if they're in the hospital where they can acquire the germs, that is another one of the increased risk factors.

Dr. Mike Patrick: Yeah, so becoming in contact with it or if your immune system isn't quite up to taking care of it once it's there.

Dr. Bill Branson: Correct.

Dr. Mike Patrick: Why did we see an explosion of this bacteria back in the 90s, Dr. Barson?

Dr. Bill Branson: I think it had a lot to do with overuse of certain antibiotics, because as you mentioned, they survived. Organisms have ways to find, to prevent antibiotics from killing themselves so they put up restrictions. And that, in conjunction with maybe some not so good infection control practices with the spread.

We saw that in certain groups of individuals, too. Sports team, for example, that there was St. Louis Rams had some problems with a MRSA infection. Other sports teams or individuals that have close contact with each other. And other ways that you can spread — inmates in prisons, men who have sex with men, other risk factors.

Dr. Mike Patrick: Dr. Kaplan, yeah?

Dr. Sheldon Kaplan: There probably are some molecular components of this as well in there because it's been the subject of a lot of investigations as you might expect. There does seem to be some evidence that his USA300 clone of community MRSA isolates has the ability to express virulence factors to a greater degree than what we had seen previously with community typical Staph aureus infections.

0:14:07

So there's probably something special about this clone in addition to all the factors that Bill mentioned that allowed it to spread very rapidly in the community.

Dr. Mike Patrick: In terms of the bacteria being able to resist the effect of antibiotics, so this just happens from just random genetic mutations that changed the character of the bacteria so that then in the presence of the antibiotic it can survive? Or is that oversimplifying that?

Dr. Bill Branson: Maybe a little bit, but the organism find ways to survive, and in this particular organism, MRSA, alters the penicillin-binding protein. Now, this penicillin-binding protein feed the enzyme through their proteins that are responsible for building the cell wall of the bacteria. And so, doing this, the antibiotics don't have affinity for this penicillin-binding proteins so it don't prevent the cell wall from being formed.

Dr. Mike Patrick: But when you say find a way, it's not like they're thinking and doing this intentionally. It's just something in their genetic code that makes them change in character, but then they can share their genetic code with each other to propagate that resistance?

Dr. Sheldon Kaplan: So with respect to MRSA, the gene that encodes this altered penicillin-binding protein that Bill mentioned is called the mecA gene. It is carried on this cassette of genes that I mentioned that can be spread from organism to organism. Obviously, Staph aureus as well as many other organisms or all organisms have the ability to rapidly, it seems, alter their genetic codes to combat this antibiotic resistance or the ability to combat antibiotics in their environment. So they're very smart and are able to come up with new ways to get around antibiotic activity.

0:16:02

Dr. Mike Patrick: Now, you talk about virulence factor. So we all know that there's bacteria on our skin, and we've talked about good bacteria versus bad bacteria. What is it about specific bacteria including MRSA that makes it more dangerous and become more invasive than other types of bacteria?

Dr. Sheldon Kaplan: Well, with respect to Staph aureus, it has a number of virulence factors that are important first in adherence to various mucosal surfaces or skin surfaces that allow it to stick and colonize the area.

Then, typically, at least with Staph aureus, you do have to have some sort of injury to the skin to allow the organism to get in and start this infectious process. And at some point and in some people, it actually then gets past the skin into the bloodstream. Now, what is going on there is not totally understood frankly. But, once it kicks into the bloodstream, this organism can go almost anywhere to cause a serious infection.

Staph aureus has these other virulence factors, other toxins that let's say destroy white blood cells or can break up red blood cells. They might be able to use iron more readily than other bacteria that just makes it more likely to cause a serious infection.

Dr. Mike Patrick: Very interesting. So when it does get pass that skin barrier, that's when you really start to worry that it could cause a blood infection, and then it could cause a pneumonia, could cause bone infection, really any place.

Dr. Sheldon Kaplan: Once the organism is in to the blood stream, it can disseminate to almost any place in the body. In pediatric patients, the most common site that Staph aureus will disseminate to is the bone and joint. We certainly see pneumonia as a result of bacteremia. But on the other hand, pneumonia may occur actually more commonly more as a result of a preceding viral infection especially influenza. So then Staph aureus becomes an important secondary bacterial invader.

0:18:15

It may also cause infections of muscles, so called myositis or polymyositis. I mentioned joints, that septic arthritis. We certainly see infections of the heart valves. So that's called endocarditis, and that occurs both in normal kids and in kids with underlying heart disease, congenital heart disease.

It rarely gets in to the central nervous system. So unlike some of the other organisms like streptococcus pneumonia or what we used to see was influenza type B. Staph aureus rarely causes bacterial meningitis.

On the other hand, it's not an uncommon cause of complications of sinusitis that might lead to abscesses close to the brain, so called epidural abscesses or subdural abscesses, complications inside an orbital cellulites or abscess.

Dr. Mike Patrick: Now, the skin injury we're talking about, in order for the bacteria to invade in, it can be a microscopic skin injury, correct? So you can have a kid with eczema. It doesn't look like much but they scratch and the organism can get in.

Dr. Sheldon Kaplan: Typically, it's an insect bite, a scratch an abrasion, some injury to the skin. There are old studies to show that if you injure the skin in some way, let's say putting in a suture, it takes something like a hundredfold less bacteria to directly cause an infection than putting the organism directly into the skin. So some injury to the skin is really necessary to cause this skin infections.

Dr. Mike Patrick: But it may be very small.

Dr. Sheldon Kaplan: Very, very minor.

0:20:12

Dr. Mike Patrick: Dr. Barson, what then does the skin infection for MRSA typically look like? What should a parent be on the lookout for?

Dr. Bill Branson: I think you originally mentioned a red bump. Usually, it starts off with the swelling, redness and frequently people think it's a spider bite. I don't know how many times you'll get that history, then "Oh, I had a spider bite." But that's not really the case. And then it just gets bigger and spreads and then oftentimes pus develops in the area.

Dr. Mike Patrick: Does fever usually come along with this?

Dr. Bill Branson: With the soft tissue infections not generally, but fever can be associated with it. It doesn't necessarily mean it's a more serious infection but it may or may not be present.

Dr. Mike Patrick: And then, if they have a fever, you worry a little bit more that it could become more invasive, like they could have now blood infection.

Dr. Bill Branson: Typically, we don't see too much of in a way of bacteremia associated with soft tissue infections and soft tissue abscesses in the normal child. It's to the point that we even instructed our emergency room staff not to be drawing blood cultures on these kids who come in with routine soft tissue infections and abscesses because you have a greater chance of having what's referred to as a contaminated blood culture than a true blood culture.

Dr. Mike Patrick: Then, it becomes confusing what's really going on.

Dr. Bill Branson: Correct, yeah.

Dr. Mike Patrick: Now, there are other bacteria than can also cause skin infections. To some degree, you might have to use a different antibiotic depending on what the organism is that's possible. How do you figure out if it's really MRSA or something else?

Dr. Bill Branson: The other organism that frequently is in the differential diagnosis is Group A strep. For any infection, you make a diagnosis by recovering the organism from the site of infection. So if an individual has an abscess with pus, we culture the pus and see what microbiological lab told you grows from that specimen.

Dr. Mike Patrick: Again, we're talking to folks who may not know exactly what happens in the medical community. Once you've isolated what bacteria it is from the priolines, the pus, then you can test that bacteria against different antibiotic to find out what antibiotic would be the best.

0:22:26

Dr. Bill Branson: That is correct.

Dr. Mike Patrick: Great.

Dr. Bill Branson: And actually, there is even a more rapid test. It looks for this penicillin-binding protein presence on this bacterial colonies once it is growing, and that can give you some information 24 hours before you have the actual susceptibility testing performed in the microbiology lab.

Dr. Mike Patrick: So this is one of the reasons that you would drain it, so that you can send material off to culture to find out what's growing. Are there other reasons to drain these abscesses?

Dr. Sheldon Kaplan: Well, if you have an abscess, the primary treatment is drainage. And for smaller abscesses, there is some pretty good studies that would indicate you don't need an antibiotic once you've drained a small abscess, which might be less than 3 to 5 centimeters in diameters. It varies obviously with the different studies and the size of the child.

I might go back to something related to what Bill said in terms of trying to distinguish the organism clinically is very difficult — is this Staph aureus or is this a Group A strep infection? Those are usually the two major differentials, considerations.

It is firstly impossible to make that distinction, so we really do like people to try and get cultures. It is important to number one, document I think what's causing these infections, to keep up with antimicrobial susceptibility patterns in the community. It also might lead to changes in what you're going to treat the patient with ultimately, because some of the antibiotics that we like to use for these community infections over time, the organism may be getting resistance to some of them like clindamycin.

Dr. Mike Patrick: The Group A streps. They are pretty susceptible to most of the antibiotics we think, but there's not a lot of resistance with those, correct? Or are we starting to see more?

0:24:27

Dr. Bill Branson: Fortunately, I think Group A strep is kind of one of the "dumb bug" from standpoint of not being able to find ways to survive and produce resisting mechanism. But from the start of the availability of penicillin, Group A strep has remained susceptible to penicillin to the point that microbiology labs don't even check for susceptibility against penicillin for the Group A Strep.

The one drug that somewhat of a concern is clindamycin because there is about 6% or so of the Group A Strep that are resistant to clindamycin. Frequently, the patients are on clindamycin initially, and then if that's the case — and especially if they have dual infections, which is another possibility — occasionally you'll have Group A strep and Staph aureus recover from the patient. If we're going to use clindamycin for both of those, you need to make sure that the Group A strep is susceptible to the clindamycin.

Dr. Mike Patrick: So for the providers who are out there listening, you would say if there's something to drain, you should send it for culture and susceptibilities. What if a kid has recurrent MRSA? It looks like it's looked in the past, clindamycin has worked in the past. Would you still send that for culture and sensitivities?

I know this is above the parent crowd now.

[Laughter]

Dr. Sheldon Kaplan: It's really a good question. It's expensive to do these cultures. There's no getting around that. But in patients who've received clindamycin repetitively, there is a chance that you'll eventually going to have some resistance.

The other thing we haven't talked about is topical antibiotics and one in particular, mupirocin or Bactroban with wide spread use now, there is growing evidence that many of these Staph aureus isolates in the community are gaining resistance to mupirocin.

0:26:13

Now, there's two different types of resistance. There's one that's so called low-level and then high-level resistance. It is the high-level resistance we're most concerned about. But nevertheless, we are seeing increasing frequencies of mupirocin resistance.

So, from my standpoint, from a research standpoint, of course, we want to keep an eye on what's going on and if you don't culture it, you're not going to find out down the road, what the optimal antibiotics might be.

Dr. Mike Patrick: Absolutely. So let's talk about a little more about antibiotics and we kind of alluded to this a little on our earlier discussion. The penicillin, so these were the first group of antibiotics that were used to treat strep and staph, correct? How do those work? How do penicillins kill bacteria?

Dr. Bill Branson: Penicillin are a group of the antibiotics called beta-lactams. The beta-lactams is a structure in these organisms. It affects the beta-lactam rings and breaks that and allows for the antibiotic to kill the organism.

Dr. Mike Patrick: So this actually disrupts synthesis of the cell wall of the bacteria, and the bacteria needs a cell wall to survive.

Dr. Bill Branson: To survive. If it doesn't have a cell wall, then the external environment can result in fluids coming in to the cell and basically explodes the cell.

Dr. Mike Patrick: So the beta-lactam ring binds to the penicillin-binding proteins and so, because it's bound there, that protein can't do its job of linking things together to make that cell wall. So the first bacterial resistance that we saw then was that the bacteria started to make a substance that broke that beta-lactam ring so that it couldn't work anymore.

Dr. Bill Branson: Correct. And those are known as beta-lactamases or penicillinases.

Dr. Mike Patrick: So how did we solve that problem?

0:28:09

Dr. Sheldon Kaplan: With the structure of the penicillin, chemist were able to modify the area around the beta-lactam ring to protect it from these beta-lactamase enzymes. So the very first synthetic penicillin was methicillin, and it was designed to prevent the breakdown of these beta-lactam ring by these beta-lactamase, these penicillinase is that Staph aureus and other bacteria it produced.

Dr. Mike Patrick: And then, we started also adding other substances to the penicillin that would break down the beta-lactamase so that the beta-lactam ring would stay intact. And then, we get things like Augmentin is one of the tradenames with amoxicillin and clavulanic acid mixed together.

Dr. Sheldon Kaplan: The development of clavulanic acid was one to… It's actually a beta-lactam ring itself, but it sort of tying up the beta-lactamases that organism is producing and then protecting the beta-lactam ring of the antibiotic that it's combined with.

Dr. Mike Patrick: So then, what did the MRSA bacteria do? You talk about the mecA gene. What happened to make them become resistant to all beta-lactam antibiotics?

Dr. Bill Branson: Well, it formed something referred to as an altered penicillin-binding protein. So this altered penicillin-binding protein always the organism to continue to make the cell wall. And the beta-lactamase resistant antibiotics like methicillin did not affect this altered penicillin-binding, didn't inhibit that particular penicillin-binding protein, so the organism continued to survive.

Dr. Mike Patrick: To make a new protein that could then link the cell wall together and the beta-lactam doesn't disrupt that site at all.

Dr. Bill Branson: Didn't have activity against this new altered binding protein.

0:30:19

Dr. Mike Patrick: So then, the oral antibiotics that are currently working for the most part for MRSA, so you mentioned clindamycin. How does that one work?

Dr. Sheldon Kaplan: So clindamycin works at a ribosomal level to inhibit protein synthesis. And so, you're inhibiting important proteins that Staph aureus needs to produce to survive. It inhibits the synthesis of protein. It keeps the organism in check so that it's inhibiting its growth, but it's not really killing the bacteria. So it's called a bacteriostatic antibiotic, as opposed to methicillin or nafcillin which is a bactericidal antibiotic, actually kills the organism.

So with clindamycin, we're inhibiting its growth and we're really also relying on host defense mechanism, so then it sort of really come in and clean up the infection.

Dr. Mike Patrick: So the ribosome, just so parents can have an idea in their mind, think back to high school biology class, that's what proteins are made. Messenger RNA are, I think… Messenger RNA, correct, yeah? I got to think back here, but goes to the ribosome and then the ribosome reads that, the genetic materials puts together amino acids to make a protein. But, it can't do that properly when the clindamycin is bound to it, and so, the bacteria can't make proteins that it needs to live.

Dr. Bill Branson: Correct.

Dr. Sheldon Kaplan: That's essentially correct.

Dr. Mike Patrick: What about the trimethoprim/sulfamethoxazole type antibiotics, Bactrim, Septra, those kind? Are those good to use for MRSA?

Dr. Bill Branson: At least in vitro, in the laboratory, there were drugs that are typically effective against MRSA, are trimethoprim/sulfa, the Bactrim, Septra that you referred to. Another old antibiotic, doxycycline, which is a tetracycline antibiotic. And those are the other two oral antibiotics.

0:32:22

Then, there's some newer antibiotics, ones referred to as linezolid, and that's also a bacteriostatic agent working at ribosomal level. The problem with that particular medication is it's effective but it's very cost-prohibitive. It's one of our more expensive antibiotics.

Dr. Mike Patrick: I think out in the community, there is still a lot of the sulfa-type antibiotics being used that we see out there. Would you say that clindamycin is the better choice?

Dr. Sheldon Kaplan: I can't really say there are now some really good randomized clinical trials. One in particular that included kids show that if you have a patient with an abscess to the Staph aureus — and it can be methicillin-susceptible, or methicillin-resistant — and especially if it's drained, it doesn't seem to make all that much difference if you use clindamycin versus trimethoprim/sulfa to treat the patient.

There may be slight evidence that recurrent infections are a little more common in the group that gets trimethoprim/sulfamethoxazole as opposed to clindamycin. But overall, the two are quite equivalent for skin and soft tissue infections. And by the way, that's true for either an abscess or cellulitis that's not joining or draining, either way.

These two antibiotics seem to be quite comparable at least in large clinical trials that have been conducted primarily in adults, but one in particular also included kids.

Dr. Mike Patrick: You've talked about possibly not needing an antibiotic if you drained the smaller abscesses. And I want to point out that we're really always looking at risk versus benefit with anything that we do. Although antibiotic certainly have lots of benefit, there's also a small amount of risk that can be associated with antibiotics as well. What are those risks?

0:34:20

Dr. Bill Branson: There are adverse effects that can be seen with certain antibiotics. For some, for example, the beta-lactam antibiotics, the penicillin derivatives, there's concern that it might affect the white blood cells, that you may have a decrease in the white blood cells. Some people will recommend that if you're on a course of a therapy for greater than a week, you should have your white count CBC basically checked to make sure you're not developing what's referred to as a leucopoenia.

Also, maybe some liver enzyme abnormality is associated with the use of penicillins. So drugs have the potential for doing a good job, for taking care of what you want, but like anything else, a drug also has associated adverse effects. We try to use the ones that have the least risk but every drug has that potential.

Dr. Sheldon Kaplan: And for many of these agents, a common problem of course is loose stools or altering the normal flora of the bowel. So loose stools or diarrhea is an issue, and rashes, especially with trimethoprim/sulfamethoxazole, the sulfa components seems to be associated with the rashes. And you can have some fairly severe reactions especially to trimethoprim/sulfamethoxazole.

And then, as Bill mentioned, you can have severe allergic reactions to beta-lactams or any antibiotics or any drug for that matter. That's also a potential that you have to be aware of.

Dr. Mike Patrick: So that, in addition of course, cost is also I guess not really a risk, but you know a negative. So if something's going to get better after you drain it and it's small, that may be another reason not to do an antibiotic.

0:36:06

All right, let's talk a little bit about recurrent infections. So this can become a problem in some families where they keep getting MRSA infections. Why does that happen?

Dr. Bill Branson: Well, usually, it's because somebody's colonized with the organism and it's very easy to transmit from one person to another, and the person who is colonized may not even have any symptoms associated with it. Say it's a caregiver, a mother, a father that have constant contact with their child, and then their child is the one that shows up with recurrent episodes.

Dr. Mike Patrick: So what are some things that families can do if they've experienced recurrent MRSA infections at home? What are some things they can do to stop that cycle?

Dr. Sheldon Kaplan: Well, that's a really good question.

Dr. Bill Branson: Thank you for answering that, Sheldon.

[Laughter]

Dr. Sheldon Kaplan: This is one of the real difficult issues that we faced frequently with families where you might have kids who've had three, four, who've had one child with up to 15 episodes of MRSA skin and soft tissue infections.

As Bill mentioned, you certainly have other family members who are colonized and you might get bouncing back and forth at the organism between family members or among family members. Also, there's some evidence that Staph aureus can survive on hard surfaces for some period of time. So it's possible that we're picking up the staph over and over again from surfaces that are used frequently, let's say in the bathroom or various handles and doorknobs or whatever in the home.

So what we recommend, of course, is just some basic hygienic measures, especially for the patient, but also for all family members. Just common sense thing, try and keep fingernails cut short and clean. We've talked about injury to skin as an often, precedes these infections, so if you can prevent injury to the skin from scratching, that might help.

0:38:10

We want to change towels and wash clothes daily. Of course, we want to avoid sharing wash clothes and towels among family members. Simple things like making sure you change underwear daily. Now, we don't tell people they need to change the sheets on beds daily, but just try to keep the environment as clean as you can, but under a normal circumstances.

Then, as far as trying to decrease colonization, there is some evidence for hospital acquired infections that the application of one of these topical agents like mupirocin into the nose — which is a common place for the organism to colonize — several times during the day for perhaps five to seven days might be helpful in preventing recurrences in the community. It's really hard to say. We know this from hospital infections but not so much from a community standpoint.

And then, some of us had tried to also address colonization into other sites of the body using various antiseptics or perhaps even household bleach in bathwater. So that adding Clorox or hydrochloride to bath water, taking a bath in that two or three times a week. Or perhaps, another product you can buy, Hibiclens, and taking a bath with that or a shower with that a couple, three times a week might be beneficial. It's really hard to say.

Dr. Mike Patrick: With the bleach baths, how do you know how much bleach to put in the bath tub?

Dr. Sheldon Kaplan: Well, we know from old studies that putting in a teaspoon of bleach, or 5 cc per gallon of Clorox into bathwater leads to a fairly dilute solution. Actually, it leads to a concentration of chlorine that's about what you see in a swimming pool. So this is not a heavy chlorine concentrated solution. But we know that dilute solution in a test tube actually kills Staph aureus. There is a study looking at the very solution, so it does kill staph.

0:40:37

So if you take a bath in this bath water twice a week for three months, there are some reduction in recurrences. We did a randomized trial and this is published last year, where we had 500 kids that we randomized to take just normal hygienic practices and another 500 kids who did normal hygienic practices and had a bleach bath 2 times a week for 15 minutes as I mentioned.

The recurrence rate for what we call medically-attended skin and soft tissue infections. So that is, the family actually sought medical care either through their doctor or a clinic or an emergency center for their child. It wasn't just a little pimple that they popped at home. But in the kids who had simple hygienic measures, there was a recurrence of a medically attended skin and soft tissue and 21% of those patients within 12 months have enrollment of the study, as compared to 17% of the kids who have hygiene plus bleach baths.

Now, this didn't quite reach statistical significance. We weren't powered to pick up a small difference. We were powered to pick up a 50% decrease. But I still believe that it helped some. I can't say that it's fantastic.

0:42:04

Dr. Mike Patrick: Do you have to measure that one gallon at a time when they're filling their bathtub?

Dr. Sheldon Kaplan: As part of the study, what we did for the family was we actually gave them a one-gallon bucket. We told them to measure the amount of water that they put in the bathtub to give their child a bath one time, so see if that's 10 gallons or 15 gallons. And then we gave them a tape to mark off, "Well, this is gallon," so you don't do it every time. Then, we gave them also a syringe to be able to say, "Well, this is then 5 cc per gallon," and if it's 10 gallons, you're going to put in then 50 ccs of bleach.

So in the normal situation, it would be one teaspoon per gallon. I would try to have the family though measure the amount of water that they're going to use for the bath at least one time and mark it, to try to be as accurate as possible in estimating the one teaspoon per gallon.

Dr. Mike Patrick: Now, would you have everyone in the family do this?

Dr. Sheldon Kaplan: That's a really good question. We haven't instructed families to do that unless other family members also had recurrent infections.

Stephanie Fritz and her colleagues from Washington University had also done a randomized trial where they did do entire families versus the child alone. What they did show was some reduction. They did show a significant reduction in the group where everyone in the family did it.

But in her study, if I remember correctly, there is a recurrence of 30-semi percent in the family group compared to 50% in the patient only group. And they only did this for one week. So it could be that it's duration, it's the number of people in the household.

0:44:12

We really don't know the best way to prevent recurrent infections. I think it's a person on the physician side, on the healthcare worker side, their own personal experience with various preventive measures. Some families can't undertake this. There are others where they can't take it anymore. They've had so many recurrences in their child, they'll do just about anything to try and prevent these infections.

Dr. Mike Patrick: You talked about topical agents in the nose like mupirocin. So something over the counter or antibiotic ointment is not going to do it.

Dr. Sheldon Kaplan: Typically, the antibiotics that contain polymyxin B and other things you can get over the counter are not effective against MRSA. Now, there are other things that you read about that rather it's tar or other things that I've seen as proposed topical agents to prevent these infections, whether they work or not, I don't think I can say. I haven't seen any scientific studies.

Dr. Mike Patrick: I'm going to go back to the mupirocin in the nose, is that also just for the kids who keeps getting the MRSA infection, or should that be the whole family? Had there been any studies to look at that?

Dr. Sheldon Kaplan: So what people have done is apply it to everyone in the family. If we're going to do the measures for the entire family, then you do it all. You do the mupirocin in the nose. You do the bleach bath.

Now, the mupirocin in the nose is obviously just addressing the colonization in the nose. But we know from many studies including our own that when kids come in with the skin infection, actually the most common site where they're colonized is in the groin. So that's where these other topical measures whether bleach baths or Hibiclens baths or chlorhexidine baths comes in, to try to decrease the density of bacteria in these other areas.

Dr. Mike Patrick: Sure.

0:46:15

Dr. Bill Branson: My normal practice for these kids as Sheldon mentioned it's frequently they're colonized in the groin. That's probably one of the more common sites where you're going to see infection. It's in the underpants diaper area, so buttocks are, perennial areas, labial areas.

I think we're talking about two different issues. One is the child who comes in with a first time infection. What do you do for that child? I usually treat them with the antibiotic, and then after the wound is healed, do the Clorox baths. Not the mupirocin because as Sheldon mentioned, the more we're using mupirocin, it's becoming resistant.

The other issue is a child who comes back again and again, or you get this history that brothers had it, sisters had it. Then, that's when you kind of throw up your hands, OK, we're going to try to take care of the entire family, use the intranasal Bactroban, mupirocin for everybody's nose, use the bleach bath for everybody or the Hibiclens bath for everybody as a kind of last ditch effort to see if you can stop the communication of the germ.

Dr. Mike Patrick: Absolutely. We talked a little bit about research studies involving what the best practices are to prevent recurrent MRSA infections. What are some of the other hot topics right now in research regarding methicillin resistance staph?

Dr. Sheldon Kaplan: One certainly the development of new antibiotics that had been primarily studied in adults, but they're moving to pediatric patients. So there's one antibiotic that was approved in adults several years ago called daptomycin. It is very effective in vitro in killing Staph aureus. It may be the best drug actually to use for MRSA bacteremia when it doesn't involve the lung, and it's being studied in children currently.

0:48:09

There's another IV antibiotic called Ceftaroline, which is actually a beta-lactam antibiotic. It's called the fifth generation cephalosporin, but in this case, this particular cephalosporin has a beta-lactam ring that is effective against this altered penicillin-binding protein. So Ceftaroline is a cephalosporin that is effective against MRSA, something that all the older cephalosporin are not effective against.

So Ceftaroline has been studied in adults with skin and soft tissue infections due to MRSA. It's being studied in more severe infections in adults. It's also being studied now in kids with pneumonia. Hopefully, down the road, we'll have some more information about Ceftaroline for more serious MRSA infections in kids. Because it's a cephalosporin, it's expected to be safe. We have a lot of experience with this particular drug.

Then there are some newer drugs that are really interesting in the adult world, where they have very prolonged half lives. So they might be given just once a day, or in one case, just once a week for skin and soft tissue infections. These agents hopefully will be studied in kids. They might already being studied, I'm not certain about that, but it would be nice to have a single dose of an antibiotic to treat skin and soft tissue infection. It might be pretty expensive. And then the other concern might be that if you have an adverse event, the antibiotics are going to be around for awhile. But those are the hot topics at least from an antibiotic development standpoint.

0:50:00

Dr. Bill Branson: Now, I agree and they're actually trying to enroll patients in this one study with a drug that can be given once a week. We'll just have to see the results of the study, but it's very promising.

Dr. Sheldon Kaplan: The other really hot topic with Staph is a vaccine. So this has been obviously some dreams for many years to come up with a Staph aureus vaccine, but unfortunately, nothing has worked.

There had been vaccine studies primarily looking at adults who are vaccinated prior to surgery — especially let's say, hip surgery or prosthetic joint surgery, surgery involving an incision in the media sternum, heart surgery — to try and prevent post-operative Staph aureus wound infections and so far, there has not been a successful Staph aureus vaccine developed. But they're still trying. They're still trying.

Dr. Mike Patrick: My final question is a very practical question for parents, and since both of you see lots of kids who take antibiotics and clindamycin, one of the main ones that we use for soft tissue infections with MRSA, it doesn't taste very good. What advice do you have for families on getting their kids to actually take the antibiotic without a fight?

Dr. Bill Branson: One of the things we try to do in the hospital before we know we'll send a child home on clindamycin is give them a test dose to see how they tolerate it. If they don't tolerate it, then there's some things you can do. A lot of times, people suggest using chocolate. Chocolate is a good way to deaden the taste and I usually preface the statement of you're going to be on antibiotic to say "Do you like chocolate syrup?" and if they say, yes, I say "I got a deal for you. You're going to get it three times a day for ten days." I don't tell them they have to take an antibiotic with it, but oftentimes the chocolate may help to kind of deaden the taste.

Dr. Mike Patrick: Great. All right, we really appreciate both of you taking time to stop by the studio and talk about MRSA. Thank you very much.

Dr. Sheldon Kaplan: Thank you Mike. It's been a pleasure.

Dr. Bill Branson: Thank you.

Dr. Mike Patrick: We're going to take a quick break and I'll be back to wrap up the show right after this?

0:52:11

[Music]

Dr. Mike Patrick: We have just enough time to say thank you to all of you for taking time out of your day to make PediaCast a part of it. Really do appreciate that. Also, thanks to Dr. Sheldon Kaplan, Chief of Pediatric Infectious Disease at Texas Children's Hospital and Baylor College of Medicine, and Dr. Bill Barson, Infectious Disease Specialist here at Nationwide Children's.

PediaCast is a production of Nationwide Children's Hospital.

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0:54:14

And, while you have your providers' ear, let them know we have a podcast for them as well, PediaCast CME. Similar to this program, but we turned up the science a couple notches and provide free Category 1 Continuing Medical Education Credit for listening. Shows and details are available at PediaCastCME.org.

So thanks again for stopping by. Until next time, this is Dr. Mike, saying stay safe, stay healthy, and stay involved with your kids. So long, everybody.

[Music]

Announcer 2: This program is a production of Nationwide Children's. Thanks for listening. We'll see you next time on PediaCast.

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