Strains of Staphylococcus aureus that are resistant to penicillinase resistant penicillins such as oxacillin, methicillin, cloxacillin and nafcillin are termed methicillin-resistant S. aureus (MRSA). They are resistant to all β-lactam antibiotics, including cephalosporins and carbapenems. MRSA isolates often are multiply resistant to commonly used antimicrobial agents, including erythromycin, clindamycin, and tetracycline. MRSA is also referred as Oxacillin Resistant S.aureus (ORSA). When resistance was first described in 1968, methicillin was used to test and treat infections caused by S.aureus. Even though methicillin is no longer used to treat susceptible staphylococcal infections, the acronym MRSA is still used by many to describe these isolates because of its historic role. The drug methicillin has now been renamed as meticillin.

Mechanism of resistance: 

The resistance to penicillin in S.aureus is due to production of penicillin degrading enzyme penicillinase (also called beta-lactamase). The resistance to oxacillin, meticillin and nafcillin is not mediated by these enzymes, instead is a result of mutation in Penicillin Binding Protein (PBP). The antibiotic must bind to PBP for them to act. A mutation in the gene mecA that codes for PBP results in the expression of a novel PBP that has reduced affinity for penicillins. The new PBP is designated as PBP' or PBP2a.

Significance of MRSA:

MRSA are pathogenic and are common causes of hospital-acquired infections. These organisms are commonly isolated from infected IV drug abusers and patients in ICUs, although they can be isolated from patients with community-acquired infections. A MRSA outbreak can occur when one strain is transmitted to other patients. Often this occurs when a patient or health care worker is colonized with an MRSA strain and by contact with others spreads the strain. Since MRSA strains are resistant to many antibiotics, infections caused by them are difficult to treat.

Detection of MRSA:

Accurate detection of oxacillin/meticillin resistance can be difficult due to the presence of two subpopulations (one susceptible and the other resistant) that may coexist within a culture. All cells in a culture may carry the genetic information for resistance but only a small number can express the resistance in vitro. This phenomenon is termed heteroresistance. Heteroresistance is a problem for clinical laboratory personnel because cells expressing resistance may grow more slowly than the susceptible population. Oxacillin is preferred to meticillin for testing because it is more resistant to degradation in storage, and because it is more likely to detect heteroresistance in a population. MRSA are now detected even better using cefoxitin disk diffusion test.

1. Agar screen method (growth on Mueller Hinton agar containing 6 µg/ml of oxacillin and added 4% NaCl)

2. Disk diffusion method (having zone diameter of <10 mm around 1-µg oxacillin disk on Mueller Hinton agar with 4% NaCl)

3. Disk diffusion method (having zone diameter of <21 mm around 30-µg cefoxitin disk on Mueller Hinton agar)

4. Agar or broth microdilution (strains having MICs to oxacillin ≥ 4 µg/ml)

5. E test to detect oxacillin MIC

6. Chromogenic media that screens for MRSA by producing coloured colonies

7. Latex agglutination method for detection of PBP2a protein

8. Detection of mecA gene by PCR

Treatment of infections by MRSA:
Glycopeptides such as Vancomycin and Teicoplanin are often the only drugs of choice for treatment of severe MRSA infections. The preferred alternative to vancomycin for treating MRSA infection is linezolid, tigecycline and daptomycin. Cloxacillin, dicloxacillin, TMP-SMX, ciprofloxacin, and topical mupirocin have been useful in treating MRSA in the carrier state, but the MRSA may become resistant to all of them. MRSA isolates with intermediate resistance to vancomycin have recently been detected in Japan and the USA.

Prevention of MRSA spread:
In hospitals, the most important reservoirs of MRSA are infected or colonized patients. Although hospital personnel can serve as reservoirs for MRSA, they have been more commonly identified as a link for transmission between colonized or infected patients. The main mode of transmission of MRSA is via health care workers' hands, colonized or infected body sites of the personnel themselves, or devices, items, or environmental surfaces contaminated with body fluids containing MRSA. 

Standard Precautions to control the spread of MRSA include: 

• Washing hands between patient contacts. It may be necessary to wash hands between procedures on the same patient to prevent cross-contamination of different body sites.

• Wearing gloves when touching blood, body fluids, secretions, excretions, and contaminated items.

• Wearing a mask and eye protection or a face shield to protect mucous membranes of the eyes, nose, and mouth during procedures.

• Placing a patient with MRSA in isolation and limiting the movement and transport of the patient from the room.

• Appropriate handling and transport of used linen soiled with blood, body fluids, secretions, and excretions.

• Ensuring that patient-care items, bedside equipment, and frequently touched surfaces receive daily cleaning.

  Print This Page