Anti-infective Agents

Bacterial Morphology

 Bacteria are classified by bacterial shape and colony

arrangement
 Cocci are spherical in shape and usually arranged in
pairs (diplo), chains (strepto), or clusters (staphylo)
 Bacilli are rod-like in shape
 Spirilla are curved and rod-like in shape
Gram Staining
 Gram staining classification is based on
ability of the bacterial membrane to stain
either red or blue
 Bacteria that take up the red stain are
classified as gram positive, Gm(+)
 Bacteria that take up the blue stain are
classified as gram negative, Gm(-)
 Gm(-) bacteria have an additional outer
lipopolysaccharide membrane layer
(endotoxin) that is toxic and that can
produce endotoxic shock
Antibacterial Chemotherapy
 Defined as the use of drugs to kill or inhibit the growth of infectious
bacteria
 Bactericidal drugs kill the bacteria
 Bacteriostatic drugs inhibit the growth of bacteria and body defenses
and immune mechanisms are required to rid the body of infecting
bacteria
Antibacterial Spectrum

 Refers to the range of bacteria that are killed or

inhibited by any antibacterial drug
 Narrow spectrum drugs are effective against a limited
number of different bacterial species
 Broad spectrum drugs are effective against a wide range
of different bacterial species
 Bacterial Resistance
 Bacteria have the ability to produce proteins
that help them resist antimicrobial drug actions
 Some bacteria produce beta-lactamase enzymes
that inactivate penicillins and cephalosporins
 Some bacteria produce proteins that prevent
drugs from penetrating the bacterial membrane
or proteins that remove the drugs once they
have passed through the bacterial membrane
 When bacterial resistance occurs other drugs
must be used to treat the infection
Penicillins

 Bacteriocidal drugs that inhibit cell wall

synthesis
 1st generation drugs have a narrow
spectrum and indicated mostly for Gm(+)
infections
 2nd generation drugs have a wider
spectrum that includes most common
Gm(+) / Gm(-) bacterial infections
 3rd and 4th generation drugs have a broad
spectrum and are effective against most
Gm(-) bacteria
Cephalosporins

 Bacteriocidal drugs that inhibit cell wall

synthesis
 1st generation drugs are effective against
most common Gm(+) and Gm(-) bacteria
 2nd, 3rd, and 4th generation cephalosporins
have increasing activity against Gm(-)
bacteria
 Cephalosporins are the drugs of choice for
infections caused by Klebsiella pneumoniae
 Cephalosporins are more resistant to
inactivating beta-lactamase enzymes than
penicillins
Adverse Effects Common
to Penicillins and Cephalosporins
 Minor GI disturbances and diarrhea
 Hypersensitivity or allergic reactions that include delayed skin reactions or
immediate anaphylactic reactions
 Higher dosages may cause bleeding problems
 Higher dosages may cause CNS disturbances and possible seizures
Aminoglycosides

 Classified as broad spectrum antibiotics

 Bacteriocidal drugs that inhibit bacterial protein
synthesis
 Administered IM or IV for systemic effects
 Usually the drugs of choice for serious gram negative
infections
 Nephrotoxicity and ototoxicity are the most serious
adverse effects
Tetracyclines

 Basteriostatic drugs that inhibit bacterial

protein synthesis
 Administered orally, but not with dairy or
antacid products
 Doxycycline is the most widely used
tetracycline and usually taken once per
day
 Adverse effects include GI disturbances,
rash, and photosensitivity
 Tetracyclines are contraindicated during
pregnancy, nursing, and in children < age
8
Sulfonamides

 Bacteriostatic drugs that inhibit bacterial folic acid

synthesis
 Sulfonamides are mainly indicated for treatment of
urinary tract infections
 Trimethoprim/sulfamethoxazole has a broad
antibacterial spectrum and many indications
 Adverse effects include rash, allergy, blood disorders,
and renal tubule damage
Macrolide Antibiotics

 Bacteriostatic drugs that inhibit bacterial

protein synthesis, effective with oral
administration
 Erythromycin often used in penicillin
allergic patients for minor ear and throat
infections
 Azithromycin and clarithromycin have a
broader antibacterial spectrum and
clinical uses
 Adverse effects include heartburn, rashes,
and GI disturbances
Fluroquinolones

 Bactericidal drugs that inhibit an enzyme

essential to the function of bacterial DNA
 Administered orally
 Indicated for a wide variety of urinary,
soft tissue, bone, and respiratory
infections
 Adverse effects include GI disturbances,
rash, photosensitivity, and joint pain
 Contraindicated in pregnancy and young
children
Miscellaneous Antimicrobials

 Chloramphenicol is reserved for

serious infections such as typhoid
fever and meningitis
 Clindamycin indicated for Gm(+) and
anaerobic infections
 Vancomycin indicated for resistant
Gm(+) staphylococcal infections
 Quinupristin-dalfopristin and linezolid
indicated for Gm(+) infections
resistant to vancomycin
Drugs Used to Treat Tuberculosis

 Tuberculosis requires prolonged treatment with

multiple drugs, usually 3 or 4 different drugs
 The first line drug regimen includes isoniazid,
rifampin, pyrazinamide, and ethambutol
 After 2–4 months of treatment ethambutol and
pyrazinamide are usually eliminated
 Isoniazid
and rifampin therapy is continued for
6–12 months
 Drug resistance is a major problem
Anti-viral and Anti-fungal
drugs
Clinical Indication
Antifungal drugs
Prevention or treatment of mild to severe fungal infections

Antiviral drugs
Prevention and treatment of viral infections, especially seriously ill and
elderly patients
 Fungal Infections
Infections Site Drug Action
Systemic Blood, brain, lungs fungicidal
aspergillosis amphotericin B,
histoplasmosis ketaconazole
candidiasis miconazole
cryptococcosis nystatin

Dermatophytic Hair, skin, nails fungicidal

Athlete’s foot haloprogin
Ringworm tolnaftate

fungistatic
griseofulvin

Candida albicans Skin fungicidal

mucous membranes ketaconazole
vagina miconazole
nystatin
 Mechanism of Antifungal Action

Fungicidal: Capable of killing fungi

Drugs bind to fungal membranes and increase permeability,

nutrients leak out, and fungi die

Drugs: amphotericin B, ketaconazole, miconazole, nystatin

Fungistatic: Limits the growth of active fungi but does not

eradicate the microorganisms

Drug binds to keratin in the skin and hair so fungi cannot

enter the tissue and undergo further growth

Drug: griseofulvin
Contraindications

Antifungal drugs are contraindicated in

patients with history of hypersensitivity

Griseofulvin is contraindicated in patients with Porphyria and hepatic failure.

It should not be used during pregnancy
 Viral Diseases
Acquired immunity
Protection against developing a clinical viral
infection
obtained by
 experiencing the infection
or
 vaccination with the weakened or dead virus

The immune system produces proteins that recognize

viruses at the next infection and inhibit viral
interaction with the host cells

Examples- smallpox, chicken pox, measles, polio

 Viral Diseases
No immunity transferred with infection

 Influenza
 Herpes simplex
 Human immunodeficiency virus (HIV)
 virus goes undetected within the human
cells for years
 virus attacks the lymphocytes
 progressive immunosuppression
 opportunistic infections develop
 clinical signs and symptoms characterize
AIDS (acquired immunodeficiency syndrome)
 Propagation of Viruses
 Totally dependent on the metabolic system of the human host cells
 Attach to cell membranes to inject viral DNA or RNA into the cell
 Enter nucleus to direct production of more viruses according to the
nucleic acid blue print
 Cells rupture to “shed” new viruses to infect other host cells
 Antiviral Drugs
Influenza
Amantadine, rimantadine
HIV
Didanosine, lamivudine, saquinavir, zidovudine
Cytomegalovirus
Cidofovir, foscarnet, ganciclovir
Genital Herpes, Herpes zoster, chicken pox
Acyclovir, famciclovir, valacyclovir
Herpes simplex keratitis
Idoxuridine, trifluridine, vidarabine
 Antiviral Drugs—Mechanisms of Action
 Inhibition of cell penetration
Amantadine stops Asian strain (A2) when administered
prophylactically (20 hrs ahead)
 Transcription of viral proteins
Didanosine, lamivudine, stavudine, zalcitabine, zidovudine
inhibit reverse transcriptase so HIV RNA cannot be duplicated
 Inhibition of viral synthesis
Acyclovir, idoxuridine, vidarabine incorporate into HIV DNA
and impair protein synthesis
 Protease inhibitors
Indinavir, ritonavir, saguinavir inhibit HIV proteases that are
essential to make HIV infectious
 Special Considerations
HIV protease inhibitors inhibit liver metabolism
centers (P450) so that other medications may
accumulate in the blood because of blocked or
delayed metabolism

Renal impairment will cause antiviral drugs to

accumulate in the blood. Dose adjustment will be
required

Amantadine and rimantidine doses must be reduced in the

elderly where renal clearance has decreased
Anti-HIV Drugs Adverse
Effects
 Nausea Nephrotoxicity
 Gastritis Inhibition of hepatic metabolism
 Vomiting anemias
 Diarrhea
 Headache
 Confusion
 Dizziness
 Insomnia
 Arthralgia
 Allergic reactions, edema, rash
 Hypertension
Characteristics of
Antimalarials
Highly bound to plasma proteins
Metabolized in the liver
Produce antiinflammatory response in immuno/inflammatory conditions e.g.
rheumatoid arthritis, lupus, polymositis
Relax skeletal muscle
Stimulate contraction of uterine muscle
Depress cardioconduction (increase PR & QT intervals on the ECG)
 Adverse Effects of
Antimalarials
Adverse effects are related to the magnitude of the
dose and chronic use of the drugs
 Nausea
 Diarrhea
 Headache
 Blurred vision
 Vertigo
 Rash
 Cinchonism – sensitive individuals experience
ringing in the ears (tinnitus) and headache from
CNS stimulation
Protozoal Dysentary
Giardia lamblia and Entameba histolytica enter
the gastrointestinal tract

Symptoms of acute infection

Irritation of intestinal tissue
Inflammation and pain
Spasm of anal sphincter (tenesmus)
Diarrhea
Fatigue and muscle weakness
Loss of body water and electrolytes
Chronic Entamebic
Dysentary
Entamebic histolytica can burrow into the wall of the liver
creating an inflammation and abscess in the absence of
other typical symptoms
 Antidysentery Drugs
Paromomycin Antibiotics inhibit the growth
Tetracyclines of intestinal bacteria that
provide critical nutrients to
the protozoa
Metronidazole Antibiotic that distributes to
all tissues including bone,
bile, liver abscesses and
intestines to reach all
protozoa. Amebicidal.

Chloroquine, Attach to protozoa DNA and

iodoquinol impair critical protein
synthesis
Parasitic Worm Infestation
Enter the gastrointestinal
tract with food or soil
 Pinworms containing worm eggs

Worms hatch with the

 Roundworms
intestines
 Tapeworms

Worms are shed in the

feces
Symptoms of Worm Infestation
Common symptoms
Diarrhea
Nausea
Loss of appetite
Abdominal cramping
Itching (anus)

Hookworms, tapeworms
Perforate intestines
Blood loss
Anemia
Anthelmintic Drugs

 Pinworms, roundworms
Mebendazole, pyrantil pamoate,
thiabendazole

 Tapeworms
Praziquantel
Anthelmintic Drugs

 Remain within the intestine

 Decrease worm motility by paralyzing the
parasites’ muscles
 Peristalsis and laxatives move the worms and eggs out of the
intestines
Anthelmintic Drugs:
Adverse Effects
 Nausea
 Fever
 Headache
 Cramps
 Diarrhea
 Tinnitus
 Hypotension
Antiseptics and Disinfectants
Clinical Indication
Prevent or control infection of living (antiseptics) surfaces and nonliving
(disinfectants) surfaces including:

 countertops, floors, equipment, instruments

 skin, mucous membranes
Forms of Antiseptics & Disinfectants
Chemical solutions containing

 Alcohols (ethanol, isopropanol)

 Aldehydes (formaldehyde)
 Halogenated compounds (iodine)
 Iodophors (povidone-iodine)
 Phenols (hexachlorophene, triclosan)
 Oxidizers (hydrogen peroxide)
 Heavy metals (silver nitrate, mercurial)
 Quaternary ammoniums (benzalkonium chloride)
Method or Route of Administration
Topical application or wash-down surfaces

• Swab, sponge, scrub

• Mouthwash (occasionally)
 Terminology
Cidal- Kills the microorganisms
e.g., bacteriocidal, virucidal, germicidal

Static- Inhibit or slow the growth of microorganisms but does

not eradicate all organisms e.g. bacteriostatic,
fungistatic

Sterilization- complete eradication of all microorganisms

Spectrum of activity- broad (or narrow) indicates the potency to

eliminate a large variety of organism types (or limited in the
type of microorganisms it affects)
 Terminology
Nosocomial – infection acquired while staying in a hospital or
institution such as nursing home

Irrigation – method of washing a fluid antiseptic over the

tissue(s) to remove the organisms

Active vehicle – the solution used to dissolve an antiseptic has

separate definite ability to destroy microorganisms

Topical – applied to a surface, not swallowed or

injected

Systemic – reaches the blood stream (circulation) after

administration
Main Uses

 Reduce the need for antibiotics by eliminating potential

pathogenic infectious organic material on nonliving
surfaces
 Reduce the growth and contamination of wounds (burns,
skin ulcers)
 Eliminate microorganism from entering punctures
encountered in procedures such as spinal, regional
anesthesia, blood draws for clinical laboratory analysis
Adverse Effects
From Topical Application
 Dry skin, rash, hypersensitivity
 Eczamoid dermatitis (high dose long term
exposure)
 Hypothyroidism (iodine absorption)
 Neurotoxicitity (hexachlorophene)

From Internal Absorption

• Anorexia
• Vomiting
• Internal cramping
• Convulsions
• Death