Wound Care in the Era of MRSA: My Pearls and Pitfalls

Although it’s been almost 10 years, I’ll never forget the tone and inflection from my attending when she impressed upon me just how serious she considered ‘staph’ to be as a pathogen. At the time I was a new Infectious Diseases Fellow and I remember thinking that surely there must be some other bugs that would rate the same serious consideration. However, what I didn’t appreciate then—I do now.

Understanding Staph
In today’s ecology of microorganisms, the word ‘staph’ automatically brings to mind Methicillin Resistant Staphylococcus aureus (MRSA). However, over the last several years I have developed a much greater sense of appreciation for something that my attending knew back then—this germ should never be taken lightly. MRSA can cause a broad range of illnesses from simple recurrent furunculosis to severe invasive necrotizing pneumonia. For reasons—some that still elude me—MRSA can be cultured from wounds that seem to be on track toward healing; causing no obvious problem. Likewise, I have also seen MRSA cause severe, tissue/limb/life threatening, fulminant disease in patients who do not have the traditional risk factors of being colonized with or infected by staph aureus. It’s the great masquerader.

Lessons Learned In Time
In preparation for this article, I reviewed numerous medical publications including full peer reviewed articles and case reports; information available through the CDC; and Emerging Infectious Diseases. All of my resources were recent and published within the last 6 years. In order to fully appreciate MRSA as a pathogen, I think it is worthwhile to take a look at the historical arrival of MRSA on the clinical stage. MRSA was first identified in 1958. By 1961, it was documented as the cause of an infection in the United Kingdom. In 1968, reports of MRSA isolation were noted in the United States. By 1990, MRSA was found worldwide and was recognized as a cause of infection in ‘nontraditional’ patient groups. In 2003, continent - specific clones (ie, genetically distinct germs) were identified. We now have region specific clones across the U.S.

MRSA or Not MRSA
Whenever a provider writes an order for a ‘culture’, not only is extra cost added to the bottom line but a series of multiple events is set into motion—much like tipping over the first of many closely standing dominos. Hopefully the culture report will provide meaningful information to the provider thus enabling him to make an informed decision regarding possible changes in the patient’s treatment plan. This is why it is so imperative that, when a wound is cultured it is not collected from a haphazardly prepared wound bed or tissue space.
For those unfamiliar with what is involved in a microbiology lab in order to identify an organism, the first step is that a technician (or first year Infectious Diseases Fellow) - using the swab that was received in the lab - streaks a small glass slide and then inoculates an agar plate (plastic dish filled with a nutrient rich jelly-like substance that enhances bacterial growth). The agar plate is set aside to incubate and, the slide is streaked and allowed to dry. Once the streaked slide is sufficiently dried, various chemicals are applied sequentially, which will strain bacteria that were hopefully deposited there when it was streaked. This series of steps is called a ‘Gram Stain’; developed in 1882 by and named after Dr. Hans Christian Gram. Bacteria that stain darker violet to bluish purple are called ‘Gram positive’. Those that don’t are called ‘Gram Negative’. By microscopic examination, the now visible stained bacteria can be further described and identified based on their morphologic appearance. If the stained bacteria appear in clusters or in tetrads of round balls (cocci), they are called gram positive cocci (GPC’s), which are Staphylococci. Not know at the point is if the germ is Staph aureus or one of many other Staph species. GPC’s appearing in chains or pairs usually
are Streptococci.
Unfortunately, the next step in this determination cannot be completed until there is enough growth of the organism on the agar plate to allow the next chemical test to be performed. This usually takes a minimum of 24 hours for a colony of bacteria to appear on an agar plate. Only then can a “coagulase” test be done. This test capitalizes on the fact that Staphylococcus aureus is—of all the GPC’s—the only one with a cell wall protein called “coagulase”. It is one of many cell wall proteins found in Staphylococcus aureus that confers the potentially toxic effects to tissues. Through a one step bench-side test it can be determined whether or not the protein coagulase is present. If the test is positive, the organism is a “coagulase positive GPC”, which means that it is a Staphylococcus aureus. However, what is still unknown is whether the Staphylococcus aureus is MRSA or not. This determination requires testing against a panel of antibiotics and takes an additional 24 to 48 hours. If the coagulase test is negative, the organism is called a “coagulase negative GPC”. By convention, all coagulase negative staphylococci are collectively referred as ‘coag-negative staph’ and sometimes all non-aureus staph are collectively called ‘staph epidermidis’.

Life or Death
This understanding and my clinical experiences - particularly over the last five years have influenced how I utilize the information offered by the Gram stain. If your lab does not automatically perform this test, you should be sure to order that it be done. It may mean the difference between life and death—or at least potentially severe tissue destruction for your patient.
I have a very low threshold for further investigation of any wound (surgical or not) that has redness, edema, or pain that is present beyond the expected, normal phases of wound healing. In 2003, SENTRY, an antimicrobial surveillance group in the U.S. and Canada reported that Staphylococcus aureus accounted for 46% of nosocomial skin and skin structure infections (SSSI) that occurred in 2000. Of these, 14% were identified as MRSA. By 2004, this percentage doubled to 35%. In 2005, the CDC reported that MRSA was responsible for over 94,000 serious infections and over 18,000 deaths in the U.S. There were over 12 million documented physician/healthcare provider visits for suspected MRSA in 2008. MRSA now accounts for 59% of SSSI’s and 14% of invasive disease. Practically speaking, as a caregiver/clinician, you should now take very seriously any Gram stain report that is positive for GPC’s because you may be dealing with MRSA.

More Knowledge
Further classification of MRSA’s developed over the last several years and is based on various genetic characteristics of the MRSA community. Microbiologically speaking, an MRSA can be a hospital acquired (HA) or community acquired (CA) MRSA. HA-MRSA typically has large genetic elements called cassettes. The first 3 of these to be identified were labeled types - I, II, and III. Type II was found to be the most common in HA-MRSA isolates. It contains multiple drug resistance genes (all closely associated on the gene) confers resistance to multiple classes of antibiotics. The main “clone” that was first identified was named “USA 100”. In contradistinction, the CA-MRSA was found to have a fourth genetic element, which is small, mobile, able to parasitize numerous other host strains, and mediates methicillin resistance. This fourth element is the hallmark of CA-MRSA. It usually does not have such broad antibiotic class resistance as does HA-MRSA and has been more associated with SSSI’s than HA-MRSA strains.
Will you be able to tell whether or not your patient has an HA-MRSA or CA-MRSA right off the bat? It’s doubtful that you will. Clinically, wounds infected with HA-MRSA or CA-MRSA look the same on patients. As if coagulase isn’t enough to worry about, MRSA sports other proteins that make them particularly nasty bugs. Panton - Valentine - Leukocidin (PVL) is a protein that was first introduced in the 1930’s and is present in over 50% of all MRSA isolates. This protein allows the staph to bore a hole (form a pore) in the host wbc’s, in effect disabling them. Also, some CA-MRSA clones have a protein called ACME (argenine catabolic mobile element) that inhibits wbc formation. You may be asking yourself, what does this mean? No functioning wbc’s = no formation of pus = nothing to ‘drain’ through a therapeutic stab wound = ineffective evacuation of infected and nonviable tissue. Recall that the treatment of an abscess is and always will be drainage. A treatment plan for suspected MRSA SSSI should start with effective evacuation of the involved tissue either locally or formally in the operating room theater. If a patient appears “ill” due to an abscess or SSSI, a broad-spectrum systemic antibiotic is probably in order as adjunctive therapy to removal of the affected tissue. Once the sensitivities from the culture are back from the lab, antimicrobial therapy should be targeted or narrowed if possible. Lengths of antibiotic therapy should be based on clinical response.

The Risk Factor
So, the next time you examine a patients “boil/sore/risen/abscess/suture line/staple line/drainage tube/non healed calcaneal pressure ulcer/post op C-section incision line/or surgically created pain-pump pocket site, take a second look for signs of this often times non-pus forming organism.
Clues that I use in order to determine whether or not I believe a patient has a reasonable risk of having MRSA infection in order of most important to less important are:
1) do they have close contact (live in the same home, share toiletries, have sex) with someone who has had MRSA SSSI’s;
2) do they have a personal history of having had MRSA;
3) have they been incarcerated within the last 12 months;
4) do they snort or smoke illicit drugs; is their chief complaint having a “spider bite”;
5) have they had oral or intravenous antibiotics within the
last month.
6) and is there paint out of proportion to how the wound looks?

Groups at high-risk for developing SSSI’s are: military recruits; native populations; homosexual males; HIV+ patients; those who participate in football, wrestling, gymnastics, fencing teams; homeless and IV drug users. There are also documented cases of patients contracting MRSA from their pets. Depending on other patient factors (co-morbid conditions; systemic signs and symptoms) and what you are able to safely do in your clinic will determine your next steps.

Complex I&D’s
Patients on whom I have chosen to perform complex I&D’s are characterized by not really being too systemically ill as a result of their abscess/infection/SSSI (ie, - no persistent fever/chills; not feeling totally rotten; well demarcated area of induration and erythema). They are able to return to clinic within 48 hours; have adequate support system; are reliable; not on anticoagulants and can demonstrate proper care of the wound. It has been my experience that the area of nonviable subcutaneous tissue mirrors the demarcation of edema/induration/erythema. Not infrequently upon incision of the area, there will be no purulence; nothing to ’drain’. Rather, the exposed subcutaneous tissue appears dusky brown; almost like bad hamburger meat. The nonviable tissue can be evacuated with a small curette, aggressively irrigated; and packed with one of many possible antimicrobial dressings. The benefits of performing this in the outpatient setting include but are not limited to the fact that there has been one less patient with ‘staph’ admitted to the hospital; there has been better stewardship of the use of antibiotics (orals vs. intravenous if used); and there has been better/more efficient use of healthcare resources.

Antibiotics
If adjunctive emperic antimicrobial therapy is prescribed you should be aware of the MRSA sensitivity patterns in your hospital system and/or community. This information is readily available through the laboratory that performs your cultures. The infection control nurse or your local infectious diseases physician is also a good starting points to retrieve this information. Once an antibiotic has been selected, make sure the patient can obtain the prescription; many are cost prohibitive even with insurance plans. Be aware that tetracycline resistance does not equal minocycline or doxycycline resistance so get the lab to specifically check for this. Try to choose an antibiotic that your patient has a higher likelihood of being compliant with (BID dosing always trumps QID or TID dosing). Always advise and teach patients about the nuances of particular antimicrobial agents such as dosing around cations (magnesium, calcium; cheese; dairy products) so that the drug actually gets absorbed and not bound with a cation in the GI tract and flushed down the toilet. Double check for drug allergies and potential serious interactions an antibiotic may have with one or more of a patient’s other medications. Depending on these and other factors unique to your patient, it may be prudent to prescribe intravenous outpatient therapy; preferably a once daily agent. I reserve picc lines for patients who are going to receive at least 4 weeks of therapy and do not have Chronic Renal Insufficiency. This always keeps me in good stead with my Nephrology colleagues as these patients will likely need their deeper arm veins for dialysis access.

Wash Your Hands
Remember that there are no new oral antibiotics on the horizon so we all must be good stewards of the ones we have. Agents available for oral and/or intravenous treatment for MRSA include clindamycin; tetracycline; bactrim; zyvox; vancomycin and daptomycin. If needed, the selection should be tailored to your patient’s particular needs/considerations. Lastly, we must all commit to adhering to our institutions infection control policies; use of hand cleansing gels and most importantly: Wash Your Hands. Become your clinic’s self-appointed hand washing police and demonstrate good hand hygiene to your patients. Believe me, they will appreciate it.

Harriet Jones, MD is the Medical Director and first full-time physician at the Wound Care and Hyperbaric Medicine Center at River Oaks in Flowood, Mississippi. To find out more about her skills and experience you can contact her via email at harriet.jones@hma.com

　Dr. Jones put together this Call-Out resource for use and posting in your wound care clinic.

Micro 101
• Gram’s Stain differentiates
o Gram Positive Cocci (GPC’s) from Gram Negative Organisms
o GPC
• Staph spp
• Strep spp
• Coagulase Test
o Coagulase positive = unique to Staph aureus
o Coagulase negative = any other Staph spp
• No quick test identifies MRSA from MSSA

Groups at Risk for SSSI’s
• Military Recruits
• Native populations
• Homosexual males
• HIV+ pts
• Football teams
• Wrestlers
• Gymnasts
• Fencing teams
• IV drug users
• Homeless
These groups have a low threshold for consideration of MRSA.

Oral Options for Presumed MRSA
• Bactrim
o SS or DS
• Tetracycline
o Vibratabs
o Doxycycline
• Clindamycin
• Zyvox

Considerations for I&D in clinic…
If yes to below – probably can do…
• Afebrile
• Hemodynamically stable
• Not on anticoagulation
• Clinic set up to do
o Curette
o Scalpels
o Injectible and topical anesthetic
• No anatomic contraindications
• Reliable pt; good support system
• Available for follow up within 48 hours

IV or PO antibiotics
• Considerations for IV
o End organ effects of DM, gastroparesis; pvd
o Doubtful compliance with oral regimen
o Systemically ill
• Hemodynamically unstable
• Elevated glucose
• Elevated temperature
o No oral options
• Considerations for oral
o CRI; save deep veins
o Adequate GI absorption
o Adequate vascular delivery
o Probable compliance
o Preserved sensitivities to oral agents
o Affordability