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C H A P T E R 6

Anti-infective Agents
JOHN M. BEALE, JR.

C H A P T E R O V E R V I E W

The history of work on the prevention of bacterial infection

can be traced back to the 19th century when Joseph Lister (in
1867) introduced antiseptic principles for use in surgery and
posttraumatic injury.1 He used phenol (carbolic acid) as a
wash for the hands, as a spray on an incision site, and on
bandages applied to wounds. Lister’s principles caused a dra-
matic decrease in the incidence of postsurgical infections.
Around 1881 and continuing to 1900, microbiologist
Paul Ehrlich, a disciple of Robert Koch, began work with a
set of antibacterial dyes and antiparasitic organic arsenicals.
His goal was to develop compounds that retained antimicro-
bial activity at the expense of toxicity to the human host; he
called the agents that he sought “magic bullets.” At the time
that Ehrlich began his experiments, there were only a few
compounds that could be used in treating infectious dis-
eases, and none was very useful in the treatment of severe
Gram-positive and Gram-negative infections. Ehrlich dis-
covered that the dyes and arsenicals could stain target cells
selectively and that the antimicrobial properties of the dyes Until the 1920s, most successful anti-infective agents
paralleled the staining activity. This discovery was the first were based on the group-IIB element mercury and the
demonstration of selective toxicity, the property of certain group-VA elements arsenic and antimony. Atoxyl (sodium
chemicals to kill one type of organism while not harming arsanilate and arsphenamine) was used for sleeping sick-
another. Selective toxicity is the main tenet of modern an- ness.4 Certain dyes, such as gentian violet and methylene
timicrobial chemotherapy, and Ehrlich’s seminal discovery blue, were also found to be somewhat effective, as were a
paved the way for the development of the sulfonamides and few chemical congeners of the quinine molecule. Some of
penicillins and the elucidation of the mechanisms of their these agents represented significant achievements in anti-
selective toxicity. Prior to Ehrlich’s studies, the local an- infective therapy, but they also possessed some important
timicrobial properties of phenol and iodine were well limitations. Heavy metal toxicity after treatment with mer-
known, but the only useful systemic agents were the herbal cury, arsenic, and antimony severely limited the usefulness
remedies cinchona for malaria and ipecac for amebic dysen- of agents containing these elements.
tery. Ehrlich’s discovery of compound 606, the effective an- Just prior to 1950, great strides were made in anti-infective
tisyphilitic drug Salvarsan,2,3 was a breakthrough in the therapy. The sulfonamides and sulfones (this chapter), more
treatment of a serious, previously untreatable disease. effective phenolic compounds such as hexachlorophene,

179
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180 Wilson and Gisvold’s Textbook of Organic Medicinal and Pharmaceutical Chemistry
synthetic antimalarial compounds (Chapter 7), and several
antibiotics (Chapter 8) were introduced to the therapeutic
armamentarium.
Anti-infective agents may be classified according to var-
ious schemes. The chemical type of the compound, the bio-
logical property, and the therapeutic indication may be used
singly or in combination to describe the agents. In this text-
book, a combination of these classification schemes is used
to organize the anti-infective agents. When several chemi-
cally divergent compounds are indicated for a specific dis-
ease or group of diseases, the therapeutic classification is
used, and the drugs are subclassified according to chemical
type. When the information is best unified and presented in
a chemical or biological classification system, as for the sul-
fonamides or antibacterial antibiotics, then one of these clas-
sification systems is used.
This chapter addresses an extremely broad base of anti-
infective agents, including the local compounds (alcohols,
phenols, oxidizing agents, halogen-containing compounds,
cationic surfactants, dyes, and mercurials), preservatives,
antifungal agents, synthetic antibacterial drugs, antitubercu-
lar and antiprotozoal agents, and anthelmintics. Other chap-
ters in this text are devoted to antibacterial antibiotics
(Chapter 8), antiviral agents (Chapter 9), and antineoplastic
antibiotics (Chapter 10).
Anti-infective agents that are used locally are called ger-
micides, and within this classification, there are two pri-
mary subtypes (see Table 6.1) and several other definitions
of sanitization. Antiseptics are compounds that kill (-cidal)
or prevent the growth of (-static) microorganisms when ap-
plied to living tissue. This caveat of use on living tissue
points to the properties that the useful antiseptic must have.
The ideal antiseptic must have low-enough toxicity that it
can be used directly on skin or wounds; it will exert a rapid
and sustained lethal action against microorganisms (the
spectrum may be narrow or broad depending on the use).
The agent should have a low surface tension so that it will
spread into the wound; it should retain activity in the pres-
ence of body fluids (including pus), be nonirritating to tis-
TABLE 6.1 Definitions and Standards for Removing
Microorganisms
Antisepsis Application of an agent to living
tissue for the purpose of preventing
infection
Decontamination Destruction or marked reduction in
the number or activity of
microorganisms
Disinfection Chemical or physical treatment that
destroys most vegetative microbes
or viruses, but not spores, in or on
inanimate surfaces
Sanitization Reduction of microbial load on an
inanimate surface to a level
considered acceptable for public
health purposes
Sterilization A process intended to kill or remove
all types of microorganisms,
including spores, and usually
including viruses with an acceptably
low probability of survival
Pasteurization A process that kills nonsporulating
microorganisms by hot water or
steam at 65°C–100°C
sues, be nonallergenic, lack systemic toxicity when applied
to skin or mucous membranes, and not interfere with heal-
ing. No antiseptic available today meets all of these crite-
ria. A few antibiotics, such as bacitracin, polymyxin, silver
sulfadiazine, and neomycin, are poorly absorbed through
the skin and mucous membranes and are used topically for
the treatment of local infections; they have been found very
effective against infections such as these. In general, how-
ever, the topical use of antibiotics has been restricted by
concern about the development of resistant microbial
strains and possible allergic reactions. These problems can
reduce the usefulness of these antibiotics for more serious
infections.
A disinfectant is an agent that prevents transmission of
infection by the destruction of pathogenic microorganisms
when applied to inanimate objects. The ideal disinfectant
exerts a rapidly lethal action against all potentially patho-
genic microorganisms and spores, has good penetrating
properties into organic matter, shares compatibility with or-
ganic compounds (particularly soaps), is not inactivated by
living tissue, is noncorrosive, and is aesthetically pleasing
(nonstaining and odorless). Locally acting anti-infective
drugs are widely used by the lay public and are prescribed
by members of the medical profession (even though the ef-
fectiveness of many of the agents has not been established
completely). The germicide may be harmful in certain cases
(i.e., it may retard healing). Standardized methods for eval-
uating and comparing the efficacy of germicides have only
recently been developed.
Numerous classes of chemically divergent compounds
possess local anti-infective properties. Some of these are
outlined in Table 6.2.
The most important means of preventing transmission of
infectious agents from person to person or from regions of
high microbial load, such as the mouth, nose, or gut, to po-
tential sites of infection is simply washing the hands. In fact,
one of the breakthroughs in surgical technique in the 1800s
was the finding that the incidence of postsurgical infection
decreased dramatically if surgeons washed their hands be-
fore operating. Regular hand washing is properly done with-
out disinfection to minimize drying, irritation, and sensitiza-
tion of the skin. Simple soap and warm water remove
bacteria efficiently. Skin disinfectants along with soap and
water are usually used as preoperative surgical scrubs and
sterilants for surgical incisions.
EVALUATION OF THE EFFECTIVENESS
OF A STERILANT
Evaluation of the effectiveness of antiseptics, disinfectants,
and other sterilants (Table 6.1), although seemingly simple
in principle, is an extremely complex task. One must con-
sider the intrinsic resistance of the microbe, the microbial
load, the mixture of the population of microorganisms pres-
ent, the amount and nature of organic material present (e.g.,
blood, feces, tissue), the concentration and stability of the
disinfectant or sterilant, the time and temperature of expo-
sure, the pH, and the hydration and binding of the agent to
surfaces. In summary, a host of parameters must be consid-
ered for each sterilant, and experimental assays may be dif-
ficult. Specific, standardized assays of activity are defined
for each use. Toxicity for human subjects must also be eval-
uated. The Environmental Protection Agency (EPA)
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Chapter 6 Anti-infective Agents 181

TABLE 6.2 Common Sterilants and Their Range of Use

Bacteria Viruses Other
Gram- Gram- Amebic
positive negative Acid-fast Spores Lipophilic Hydrophilic Fungi Cysts Prions

Alcohols       N/A N/A 

(isopropanol,
ethanol)
Aldehydes        N/A 
(glutaraldehyde,
formaldehyde)
Chlorhexidine       N/A N/A 
gluconate
Sodium     (pH   (high   
hypochlorite, 7.6) conc.) (high
chlorine dioxide conc.)
Hexachlorophene         
Povidone-Iodine     (high     
conc.)
Phenols,       N/A N/A 
quaternary
ammonium
Strong oxidizing         
agents, cresols

regulates disinfectants and sterilants and the Food and Drug
Administration (FDA) regulates antiseptics.
There are some problems with improper use of these
agents. Antiseptics and disinfectants may become contam-
inated by resistant microorganisms (e.g., spores),
Pseudomonas aeruginosa, or Serratia marcescens and may
actually transmit infection. Most topical antiseptics inter-
fere with wound healing to some degree, so they should be
used according to the proper directions and for a limited
length of time.
ALCOHOLS AND RELATED
COMPOUNDS
Alcohols and aldehydes have been used as antiseptics and
disinfectants for many years.5 Two of the most commonly
used antiseptics and disinfectants are ethyl and isopropyl
alcohol.
The antibacterial potencies of the primary alcohols
(against test cultures of Staphylococcus aureus) increase
with molecular weight until the 8-carbon atom octanol is
reached. In general, one oxygen atom is capable of solubi-
lizing seven or eight carbon atoms in water. As the primary
alcohol chain length increases, van der Waals interactions
increase, and the ability to penetrate microbial membranes
increases. As water solubility decreases, the apparent an-
timicrobial potency diminishes with molecular weight.
Branching of the alcohol chain decreases antibacterial po-
tency; weaker van der Waals forces brought about by
branching do not penetrate bacterial cell membranes as
efficiently. The isomeric alcohols’ potencies decrease in
the order primary > secondary > tertiary. Despite this fact,
2-propanol (isopropyl alcohol) is used commercially instead
of n-propyl alcohol, because it is less expensive. Isopropyl
alcohol is slightly more active than ethyl alcohol against
vegetative bacterial growth, but both alcohols are largely in-
effective against spores. The activity of alcohols against mi-
croorganisms is the result of their ability to denature impor-
tant proteins and carbohydrates.
Alcohol
Ethanol (ethyl alcohol, wine spirit) is a clear, colorless,
volatile liquid with a burning taste and a characteristic
pleasant odor. It is flammable, miscible with water in all
proportions, and soluble in most organic solvents.
Commercial ethanol contains approximately 95% ethanol
by volume. This concentration forms an azeotrope with
water that distills at 78.2°C. Alcohol has been known for
centuries as a product of fermentation from grain and many
other carbohydrates. Ethanol can also be prepared syntheti-
cally by the sulfuric-acid–catalyzed hydration of ethylene
The commerce in, and use of, alcohol in the United States
is strictly controlled by the Treasury Department, which has
provided the following definition for “alcohol”: “The term
alcohol means that substance known as ethyl alcohol, hy-
drated oxide of ethyl, or spirit of wine, from whatever
source or whatever process produced, having a proof of 160
or more and not including the substances commonly known
as whiskey, brandy, rum, or gin.”
Denatured alcohol is ethanol that has been rendered unfit
for use in intoxicating beverages by the addition of other
substances. Completely denatured alcohol contains added
wood alcohol (methanol) and benzene and is unsuitable for
either internal or external use. Specially denatured alcohol
is ethanol treated with one or more substances so that its use
may be permitted for a specialized purpose. Examples are
iodine in alcohol for tincture of iodine, methanol, and other
substances in mouthwashes and aftershave lotions, and
methanol in alcohol for preparing plant extracts.
The primary medicinal use of alcohol is external, as an
antiseptic, preservative, mild counterirritant, or solvent.
Rubbing alcohol is used as an astringent, rubefacient, and a
mild local anesthetic. The anesthetic effect is results from
the evaporative refrigerant action of alcohol when applied to
the skin. Ethanol has even been injected near nerves and
ganglia to alleviate pain. It has a low narcotic potency and
has been used internally in diluted form as a mild sedative,
a weak vasodilator, and a carminative.
Alcohol is metabolized in the human body by a series of
oxidations:
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182 Wilson and Gisvold’s Textbook of Organic Medicinal and Pharmaceutical Chemistry
Acetaldehyde causes nausea, vomiting, and vasodilatory
flushing. This fact has been used in aversion therapy with
the drug disulfiram, which blocks aldehyde dehydrogenase,
allowing acetaldehyde to accumulate.
Alcohol is used in the practice of pharmacy for the prepa-
ration of spirits, tinctures, and fluidextracts. Spirits are
preparations containing ethanol as the sole solvent, whereas
tinctures are hydroalcoholic mixtures. Many fluidextracts
contain alcohol as a cosolvent.
The accepted bactericidal concentration of 70% alcohol
is not supported by a study that discovered that the kill rates
of microorganisms suspended in alcohol concentrations be-
tween 60% and 95% were not significantly different.6
Concentrations below 60% are also effective, but longer
contact times are necessary. Concentrations above 70% can
be used safely for preoperative sterilization of the skin.7
Alcohols are flammable and must be stored in cool, well-
ventilated areas.
Dehydrated Ethanol
Dehydrated ethanol, or absolute ethanol, contains not less
than 99% w/w of C2H5OH. It is prepared commercially by
azeotropic distillation of an ethanol–benzene mixture, with
provisions made for efficient removal of water. Absolute
ethanol has a very high affinity for water and must be stored
in tightly sealed containers. This form of ethanol is used pri-
marily as a chemical reagent or solvent but has been injected
for the local relief of pain in carcinomas and neuralgias.
Absolute alcohol cannot be ingested because there is always
some benzene remaining from the azeotropic distillation
that cannot be removed.
Isopropyl Alcohol
Isopropanol (2-propanol) is a colorless, volatile liquid with
a characteristic odor and a slightly bitter taste. It is consid-
ered a suitable substitute for ethanol in most cases but must
not be ingested. Isopropyl alcohol is prepared commercially
by the sulfuric-acid–catalyzed hydration of propylene:
The alcohol forms a constant-boiling mixture with water
that contains 91% v/v of 2-propanol. Isopropyl alcohol is used
primarily as a disinfectant for the skin and for surgical instru-
ments. The alcohol is rapidly bactericidal in the concentration
range of 50% to 95%. A 40% concentration is considered
equal in antiseptic efficacy to a 60% ethanol in water solution.
Azeotropic isopropyl alcohol, United States Pharmacopeia
(USP), is used on gauze pads for sterilization of the skin prior
to hypodermic injections. Isopropyl alcohol is also used in
pharmaceuticals and toiletries as a solvent and preservative.
Ethylene Oxide
Ethylene oxide, C2H4O, is a colorless, flammable gas that
liquefies at 12°C. It has been used to sterilize temperature-
sensitive medical equipment and certain pharmaceuticals
that cannot be heat sterilized in an autoclave. Ethylene oxide
diffuses readily through porous materials and very effec-
tively destroys all forms of microorganisms at ambient tem-
peratures.8
Ethylene oxide forms explosive mixtures in air at con-
centrations ranging from 3% to 80% by volume. The explo-
sion hazard is eliminated when the gas is mixed with suffi-
cient concentrations of carbon dioxide. Carboxide is a
commercial sterilant containing 10% ethylene oxide and
90% carbon dioxide by volume that can be handled and re-
leased in air without danger of explosion. Sterilization is ac-
complished in a sealed, autoclave-like chamber or in gas-
impermeable bags.
The mechanism of the germicidal action of ethylene
oxide probably involves the alkylation of functional groups
in nucleic acids and proteins by nucleophilic opening of the
oxide ring. Ethylene oxide is a nonselective alkylating
agent, and for that reason is extremely toxic and potentially
carcinogenic. Exposure to skin and mucous membranes
should be avoided, and inhalation of the gas should be pre-
vented by use of an appropriate respiratory mask during
handling and sterilization procedures.
Aldehydes
Formaldehyde Solution
Formalin is a colorless aqueous solution that officially
contains not less than 37% w/v of formaldehyde (HCHO),
with methanol added to retard polymerization. Formalin is
miscible with water and alcohol and has a characteristic pun-
gent aroma. Formaldehyde readily undergoes oxidation and
polymerization, leading to formic acid and paraformalde-
0179-0241_17865_Ch06.qxd 12/8/09 10:54 PM Page 183
hyde, respectively, so the preparation should be stored in
tightly closed, light-resistant containers. Formalin must be
stored at temperatures above 15°C to prevent cloudiness,
which develops at lower temperatures.
The germicidal action of formaldehyde is slow but pow-
erful. The mechanism of action is believed to involve direct,
nonspecific alkylation of nucleophilic functional groups
(amino, hydroxyl, and sulfhydryl) in proteins and nucleic
acids to form carbinol derivatives. The action of formalde-
hyde is not confined to microorganisms. The compound is
irritating to mucous membranes and causes hardening of the
skin. Oral ingestion of the solution leads to severe gastroin-
testinal distress. Contact dermatitis is common with forma-
lin, and pure formaldehyde is suspected to be a carcinogen.
Glutaraldehyde Disinfectant Solution
Glutaraldehyde (Cidex, a 5-carbon dialdehyde) is used as a
dilute solution for sterilization of equipment and instru-
ments that cannot be autoclaved. Commercial glutaralde-
hyde is stabilized in alkaline solution. The preparation actu-
ally consists of two components, glutaraldehyde and buffer,
which are mixed together immediately before use. The acti-
vated solution contains 2% glutaraldehyde buffered at pH
7.5 to 8.0. Stabilized glutaraldehyde solutions retain more
than 80% of their original activity 30 days after prepara-
tion,9 whereas the nonstabilized alkaline solutions lose
about 44% of their activity after 15 days. At higher pH
(8.5), glutaraldehyde rapidly polymerizes. Nonbuffered
solutions of glutaraldehyde are acidic, possibly because of
an acidic proton on the cyclic hemiacetal form. The acidic
solutions are stable but lack sporicidal activity.
PHENOLS AND THEIR DERIVATIVES
Phenol, USP, remains the standard to which the activity of
most germicidal substances is compared. The phenol coeffi-
Chapter 6 Anti-infective Agents 183
cient is defined as the ratio of a dilution of a given test dis-
infectant to the dilution of phenol that is required to kill (to
the same extent) a strain of Salmonella typhi under carefully
controlled time and temperature conditions. As an example,
if the dilution of a test disinfectant is 10-fold greater than the
dilution of phenol, the phenol coefficient is 10. Obviously,
the phenol coefficient of phenol itself is 1. The phenol coef-
ficient test has many drawbacks. Phenols and other germi-
cides do not kill microorganisms uniformly, so variations in
the phenol coefficient will occur. Moreover, the conditions
used to conduct the test are difficult to reproduce exactly, so
high variability between different measurements and labora-
tories is expected. Hence, the phenol coefficient may be
unreliable.
Several phenols are actually more bactericidal than phe-
nol itself. Substitution with alkyl, aryl, and halogen (espe-
cially in the para position) groups increases bactericidal ac-
tivity. Straight-chain alkyl groups enhance bactericidal
activity more than branched groups. Alkylated phenols and
resorcinols are less toxic than the parent compounds while
retaining bactericidal properties. Phenols denature bacterial
proteins at low concentrations, whereas lysis of bacterial
cell membranes occurs at higher concentrations.
Phenol
Phenol (carbolic acid) is a colorless to pale-pink crystalline
material with a characteristic “medicinal odor.” It is soluble
to the extent of 1 part to 15 parts water, very soluble in al-
cohol, and soluble in methanol and salol (phenyl salicylate).
Phenol exhibits germicidal activity (general protoplas-
mic poison), is caustic to skin, exerts local anesthetic ef-
fects, and must be diluted to avoid tissue destruction and
dermatitis.
Sir Joseph Lister introduced phenol as a surgical antisep-
tic in 1867, and it is still used occasionally as an antipruritic
in phenolated calamine lotion (0.1%–1% concentrations). A
4% solution of phenol in glycerin has been used to cauterize
small wounds. Phenol is almost obsolete as an antiseptic and
disinfectant.
Liquified Phenol
Liquified phenol is simply phenol containing 10% water.
The liquid form is convenient for adding phenol to various
pharmaceutical preparations because it can be measured and
transferred easily. The water content, however, precludes its
use in fixed oils or liquid petrolatum, because the solution is
not miscible with lipophilic ointment bases.
p-Chlorophenol
p-Chlorophenol is used in combination with camphor in liq-
uid petrolatum as an external antiseptic and anti-irritant. The
compound has a phenol coefficient of about 4.
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184 Wilson and Gisvold’s Textbook of Organic Medicinal and Pharmaceutical Chemistry
p-Chloro-m-xylenol
p-Chloro-m-xylenol (PC-MX; Metasep) is a nonirritating
antiseptic agent with broad-spectrum antibacterial and anti-
fungal properties. It is marketed in a 2% concentration as a
shampoo. It has also been used topically for the treatment of
tinea (ringworm) infections such as athlete’s foot (tinea
pedis) and jock itch (tinea cruris).
Hexachlorophene
Hexachlorophene, 2,2-methylenebis (3,4,6-trichlorophe-
nol); 2,2-dihydroxy-3,5,6,3,5, 6-hexachlorodiphenyl-
methane (Gamophen, Surgicon, pHisoHex) is a white to
light-tan crystalline powder that is insoluble in water but is
soluble in alcohol and most other organic solvents. A biphe-
nol such as hexachlorophene will, in general, possess
greater potency than a monophenol. In addition, as ex-
pected, the increased degree of chlorination of hexa-
chlorophene increases its antiseptic potency further.
Hexachlorophene is easily adsorbed onto the skin and
enters the sebaceous glands. Because of this, topical appli-
cation elicits a prolonged antiseptic effect, even in low con-
centrations. Hexachlorophene is used in concentrations of
2% to 3% in soaps, detergent creams, lotions, and shampoos
for various antiseptic uses. It is, in general, effective against
Gram-positive bacteria, but many Gram-negative bacteria
are resistant.
The systemic toxicity of hexachlorophene in animals after
oral and parenteral administration had been known for some
time, but in the late 1960s and early 1970s, reports of neuro-
toxicity in infants bathed in hexachlorophene and in burn pa-
tients cleansed with the agent prompted the FDA to ban its
use in over-the-counter (OTC) antiseptic and cosmetic prepa-
rations.10 Hexachlorophene is still available by prescription.
Cresol
Cresol is actually a mixture of three isomeric methylphenols:
The mixture occurs as a yellow to brownish yellow liq-
uid that has a characteristic odor of creosote. Cresol is ob-
tained from coal tar or petroleum by alkaline extraction into
aqueous medium, acidification, and fractional distillation.
The mixture is an inexpensive antiseptic and disinfectant. It
possesses a phenol coefficient of 2.5. Cresol is sparingly
soluble in water, although alcohols and other organic sol-
vents will solubilize it. The drawback to its use as an anti-
septic is its unpleasant odor.
Chlorocresol
4-Chloro-3-methylphenol occurs as colorless crystals.
Chlorocresol is only slightly soluble in water. At the low
concentration that can be achieved in aqueous media, the
compound is only useful as a preservative.
Thymol
Isopropyl m-cresol is extracted from oil of Thymus vulgaris
(thyme, of the mint family) by partitioning into alkaline
aqueous medium followed by acidification. The crystals ob-
tained from the mother liquor are large and colorless, with a
thymelike odor. Thymol is only slightly soluble in water,
but it is extremely soluble in alcohols and other organic sol-
vents. Thymol has mild fungicidal properties and is used in
alcohol solutions and in dusting powders for the treatment
of tinea (ringworm) infections.
Eugenol
4-Allyl-2-methoxyphenol is obtained primarily from clove
oil. It is a pale-yellow liquid with a strong aroma of cloves
and a pungent taste. Eugenol is only slightly soluble in water
but is miscible with alcohol and other organic solvents.
Eugenol possesses both local anesthetic and antiseptic activ-
ity and can be directly applied on a piece of cotton to relieve
toothaches. Eugenol is also used in mouthwashes because of
its antiseptic property and pleasant taste. The phenol coeffi-
cient of eugenol is 14.4.
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Resorcinol
m-Dihydroxybenzene (resorcin), or resorcinol, is prepared
synthetically. It crystallizes as white needles or as an amor-
phous powder that is soluble in water and alcohol.
Resorcinol is light sensitive and oxidizes readily, so it must
be stored in tight, light-resistant containers. It is much less
stable in solution, especially at alkaline pH. Resorcinol is
only a weak antiseptic (phenol coefficient 0.4). Nevertheless,
it is used in 1% to 3% solutions and in ointments and pastes
in concentrations of 10% to 20% for the treatment of skin
conditions such as ringworm, eczema, psoriasis, and sebor-
rheic dermatitis. In addition to its antiseptic action, resorcinol
is a keratolytic agent. This property causes the stratum
corneum of the skin to slough, opening the barrier to penetra-
tion for antifungal agents.
Hexylresorcinol
4-Hexylresorcinol, or “hexylresorcinol,” is a white crys-
talline substance with a faint phenolic odor. When applied
to the tongue it produces a sensation of numbness. It is
freely soluble in alcohol but only slightly soluble in water
(1–20,000 parts). Hexylresorcinol is an effective antisep-
tic, possessing both bactericidal and fungicidal properties.
The phenol coefficient of hexylresorcinol against S. aureus
is 98. As is typical for alkylated phenols, hexylresorcinol
possesses surfactant properties. The compound also has
local anesthetic activity. Hexylresorcinol is formulated
into throat lozenges because of its local anesthetic and an-
tiseptic properties. These preparations are probably of lit-
tle value. Hexylresorcinol (in the concentration in the
lozenge) is probably not antiseptic, and the local anesthetic
property can anesthetize the larynx, causing temporary
laryngitis.
OXIDIZING AGENTS
In general, oxidizing agents that are of any value as germi-
cidal agents depend on their ability to liberate oxygen in the
tissues. Many of these agents are inorganic compounds, in-
cluding hydrogen peroxide, several metal peroxides, and
sodium perborate. All of these react in the tissues to gener-
ate oxygen and oxygen radicals. Other oxidizing agents,
such as KMnO4, denature proteins in microorganisms
through a direct oxidation reaction. Oxidizing agents are
especially effective against anaerobic bacteria and can be
used in cleansing contaminated wounds. The bubbles that
form during the liberation of oxygen help to dislodge debris.
The effectiveness of the oxidizing agents is somewhat lim-
ited by their generally poor penetrability into infected tis-
sues and organic matter. Additionally, the action of the oxi-
dizers is typically transient.
Chapter 6 Anti-infective Agents 185
Carbamide Peroxide Topical Solution
Carbamide peroxide (Gly-Oxide) is a stable complex of urea
and hydrogen peroxide. It has the molecular formula
H2NCONH2 H2O2. The commercial preparation is a solu-
tion of 12.6% carbamide peroxide in anhydrous glycerin.
When mixed with water, hydrogen peroxide is liberated.
Carbamide peroxide is used as both an antiseptic and disin-
fectant. The preparation is especially effective in the treat-
ment of oral ulcerations or in dental care. The oxygen bub-
bles that are liberated remove debris.
Hydrous Benzoyl Peroxide
Hydrous benzoyl peroxide (Oxy-5, Oxy-10, Vanoxide) is a
white granular powder. In its pure powder form, it is explo-
sive. The compound is formulated with 30% water to make
it safer to handle.
Compounded at 5% and 10% concentrations, benzoyl
peroxide is both keratolytic and keratogenic. It is used in the
treatment of acne. Benzoyl peroxide induces proliferation of
epithelial cells, leading to sloughing and repair.11
HALOGEN-CONTAINING COMPOUNDS
IODOPHORS
Elemental iodine (I2) is probably the oldest germicide still in
use today. It was listed in 1830 in USP-II as a tincture and a
liniment. Iodine tincture (2% iodine in 50% alcohol with
sodium iodide), strong iodine solution (Lugol’s solution, 5%
iodine in water with potassium iodide), and iodine solution
(2% iodine in water with sodium iodide) are currently offi-
cial preparations in the USP. The iodide salt is admixed to
increase the solubility of the iodine and to reduce its volatil-
ity. Iodine is one of the most effective and useful of the ger-
micides. It probably acts to inactivate proteins by iodination
of aromatic residues (phenylalanyl and tyrosyl) and oxida-
tion (sulfhydryl groups). Mixing with several nonionic and
cationic surfactants can solubilize iodine. Complexes form
that retain the germicidal properties of the iodine while re-
ducing its volatility and removing its irritant properties.12 In
some of the more active, nonionic surfactant complexes, it
is estimated that approximately 80% of the dissolved iodine
remains available in bacteriologically active form. These ac-
tive complexes, called iodophors, are both bactericidal and
fungicidal.
Povidone–Iodine
Povidone–iodine (Betadine, Isodine, polymer polyvinylpyrroli-
done [PVP]–iodine) is a charge-transfer complex of iodine with
the nonionic surfactant PVP. The complex is extremely water
soluble and releases iodine very slowly. Hence, the preparation
provides a nontoxic, nonvolatile, and nonstaining form of io-
dine that is not irritating to the skin or to wounds.
Approximately 10% of the iodine in the complex is bioavail-
able. Povidone–iodine is used as an aqueous solution for
presurgical disinfection of the incision site. It can also be used
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186 Wilson and Gisvold’s Textbook of Organic Medicinal and Pharmaceutical Chemistry
to treat infected wounds and damage to the skin, and it is effec-
tive for local bacterial and fungal infections. Several other
forms of PVP–iodine are available, including aerosols, foams,
ointments, surgical scrubs, antiseptic gauze pads, sponges,
mouthwashes, and a preparation that disinfects whirlpool baths
and hot tubs.
CHLORINE-CONTAINING COMPOUNDS
Chlorine and chlorine-releasing compounds have been used
in the disinfection of water supplies for more than a cen-
tury. The discovery that hypochlorous acid (HClO) is the
active germicidal species that is formed when chlorine is
dissolved in water led to the development and use of the
first inorganic hypochlorite salts such as NaOCl and
Ca(OCl)2. Later, organic N-chloro compounds were devel-
oped as disinfectants. These compounds release hypochlor-
ous acid when dissolved in water, especially in the presence
of acid. Two equally plausible mechanisms have been pro-
posed for the germicidal action of hypochlorous acid: the
chlorination of amide nitrogen atoms and the oxidation of
sulfhydryl groups in proteins. Organic compounds that
form stable N-chloro derivatives include amides, imides,
and amidines. N-Chloro compounds slowly release HOCl
in water. The antiseptic effect of these agents is optimal at
around pH 7.
Halazone
p-Dichlorosulfamoylbenzoic acid is a white, crystalline,
photosensitive compound with a faint chlorine odor.
Halazone is only slightly soluble in water at pH 7 but be-
comes very soluble in alkaline solutions. The sodium salt of
halazone is used to disinfect drinking water.
Chloroazodin
N,N-Dichlorodicarbonamidine (Azochloramid) is a bright
yellow crystalline solid with a faint odor of chlorine. It is
mostly insoluble in water and organic solvents and is unsta-
ble to light or heat. Chloroazodin will explode if heated
above 155°C. The compound is soluble enough in water to
be used in very dilute solution to disinfect wounds, as pack-
ing for dental caries, and for lavage and irrigation. A glyc-
eryltriacetate solution is used as a wound dressing. The an-
tiseptic action of chloroazodin is long lasting because of its
extremely slow reaction with water.
Oxychlorosene Sodium
Oxychlorosene (Clorpactin) is a complex of the sodium salt
of dodecylbenzenesulfonic acid and hypochlorous acid. The
complex slowly releases hypochlorous acid in solution.
Oxychlorosene occurs as an amorphous white powder
that has a faint odor of chlorine. It combines the germicidal
properties of HOCl with the emulsifying, wetting, and kera-
tolytic actions of an anionic detergent. The agent has a
marked and rapid-cidal action against most microorgan-
isms, including both Gram-positive and Gram-negative bac-
teria, molds, yeasts, viruses, and spores. Oxychlorosene is
used to treat localized infections (especially when resistant
organisms are present), to remove necrotic tissue from mas-
sive infections or radiation necrosis, to counteract odorous
discharges, to act as an irritant, and to disinfect cysts and fis-
tulas. Oxychlorosene is marketed as a powder for reconsti-
tution into a solution. A typical application uses a 0.1% to
0.5% concentration in water. Dilutions of 0.1% to 0.2% are
used in urology and ophthalmology.
CATIONIC SURFACTANTS
All of the cationic surfactants are quaternary ammonium
compounds (Table 6.3). For that reason, they are always
ionized in water and exhibit surface-active properties. The
compounds, with a polar head group and nonpolar hydro-
carbon chain, form micelles by concentrating at the inter-
face of immiscible solvents. The surface activity of these
compounds, exemplified by lauryl triethylammonium sul-
fate, results from two structural moieties: (a) a cationic
head group, which has a high affinity for water and (b) a
long hydrocarbon tail, which has an affinity for lipids and
nonpolar solvents.
At the right concentration (the critical micelle concentra-
tion), the molecules concentrate at the interface between
immiscible solvents, such as water and lipid, and water-in-oil
or oil-in-water emulsions may be formed with the ammo-
nium head group in the water layer and the nonpolar hydro-
carbon chain associated with the oil phase. The synthesis and
antimicrobial actions of the members of this class of com-
0179-0241_17865_Ch06.qxd 12/8/09 10:54 PM Page 187
TABLE 6.3 Analogs of Dimethylbenzylammonium Chloride
pounds were first reported in 1908, but it was not until the pi-
oneering work of Gerhard Domagk in 193513 that attention
was directed to their usefulness as antiseptics, disinfectants,
and preservatives.
The cationic surfactants exert a bactericidal action against
a broad spectrum of Gram-positive and Gram-negative bac-
teria. They are also active against several pathogenic species
of fungi and protozoa. All spores resist these agents. The
mechanism of action probably involves dissolution of the
surfactant into the microbial cell membrane, destabilization,
and subsequent lysis. The surfactants may also interfere with
enzymes associated with the cell membrane.
The cationic surfactants possess several other properties.
In addition to their broad-spectrum antimicrobial activity,
they are useful as germicides. They are highly water solu-
ble, relatively nontoxic, stable in solution, nonstaining, and
noncorrosive. The surface activity causes a keratolytic ac-
tion in the stratum corneum and, hence, provides good tis-
sue penetration. In spite of these advantages, the cationic
Chapter 6 Anti-infective Agents 187
surfactants present several difficulties. Soaps and other an-
ionic detergents inactivate them. All traces of soap must be
removed from skin and other surfaces before they are ap-
plied. Tissue debris, blood, serum, and pus reduce the ef-
fectiveness of the surfactants. Cationic surfactants are also
adsorbed on glass, talc, and kaolin to reduce or prevent
their action. The bactericidal action of cationic surfactants
is slower than that of iodine. Solutions of cationic surfac-
tants intended for disinfecting surgical instruments, gloves,
etc. should never be reused because they can harbor infec-
tious microorganisms, especially Pseudomonas and
Enterobacter spp.
Benzalkonium Chloride
Alkylbenzyldimethylammonium chloride (Zephiran) is a mix-
ture of alkylbenzyldimethylammonium chlorides of the gen-
eral formula [C6H5CH2N(CH3)2R]Cl, where R represents a
mixture of alkyl chains beginning with C8H17 and extending
to higher homologues with C12H25, C14H29, and C16H33. The
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188 Wilson and Gisvold’s Textbook of Organic Medicinal and Pharmaceutical Chemistry
higher–molecular-weight homologues compose the major
fractions. Although variations in the physical and antimicro-
bial properties exist between individual members of the mix-
ture, they are of little importance in the chemistry of the over-
all product. Benzalkonium chloride occurs as a white gel that
is soluble in water, alcohol, and organic solvents. Aqueous so-
lutions are colorless, slightly alkaline, and very foamy.
Benzalkonium chloride is a detergent, an emulsifier, and
a wetting agent. It is used as an antiseptic for skin and mu-
cous membranes in concentrations of 1:750 to 1:20,000. For
irrigation, 1:20,000 to 1:40,000 concentrations are used. For
storage of surgical instruments, 1:750 to 1:5,000 concentra-
tions are used, with 0.5% NaNO3 added as a preservative.
Methylbenzethonium Chloride
Benzyldimethyl[2-[2-[[4-(1,1,3,3-tetramethylbutyl)
tolyl]oxy]ethoxy]ethyl]ammonium chloride (Diaparene) is a
mixture of methylated derivatives of methylbenzethonium
chloride. It is used specifically for the treatment of diaper
rash in infants, caused by the yeast Candida albicans, which
produces ammonia. The agent is also used as a general anti-
septic. Its properties are virtually identical to those of ben-
zethonium chloride.
Benzethonium Chloride
Benzyldimethyl[2-[2-[p-(1,1,3,3-tetramethylbutyl)phe-
noxy]ethoxy]ethyl]ammonium chloride (Phemerol chloride)
is a colorless crystalline powder that is soluble in water, al-
cohol, and most organic solvents. The actions and uses of
this agent are similar to those of benzalkonium chloride. It
is used at a 1:750 concentration for skin antisepsis. For the
irrigation of mucous membranes, a 1:5,000 solution is used.
A 1:500 tincture is also available.
Cetylpyridinium Chloride
1-Hexadecylpyridinium chloride is a white powder that is
very soluble in water and alcohol. In this compound, the
quaternary nitrogen atom is a member of an aromatic pyri-
dine ring.
Chlorhexidine Gluconate
The cetyl derivative is the most active of a series of
alkylpyridinium compounds. It is used as a general antisep-
tic in concentrations of 1:100 to 1:1,000 for intact skin,
1:1,000 for minor lacerations, and 1:2,000 to 1:10,000 for
the irrigation of mucous membranes. Cetylpyridinium chlo-
ride is also available in the form of throat lozenges and a
mouthwash at a 1:20,000 dilution.
Chlorhexidine Gluconate
1,6-Di(4-chlorophenyldiguanido)hexane gluconate (Hibiclens)
is the most effective of a series of antibacterial biguanides orig-
inally developed in Great Britain.14
The antimicrobial properties of the biguanides were dis-
covered as a result of earlier testing of these compounds as
possible antimalarial agents (Chapter 7). Although the
biguanides are technically not bisquaternary ammonium
compounds and, therefore, should probably be classified
separately, they share many physical, chemical, and antimi-
crobial properties with the cationic surfactants. The
biguanides are strongly basic, and they exist as dications at
physiological pH. In chlorhexidine, the positive charges are
counterbalanced by gluconate anions (not shown). Like
cationic surfactants, these undergo inactivation when mixed
with anionic detergents and complex anions such as phos-
phate, carbonate, and silicate.
Chlorhexidine has broad-spectrum antibacterial activity
but is not active against acid-fast bacteria, spores, or
viruses. It has been used for such topical uses as preopera-
tive skin disinfection, wound irrigation, mouthwashes, and
general sanitization. Chlorhexidine is not absorbed
through skin or mucous membranes and does not cause
systemic toxicity.
DYES
Organic dyes were used very extensively as anti-infective
agents before the discovery of the sulfonamides and the an-
tibiotics. A few cationic dyes still find limited use as anti-
infectives. These include the triphenylmethane dyes gentian
violet and basic fuchsin and the thiazine dye methylene blue.
The dyes form colorless leucobase forms under alkaline con-
ditions. Cationic dyes are active against Gram-positive bac-
teria and many fungi; Gram-negative bacteria are generally
resistant. The difference in susceptibility is probably related
to the cellular characteristics that underlie the Gram stain.
0179-0241_17865_Ch06.qxd 12/8/09 10:54 PM Page 189
Gentian Violet
Gentian violet is variously known as hexamethyl-p-rosani-
line chloride, crystal violet, methyl violet, and methyl-
rosaniline chloride. It occurs as a green powder or green
flakes with a metallic sheen. The compound is soluble in
water (1:35) and alcohol (1:10) but insoluble in nonpolar or-
ganic solvents. Gentian violet is available in vaginal suppos-
itories for the treatment of yeast infections. It is also used as
a 1% to 3% solution for the treatment of ringworm and yeast
infections. Gentian violet has also been used orally as an an-
thelmintic for strongyloidiasis (threadworm) and oxyuriasis.
Basic Fuchsin
Basic fuchsin is a mixture of the chlorides of rosaniline and
p-rosaniline. It exists as a green crystalline powder with a
metallic appearance. The compound is soluble in water and
in alcohol but insoluble in ether. Basic fuchsin is a compo-
nent of carbol–fuchsin solution (Castellani’s paint), which is
used topically in the treatment of fungal infections, notably
ringworm and athlete’s foot.
Methylene Blue
Methylene blue is 3,7-bis(dimethylamino)-phenazathionium
chloride (Urised). The compound occurs as a dark green
crystalline powder with a metallic appearance that is soluble
in water (1:25) and alcohol (1:65).
Methylene blue has weak antiseptic properties that make
it useful for the treatment of cystitis and urethritis. The ac-
tion of methylene blue is considered to be bacteriostatic.
The compound colors the urine and stool blue green.
Chapter 6 Anti-infective Agents 189
MERCURY COMPOUNDS (MERCURIALS)
Mercury and its derivatives have been used in medicine for
centuries. Elemental mercury incorporated into ointment
bases was used topically for the treatment of localized infec-
tions and syphilis. Several inorganic salts of mercury, such
as mercuric chloride (HgCl2) and mercurous chloride
(calomel, Hg2Cl2) were at one time widely used as antisep-
tics. Ammoniated mercury [Hg(NH2)Cl] is still occasionally
used for skin infections such as impetigo, psoriasis, and
ringworm. Mercuric oxide is sometimes used to treat in-
flammation resulting from infection of the eye. Although the
potential interaction of mercuric ion with the tissues is
greatly reduced by the low water solubility of these agents,
they can be irritating and can cause hypersensitivity reac-
tions; therefore, their use is not recommended.
The comparatively few organomercurials still in use are
employed as antiseptics, preservatives, or diuretics.
Organomercurials can be grouped into two general classes:
(a) compounds with at least one carbon–mercury bond that
does not ionize readily and (b) compounds with mercury
bonded to heteroatoms (e.g., oxygen, nitrogen, sulfur) that
ionize partially or completely. In addition to its effect on
ionization, the organic moiety may increase the lipid solu-
bility of an organomercurial compound, thereby facilitating
its penetration into microorganisms and host tissues.
The antibacterial action of mercury compounds is be-
lieved to result from their reaction with sulfhydryl (-SH)
groups in enzymes and other proteins to form covalent com-
pounds of the type R-S-Hg-R. This action is reversible by
treatment with thiol-containing compounds such as cysteine
and dimercaprol (BAL); hence, organomercurials, reacting
reversibly, are largely bacteriostatic. The antibacterial activ-
ity of organomercurial antiseptics is greatly reduced in
serum because of the presence of proteins that inactivate
mercury compounds. Organomercurial antiseptics are not
very effective against spores.
The disadvantages of mercurials for antiseptic and disin-
fectant uses far outweigh any possible advantages that they
might have. Hence, other more effective and less potentially
toxic agents are preferable.
Nitromersol
3-(Hydroxymercuri)-4-nitro-o-cresol inner salt (Metaphen)
occurs as a yellow powder that is practically insoluble in
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190 Wilson and Gisvold’s Textbook of Organic Medicinal and Pharmaceutical Chemistry
water and is sparingly soluble in alcohol and most organic Methylparaben
solvents. The sodium salt probably has the “inner salt” Methyl p-hydroxybenzoate, or methylparaben, is a white
structure in which the inner shell electrons of mercury are crystalline powder. It is soluble in water and alcohol but
occupied.15 The bonding to mercury in this salt should be only slightly soluble in nonpolar organic solvents.
collinear, thus the following structure is somewhat improb- Methylparaben is used as a safeguard against mold growth.
able. Nevertheless, this structure is shown in the USP and
the Merck Index.
Nitromersol is nonirritating to mucous membranes and is
nonstaining. Therefore, at one time, it was a very popular
antiseptic for skin and ocular infections. Nitromersol has
largely been replaced by superior agents.
Propylparaben
Propyl p-hydroxybenzoate, or propylparaben, occurs as a
white crystalline powder that is slightly soluble in water but
soluble in most organic solvents. It is used as a preservative,
primarily to retard yeast growth. Propylparaben sodium is a
water-soluble sodium salt of the 4-phenol group. The pH of
solutions of propylparaben sodium is basic (pH ⬃10).
Thimerosal
[(o-Carboxyphenyl)-thio]ethylmercury sodium salt
(Merthiolate) is a cream-colored, water-soluble powder. It is
nonstaining and nonirritating to tissues. Thimerosal is a
weakly bacteriostatic antiseptic that is applied topically in
ointments or aqueous solutions.
Butylparaben
n-Butyl p-hydroxybenzoate (butylparaben) occurs as a white
crystalline powder that is sparingly soluble in water but very
soluble in alcohols and in nonpolar organic solvents.

PRESERVATIVES
Ethylparaben
Preservatives are added to various dosage forms and cos- Ethyl p-hydroxybenzoate (ethylparaben) is a white crys-
metic preparations to prevent microbial contamination. In talline powder that is slightly soluble in water but soluble in
parenteral and ophthalmic preparations, preservatives are alcohol and most organic solvents.
used to maintain sterility in the event of accidental contam-
ination during use. An ideal preservative would be effective
at low concentrations against all possible microorganisms,
be nontoxic and compatible with other constituents of the
preparation, and be stable for the shelf life of the prepara-
tion. The ideal preservative does not exist, but there is quite
a bit of experience with some of them. In some cases, com-
binations of preservative agents are used to approximate a Other Preservatives
mixture of ideal features. Chlorobutanol
1,1,1-Trichloro-2-methyl-2-propanol is a white crystalline
p-Hydroxybenzoic Acid Derivatives solid with a camphorlike aroma. It occurs in an anhydrous
Esters of p-hydroxybenzoic acid (parabens) have distinct form and a hemihydrate form, both of which sublime at room
antifungal properties. Their toxicity to the human host is temperature and pressure. Chlorobutanol is slightly soluble in
typically low because they undergo rapid hydrolysis in vivo water and soluble in alcohol and in organic solvents.
to p-hydroxybenzoic acid, which is quickly conjugated and
excreted. This property makes the parabens useful as preser-
vatives for liquid dosage forms. The preservative activity
generally increases with molecular weight, but the methyl
ester is most effective against molds, whereas the propyl
ester is most effective against yeasts. The more lipid-soluble Chlorobutanol is used as a bacteriostatic agent in phar-
propyl ester is the preferred preservative for drugs in oil or maceuticals for injection, ophthalmic use, and intranasal ad-
lipophilic bases. ministration. It is unstable when heated in aqueous solution,
0179-0241_17865_Ch06.qxd 12/8/09 10:55 PM Page 191
especially at pH greater than 7. Under these conditions,
chlorobutanol undergoes elimination. Solutions with a pH
of approximately 5 are reasonably stable at 25°C.
Chlorobutanol is stable in oils and organic solvents.
Benzyl Alcohol
Benzyl alcohol (phenylcarbinol, phenylmethanol) occurs
naturally as the unesterified form in oil of jasmine and in es-
ters of acetic, cinnamic, and benzoic acids in gum benzoin,
storax resin, Peru balsam, tolu balsam, and some volatile
oils. It is soluble in water and alcohol and is a clear liquid
with an aromatic odor.
Benzyl alcohol is commonly used as a preservative in
vials of injectable drugs in concentrations of 1% to 4% in
water or saline solution. Benzyl alcohol has the added ad-
vantage of having a local anesthetic action. It is commonly
used in ointments and lotions as an antiseptic in the treat-
ment of various pruritic skin conditions.
Phenylethyl Alcohol
Phenylethyl alcohol (2-phenylethanol, orange oil, rose oil,
C6H5CH2CH2OH) is a clear liquid that is sparingly soluble
in water (⬃2%). It occurs naturally in rose oil and pine-
needle oil. It is used primarily in perfumery.
Benzoic Acid
Benzoic acid and its esters occur naturally in gum benzoin
and in Peru and tolu balsams. It is found as a white crys-
talline solid that slowly sublimes at room temperature and is
steam distillable. It is slightly soluble in water (0.3%) but
more soluble in alcohol and in other polar organic solvents.
It has a pKa of 4.2. Benzoic acid is used externally as an an-
tiseptic in lotions, ointments, and mouthwashes. It is more
effective as a preservative in foods and pharmaceutical
products at low pH (less than the pKa). When used as a pre-
servative in emulsions, its effectiveness depends on both pH
and distribution into the two phases.16
Sodium Benzoate
Sodium benzoate is a white crystalline solid that is soluble
in water and alcohol. It is used as a preservative in acidic
liquid preparations in which benzoic acid is released.
Sodium Propionate
Sodium propionate occurs as transparent colorless crystals
that are soluble in water and alcohol. It is an effective anti-
fungal agent that is used as a preservative. Sodium propi-
onate is most effective at low pH.
Sorbic Acid
2,4-Hexadienoic acid is an effective antifungal preservative.
It is sparingly soluble in water and has a pKa of 4.8. Sorbic
acid is used to preserve syrups, elixirs, ointments, and lo-
tions containing components such as sugars that support
mold growth.
Chapter 6 Anti-infective Agents 191
Potassium Sorbate
Potassium sorbate occurs as a white crystalline material that
is soluble in water and alcohol. It is used in the same way as
sorbic acid when greater water solubility is required.
Phenylmercuric Nitrate
Phenylmercuric nitrate is a mixture of phenylmercuric ni-
trate and phenylmercuric hydroxide. It occurs as a white
crystalline material that is sparingly soluble in water and
slightly soluble in alcohol. It is used in concentrations of
1:10,000 to 1:50,000 to preserve injectable drugs against
bacterial contamination. A disadvantage to organomercuri-
als is that their bacteriostatic efficacy is reduced in the pres-
ence of serum.
Phenylmercuric Acetate
Acetoxyphenylmercury occurs as white prisms that are sol-
uble in alcohol but only slightly soluble in water. It is used
as a preservative.
ANTIFUNGAL AGENTS
General Introduction to Fungi:
Medical Mycology
The discovery that some infectious diseases could be attrib-
uted to fungi actually preceded the pioneering work of
Pasteur and Koch with pathogenic bacteria by several years.
Two microbiologists, Schönlein and Gruby, studied the fun-
gus Trichophyton schoenleinii in 1839. In that same year,
Langenbeck reported the yeastlike microorganism responsi-
ble for thrush (C. albicans). Gruby isolated the fungus re-
sponsible for favus on potato slices, rubbed it on the head of
a child, and produced the disease. Hence, he fulfilled Koch’s
postulates 40 years before they were formulated.17 In spite
of its earlier beginnings, medical mycology was quickly
overshadowed by bacteriology, and it has only recently
begun to receive the serious attention that it deserves. This
is perhaps attributable to the relatively benign nature of the
common mycoses, the rarity of the most serious ones, and
the need for a morphological basis for differential identifi-
cation of these structurally complex forms.
Cursory examination shows that fungal infections fall
into two well-defined groups: the superficial and the deep-