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Managing CA-MRSA

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Julia Ernst, MS, Assistant Editor

In the last decade, community-acquired methicillin-resistant Staphylococcus aureus (MRSA) has replaced hospital-acquired MRSA as the more prevalent — and problematic —subtype. This article reviews this ongoing shift, focusing on the changes in the typical patient population, symptomatology, treatment and the ongoing efforts to halt the spread of the disease.

Among the many countries in the world affected by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), the disease is most prevalent in the United States, as well as Japan.1 In comparison to healthcare-acquired MRSA (HA-MRSA), CA-MRSA presents with significantly increased cutaneous symptoms, including skin and soft tissue infections (SSTIs).2 It is currently the leading cause of skin infections and also causes boils, cellulitis and abscesses.

Boils and skin abscesses are “certainly not the worst symptoms that we stay up at night thinking about the most, but they’re certainly, by volume, the most problematic,” explains Buddy Creech, MD, MPH, assistant professor of pediatrics at Vanderbilt University in Nashville, TN. “In 2001, our large emergency room drained about 150 abscesses in people — one every 3 or 4 days. By 2007, we were draining about 1,800. And it’s not because the population of Nashville doubled during that time — it’s because we were seeing four or five abscesses a day, about 80% of which were due to CA-MRSA.”

Figure 1Figure 2The literature confirms the anecdotal evidence. In 2008, Talan and colleagues found that about 83% of patients who presented to the emergency department with purulent SSTIs had abscesses, compared to about 79% of admissions for the same complaint in 2004.3 Another study found that severe skin infections are the seventh most common reason for hospital admissions among children, whereas, in 2000, they ranked 13th.4 Cellulitis, folliculitis/furunculosis and impetigo have also been identified as cutaneous presentations of CA-MRSA5 (see Figures 1 and 2, above, left to right).

“CA-MRSA infections typically begin as skin infections, with patients presenting with single or multiple forms of erythematous pustular skin lesions, commonly progressing to skin abscesses that are usually painful, swollen, draining (pus) and causing fever,” explains Noel Manyindo, MD, MBA, of the Department of Global Health & Population at Harvard School of Public Health. “Central ulceration is sometimes present. Misdiagnosis as folliculitis or insect bite is not uncommon.”

The emergence of CA-MRSA as a more significant problem than HA-MRSA has occurred in conjunction with the prevalence of cutaneous symptoms over more severe MRSA complications like bone infections and pneumonia. A significant majority of MRSA-related SSTIs are caused by the community-acquired strain compared to the hospital-acquired strain (75% vs. 37%, respectively).6 This statistic, from 2003, coincides with the time period that CA-MRSA first started to appear.

Dr. Romano“The emergence of CA-MRSA was really in the first half of the last decade, between about 2000 and 2004,” explains Patrick S. Romano, MD, professor of medicine and pediatrics at the University of California, Davis School of Medicine. “It was only episodically reported in series before 2000, and then, in larger series starting in 2004, it was apparent that it had become a prominent pathogen, at least for skin and soft tissue infections presenting to emergency departments.”

With these shifts in MRSA subtype and symptomatology, a new patient population has emerged that is atypical of the standard MRSA patient.

MRSA “has always had the potential to affect healthy people,” explains Robert L. Buka, MD, JD, Section Chief of the Department of Dermatology at Mount Sinai School of Medicine and Founder and Medical Director of Upper West and Williamsburg Dermatology in New York, NY. “Doctors and nurses and respiratory techs go home at the end of the day, and, unless everybody’s washing 100% of the time, they’re going home to kids who have underdeveloped immune systems and diabetic parents who don’t have fully immune-competent immune systems. Those are examples of how CA-MRSA got a foothold in the community. Once it gains that foothold in non-hospitalized patients, we start to see the infection in certain categories [of people] — wrestlers, boarding schools and dormitory [students] and [people living in] close quarters in the community setting and metropolitan areas. We’re seeing this expanding bubble get larger and larger.”

The emergence of CA-MRSA in these healthy individuals is indicative of the impact that this new strain is having on people who would not generally be perceived as susceptible to MRSA.

“You have to look no further than those who we would say are some of the healthiest people in our society — young athletes and the military who are on active deployment,” explains Dr. Creech. “Those are the people that we typically think of as being in very good medical shape and very good physical shape, and they are two groups that have been disproportionately affected by CA-MRSA.”

Treatment

At its core, MRSA, in any form, is a staph infection, which is not a significant challenge clinically, but resistance to the beta-lactam class of antibiotics — the penicillin and cephalosporin antibiotics — is what makes treating this disease so difficult.

“We’ve created this bug” with the overuse of antibiotics, Dr. Buka explains. “When we talk about MRSA, we’re talking about resistance — it’s still staph, it just has resistance to one of our usual antibiotics that we use to fight it.”

Currently, several strategies are utilized to combat CA-MRSA: antibiotics, incision and drainage (I&D) and prevention of recurrence.

Antibiotics

In January 2011, the Infectious Diseases Society of America (IDSA) issued an updated version of its clinical guidelines for treating MRSA infections. These guidelines recommend a variety of antibiotics for CA-MRSA: clindamycin (Cleocin), doxycycline (Adoxa, others), tigecycline (Tygacil), trimethoprim-sulfamethoxazole (Bactrim, TMP-SMX) and vancomycin (Vancocin).7

Clindamycin. This lincomycin antibiotic is FDA-approved for treating serious infections caused by S. aureus.7 It is widely used in the treatment of SSTIs and has been effective against CA-MRSA in children.7,8 Some research has suggested that the drug works by inhibiting the toxin production that may play a role in MRSA pathogenicity.9

There are side effects associated with clindamycin, and some resistance to the drug in recent years has raised questions.5,7 In addition to a resistance that seems, to a degree, regional, clindamycin resistance is also particularly increased in cystic fibrosis patients, making the drug a poor choice for these individuals.5 Side effects of clindamycin are primarily gastrointestinal problems.7

Doxycycline. Of the tetracyclines available for CA-MRSA, doxycycline is preferred, as it has been shown to have adequate coverage against MRSA and better anti-streptococcal activity.5 Doxycycline is FDA-approved for the treatment of SSTIs due to S. aureus, although not specifically for S. aureus infections caused by MRSA.7 Data on such use are limited.7

Recently, there have been concerns about resistance. It appears that doxycycline may have inducible resistance against CA-MRSA through the tetracycline resistance gene tet(K).5 Doxycycline is not suggested for use in children under 9 years of age because of adverse effects, including discoloration of teeth and inhibition of bone growth.5 Other side effects to doxycycline include gastrointestinal intolerance, photosensitivity, drug hypersensitivity and skin pigmentation.5

Tigecycline. This glycylcycline, a derivative of the tetracyclines, is FDA-approved for adults with cSSTIs and intra-abdominal infections.7 Because it has demonstrated a large volume of distribution and high concentration in tissues and low concentrations in serum, as well as bacteriostatic activity against MRSA, it is not recommended for the treatment of patients with bacteremia.7

Trimethoprim-sulfamethoxazole. Known by the brand name Bactrim and abbreviated as TMP-SMX, this drug is “a valuable antibiotic of choice for CA-MRSA.”5 While the drug is not FDA-approved for the treatment of any staphylococcal infections, 95% to 100% of MRSA strains have been demonstrated as susceptible in vitro, and it has become a strong option for outpatient treatment.7 In addition, antibiotic resistance to TMP-SMX has not been identified as a significant problem in facilities where the treatment is used routinely.9

Vancomycin. A 15-year study of the changing epidemiology of MRSA revealed that all CA-MRSA isolates in the series were susceptible to vancomycin.10 Another study states that the drug “is reserved for treatment of infections caused by multi-resistant MRSA strains and for patients with severe systemic infections.”6 It is safe and effective for both children and adults.7

The ISDA guidelines state that vancomycin has been “the mainstay of parenteral therapy for MRSA infections,” though it is noted that efficacy has come into question in recent years, particularly because of its slow bactericidal activity, the emergence of resistant strains and possible “MIC creep” among susceptible strains.7

MRSA “is certainly widespread,” Dr. Buka explains. “The outlook, I think, depends upon how rapidly these bacteria adjust to the agents we now have for MRSA. And that’s happening with some of the new antibiotics, like lincomycin, which we use in acute cases where we find a bactrim-doxycycline-clindamycin resistance. That’s happening, which is frightening, but it’s happening on a very small scale, currently.”

Dr. Romano concurs.

“I think that our data and others suggests that we’ve probably reached a new equilibrium in terms of the prevalence of the organism in the community and the incidence of associated infections,” he explains. “This is not something that’s rising exponentially, it’s not a true epidemic at this point, so we’re at a new equilibrium and it’s changed how we practice medicine, in that you have to use antibiotics that are active against most strains of CA-MRSA, and we have to have a little more readiness with the knife, so to speak, to drain these abscesses before they get too large.”

Incision and Drainage

Figure 3Figure 4The incision and drainage procedure (see Figures 3 and 4, left to right) can be done alone or in combination with antibiotics — the choice of one or both is made on a case-by-case basis.

“A decade ago, two decades ago, the standard of care for these types of boils was to lance it at the doctor’s office or the emergency room and, as long as the lancing went well, you probably didn’t even need antibiotics,” Dr. Creech explains. “By getting the pus out, you’re also getting the bacteria out. When CA-MRSA came around, people were a little bit nervous to do that, just because we didn’t have proof that it would work, but, over the last 5 years or so, people have felt more and more comfortable in just draining it and not putting [the patient] on antibiotics.”

Evaluation of each patient for specific symptoms is the key to determining if and when antibiotics are needed in addition to I&D.

“It’s differentiating whether it’s just cellulitis without a collection of pus or is there an abscess?” Dr. Romano explains. “I think it’s generally accepted that, if there’s an abscess or a collection of pus, that pus needs to be drained — incision and drainage. It’s draining the pus, but usually the abscess is surrounded by some cellulitis, some soft tissue infection, and so then the patient usually has to be treated with antibiotics. There are some patients who present only with cellulitis without abscess. One of the features of this organism is that it tends to be more likely to form abscesses than the other pathogens that cause cellulitis.”

A literature review of CA-MRSA in the United States from 2011 cites “incision and drainage of purulence and application of heat as the most effective treatment of abscesses regardless of the infecting organism… Antibiotic management of CA-MRSA is different from infections caused by HA-MRSA; therefore, it is important to differentiate the organism through culture and susceptibility confirmation to determine whether CA-MRSA is susceptible to less costly antimicrobials and leave more expensive antibiotics as last resorts.”11

Preventing Recurrence

Dr. BukaGetting rid of MRSA “is the easier part,” explains Dr. Buka. “Preventing it from becoming recurrent can be more challenging. Some of the things we do are bleach baths, where we put a half of cup of bleach in a full bathtub for 10 minutes — that brings bacterial counts down on the skin. We’ll do mupirocin for the nose, peri-anal, axilla, groin area, three times a day for 5 days, in an effort to draw up the bacterial counts in these warm, dark, moist places where we know the bacteria lives.”

Mupirocin is recommended, specifically, for nasal decolonization, given twice a day for 5 to 10 days.8

Chlorhexidine is an agent used by surgeons before a procedure for hand washing, explains Dr. Romano, but it is also available in a weaker concentration that can be used for bathing. Some evidence supports the use of these chlorhexidine baths for the prevention of recurrent CA-MRSA infections.8 These baths work by bringing the bacterial counts on the skin down, according to Dr. Buka.

Another crucial part of preventing recurrence is halting the spread of the disease among families and individuals in close living quarters. One standard strategy for doing this is “to put an antibiotic ointment in the nose and to do some disinfecting of the skin for about a week,” explains Dr. Creech. “You do that for about a week in every family member and that tends to break the cycle of it being spread from one to another and the abscesses from occurring over and over again in the same person.”

A study in Clinical Infectious Diseases from December 2011 compared decolonization of the CA-MRSA-infected individual alone to decolonization of the entire household. The results showed that, while household decolonization was not more effective than individual decolonization for eradication of CA-MRSA, decolonization of every individual in the household did decrease recurrent SSTIs.12

Among 126 of 147 total cases completing the 12-month follow up, “S. aureus was eradicated from 54% of the index group versus 66% of the household group (P = .28). Over 12 months, recurrent SSTI was reported in 72% of cases in the index group and 52% in the household group (P = .02). SSTI incidence in household contacts was significantly lower in the household versus index group during the first 6 months; this trend continued at 12 months.”12

This is a key role for dermatologists in the battle against CA-MRSA.

“I think more and more of the [medical] community is becoming more comfortable with treating MRSA and infectious diseases, and I think dermatologists can be particularly helpful, especially in that phase of preventing recurrence,” explains Dr. Buka.

The Need for Proactive Prevention

Proper hygiene is the key to controlling CA-MRSA from the onset (see “Hand Hygiene is the Key to Prevention," below). Strategies for halting the spread of the disease can lessen the impact once an individual becomes ill, and there are effective treatment options, but efforts are still needed to get ahead of the disease.

“Given that there’s this uncertainty about whether prevention works, our strategy still relies, principally, on early detection of infections and proper treatment when infections arise,” says Dr. Romano. “That’s still going to be the primary focus, but that may change as we get more evidence about prevention.”

Dr. CreechCA-MRSA is “the most common infection in the United States right now,” explains Dr. Creech. “What we desperately need is a proactive way to prevent it, because those who have been practicing for a long time will tell you that, about every 10 to 15 years, there’s another wave of a new sort of version of staph infections. It was toxic shock syndrome in women who were menstruating, it was nursery outbreaks in the 50s — every 10 to 15 years, it pops its head up in an interesting way — so what we really need, what we really, really need, is a vaccine, and there are finally two or three candidates that are in the pipeline so that, within the next decade, we may see a vaccine that, especially in those who are the highest-risk, could prevent the disease from the get-go."

SIDEBAR: Hand Hygiene is the Key to Prevention

One of the most effective strategies for dealing with CA-MRSA is preventing its emergence in the first place. A tip sheet from the Centers for Disease Control and Prevention (CDC) cites universal good hygiene practices as “the key to preventing MRSA infections.”13 The first step in this process is proper hand washing with soap and water or an alcohol-based hand rub.13

The use of hand sanitizers and antiseptic products can be an effective substitute for washing with soap and water if the product is used properly. A recent consumer update from the FDA highlights an important contingency to this claim, however. While hand sanitizers are effective for cleanliness and hygiene purposes, the assertion that they can also prevent MRSA infections is inaccurate.14

In an FDA consumer update from December 2011, Deborah Autor, compliance director at the FDA’s Center for Drug Evaluation and Research, says: “Consumers are being misled if they think these products you can buy in a drug store or from other places will protect them from a potentially deadly infection.”14

Some of these unproven claims include statements that hand sanitizers and similar products can kill more than 99.9% of MRSA, that they help prevent skin infections caused by MRSA and other germs, and that they are effective against a broad spectrum of pathogens, including MRSA.14

The FDA “has not approved any products claiming to prevent infection from MRSA, E. coli, Salmonella or H1N1 flu that a consumer can just walk into a story and buy,” Autor says.

J. Hudson Garrett Jr., PhD, MSN, FNP-BC, VA-BC, is the senior director of Clinical Affairs at PDI Healthcare, a company that develops and manufactures infection control products like sanitizers and wipes. According to Dr. Garrett, the FDA update was specifically about “the inappropriate advertising regarding MRSA that many hand hygiene manufacturers were releasing, especially with recent community outbreaks.”

Manufacturers of these hand hygiene products cannot make claims about specific infections, Dr. Garrett explains — they can only speak to microorganisms. An example of this would be claiming efficacy against MRSA as a pathogen — but not MRSA as the infection.

While healthcare professionals must be conscientious about the specific products that they use in the healthcare setting and recommend to patients, proper hand hygiene is, as the CDC guidelines state, the key to preventing CA-MRSA.

“Hand hygiene, no matter how it’s defined, is an effective mechanism for reducing transmission of any organism,” explains Dr. Creech. “And hygiene that is gel-based or foam-based, the hand sanitizers outside the room, typically are easier to be compliant with than a 20-second or 30-second hand wash.”