Few infection problems are more perplexing than nosocomial methicillin-resistant Staphylococcus aureus (MRSA), a condition for which even appropriate treatment has emerged as a significant risk factor.1,2 Selective pressure favoring resistant strains is attributable to widespread misuse and overuse of antimicrobial agents, increases in numbers of immunocompromised patients, failure of infection control procedures, increases in invasive procedures, and antibiotic use in agriculture and animal husbandry.2 MRSA is such a problem that both the Centers for Disease Control (CDC)3 and World Health Organization (WHO) 2 have published guidelines for treatment and prevention, with emphasis on strategies to prevent spread, eliminate inappropriate antibiotic usage, and delay resistance development. MRSA provides a genetic reservoir for resistance against other antimicrobials, including quinolones, streptomycin, tetracycline, sulfonamides, chloramphenicol, erythromycin, and neomycin. 4,5

MRSA Virulence Factors
     Staphylococcus aureus is the found to be a causative organism in a variety of human suppurative (pus-forming) infections and toxinoses, including food poisoning, toxic shock syndrome, superficial skin lesions, pneumonia, mastitis, phlebitis, meningitis, urinary tract infections, osteomyelitis and endocarditis; and it is a major cause of nosocomial infections of surgical wounds and those associated with indwelling medical devices. Few organisms are better equipped to thrive pathologically in the otherwise hostile environment of the healthy human body in such a variety of conditions. The bacterium’s armament of virulence factors plays a large role in its ability to cause infection, evade host defenses, and resist antimicrobial assault. It includes: 4,5

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  1. Surface proteins that promote colonization of host tissues;
  2. Leukocidin, kinases, and hyaluronidase, invasins that promote bacterial spread within tissues;
  3. Bacterial capsule and Protein A, surface factors that help to avoid phagocytocis;
  4. Carotenoids and catalase that enable survival with successful phagocytes;
  5. Protein A, coagulase, and clotting factor that act as immunological disguises;
  6. Hemolysins, leukotoxin, and leukocidin that lyse eukaryotic cell membranes; and
  7. Resistance to antimicrobial agents, both inherent and acquired.
  
        Resistance to antimicrobials is effected primarily by genetic mutation followed by selection of resistant strains, and resistance genes are acquired via plasmids, transducing particles, transposons, and other types of DNA transfer, conferring a variety of resistance mechanisms.4

Colonization or Infection?
     Whether or not the presence of MRSA in individual culture isolates indicates active infection by the organism or simply colonization of the infection actually caused by another organism is of paramount importance. The presence of MRSA does not necessarily indicate active infection by that organism, but may instead indicate a carrier state.
     While effective treatment of the primary infection must be a primary goal, avoiding cultivation of a colonizing MRSA must also be a prime consideration, both to prevent resulting overgrowth of non-targeted organisms and to prevent enhancement of MRSA’s resistance emergence. Existence of MRSA in the health care facility, in a given unit (intensive care), and in and on attending health care workers must also play a part in control of such infections; and topical treatment of and/or prophylaxis of health care workers (mupirocin) may be an appropriate control measure.1,2,4

Prevention of Spread
     The CDC recognizes that infected or colonized patients are the most frequent sources of MRSA infection. Though infected or colonized health care workers are a significant secondary source, their role in transmission between patients is considered more significant; and contact recommendations may vary with facility and perception of spread potential.
     Accordingly, the first recommendation is isolation of the infected patient in order to limit contact, either in a private room or with another patient with active MRSA infection but without other infection(s). Movement of the patient should be limited to essential purposes only in order to avoid spreading to other patients directly or to objects, equipment, and environmental surfaces that can become contaminated. 3 Other people who enter the room should follow common-sense procedures for avoiding contamination. 3

1.  Wash hands after patient contact and before contacting other patients, and especially after contact with potentially contaminated body fluids or even objects in the room. This may be appropriate even between procedures on the same patient to avoid cross-contamination between wounds or areas of the body. While handwashing is a basic precaution to be rigorously utilized routinely even in the absence of contagious outbreaks, statistics indicate that it is frequently ignored, even and especially by physicians. Its impact cannot be overlooked.

2.  Wearing non-sterile gloves is recommended in addition to handwashing procedures, especially when contact with body fluids is necessary; and gloves used for other contact should be changed before contact with the patient’s mucous membranes or non-intact skin.

3.  Gowns and face shields (or masks and eye-protection) can protect mucous membranes from contamination, especially during procedures that may generate splashes or sprays of any body fluids. Such protective measures should obviously be removed before contact with other patients or non-contaminated surfaces.

4.  Proper handling of disposables and laundry must be considered, and contact with reusable items like stethoscopes and even pens and charts should be patient-limited with appropriate handwashing between contact with these items strictly observed. Appropriate patient contact items (and even medical equipment when possible) should be not only limited to use by the individual patient, but disinfected on a daily basis.

Prevention of Resistance
     According the to the CDC, some 30% of prescriptions dispensed for antibiotics constitute inappropriate use, with about 80% of prescribing physicians admitting to having prescribed antibiotics in response to pressure from patients’ requests rather than actual indication.1,3 This doesn’t account for the millions of such prescriptions that are used improperly, with the patient terminating therapy prematurely or missing doses, stockpiling antibiotics for self-medication or medicating friends or relatives only to perpetuate resistance development. Thus, both the public and prescribers must be perpetually educated on the proper prescribing and use of antibiotics. 2,3
     This brings up the issue of control. While such agents are available only by prescription in some countries, purchase is unrestricted in other countries. Anyone with the financial resources to purchase a sandwich can buy a wide variety of antibiotics in many developing countries. Not only does such easy availability perpetuate resistance development, the more advanced and more expensive agents available in the more industrial nations may be unavailable in such areas when their legitimate need arises to appropriately combat resistant strains.1,2
     Many of the same antibiotics used in human populations are used in animal populations, effectively reducing the incidence of disease in food animals and promoting their growth, all efforts to become more efficient in the process of producing meat. It’s a tactic that works well for the meat industries, and some 40% of all antibiotics used in the United States are used in animal populations for this purpose.1 Though the small residual amounts officially allowed in human food products may be miniscule, the broader impact of subjecting large populations to what amount to subtherapeutic doses of antimicrobials obviously provide an excellent opportunity for proliferation of bacterial populations resistant to progressive varieties of antimicrobial agents used in human infection. The presence of these medications themselves in meats may have negligible direct impact on the human population that consumes them, but the overall impact on the microbial ecology can be very significant. 1,2
     Similarly, large quantities of antibiotics are sprayed on various crops (fruit trees in particular) to prevent or control bacterial infection. While applied amounts may be sufficient to eliminate targeted bacterial populations, the inevitable misapplication of these agents in more dilute concentrations by accident as a byproduct of proper application tends to select for resistant strains in adjacent crops. Then too, amounts of antimicrobial agents on fruits appropriately treated find their way to processing, packaging, and shipping facilities in suboptimal concentrations, often selecting for resistant strains in those aspects of food delivery. 1,2
     Obviously, while the cause of resistance development is simply wide usage of the agents that do so much good, the solution is not to simply eliminate their use, but to use them most appropriately. Means of reducing or eliminating the need for their use in agricultural applications is admittedly difficult, yet possible by improving sanitation and by development of alternative methods of bacterial control that don’t involve antibacterial agents. 1,2 In the clinical setting, the situation is equally difficult. In addition to educational efforts aimed at both the prescriber and the patient to promote appropriate use, as resistance becomes a more critical issue, the importance of targeting therapy with the most specific available agents to which infecting bacteria are susceptible becomes more important. Particularly with bacterial populations inclined to resistance development like MSRA, culture and sensitivity and avoidance of broad-spectrum agents in favor of more targeted therapy is not only more effective at treating the individual infection but reduces development of resistance in subsequent generations that will infect the next host in the facility and in the population in general.1,2

References

1. The Challenge of Antibiotic Resistance. Scientific American. Available at http://www.sciam.com/1998/0398issue/0398levy.html. Accessed 11/10/2000.
2. Overcoming Antimicrobial Resistance. World Health Report on Infectious Diseases 2000. Available at http://www.who.int/infectious-disease-report/2000/other_versions/index-rpt2000_text.html#ch5. Accessed 11/10/2000.
3. CDC on MRSA. Information for health care personnel. Available at http://www.cdc.gov/ncidod/hip/ARESIST/mrsahcw.htm. Accessed 11/10/2000.
4. Mechanisms of bacterial resistance to antimicrobial agents. American Journal of Health-System Pharmacy. Available at http://www.ashp.org/public/pubs/ajhp/vol54/num12/resistance.html. Accessed 11/10/2000.
5. Staphylococcus. Microbiology Webbed Out. Online Microbiology Textbook. http://www.bact.wisc.edu/microtextbook/disease/staph.html. Accessed 11/10/2000.