Post on 21-Dec-2015
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
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 InfectionsInfections Site Drug Action Systemic Blood, brain, lungs fungicidalaspergillosis amphotericin B,histoplasmosis ketaconazolecandidiasis miconazolecryptococcosis nystatin
Dermatophytic Hair, skin, nails fungicidalAthlete’s foot haloproginRingworm tolnaftate
fungistaticgriseofulvin
Candida albicans Skin fungicidalmucous membranes ketaconazolevagina 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 immunityProtection against developing a clinical viral infectionobtained 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 DrugsInfluenzaAmantadine, rimantadine
HIVDidanosine, lamivudine, saquinavir, zidovudine
CytomegalovirusCidofovir, foscarnet, ganciclovir
Genital Herpes, Herpes zoster, chicken poxAcyclovir, famciclovir, valacyclovir
Herpes simplex keratitisIdoxuridine, trifluridine, vidarabine
Antiviral Drugs—Mechanisms of Action• Inhibition of cell penetrationAmantadine stops Asian strain (A2) when administered prophylactically (20 hrs ahead)
• Transcription of viral proteinsDidanosine, lamivudine, stavudine, zalcitabine, zidovudineinhibit reverse transcriptase so HIV RNA cannot be duplicated
• Inhibition of viral synthesisAcyclovir, idoxuridine, vidarabine incorporate into HIV DNA and impair protein synthesis
• Protease inhibitorsIndinavir, ritonavir, saguinavir inhibit HIV proteases that are essential to make HIV infectious
Special ConsiderationsHIV protease inhibitors inhibit liver metabolism centers (P450) so that other medications mayaccumulate in the blood because of blocked ordelayed metabolism
Renal impairment will cause antiviral drugs toaccumulate in the blood. Dose adjustment will be required
Amantadine and rimantidine doses must be reduced in theelderly 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 AntimalarialsHighly bound to plasma proteinsMetabolized in the liverProduce antiinflammatory response in
immuno/inflammatory conditions e.g. rheumatoid arthritis, lupus, polymositis
Relax skeletal muscleStimulate contraction of uterine muscleDepress cardioconduction (increase PR & QT
intervals on the ECG)
Adverse Effects of AntimalarialsAdverse 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 DysentaryGiardia lamblia and Entameba histolytica enter
the gastrointestinal tract
Symptoms of acute infectionIrritation of intestinal tissueInflammation and painSpasm of anal sphincter (tenesmus)DiarrheaFatigue 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 DrugsParomomycinTetracyclines
Metronidazole
Chloroquine, iodoquinol
Antibiotics inhibit the growth of intestinal bacteria that provide critical nutrients to the protozoa
Antibiotic that distributes to all tissues including bone, bile, liver abscesses and intestines to reach all protozoa. Amebicidal.
Attach to protozoa DNA and impair critical protein synthesis
Parasitic Worm Infestation
• Pinworms
• Roundworms
• Tapeworms
Enter the gastrointestinal tract with food or soil containing worm eggs
Worms hatch with the intestines
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, roundwormsMebendazole, pyrantil pamoate,
thiabendazole
• Tapeworms Praziquantel
Anthelmintic Drugs
• Remain within the intestine
• Decrease worm motility by paralyzing theparasites’ muscles
• Peristalsis and laxatives move the worms and eggs out of the intestines
Anthelmintic Drugs: Adverse Effects• Nausea
• Fever
• Headache
• Cramps
• Diarrhea
• Tinnitus
• Hypotension
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 & DisinfectantsChemical 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)
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
Terminology
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