MELANY C.
CAGABCAB INSTRUCTOR: JAY-EM AJOC
BSN-1
CHAPTER 9:
INHIBITING THE GROWTH OF PATHOGENS IN
VITRO USING ANTIMICROBIAL AGENTS
Chemotherapy- used in conjunction with cancer (i.e.,
cancer chemotherapy), chemotherapy actually refers to
the use of any chemical (drug) to treat any disease or
condition. The chemicals (drugs) used to treat diseases
are referred to as chemotherapeutic agents.
- A chemotherapeutic agent is any drug used to
treat any condition or disease.
- A chemotherapeutic agent is any drug used to
treat any condition or disease.
The Father of Chemotherapy- The true beginning of
modern chemotherapy came in the late 1800s when
Paul Ehrlich, a German chemist, began his search for
chemicals (referred to as “magic bullets”) that would
destroy bacteria, yet would not damage normal body
cells. By 1909, he had tested more than 600 chemicals,
without success. Finally, in that year, he discovered an
arsenic compound that proved effective in treating
syphilis. Because this was the 606th compound Ehrlich
had tried, he called it “Compound 606.” The technical
name for Compound 606 is arsphenamine, and the trade
name was Salvarsan. Until the availability of penicillin in
the early 1940s, Salvarsan and a related compound—
Neosalvarsan—were used to treat syphilis. Ehrlich also
found that rosaniline was useful for treating African
trypanosomiasis.
- The chemotherapeutic agents used to treat
infectious diseases are collectively referred to as
antimicrobial agents.
- an antimicrobial agent is any chemical (drug)
used to treat an infectious disease, either by
inhibiting or by killing pathogens in vivo.
- Drugs used to treat bacterial diseases are called
antibacterial agents, whereas those used to treat
fungal diseases are called antifungal agents.
- Drugs used to treat protozoal diseases are
called antiprotozoal agents,
- and those used to treat viral diseases are called
antiviral agents.
- The chemotherapeutic agents used to treat
infectious diseases are collectively referred to as
antimicrobial agents.
Clarifying Drug Terminology
Imagine that all chemotherapeutic agents are
contained within one very large wooden box. Within that
large box are many smaller boxes. Each of the smaller
boxes contains drugs to treat one particular category of
diseases. For example, one of the smaller boxes
contains drugs to treat cancer; these are called cancer
chemotherapeutic agents. Another of the smaller boxes
contains drugs to treat hypertension (high blood
pressure). Another of the smaller boxes contains drugs
to treat infectious diseases; these are called
antimicrobial agents. Now imagine that the box
containing antimicrobial agents contains even smaller
boxes. One of these very small boxes contains drugs to
treat bacterial diseases; these are called antibacterial
agents. Another of these very small boxes contains
drugs to treat fungal diseases; these are called
antifungal agents. Other very small boxes contain
drugs to treat protozoal diseases (antiprotozoal
agents) and drugs to treat viral infections (antiviral
agents). To appropriately treat a particular disease, a
clinician must select a drug from the appropriate box. To
treat a fungal infection, for example, the clinician must
select a drug from the box containing antifungal agents.
- An antibiotic is a substance produced by a
microorganism that is effective in killing or
inhibiting the growth of other microorganisms.
- An antibiotic is a substance produced by a
microorganism that is effective in killing or
inhibiting the growth of other microorganisms.
-
Antibiotics are produced by certain moulds and
bacteria, usually those that live in soil. The antibiotics
produced by soil organisms give them a selective
advantage in the struggle for the available nutrients in
the soil.
- Penicillin and cephalosporins are examples of
antibiotics produced by moulds; bacitracin,
erythromycin, and chloramphenicol are
examples of antibiotics produced by bacteria.
- Antibiotics are primarily antibacterial agents and
are thus used to treat bacterial diseases.
- Antibiotics have been chemically modified to kill
a wider variety of pathogens or reduce side
effects; these modified antibiotics are called
semisynthetic antibiotics.
The First Antibiotics
In 1928, Alexander Fleming (Fig. 9-1), a Scottish
bacteriologist, accidentally discovered the first
antibiotic when he noticed that growth of
contaminant Penicillium notatum mould colonies on
his culture plates was inhibiting the growth of
Staphylococcus bacteria (Fig. 9-2). Fleming gave the
name “penicillin” to the inhibitory substance being
produced by the mould. He found that broth cultures
of the mould were not toxic to laboratory animals
and that they destroyed staphylococci and other
bacteria. He speculated that penicillin might be
useful in treating infectious diseases caused by
these organisms. As was stated by Kenneth B.
Raper in 1978, “Contamination of his
Staphylococcus plate by a mould was an accident;
but Fleming’s recognition of a potentially important
phenomenon was no accident, for Pasteur’s
observation that ‘chance favors the prepared mind’
was never more apt than with Fleming and
penicillin.”
During World War II, two biochemists, Sir Howard Walter
Florey and Ernst Boris Chain, purified penicillin and
demonstrated its effectiveness in the treatment of
various bacterial infections. By 1942, the US drug
industry was able to produce sufficient penicillin for
human use, and the search for other antibiotics began.
(Earlier—in 1935—a chemist named Gerhard Domagk
discovered that the red dye, Prontosil, was effective
against streptococcal infections in mice. Further
research demonstrated that Prontosil was degraded or
broken down in the body into sulfanilamide, and that
sulfanilamide [a sulfa drug] was the effective agent.
Although sulfanilamide is an antimicrobial agent, it is not
an antibiotic because it is not produced by a
microorganism.) In 1944, Selman Waksman and his
colleagues isolated streptomycin (the first
antituberculosis drug) and subsequently discovered
antibiotics such as chloramphenicol, tetracycline, and
erythromycin in soil samples. It was Waksman who first
used the term “antibiotic.” For their outstanding
contributions to medicine, these investigators—Ehrlich,
Fleming, Florey, Chain, Waksman, and Domagk—were
all Nobel Prize recipients at various times. synthesis and cross-linking of peptidoglycan, a
component of bacterial cell walls.

 Gramnegative bacteria, are referred to as

narrow-spectrum antibiotics. Those that destroy
both Gram-positive and Gram-negative bacteria
are called broad-spectrum antibiotics.

Characteristics of an Ideal:
Antimicrobial Agent - Narrow-spectrum antibiotics kill either Gram-
The ideal antimicrobial agent should:
positive or Gram-negative bacteria, whereas
• Kill or inhibit the growth of pathogens
broad-spectrum antibiotics kill both Gram
• Cause no damage to the host
positives and Gram negatives.
• Cause no allergic reaction in the host
• Be stable when stored in solid or liquid form
• Remain in specific tissues in the body long enough
to be effective
• Kill the pathogens before they mutate and become
Resistant to it unfortunately, most antimicrobial agents
have some side effects, produce allergic reactions, or
permit development of resistant mutant pathogens.

How Antimicrobial Agents Work

To be acceptable, an antimicrobial agent must inhibit or
destroy the pathogen without damaging the host (i.e.,
the infected person). To accomplish this, the agent must
target a metabolic process or structure possessed by the
pathogen but not possessed by the host. The five most
common mechanisms of action of antimicrobial agents
are as follows:
• Inhibition of cell wall synthesis
• Damage to cell membranes
• Inhibition of nucleic acid synthesis (either DNA or
RNA synthesis)
• Inhibition of protein synthesis
• Inhibition of enzyme activity

Antibacterial Agents:
Sulfonamide drugs inhibit production of folic acid (a
vitamin) in those bacteria that require p-aminobenzoic
acid (PABA) to synthesize folic acid. Because the
sulfonamide molecule is similar in shape to the PABA
molecule, bacteria attempt to metabolize sulfonamide to
produce folic acid (Fig. 9-3). However, the enzymes that
convert PABA to folic acid cannot produce folic acid from
the sulfonamide molecule. Without folic acid, bacteria
cannot produce certain essential proteins and finally die.
Sulfa drugs, therefore, are called competitive inhibitors,
that is, they inhibit growth of microorganisms
by competing with an enzyme required to produce an
essential metabolite. Sulfa drugs are bacteriostatic,
meaning that they inhibit growth of bacteria (as opposed - Antimicrobial agents work well against
to a bactericidal agent, which kills bacteria). Cells of bacterial pathogens because the bacteria
humans and animals do not synthesize folic acid from (being prokaryotic) have different cellular
PABA; they get folic acid from the food they eat. structures and metabolic pathways that
Consequently, they are unaffected by sulfa drugs. can be disrupted or destroyed by drugs
that do not damage the eukaryotic host’s
- Bacteriostatic drugs inhibit growth of bacteria, cells.
whereas bactericidal agents kill bacteria. - Bacteriostatic agents should not be used in
immunosuppressed or leukopenic patients
 Gram-positive bacteria, including streptococci (patients having an abnormally low number of
and staphylococci, penicillin interferes with the white blood cells) because the host defense
 mechanisms of such patients would be unable to are considered bacteriostatic at lower doses and
eliminate the nongrowing bacteria. bactericidal at higher doses. The macrolides include
erythromycin, clarithromycin, and azithromycin. They are
Some Major Categories of Antibacterial Agents effective against chlamydias, mycoplasmas, T. pallidum,
Penicillins- are referred to as β-lactam drugs because and Legionella spp.
their molecular structure includes a foursided ring
structure known as a β-lactam ring (shown in Fig. 9-4).c Fluoroquinolones. Fluoroquinolones are bactericidal
Penicillins interfere with the synthesis of bacterial cell drugs that inhibit DNA synthesis. The most commonly
walls and have maximum effect on bacteria that are used fluoroquinolone, ciprofloxacin, is effective against
actively dividing. They are bactericidal drugs. Penicillin G members of the family Enterobacteriaceae and P.
and penicillin V are referred to as natural penicillins aeruginosa.
because they are produced and can be purified directly
from cultures of Penicillium moulds. Natural penicillins Multidrug Therapy
are effective against some Gram-positive bacteria In some cases, a single antimicrobial agent is not
(especially Streptococcus spp.), some anaerobic sufficient to destroy all the pathogens that develop
bacteria, and some spirochetes. A few Gram-negative during the course of a disease; thus, two or more drugs
bacteria (e.g., N. meningitidis and some strains of may be used simultaneously to kill all the pathogens and
Haemophilus influenzae) remain susceptible to natural to prevent resistant mutant pathogens from emerging. In
penicillins. Some extended spectrum penicillins (e.g., tuberculosis, for example, in which multidrug-resistant
aminopenicillins and extended-spectrum penicillins) are strains of Mycobacterium tuberculosis are frequently
used to treat infections caused by Gram-negative bacilli. encountered, four drugs (isoniazid, rifampin,
pyrazinamide, and ethambutol) are routinely prescribed,
Cephalosporins. The cephalosporins are also β-lactam and as many as 12 drugs may be required for especially
antibiotics and, like penicillin, are produced by moulds. resistant strains.
Also like penicillins, cephalosporins interfere with cell
wall synthesis and are bactericidal. The cephalosporins
are classified as first-, second-, third-, fourth-, and fifth-
generation cephalosporins. The first-generation agents
are active primarily against Gram-positive bacteria.
Second-generation cephalosporins have increased
activity against Gram-negative bacteria, and third-
generation cephalosporins have even greater activity
against Gram negatives (including Pseudomonas
aeruginosa). Cefepime is an example of a fourth-
generation cephalosporin with activity against both Gram
positives and Gram negatives, including P. aeruginosa).
Ceftaroline is a fifth-generation cephalosporin that has
expanded activity against aerobic Gram-positive cocci,
including methicillin-resistant Staphylococcus aureus
(MRSA) and methicillin-resistant Staphylococcus
epidermidis MRSE. Its activity against aerobic Gram-
negative bacteria mimics that of the third-generation
cephalosporins.

Carbapenems. Carbapenems, including imipenem, are

among the most powerful antibacterial agents in use
today. They target the cell envelope and have excellent
activity against a broad spectrum of bacteria, including
many aerobic Gram-positive bacteria, most aerobic
Gram-negative bacteria, and most anaerobes.

Glycopeptides. Glycopeptides, including vancomycin,

target the cell envelope. They have excellent activity
against most aerobic and anaerobic Gram-positive
bacteria. Unfortunately, these popular drugs have
several drawbacks. Bacteria, especially enterococci, are
becoming resistant to these drugs, and they have a
number of toxic side effects.

Tetracyclines. Tetracyclines are broad-spectrum drugs

that exert their effect by targeting bacterial ribosomes.
They are bacteriostatic. Tetracyclines are effective
against a wide variety of bacteria, including chlamydias,
mycoplasmas, rickettsias, Vibrio cholerae, and
spirochetes such as Borrelia spp. and Treponema
pallidum.

Aminoglycosides. Aminoglycosides are bactericidal

broad-spectrum drugs that inhibit bacterial protein
synthesis. The major factor that limits their use is their
toxicity. Aminoglycosides are effective against a wide
variety of aerobic Gram-negative bacteria, but are
ineffective against anaerobes. They are used to treat
infections with members of the family
Enterobacteriaceae (e.g., Escherichia coli and
Enterobacter, Klebsiella, Proteus, Serratia, and Yersinia
spp.), as well as P. aeruginosa and Vibrio cholerae.
Macrolides. Macrolides inhibit protein synthesis. They
Synergism versus Antagonism
The use of two antimicrobial agents to treat an infectious
disease sometimes produces a degree of pathogen
killing that is far greater than that achieved by either drug
alone. This is known as synergism. Synergism is a good
thing! Many urinary, respiratory, and gastrointestinal
infections respond particularly well to a combination of
trimethoprim and sulfamethoxazole, a combination
referred to as co-trimoxazole; brand names include
Bactrim and Septra. There are situations, however,
when two drugs are prescribed (perhaps by two different
clinicians who are treating the patient’s infection) that
actually work against each other. This is known as
antagonism. The extent of pathogen killing is less than
that achieved by either drug alone. Antagonism is a bad
thing!
- Antiviral Agents are the newest weapons in
antimicrobial methodology. Until the 1960s,
there were no drugs for the treatment of viral
diseases. Antiviral agents are particularly difficult
to develop and use because viruses are
produced within host cells, but, as can be seen
in Table 9-5, quite a few drugs have been found
to be effective in certain viral infections.

- When the use of two antimicrobial agents to

treat an infectious disease produces a degree of
pathogen killing that is far greater than that
achieved by either drug alone, the phenomenon
is known as synergism.
- When the use of two drugs produces an extent
of pathogen killing that is less than that achieved
by either drug alone, the phenomenon is known
as antagonism.

Antifungal Agents- It is much more difficult to use

antimicrobial drugs against fungal and protozoal
pathogens, because they are eukaryotic cells; thus, the
drugs tend to be more toxic to the patient. Most
antifungal agents work in one of three ways:
• By binding with cell membrane sterols (e.g.,
nystatin
and amphotericin B)
• By interfering with sterol synthesis
(e.g., clotrimazole and
miconazole)
• By blocking mitosis or nucleic
acid synthesis (e.g., griseofulvin
and 5-flucytosine)

- Antifungal and antiprotozoal drugs tend to be

more toxic to the patient because, like the
infected human, they are eukaryotic organisms.

- The first antiviral agent effective against human
immunodeficiency virus (HIV) (the causative
agent of acquired immune deficiency syndrome
or acquired immunodeficiency syndrome [AIDS])
—zidovudine (also known as azidothymidine
[AZT])—was introduced in 1987. A variety of
additional drugs for the treatment of HIV
infection were introduced subsequently. Certain
of these antiviral agents are administered
simultaneously, in combinations referred to as
“cocktails.” Unfortunately, such cocktails are
quite expensive, and some strains of HIV have
become resistant to some of the drugs.
Drug Resistance
“Superbugs”
These days, it is quite common to hear about drug-
resistant bacteria, or “superbugs,” as they have been
labeled by the press (Fig. 9-5). Although “superbug” can
refer to an organism that is resistant to only one
antimicrobial agent, the term usually refers to multidrug
resistant organisms (i.e., organisms that are resistant to
more than one antimicrobial agent). Infections caused by
superbugs are much more difficult to treat. Especially
troublesome superbugs are listed in Table 9-6. It is
important to note that bacteria are not the only microbes
that have developed resistance to drugs. Certain viruses
(including HIV, herpes simplex viruses, and influenza
viruses), fungi (both yeasts and moulds), parasitic
protozoa, and helminths have also developed resistance
to drugs. Parasitic protozoa that have become drug-
resistant include strains of P. falciparum, Trichomonas
vaginalis, Leishmania spp., and Giardia lamblia.
How Bacteria Become Resistant to Drugs
How do bacteria become resistant to antimicrobial
agents? Some bacteria are naturally resistant to a
particular antimicrobial agent because they lack the
specific target site for that drug (e.g., mycoplasmas have
no cell walls and are, therefore, resistant to any drugs
that interfere with cell wall synthesis). Other bacteria are
naturally resistant because the drug is unable to cross
the organism’s cell wall or cell membrane and, thus,
cannot reach its site of action (e.g., ribosomes). Such
resistance is known as intrinsic resistance. It is also
possible for bacteria that were once susceptible to a
particular drug to become resistant to it; this is called
acquired resistance. Bacteria usually acquire resistance
to antibiotics and other antimicrobial agents by one of
four mechanisms.
- Although the term superbug most often refers to
multidrug-resistant bacteria, other types of
microbes (e.g., viruses, fungi, protozoa) have
also become multidrug-resistant.
• Before a drug can enter a bacterial cell, molecules of
the drug must first bind (attach) to proteins on the
surface of the cell; these protein molecules are called
drug-binding sites. A chromosomal mutation can result
in an alteration in the structure of the drug-binding site,
so that the drug is no longer able to bind to the cell. If the
drug cannot bind to the cell, it cannot enter the cell, and
the organism is, therefore, resistant to the drug.
• To enter a bacterial cell, a drug must be able to pass
through the cell wall and cell membrane. A chromosomal
mutation can result in an alteration in the structure of the
cell membrane, which in turn can change the
permeability of the membrane. If the drug is no longer
able to pass through the cell membrane, it cannot reach
its target (e.g., a ribosome or the DNA of the cell), and
the organism is now resistant to the drug.
• Another way in which bacteria become resistant to a
certain drug is by developing the ability to produce an
enzyme that destroys or inactivates the drug. Because
enzymes are coded for by genes, a bacterial cell would
have to acquire a new gene for the cell to be able to
produce an enzyme that it never before produced.

The primary way in which bacteria acquire new genes is
by conjugation (Chapter 7). Often, a plasmid containing
such a gene is transferred from one bacterial cell (the
donor cell) to another bacterial cell (the recipient cell)
during conjugation. For example, many bacteria have
become resistant to penicillin because they have
acquired the gene for penicillinase production during
conjugation. (Penicillinase is described in the following
section.) A plasmid containing multiple genes for drug
resistance is called a resistance factor (R-factor). A
recipient cell that receives an R-factor becomes
multidrugresistant (i.e., it becomes a superbug). Bacteria
can also acquire new genes by transduction (whereby
bacteriophages carry bacterial DNA from one bacterial
cell to another) and transformation (the uptake of naked
DNA from the environment). (Transduction and
transformation were discussed in Chapter 7.)
• A fourth way in which bacteria become resistant to
drugs is by developing the ability to produce multidrug-
resistance (MDR) pumps (also known as MDR
transporters or efflux pumps). An MDR pump enables
the cell to pump drugs out of the cell before the drugs
can damage or kill the cell. The genes encoding these
pumps are often located on plasmids that bacteria
receive during conjugation. Bacteria receiving such
plasmids become multidrugresistant (i.e., they become
resistant to several drugs).
- Bacteria can acquire resistance to antimicrobial
agents as a result of chromosomal mutation or
the acquisition of new genes by transduction,
transformation, and, most commonly,
conjugation.
a-Lactamases- At the heart of every penicillin and
cephalosporin molecule is a double-ringed structure,
which in penicillins resembles a “house and garage”.
The “garage” is called the β-lactam ring. Some
bacteria produce enzymes that destroy the β –
lactam ring; these enzymes are known as β
lactamases. When the β-lactam ring is destroyed,
the antibiotic no longer works. Thus, an organism
that produces a β -lactamase is resistant to
antibiotics containing the β -lactam ring (collectively
referred to as β-lactam antibiotics or β-lactams).
There are two types of β-lactamases: penicillinases
and cephalosporinases. Penicillinases destroy the β-
lactam ring in penicillins; thus, an organism that
produces penicillinaseis resistant to penicillins.
- A β-lactam antibiotic is an antibiotic that contains
a β-lactam ring in its molecular structure.
- Penicillinases and cephalosporinases are
examples of β-lactamases; they destroy the β-
lactam ring in penicillins and cephalosporins,
respectively.
• Clavulanic acid (clavulanate) combined with
amoxicillin
(brand name, Augmentin)
• Clavulanic acid (clavulanate) combined with
ticarcillin
(Timentin)
• Sulbactam combined with ampicillin (Unasyn)
• Tazobactam combined with piperacillin (Zosyn)
Some Strategies in the War against Drug Resistance
• Education is crucial—education of healthcare
professionals and, in turn, education of patients.
• Patients should never pressure clinicians to prescribe
antimicrobial agents. Parents must stop demanding
antibiotics every time they have a sick child. The majority
of sore throats and many respiratory infections are
caused by viruses, and viruses are unaffected by
antibiotics. Because viruses are not killed by antibiotics,
patients and parents should not expect antibiotics when
they or their children have viral infections. Instead of
demanding antibiotics from clinicians, they should be
asking why one is being prescribed.
• It is important that clinicians not allow themselves to
be pressured by patients. They should prescribe
antibiotics only when warranted (i.e., only when there is
a demonstrated need for them). Whenever possible,
clinicians should collect a specimen for culture and have
the Clinical Microbiology Laboratory perform
susceptibility testing (Chapter 13) to determine which
antimicrobial agents are likely to be effective.
• Clinicians should prescribe an inexpensive, narrow
spectrum drug whenever the laboratory results
demonstrate that such a drug effectively kills the
pathogen. According to Dr. Stuart B. Levy,d by some
estimates, at least half of current antibiotic use in the
United States is inappropriate—antibiotics are either not
indicated at all or incorrectly prescribed as the wrong
drug, the wrong dosage, or the wrong duration. One
study showed that antibiotics were prescribed in 68% of
acute respiratory tract visits, and of those, 80% were
unnecessary according to CDC guidelines.e Table 9-8
lists upper respiratory infections that typically do not
benefit from antibiotics. Taking antibiotics for these viral
infections will not cure the infections, will not keep other
individuals from catching the illness, and will not help the
patient feel better.
• Patients must take their antibiotics in the exact manner
in which they are prescribed. Healthcare professionals
should emphasize this to patients and do a better job
explaining exactly how medications should be taken.
• It is critical that clinicians prescribe the appropriate
amount of antibiotic necessary to cure the infection.
Then, unless instructed otherwise, patients must take all
their pills—even after they are feeling better. Again, this
must be explained and emphasized. If treatments are cut
short, there is selective killing of only the most
susceptible members of a bacterial population. The more
resistant variants are left behind to multiply and cause a
new infection.
• Patients should always destroy any excess
medications and should never keep antibiotics in their
medicine cabinet. Antimicrobial agents, including
antibiotics, should be taken only when prescribed and
only under a clinician’s supervision.
• Unless prescribed by a clinician, antibiotics should
never be used in a prophylactic manner—such as to
avoid “traveler’s diarrhea” when traveling to a foreign
country. Taking antibiotics in that manner actually
increases the chances of developing traveler’s diarrhea.
The antibiotics kill some of the beneficial indigenous
intestinal microbes, eliminating the competition for food
and space, making it easier for pathogens to gain a
foothold.
• Healthcare professionals must practice good infection
prevention and control procedures (Chapter 12).
Frequent and proper handwashing is essential to
prevent the transmission of pathogens from one patient
to another. Healthcare professionals should monitor for
important pathogens (such as MRSA) within healthcare
settings and always isolate patients infected with
multidrug-resistant pathogens.
Empiric Therapy
In some cases, a clinician must initiate therapy before
laboratory results are available. This is referred to as
empiric therapy. In an effort to save the life of a patient, it
is sometimes necessary for the clinician to “guess” the
most likely pathogen and the drug most likely to be
effective. It will be an “educated guess,” based on the
clinician’s prior experiences with the particular type of
infectious disease that the patient has. Before writing a
prescription for a certain antimicrobial agent, several
factors must be taken into consideration by the clinician;
some of these are in the following list:
• If the laboratory has reported the identity of the
pathogen, the clinician can refer to a “pocket chart” that
is available in most hospitals. This pocket chart, which is
technically known as an antibiogram, is published by the
Clinical Microbiology Laboratory; it usually contains
antimicrobial susceptibility test data that have been
accumulated during the past year. The pocket chart
provides important information regarding drugs to which
various bacterial pathogens were susceptible and
resistant (Fig. 9-7).
• Is the patient allergic to any antimicrobial agents?
Obviously, it would be unwise to prescribe a drug to
which the patient is allergic.
• What is the age of the patient? Certain drugs are
contraindicated in very young or very old patients.
• Is the patient pregnant? Certain drugs are known to be
or suspected to be teratogenic (i.e., they cause birth
defects).
• Is the patient an inpatient or outpatient? Certain drugs
can be administered only intravenously and, therefore,
cannot be prescribed for outpatients.
• If the patient is an inpatient, the clinician must prescribe
a drug that is available in the hospital pharmacy (i.e., a
drug that is listed in the hospital formulary).
• What is the site of the patient’s infection? If the patient
has cystitis (urinary bladder infection), the clinician might
prescribe a drug that concentrates in the urine. Such a
drug is rapidly removed from the blood by the kidneys,
and high concentrations of the drug are achieved in the
urinary bladder. To treat a brain abscess, the clinician
would select a drug capable of crossing the blood–brain
barrier.
• What other medications is the patient taking or
receiving? Some antimicrobial agents will cross-react
with certain other drugs, leading to a drug interaction
that could be harmful to the patient.
• What other medical problems does the patient have?
Certain antimicrobial agents are known to have toxic
side effects (e.g., nephrotoxicity, hepatotoxicity,
ototoxicity). For example, a clinician would not prescribe
a nephrotoxic drug to a patient who has prior kidney
damage.
• Is the patient leukopenic or immunocompromised? If
so, it would be necessary to use a bactericidal agent to
treat the patient’s bacterial infection, rather than a
bacteriostatic agent. Recall that bacteriostatic agents
should be used only in patients whose host defense
mechanisms are functioning properly (i.e., only in
patients whose bodies are capable of killing the
pathogen once its multiplication is stopped).
- Although the patient’s weight will influence the
dosage of a particular drug, it is usually not
taken into consideration when deciding which
drug to prescribe.
Undesirable Effects of Antimicrobial Agents:
Listed below are some of the many reasons why
antimicrobial agents should not be used indiscriminately.
• Whenever an antimicrobial agent is administered to
a patient, any organisms within that patient that are
susceptible to the agent will die, but resistant ones
will survive. This is referred to as selecting for
resistant organisms (Fig. 9-8). The resistant
organisms then multiply, become dominant, and can
be transmitted to other people. To prevent the
overgrowth of resistant organisms, sometimes
several drugs, each with a different mode of action,
are administered simultaneously.
• The patient may become allergic to the agent. For
example, penicillin G in low doses often sensitizes
those who are prone to allergies; when these
 persons receive a second dose of penicillin at some
later date, they may have a severe reaction known
as anaphylactic shock, or they may break out in
hives.
• Many antimicrobial agents are toxic to humans,
and some are so toxic that they are administered
only for serious diseases for which no other agents
are available. One such drug is chloramphenicol,
which, if given in high doses for a long period, may
cause a very severe type of anemia called aplastic
anemia. Another is streptomycin, which can damage
the auditory nerve and cause deafness. Other drugs
are hepatotoxic or nephrotoxic, causing liver or
kidney damage, respectively.
• With prolonged use, broad spectrum antibiotics may
destroy the indigenous microbiota of the mouth,
intestine, or vagina. The person no longer has the
protection of the indigenous microbiota and thus
becomes much more susceptible to infections caused by
opportunists or secondary invaders. The resultant
overgrowth by such organisms is referred to as a
superinfection. A superinfection can be thought of as a
“population explosion” of organisms that are usually
present only in small numbers. For example, the
prolonged use of oral antibiotics can result in a
superinfection of Clostridium difficile in the colon, which
can lead to such diseases as antibiotic-associated
diarrhea and pseudomembranous colitis. Yeast vaginitis
often follows antibacterial therapy because many
bacteria of the vaginal microbiota were destroyed,
leading to a superinfection
of the indigenous yeast, Candida albicans.