How To Recognize And Treat Community-Acquired MRSA

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In the past few months, we have heard numerous reports in the news about a “new super bug” that is resistant to conventional antibiotics and is sweeping through high school sports locker rooms and classrooms. The alleged new super bug is methicillin resistant Staphylococcus aureus (MRSA) and, more specifically, community-acquired MRSA (CA-MRSA).
However, MRSA is not a new type of bacteria that has suddenly appeared in the community. The organism has actually been around for quite a few decades.
In 1941, all S. aureus isolates were susceptible to penicillin and relatively low doses of penicillin (PCN) were required to treat it. However, by 1944, penicillin resistant strains were identified in both hospitals and the community. Around this same time, physicians saw the emergence of semisynthetic PCNs including methicillin, nafcillin and oxacillin. These became the antibiotics of choice for Staph infections. However, Staph aureus soon developed resistance to these semisynthetic penicillins. The first strain of MRSA was identified in 1961 and became prevalent by the late 1970s. In the 1980s, sporadic cases of CA-MRSA emerged in previously healthy children and young adults having no recent contact with hospitals or other healthcare settings. [7]¹
Indeed, CA-MRSA is not a new pathogen that has suddenly begun to run rampant throughout our communities, schools and athletic facilities. In fact, the CDC reports that approximately 30 percent of healthy, asymptomatic individuals and as many as 65 percent of people with Staph skin infections carry S. aureus in their anterior nares and skin. Approximately 1 percent of the population is colonized with MRSA via skin and nares.^2,3
Indeed, CA-MRSA has presented an interesting public health issue regarding the epidemiology, treatment methods and prevention of this infection in the community. It also presents an interesting dilemma to physicians regarding the most efficacious ways of recognizing and treating CA-MRSA.

Differentiating Between CA-MRSA And HA-MRSA
According to the Centers for Disease Control and Prevention (CDC), CA-MRSA infections are MRSA infections that are acquired by people who have not been recently (within the past year) hospitalized or had a medical procedure such as dialysis, surgery or catheter placement.
[3]Staph aureus is a gram-positive coccus that grows in clusters. Some S. aureus isolates have developed resistance to the semisynthetic penicillins, namely methicillin, by altering the antibiotic’s target, penicillin binding protein (PBP), a protein on the bacterial inner membrane. This alteration leads to a decreased affinity for the antibiotic and what we know as MRSA.¹
The genes for resistance of CA-MRSA are typically carried on the mec Type IVa chromosomal cassette, a mobile genetic unit.⁴ This gene cassette codes only for methicillin resistance as opposed to multiple antibiotics. This is a major characteristic that distinguishes CA-MRSA from hospital-acquired MRSA (HA-MRSA). Therefore, CA-MRSA, as opposed to HA-MRSA, remains highly susceptible to many antibiotics.⁵ In fact, CA-MRSA clones are genetically distinct from isolates of HA-MRSA and are actually more similar to methicillin sensitive Staph aureus on a genetic level.⁶

A Guide To Pertinent Diagnostic Pointers

A 2003 study suggests that CA-MRSA skin infections may look like a pimple or boil. They can be red, swollen, painful or have pus or other drainage. Greater than 90 percent of CA-MRSA infections present as skin and soft tissue infections such as carbuncles, furuncles, “boils” and abscesses, and often as lesions that resemble spider and insect bites.^5,7,8
However, CA-MRSA can present as more serious infections such as endocarditis, pneumonia and bacteremia.¹
What is it about MRSA, and specifically CA-MRSA, that causes such a high economic impact, an increased length of hospital stay, morbidity and mortality? There are certain virulence factors that lead to worse outcomes for hospitalized patients with MRSA in comparison to those with MSSA.
Panton-Valentine leukocidin (PVL) is the major virulence factor that leads to most of the skin and soft tissue manifestations of CA-MRSA.³ Panton-Valentine leukocidin is a toxin that creates lytic pores in the cell membrane of neutrophils and releases neutrophilic chemotactic factors, including interleukin-8 and leukotriene B4, which cause tissue inflammation and destruction.⁶ One study showed that injection of PVL into the skin of rabbits caused dermal necrosis.⁹
More often than not, clinicians will be faced with sporadic cases of CA-MRSA infections. When physicians see a patient present with a skin or soft tissue infection, they should remember to run down a list of differential diagnoses including but not limited to:
• impetigo;
• insect bites;
• erysipelas;
• contact dermatitis;
• lymphedema;
• herpes viral infections; and
• Strep infections.
Reviewing the patient history, including previous skin infections and identifying common CA-MRSA risk factors, is also essential.

Understanding The Common Risk
Factors For CA-MRSA Factors that have been associated with the spread of MRSA skin infections include: close skin to skin contact; openings in the skin such as cuts or abrasions; contaminated surfaces; crowded living conditions; and poor hygiene.
According to statistics, the risk for CA-MRSA is higher for athletes, prison inmates, military personnel, children in daycare and the homeless as these people are often in crowded conditions or have close contact with one another.
Most cases of CA-MRSA in the U.S. that we often see and hear about in the news tend to occur in clusters and involve sports teams such as those involved in fencing, football and wrestling. Repeated close physical contacts and skin injuries such as cuts and abrasions put this group at an increased risk for CA-MRSA infections. The first published reports of CA-MRSA involving sports teams were in 1998.²
A couple of years ago, there was an outbreak of CA-MRSA among the St. Louis Rams professional football team. Five of the 58 players (9 percent) developed CA-MRA infections at turf abrasion sites. Cultures revealed identical isolates of CA-MRSA containing the pulsed field type USA300 clone and carrying genes for Panton-Valentine leukocidin virulence factor.⁵

Are Antibiotics Necessary For CA-MRSA?

The primary indicated treatment for CA-MRSA abscess is incision and drainage. [4]In fact, many patients have responded to drainage alone without any antibiotic therapy. In one study, researchers evaluated 69 children, who all had culture-proven CA-MRSA abscesses. Treatment consisted of incision and drainage for 96 percent of the patients. Only five patients were prescribed antibiotics to which the isolates were susceptible before culture results were known.
The study concluded there was no significant difference between patients who never received an effective antibiotic versus those who did. The study also concluded that incision and drainage of abscesses bigger than 5 cm without adjuvant antibiotic treatment was effective.^5,10
[6]Hospital-acquired infections tend to be resistant to multiple antibiotics and physicians often treat these patients with vancomycin and linezolid (Zyvox, Pfizer). However, CA-MRSA is often susceptible to many non-beta-lactam antibiotic classes. One should base antibiotic selection on a previous history of CA-MRSA infection, susceptibility patterns, severity of the infection, clinical response to therapy and cost. [5]

What You Should Know About Clindamycin
Physicians have utilized clindamycin for years to treat skin and soft tissue infection caused by CA-MRSA, and it is very effective orally. However, in various geographical areas throughout the U.S., clindamycin shows trends of resistance. Strains of MRSA that are clindamycin sensitive but erythromycin resistant may exhibit the inducible macrolide-lincosamide-streptogramin B phenotype, which presents a high possibility for treatment failure.
Many labs are performing what is called a “D-test,” which tests for this inducible lincosamide resistance. For the test, one would place lincosamide (clindamycin) and macrolide (erythromycin) disks in close proximity to one another on a culture plate. The zone of inhibition around an antibiotic disk is usually round. According to the National Consensus Committee on Laboratory Standards, if the zone of inhibition around the clindamycin disk is flattened on the side toward the macrolide (erythromycin) disk, resembling the letter D, then the clinician can presume that inducible lincosamide (clindamycin) resistance is present yet clindamycin may still be effective in some patients.^5,10
Even though all antibiotics have the potential to cause Clostridium difficile colitis, clindamycin is the antibiotic most often associated with this condition. Clinicians should be aware of this potentially life-threatening adverse event if diarrhea develops after recent treatment with clindamycin.

A Primer On Other Antibiotics To Consider For CA-MRSA

Community-acquired MRSA is highly susceptible to trimethoprim-sulfamethoxazole (TMP-SMZ) and treatment is often successful, especially in children. The oral bioavailability of TMP-SMZ is excellent, resistance to CA-MRSA is rare and it is relatively inexpensive.
Since sulfamethoxazole is one-half of this antibiotic, one should be cautious about using this drug in patients who have an allergy to sulfa or those who have a G6PD deficiency in order to prevent adverse anaphylaxis or an adverse drug event. Some clinicians may be under-treating with TMP-SMZ if they are prescribing this antibiotic using the dosage recommended for urinary tract infections by giving only one double-strength tablet twice per day. The most effective dosage for treating MRSA is actually 10 mg/kg/day based on the trimethoprim component. This is equivalent to two double-strength tablets twice daily.⁴
Physicians have used rifampin to treat CA-MRSA but one should never use this alone to treat MRSA because of resistance. Some studies investigating the synergism of rifampin with other antibiotics contend that physicians may achieve success by using it in combination with fluoroquinolones.⁴
While clinicians often use fluoroquinolones alone to treat CA-MRSA infections, researchers have documented numerous cases of resistance. According to a 2005 New England Journal of Medicine article, susceptibility to fluoroquinolones varies greatly by region, being as low as 19 percent in some regions and as high as 80 percent in others.¹¹
The newer generation fluoroquinolones such as moxifloxacin, gatifloxacin and levofloxacin seem to exhibit less resistance versus older agents of this same class. Researchers have also shown that combining fluoroquinolones with other agents reduces the incidence of resistance. Daptomycin (Cubicin, Cubist), quinupristin-dalfopristin, tigecycline (Tygacil, Wyeth), minocycline, doxycycline and newer-generation carbapenems, such as ertapenem (Invanz, Merck), meropenem and penipenem, are also effective against CA-MRSA and are available orally.
Linezolid is an oxazolidinone physicians can utilize for the treatment of severe MRSA infections including bacteremia and pneumonia. Potential side effects of linezolid include thrombocytopenia, neuropathy and optic neuritis. When a patient is on linezolid for greater than two weeks, clinicians should follow-up with a CBC to monitor for the drug’s possible hematologic side effects.
Linezolid has 100 percent oral bioavailability, which negates the need for IV treatment with this drug. While the high cost of linezolid deters some physicians from prescribing it, the high efficacy rate coupled with the reduced hospital length of stay may make it cost-effective.⁵
Vancomycin remains a very important antibiotic choice when one is faced with serious CA-MRSA infections including cases of septic shock, necrotizing pneumonia, endocarditis and complicated bone and joint infections. Physicians often add gentamicin to vancomycin when it comes to serious, life-threatening infections. One must administer vancomycin intravenously for the treatment of any infection other than C. diff colitis and that includes CA-MRSA infections. Accordingly, patients must be hospitalized to receive treatment or they can have vancomycin administered through a PICC line on an outpatient basis.
Since there is a good armamentarium of antibiotics to choose from to treat CA-MRSA, physicians should be familiar with the antibiotic susceptibility patterns to S. aureus in their own communities in order to prescribe the most effective antibiotics for their patients.

Is Colonization The Key To Recurrence Of CA-MRSA?
Community-acquired MRSA infections recur at a high rate. A generally accepted school of thought behind this is the issue of colonization.
As mentioned earlier in this article, most individuals are colonized with S. aureus on the skin and in the nares. Researchers have shown that topical mupirocin 2% nasal ointment (Bactroban) is effective for the treatment of S. aureus nasal carriage. Oral and IV antibiotics do little to control skin surface colonization. Accordingly, it is common to address skin surface colonization with topical agents containing chlorhexidine, triclosan, Dakin’s solution and alcohol. Fomite disinfection with alcohol-based formulas is also helpful in controlling infection recurrence.
One study showed that the most effective disinfectants against MRSA were solutions containing 70% ethanol. This concentration of alcohol in a solution eradicated MRSA and MSSA in less than three minutes.¹²

Final Notes On Prevention
Patients should clean skin abscesses daily and clean them completely to prevent person-to-person contact and the spread of the infection. Changing clothes, towels and bed linens daily may also help to prevent re-infection. Reinforce routine hand washing to individual patients, parents, staff employed in schools and day care facilities, coaches and anyone in crowded living or work spaces to assist in decreasing the spread of CA-MRSA infections.

Dr. Pupp is a Fellow of the American College of Foot and Ankle Surgeons. He is the Director of the Foot and Ankle Clinic at Oakland Regional Hospital in Southfield, Michigan. He is also on the Residency Training Committee at Providence Hospital in Southfield, Michigan.
Dr. April is a first-year podiatric medicine and surgery resident at Providence Hospital in Southfield, Michigan.

References:

1. Le J, Lieberman JM. Management of community-associated methicillin resistant Staphylococcus aureus infections in children. Pharmacotherapy 2006; 26(12):1758-1770.
2. Rihn JA, Michaels MG, Harner CD. Community-acquired methicillin-resistant Staphylococcus aureus: an emerging problem in the athletic population. Am J Sports Med. 2005; 33, 1924-1929.
3. Romero, DV, Treston J, O’Sullivan AL. Hand-to-Hand Combat: Preventing MRSA Infection. Adv Skin Wound Care 2006; 19:328-33.
4. Ellis WE, Lewis, JS. Treatment approaches for community-acquired methicillin resistant Staphylococcus aureus infections. Curr Opin Infect Dis 18:496-501.
5. Elston DM. Community acquired methicillin resistant Staphylococcus aureus. J Am Acad Dermatology 2007; 56:1-16.
6. Kollef MH, Micek ST. Methicillin-resistant Staphylococcus aureus: a new community acquired pathogen? Curr Opin Infect Dis 19:161-168.
7. Domininguez TJ. It’s not a spider bite, it’s community-acquired methicillin-resistant Staphylococcus aureus. JABFP 17(3), 2004.
8. Performance Standards for antimicrobial susceptibility testing: fourteenth informational supplement. NCCLS, M100-S14,24(1), 2004.
9. Ward PD, Turner WH. Identification of staphylococcal Panton-Valentine leukocidin as a potent dermonecrotic toxin. Infect Immun 1980; 28:393-7.
10. Buescher ES. Community-acquired methicillin resistant Staphylococcus aureus in pediatrics. Curr Opin Pediatr 17:67-70.