Key Considerations With Diagnosing And Treating MRSA

Given the challenges of hospital-acquired strains as well as the emergence of community-acquired strains of MRSA, this author discusses clinical, practical and medicolegal aspects of the diagnosis and treatment of this condition.

Staphylococcal organisms are the most common cause of hospital-acquired infections and postoperative infections. Staphylococcal organisms are also the most common bacteria in diabetic foot infections and community-acquired infections.

   Many staphylococcal infections due to methicillin resistant Staphylococcus aureus (MRSA) result in greater morbidity and mortality. This is due to delays in recognition of MRSA as the infecting organism, which subsequently lead to a delay in the initiation of appropriate antibiotic therapy for MRSA. While MRSA is frequently regarded as a more virulent organism, initial therapy offering coverage for MRSA reduces the incidence of significant pathology associated with this organism. In general, one should consider all infection as resulting from MRSA until proven otherwise.

   The medical history may raise suspicion of the predisposition of patients to MRSA infection. One may note MRSA with increasing frequency in patients with chronic wounds, dialysis patients, immunocompromised patients or patients who are or have been in extended care facilities, hospitals, skilled nursing facility (SNF) units or an ICU. In addition, physicians may have a heightened index of suspicion of MRSA in: those exposed to prior prolonged antibiotic therapy; those with surgical site infections, particularly those who have retained hardware; patients with osteomyelitis; or patients with bacteremia and sepsis.

Community-Acquired MRSA: What You Should Know

There has also been a rise of community-acquired MRSA. Community-acquired MRSA may account for as many as 60 to 70 percent of staphylococcal infections.1 Community-acquired MRSA organisms frequently contain the Panton-Valentine leukocidin, leading to abscess formation and necrosis due to the destruction of leukocytes. Community-acquired MRSA occurs with greater frequency in prisoners, homosexuals and those participating in contact sports.

   One must consider certain groups of patients as potentially infected with community-acquired MRSA until proven otherwise. These patients include those with shorter hospital stays, patients on parenteral antibiotic therapy, patients in the community using broad-spectrum drugs, those with a history of intravenous drug use, and those with exposure to MRSA colonized individuals.

   In each of the above instances, empiric treatment of an infection should include coverage for MRSA.

   Community-acquired MRSA infection is frequently characterized by a necrotic wound center. A delay in diagnosis of MRSA is inevitable without a proper culture. Fortunately, many abscesses secondary to MRSA infection respond to incision and drainage, even in the absence of appropriate antibiotic therapy. Bear in mind that MRSA infection may be misdiagnosed as a spider or arachnoid bite. In a 2006 study, researchers found that MRSA accounted for 72 percent of nearly 400 cases of community-onset skin and soft tissue infection.2

   Data USA Surveillance Network, a cooperative of 296 laboratories in nine census regions, has established an incidence of 57.8 percent for MRSA soft tissue and skin infections.3 The network noted no difference in community versus hospital-acquired infections and ICU strains were the most resistant. The highest reported rates of MRSA occur in the central United States and the lowest rates are reported in the New England and mid-Atlantic areas. This study, conducted between 2005 and 2007, noted that linezolid (Zyvox, Pfizer) resistance continues to be rare and that trimethoprim/sulfamethoxazole (Bactrim, Roche and Septra, GlaxoSmithKline) continues to demonstrate good activity against MRSA.

A Brief Overview On MRSA Transmission

Methicillin-resistant Staph aureus is a common source of skin colonization.4 Colonized individuals may transmit MRSA. Hand washing continues to represent the most acute means to prevent the spread of MRSA. Doctors’ clothing, such as neckties, may also serve as a vector for the spread of MRSA.5 Companion animals such as cats and dogs may also serve as conduits for the spread of MRSA.6

A Closer Look At The Prevalence Of MRSA In Diabetic Foot Infections And Surgical Site Infections

When it comes to diabetic foot infection (DFI), MRSA may represent the primary pathogen. Empirical therapy for the management of DFIs should generally include coverage for MRSA until one has obtained definitive cultures. Dang and colleagues isolated MRSA in 30.2 percent of patients with diabetic foot infections.7 Of greater importance is the fact that diabetic foot infections demonstrate higher treatment failure rates when one recovers MRSA from the wound.8

   MRSA may reportedly be responsible for surgical site infection in as many as 30 percent of patients.9 When postoperative infection occurs, give serious consideration to the presence of MRSA until proven otherwise. In comparison to vancomycin, linezolid has comparable clinical cure rates when it comes to postoperative surgical site sepsis with MRSA.9

MRSA And Osteomyelitis: Can Antibiotic Beads Have An Impact?

Methicillin resistant Staph aureus may represent the infecting organism in osteomyelitis. In addition to appropriate parenteral or oral antibiotic therapy, one may employ local therapy with antibiotic beads. Options include combining non-absorbable antibiotic beads such as polymethylmethacrylate (PMMA) with an appropriate antibiotic. Alternatively, physicians may combine absorbable calcium phosphate or calcium sulfate beads with an appropriate antibiotic. One may utilize gentamycin, vancomycin or daptomycin (Cubicin, Cubist Pharmaceuticals) in combination with appropriate antibiotic beads.

   Absorbable beads offer several advantages including superior elution properties. Absorbable beads, of course, do not require a second surgery as the beads absorb and do not require extirpation. Since all of the beads are absorbed, all of the antibiotic is delivered to the infection site. The implantation of the beads provides high levels of antibiotic, reducing the frequency of recurrent osteomyelitis.

What About Topical Modalities?

A variety of topical therapies may control MRSA colonization and bioburden. Such therapies may include debridement and topical antiseptics.

   Silver dressings provide anti-MRSA activity as well as anti-inflammatory activity. Silver dressings are bactericidal on contact and are helpful in reducing MRSA bioburden. Similarly, topical agents containing iodine offer anti-MRSA activity and reduce MRSA bioburden.

   Topical application of honey is helpful in reducing MRSA colonization and bioburden. Honey may be more effective than certain antibiotics for the reduction of staphylococcal organisms.10

   One may prescribe chlorhexidine scrub for the reduction of MRSA bioburden. Chlorhexidine is broad-spectrum, acts rapidly and is effective against MRSA. Utilization of chlorhexidine as a preoperative scrub the night before surgery is a possible means to reduce the incidence of postoperative infection, including MRSA and MRSE.

   When confronted with possible postoperative surgical site sepsis, one must always consider the presence of MRSA and direct empiric therapy at MRSA/MRSE until cultures prove otherwise.

A Guide To Considerations For Antibiotic Therapy

A variety of antibiotics are available management of MRSA infection. These antibiotics include vancomycin, linezolid, minocycline (Minocin), daptomycin (Cubicin, Cubist Pharmaceuticals) and quinupristin/dalfopristin (Synercid, Monarch Pharmaceuticals). Newer antibiotics such as tigecycline (Tygacil, Wyeth) also offer MRSA coverage.

   Linezolid, an oxazolidinone antibiotic, offers an attractive parenteral alternative for the management of MRSA infection.11 Researchers have demonstrated that this agent is more effective for soft tissue infections than glycopeptides, macrolides or beta lactams. It is more effective than vancomycin for bacteremias.

   With reference to osteomyelitis, research has demonstrated that linezolid has excellent penetration to bone and it has successfully treated vertebral osteomyelitis.12,13 In addition, linezolid has demonstrated an 81.8 percent cure rate for osteomyelitis.14,15

   Research has demonstrated that linezolid is effective in the management of diabetic foot infection.16 Researchers have noted higher MIC levels of linezolid for the treatment of MRSA in the diabetic foot with penetration of tissues not affected by local tissue inflammatory changes.17

Another Take On Culturing

In the treatment of community-acquired infections, hospital-acquired infections, diabetic foot infections or postoperative infections, one must always give serious consideration to the presence of MRSA. The “gold standard” would be that of appropriate culture and sensitivity, combined with monitoring of patient progress via laboratory studies.

   One philosophy is never to culture anything that is not infected. I have never subscribed fully to this philosophy. The reason is quite simple. It is cheaper to obtain a surveillance culture and document the absence of clinical signs and symptoms of infection then it is to hire an attorney and enlist expert witnesses.

   For example, an obese patient with diabetes who had undergone prior amputation of his contralateral leg presented with an MRSA heavy growth bioburden in an ulceration on the plantar surface of the heel. Recognition of the heavy growth of MRSA resulted in topical and oral therapy directed at MRSA and eventually the patient healed in an uneventful manner.

   If the aforementioned patient’s wound had evolved into a significant infection requiring major surgery or amputation, the question would be whether or not earlier recognition of MRSA as the infecting organism would have resulted in earlier effective therapy, lessening the likelihood of the need for amputation.

   All infections begin with initial colonization, growth and eventual invasion and infection of surrounding tissues, resulting in clinical sepsis. Early recognition of responsible pathogens would certainly be helpful when such organisms are in the “bioburden” stage rather than being in an early infection stage.

Essential Insights On Documentation

In the absence of clinical signs or symptoms of an infection, one may obtain a “surveillance culture.” When obtaining cultures for the purpose of surveillance to assess the presence of possible MRSA bioburden, it is important to document the absence of any signs or symptoms of clinical infection. The medical record should clearly state that one is obtaining the surveillance culture absent any signs or symptoms suggestive of sepsis. Such a note should include the absence of fever, chills or rigors.

   The medical record should indicate the Infectious Diseases Society of America (IDSA) classification (no infection, mild, moderate or severe infection) when one is obtaining surveillance cultures.18 State the absence of erythema, edema, drainage, malodor, fluctuance or crepitus. Note the absence of vesicle or bullous formation. The medical record should indicate whether there are clinical signs or symptoms suggestive of sepsis.

   Regardless of whether one is treating MRSA or not, it is always important to document the response to treatment. Regardless of the topical or systemic therapy you use, be sure to clearly document decreasing signs and symptoms of infection or inflammation as testimony to the effectiveness of treatment.

   At follow-up visits, one should always document decreases for the following: wound or ulceration size, pain or tenderness, erythema and edema. Physicians should also note evidence of resolving cellulitis or lymphangitis. The medical record should clearly document the absence of fever, chills, rigors and the tolerance of appropriate antibiotics when prescribed without evidence of side effects or abnormal sequela.

   In addition, podiatric physicians should seek laboratory studies such as a complete blood count (CBC), erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) in order to monitor progress and the response to therapy. The response to therapy is critical to document as it indicates that the physician had a reasonable basis for which to continue a selected therapy.

What About Litigation And MRSA Infections?

Litigation involving MRSA infections generally revolves around a failure to recognize the presence of MRSA as the infecting organism, leading to a delay in diagnosis and proper treatment. As a result, plaintiffs frequently allege that increased morbidity and mortality resulted from a failure to administer appropriate antibiotic therapy due to a failure to recognize the presence of MRSA.

   In his review, Miwa notes that evidence-based medicine (EBM) is often of prime importance in the evaluation of negligence allegations.19 Miwa says there has been a transition in which EBM involves not only the provision of medical services by a healthcare provider but legal considerations as well.

   A review of malpractice claims resulting from healthcare-acquired infections in Philadelphia noted that MRSA and MRSE were responsible for the majority of such infections. Pseudomonas aeruginosa was the next most common infecting organism.20

   Out of 154 malpractice cases involving hospital-acquired infection, MRSA was responsible for 45 cases, MRSE for 27 cases and Pseudomonas for 16 cases. Twenty-seven malpractice cases were withdrawn, 27 cases settled, 11 cases were pending at the time of trial, nine cases resulted in a plaintiff verdict and one case had a defense verdict.20 The authors noted that when cases involving hospital-acquired infection were brought to trial, they more often resulted in plaintiff success because postoperative infections are seen as preventable, based upon evidence-based medicine and low published rates of postoperative infection.

In Summary

One must always consider the possible presence of MRSA as the causative organism in any infectious process. This is particularly the case when patients have the aforementioned risk factors associated with an increased incidence of MRSA. In regard to litigation, a potential problem is that of delayed diagnosis and subsequent delay in the institution of appropriate therapy.

   When it comes to the treatment of ulcerations and wounds, one should consider appropriate debridement as well as topical agents with MRSA activity. Surveillance cultures are helpful in identifying heavy growth of organisms that may preclude wound healing (bioburden) absent clinical signs and symptoms of overt infection. Physicians should consider empiric antimicrobial therapy with MRSA activity pending culture results.

   Regardless of the infecting organism or circumstances, careful documentation is critical. The medical record should indicate the patient’s complaints about symptoms, findings from the clinical exam and the response to treatment.

   Dr. Jacobs is a Fellow of the American College of Foot and Ankle Surgeons, and the American Professional Wound Care Association. He is in private practice in St. Louis.

References:

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