Antibiotic resistance is a topic that is frequently mentioned in the news. Vancomycin-resistant enterococci (VRE) and methicillin-resistant staphylococci (MRSA) have become established, unwelcome residents in some hospitals and long-term care facilities, and staphylococci that have intermediate resistance to vancomycin (VISA) have been isolated in three hospitals, two in the United States and one in Japan. These so-called "super bugs" no longer respond to our strongest antibiotics. Despite the popular view that pharmaceutical manufacturers will just keep discovering new antibiotics (and no one needs to worry about antibiotic resistance), the truth is that most "new" antibiotics are derivatives of older antibiotics (and work in a similar mode), or are too toxic or too expensive (or both) to be used routinely. The specter of a "post-antibiotic era" has been raised, and if the current patterns of antibiotic use continue, it is a definite possibility. There is a national campaign to support judicious antibiotic use headed by the Centers for Disease Control and Prevention (CDC). This article will answer five questions about antibiotic resistance:

1. What is antibiotic resistance?
2. Why do bacteria become antibiotic resistant?
3. How does the prescribing of antibiotics influence the development of bacterial resistance?
4. What can be done to curb the increase in antibiotic resistance?
5. Where can I learn more about antibiotic resistance?

What is antibiotic resistance? This is the ability of some bacteria to withstand an antibiotic that would normally interfere with its ability to grow.

Why do bacteria become antibiotic resistant? Bacteria may become resistant to antibiotics via three primary methods. 1. Some bacteria inherently possess properties that make them resistant to some antibiotics. For example, all gram-negative bacteria are resistant to vancomycin because this antibiotic cannot penetrate their complicated outer membrane (which it must do to be effective). 2. Spontaneous genetic mutations may occur that render bacteria resistant to a given antibiotic. This may occur without previous exposure to this antibiotic. For example, before tetracycline and streptomycin were ever used in people of the remote Solomon Islands, some strains of bacteria were isolated from these people that were already resistant to tetracycline and streptomycin! 3. Once there is genetic material that will confer resistance to an antibiotic (i.e., a resistance gene), this genetic material may be transferred between bacteria, either of the same or different species, or to and from bacteriophages (bacterial viruses). Both resident bacteria (normal flora) and pathogenic bacteria are capable of carrying and transferring resistance genes.

How does the prescribing of antibiotics influence the development of bacterial resistance? Bacteria with inherent resistance to some antibiotics (method 1) are not influenced by antibiotic prescribing practices. If an antibiotic with activity against that type of bacteria is prescribed, it should work (unless the bacteria are resistant to it for other reasons). If an inappropriate antibiotic is prescribed, it will not work.

For populations of bacteria that have acquired resistance (methods 2 and 3), antibiotic prescribing will favor the growth of the part of the population with resistance. If the majority of bacteria are susceptible to a given antibiotic, resistant bacteria may not present a problem to patients because, once the antibiotic has killed or inhibited the growth of the susceptible bacteria, the patient may be able to destroy the few remaining bacteria with their own immune system. When resistant bacteria dominate the population, however, it is more difficult (or impossible) for patients to gain control of these infections until an antibiotic with activity against this resistant strain is given. It is possible for bacteria to acquire resistance against multiple antibiotics, further complicating this situation. Even small numbers of resistant bacteria may present serious problems to patients who are immunocompromised or otherwise debilitated.

What can be done to curb the increase in antibiotic resistance? The appropriate selection of antibiotic therapy is typically sufficient to deal with inherent antibiotic resistance (method 1). For example, if infection with gram-negative bacteria is suspected or confirmed, an antibiotic with activity against gram-negative bacteria should be chosen for therapy. This approach is not, however, sufficient to deal with bacteria with acquired resistance (methods 2 and 3).

The spontaneous generation of and current existence of numerous resistance genes may make the elimination of all bacteria with acquired antibiotic resistance impossible. It is possible, though, through the judicious use of antibiotics, to reduce their prevalence. Several studies in hospitals show that, once the use of an antibiotic in a hospital declines, the number of bacterial isolates from patients in that facility that are resistant to that antibiotic also declines. Researchers in Finland recently found that after a nationwide campaign to reduce the use of erythromycin for outpatient therapy, the number of erythromycin-resistant group A streptococci isolates from outpatients also declined. In other words, the less frequent use of antibiotics is our best hope for reducing the number of bacteria with antibiotic resistance.

There are some basic tenets of judicious antibiotic use. (1) As a rule, antibiotics should not be prescribed for viral illnesses. Antibiotics do not work on viral infections! A second part of this tenet is that antibiotics should not be prescribed when a patient has a viral illness to "prevent" a secondary bacterial infection. When this practice was carefully examined, researchers found that it simply does not work, and has the negative effect of increasing the likelihood that antibiotic-resistant bacteria will develop in that patient. (2) Broad-spectrum antibiotics should only be used when absolutely necessary. When an antibiotic is prescribed for a bacterial infection, it should be an antibiotic with the narrowest spectrum of activity directed at the known or suspected pathogenic bacteria. When broad-spectrum antibiotics are used routinely, it increases the possibility that bacteria will be selected for that are resistant to these drugs. (3) Patients need to be educated about antibiotic use. They may not understand the difference between viral and bacterial infections, and explaining this difference to them may reduce their requests for antibiotics. Patients also need to understand that, when an antibiotic is prescribed, the entire prescription needs to be taken as directed by the person for whom the antibiotic was prescribed. They should not stop taking the antibiotic when they feel better; they should not share a prescription intended for one person between multiple household members; and, they should never save leftover antibiotics for future use. (4) Detailed recommendations for judicious antibiotic use in hospitals and long-term care facilities have been developed. Judicious antibiotic use in these settings is of particular importance because there is the potential for developing bacteria resistant to multiple antibiotics that can be readily spread among patients who are in close contact and may be debilitated or immunocompromised.

Where can learn more about antibiotic resistance? Here are a few places to start:

1. The CDC has a number of free resources for patient education, and academic detailing sheets targeted at health care providers. More information about these items or an order form may be obtained by calling Jenifer Lloyd at (801) 538-6191, or by calling or faxing Quo Vadis Harris at the CDC (404) 639-4702 (Due to a high volume of requests to the CDC, your request may take a week or longer to process.).

2. If you have access to the Internet, the American Academy of Family Physicians’ Family Medicine Online [at http://www.aafp.org/family/] and the American Academy of Pediatrics [at http://www.aap.org/] have information available. Search: antibiotics at either site. The CDC [at http://www.cdc.gov.ncidod/hip/isolat/] has Hospital Isolation Procedures and Recommendations.

3. The list of references used to write this article is also available from Jenifer Lloyd at (801) 538-6191.

The National Association of State Public Health Veterinarians has released the Compendium of Animal Rabies Control, 1998. Although the document is similar to the 1997 version, there are major changes on how to handle issues concerning ferrets.

For the past several years there has been a USDA licensed rabies vaccine for ferrets, but there was no known quarantine period for the ferret. This meant that any ferret that bit a human or animal had to be sacrificed for rabies testing regardless of the vaccination status. A recent study by the Centers for Disease Control and Prevention (CDC), suggests that a 10-day quarantine period for ferrets should be more than adequate to prevent the spread of rabies (AJVR, 58(11), November 1997, pages 1327 - 1331).

Although the Utah Department of Health, Bureau of Epidemiology still discourages the ownership of ferrets (especially in households with small children), it is our recommendation that for rabies control, (vaccinated and quarantined) ferrets should be treated like dogs and cats.

We would urge potential owners to check the local ordinance where they live to make sure they can lawfully keep a ferret. There are a number of areas in the state where owning a ferret is prohibited.

The only other major change in the 1998 Compendium is a recommendation that animals maintained in USDA licensed research facilities or accredited zoological parks be evaluated on a case by case basis after exposure to a rabid animal. In the past, unless an animal had been vaccinated with a licensed vaccine approved in that species, it would be euthanized following an exposure to a rabid animal in order to prevent further spread of the disease. The purpose of this new recommendation is to allow health departments more flexibility in dealing with valuable research or exotic wild animals exposed to a rabid animal.

ACIP Recommendations for Rabies Prevention

Sometime in the next few months CDC will also release an update of the Recommendation for Rabies Prevention from the Advisory Committee on Immunization Practices (ACIP). They have informed us that there are a number of changes that ACIP will make in the recommendations.

The first is a change in the administration of human rabies immune globulin (HRIG). The new language reads: "If anatomically feasible, the full dose of HRIG should be thoroughly infiltrated in the area around and into the wound(s). Any remaining volume should be administered intramuscularly at a site distant from the vaccine inoculation."

The second change is a revised approach to bats and Postexposure Prophylaxis (PEP). "Bats are increasingly implicated as significant wildlife reservoirs for variants of rabies virus transmitted to humans. Recent epidemiological data suggest that transmission of rabies virus may occur from minor or seemingly insignificant bites from bats. The limited injury inflicted by a bat bite (in contrast to lesions caused by terrestrial carnivores) and an often inaccurate recall of the exact exposure history may limit the ability of health care providers to determine the risk of rabies resulting from an encounter with a bat. In all instances of potential human exposures involving bats, the bat in question should be safely collected, if possible, and submitted for rabies diagnosis. Rabies PEP is recommended for all persons with bite, scratch or mucous membrane exposure to a bat, unless the bat is available for testing and is negative for evidence of rabies. PEP may be appropriate even in the absence of demonstrable bite, scratch or mucous membrane exposure, in situations in which there is reasonable probability that such exposure may have occurred (e.g. a sleeping individual awakes to find a bat in the room, an adult witnesses a bat in the room with a previously unattended child, mentally challenged person, intoxicated individual, etc.). The likely effectiveness of PEP in this setting needs to be balanced against the low risk such exposures appear to present." This recommendation, used in conjunction with current ACIP guidelines, should maximize a provider’s ability to respond to situations where accurate exposure histories may not always be obtainable, while still minimizing inappropriate PEP."