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
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
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
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 providers ability to respond to situations where accurate
exposure histories may not always be obtainable, while still
minimizing inappropriate PEP."
We expect that more changes will be in the
final document. One additional recommendation includes a vaccine
that FDA has recently licensed for use in the United States.
RabAvert is a purified chick embryo cell vaccine that the Chiron
Corporation is distributing. This vaccine is not new. At least
14 million doses of the vaccine have been used worldwide.