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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
Systemic
Site
Blood, brain, lungs
fungicidal
amphotericin B,
ketaconazole
miconazole
nystatin
Hair, skin, nails
fungicidal
haloprogin
tolnaftate
aspergillosis
histoplasmosis
candidiasis
cryptococcosis
Dermatophytic
Athlete’s foot
Ringworm
Drug Action
fungistatic
griseofulvin
Candida albicans Skin
mucous membranes
vagina
fungicidal
ketaconazole
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
Influenza
Antiviral Drugs
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
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Antiviral Drugs—Mechanisms of Action
Inhibition of cell penetration
Amantadine stops Asian strain (A2) when administered
prophylactically (20 hrs ahead)
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Transcription of viral proteins
Didanosine, lamivudine, stavudine, zalcitabine, zidovudine
inhibit reverse transcriptase so HIV RNA cannot be duplicated
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Inhibition of viral synthesis
Acyclovir, idoxuridine, vidarabine incorporate into HIV DNA
and impair protein synthesis
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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
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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
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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
Antibiotics inhibit the growth
Paromomycin
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,
iodoquinol
Attach to protozoa DNA and
impair critical protein
synthesis
Parasitic Worm Infestation
• Pinworms
• Roundworms
Enter the gastrointestinal
tract with food or soil
containing worm eggs
Worms hatch with the
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
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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
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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