Treatment of skin and soft tissue infections changing in an age of MRSA

April 2006

NEW YORK – Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is changing the way pediatricians treat skin and soft tissue infections as well as other infections, Jay M. Lieberman, MD, said here at the 18th Annual Infectious Diseases in Children Symposium.

It used to be that MRSA was not an issue for community pediatricians because it was acquired in hospitals. “Community-associated MRSA was unusual, particularly in children, until relatively recently, but it has changed how I practice, and I’m sure it’s changing the way you practice, more than anything else in the past 20 years,” said Lieberman, who is professor of clinical pediatrics at the University of California, Irvine and chief of pediatric infectious diseases at Miller Children’s Hospital in Long Beach.

New bug

“Historically, MRSA was no different than susceptible strains except it was resistant. What we’re seeing now with this MRSA is that it’s a different bug. It’s more virulent and, as a result, we’re seeing more serious staph infections,” Lieberman warned.

CA-MRSA is much more likely to carry a different gene for Panton-Valentine leukocidin (PVL), which is an extracellular cytotoxin that causes leukocyte destruction and tissue necrosis. “S. aureus strains, whether they are MRSA or not, that carry the gene for PVL have been associated with a highly lethal necrotizing pneumonia in otherwise healthy children and young adults, and with skin infections,” he explained.

A study published in 2004 examined children who had skin and soft tissue and musculoskeletal infections caused by S. aureus found PVL in most infections caused by MRSA; most cases that were methicillin susceptible did not have PVL. Infections caused by PVL-containing S. aureus were more likely to be associated with complications.

The two predominant clones of CA-MRSA circulating in the United States tend to contain PVL, and are more virulent, according to Lieberman.

“What are the clinical implications? Know the prevalence in your community. It’s going to affect how you practice,” he said. “At my hospital, about half the children hospitalized with S. aureus infections have MRSA.”

Treatment options

Children admitted with potentially life-threatening staphylococcal infections should be treated empirically with nafcillin and vancomycin until susceptibilities are known, according to Lieberman. The combination is recommended because vancomycin has activity against resistant organisms, and nafcillin is a better drug if the organism is not resistant. By using both, all bases are covered, he explained.

“If you told me a few years ago that I would be treating patients with nafcillin and vancomycin, I’d have said you’re crazy. It seems absurd,” he said. “Many of us have this idea that vancomycin is the best possible anti-staph drug and if the organism is resistant to everything else, of course it is. But everything else being equal for a susceptible strain, nafcillin is superior,” he said, adding that vancomycin and ceftriaxone is also a viable combination for life-threatening infections where S. aureus or pneumococcus are the likely pathogens.

For non-life-threatening and less serious CA-MRSA infections, such as cellulitis, osteomyelitis or severe pneumonia, Lieberman suggested clindamycin and trimethoprim-sulfamethoxazole (TMP-SMX) as possible treatment options. A 2005 study conducted at four sites in the United States found that almost all CA-MRSA isolates were susceptible to TMP-SMX, and most were susceptible to clindamycin.

“We’ve reached the point now at my hospital [that] every child with a staph infection gets coverage for MRSA. How do you choose between clindamycin and TMP-SMX?

“Let’s weigh the pluses and minuses. Clindamycin tastes bad if you’re treating orally, requires more frequent dosing, and there is concern about Clostridium difficile, although we’ve seen it very infrequently. TMP-SMX, on the other hand, can be dosed twice daily, is cheap, tastes pretty good and is easy to get. The big downside of TMP-SMX is that it is not active against group A streptococcus. Therefore, if you are treating a child with a cellulitis, and you think it could be caused by group A streptococcus or S. aureus, we recommend not using TMP-SMX because you won’t be covering one of the major pathogens,” he said, adding, “we use a lot of clindamycin.”

There are clinical clues that an infection might be MRSA: if the patient fails therapy with a ß-lactam agent, if other members of the family have similar skin infections, if the patient has a recent history of skin infections (even if it improved with a ß-lactam agent previously) or if the skin infection looks like a spider bite.

Itsy bitsy spider

“Parents will often come in saying it started off as a spider bite, bug bite or insect bite. If they don’t show me the spider, it’s MRSA. It could be a susceptible strain, but strongly consider the possibility of an MRSA infection,” Lieberman said.

MRSA passes easily from person to person, so pediatricians may see more boils and other skin infections in family members. “I always ask the question, did anybody else have boils, abscesses, spider bites? If that’s the case, then this is probably MRSA,” he said.

Remember that staph can develop inducible resistance; erythromycin-resistant staph can become clindamycin resistant during therapy, making a clindamycin-susceptible organism resistant, he said. Therefore, it is important to ask for a “D test” from the laboratory to ensure that the MRSA does not posses the capacity for inducible to clindamycin resistance, he said.

“It’s important to emphasize that the likelihood of having inducible resistance is dependent on geography. In Long Beach, in Texas, less than 5% have inducible resistance. In Chicago, it was very high. The take-home message of inducible resistance: MRSA that are erythromycin resistant may exhibit inducible resistance to clindamycin. Do not use clindamycin for long-term therapy of deep-seated MRSA infections without having confirmation that it does not have inducible resistance,” he said.

“For that local skin infection, it’s not going to matter clinically if inducible resistance is present. The bug is going to be killed so fast that the patient will be better. However, if you’re treating a patient for weeks because they have an empyema or osteomyelitis, that’s where it’s going to be clinically relevant. You need to ask your lab to do the D test when you see a clindamycin-susceptible erythromycin-resistant organism if they’re not already doing it,” he said.

Lieberman said that experts are struggling with how to deal with the patients with recurrent MRSA infections. The problem is that people carry staph in the anterior nares. “Various things have been used to try to eradicate colonization. However, the efficacy is unproven. Consider trying to eradicate the organism, if there are multiple infections caused by S. aureus and proven colonization. If you’re going to treat family members, start treatment on everybody the same day.

“I am not sure what to do with the child with recurrent infections or the household with multiple infected members. You want to talk about evidence-based medicine? We don’t have any,” he said.

How did we wind up here? The microbes have the capacity to evolve in response to their environment, and that environment is selective pressure due to antibiotic use. “We get into this vicious cycle: More resistance, we use more drugs. It leads to more resistance,” he said.

What do we do about it? Make sure that children receive the varicella vaccine, which prevents secondary bacterial pneumonia and skin infections, he said. The influenza vaccines also help prevent secondary pneumonias.

And use antibiotic judiciously. “What does judicious antibiotic use mean? Only when indicated, as narrow as possible, the right dose at the right duration. High dose/short duration is effective for many infections and reduces the risk of resistance,” Lieberman said.

“Remember antibiotics are unique among pharmaceuticals in that they treat populations as well as individuals. Every prescription for antibiotics you write impacts not only that child, but the children around them. It also gives you incredible power because it means every prescription you don’t write protects a number of children.

“It’s the overuse of antibiotics that drives the emergence and spread of resistance, and each of us can make a difference by how we prescribe,” he said.

For more information:

• Lieberman JM. Handling bacterial resistance in pneumonia and skin infections in children. Presented at: 18th Annual Infectious Diseases in Children Symposium; Nov. 19-20, 2006; New York.