Outpatient Management of Acute Bacterial Skin and Skin Structure Infections - Episode 12

Trends of ABSSSI Incidence in the Community

Segment Description:Christian Sandrock, MD, MPH, FCCP, discusses the trends of acute bacterial skin and skin structure infections incidence and the increasing number of methicillin-resistant Staphylococcus aureus infections in the community.

Christian Sandrock, MD, MPH, FCCP: Well, there has been a couple trends with skin and soft tissue infections over the past 20 or so years. One of the changes we’ve seen is that initially, we had resistance with methicillin-resistant Staphylococcus aureus (MRSA). Here in the United States we had more of a clonal resistance with USA300, where that was many of our outpatient cases. So, we started seeing this large spike in methicillin-resistant Staphylococcus aureus in the community. Clinically, that largely represented with a big increase in abscesses, deep tissue infections such as necrotizing fasciitis and myositis, and obviously accompanying bacteremia and other infections.

I would say over the last few years we’ve seen that, and we’ve obviously gotten used to dealing with community associated MRSA. We’ve seen that there’s been sort of a shift back towards methicillin-susceptible Staphylococcus aureus, or MSSA. And with those MSSA strains, we’ve actually seen some increased virulence.

For example, we might notice patients with very small abscesses, small patches of cellulitis, and they’ll actually have overwhelming bacteremia and sepsis accompanying that. I have seen an increase in things such as toxic shock and other toxin-mediated staphylococcus diseases, and we’ve also seen an increase.

Over the last few years I’ve noticed the change in skin and soft tissue associated complications, particularly with Staphylococcus aureus—things such as necrotizing fasciitis, myositis, deeper skin and soft tissue infections. Actually, we’ve had a few cases of toxic shock associated with skin and soft tissue infections with Staphylococcus aureus, and many of those have been methicillin-susceptible strains with increased virulence factors. So, we have noticed a change in the last few years and some of the research and data has borne that out over the past year or 2.

Gram-negative infections are actually relatively tricky, and gram-negative organisms have a number of ways of engendering resistance to antimicrobials. They often do that through a couple of mechanisms, but there are 2 main ways that they’ll engender resistance. One is through what we call extended spectrum enzymes, such as extended-spectrum beta-lactamases, where they actually hydrolyze certain antibiotics. It might be beta-lactam antibiotics such as piperacillin (Pipracil). It may actually be a carbapenem, such as meropenem (Merrem). Those are called carbapenemases, and that’s a very common way that certain gram-negatives such as E coli, Klebsiella, Enterobacter; the whole Enterobacteriaceae family engender their resistance. They develop this 1 enzyme and then the antibiotics hydrolyze. Usually it’s high-level resistance in most of those cases.

The nice thing is, if you can inhibit those enzymes you actually develop really easy susceptibility. Other gram-negatives like Pseudomonas, Acinetobacter, Stenotrophomonas, Burkholderia, they engender resistance through a number of different mechanisms. One mechanism that’s relatively common, is that they will have what’s called a porin channel mutation. Porin channels are these channels that allow the antibiotic to enter the bacteria. If that channel is completely absent or there’s a mutation to it, the antibiotic can’t enter in well, so that’s one potential mechanism. The other is they also have enzymes; slightly different than the enzymes we see for E coli and enterobacteriaceae. But we do see that they have some enzymes. AmpC is the name of a common one that pseudomonas has—that’s a second mechanism.

The third mechanism is, they actually have what are called efflux pumps. These are pumps— they’re kind of like bouncers in a bar where the antibiotic will enter through a porin channel and this pump will throw the antibiotic back out. The nice thing with those is they don’t really engender high level resistance. They’ll actually engender a lower level of resistance, so you can dose your antibiotics appropriately, overwhelm the efflux pump and still get some efficacy. But, when you have something such as pseudomonas, where they have multiple modalities of engendering resistance, it’s often hard to have antibiotics stay susceptible for long. For E coli and enterobacteriaceae, for example, and particularly Klebsiella, if they have one enzyme and you can block it, they sometimes don’t have other mechanisms as easily. So, this allows us different strategies for managing those gram-negative resistance.