Classic signs of inflammation (redness, swelling, heat, and pain)
Goal of Antibiotic Therapy
Decrease the population of the invading bacteria to a point where the human immune system can effectively deal with the invaders
Selecting Treatment
Identification of the causative organism
Based on the culture report, an antibiotic is chosen that is known to be effective at treating the invading organism
Bacteria Classification
Gram-positive
The cell wall retains a stain or resists decolorization with alcohol
Gram-negative
The cell wall loses a stain or is decolorized by alcohol
Aerobic
Depend on oxygen for survival
Anaerobic
Do not use oxygen
Aminoglycosides
A group of powerful antibiotics used to treat serious infections caused by gram-negative aerobic bacilli
Common medications:
Amikacin (Amikin)
Gentamicin (Garamycin)
Kanamycin (Kantrex)
Neomycin (Mycifradin)
Streptomycin
Tobramycin (Nebcin, Tobrex)
Bactericidal
Indications: treatment of serious infections caused by susceptible bacteria
Action: inhibit protein synthesis in susceptible strains of gram-negative bacteria causing cell death
Pharmacokinetics
Poorly absorbed from the GI tract but rapidly absorbed after IM injection, reaching peak levels within 1 hour
Widely distributed throughout the body, crossing the placenta and entering breast milk
Excreted unchanged in the urine and have an average half-life of 2 to 3 hours
Depend on the kidney for excretion and are toxic to the kidney
Contraindications
Known allergies, renal or hepatic disease, and hearing loss
Adverse effects
Ototoxicity and nephrotoxicity are the most significant
Drug-to-drug interactions
Diuretics and neuromuscular blockers
Cephalosporins
Similar to penicillin in structure and activity
Action
Interfere with the cell-wall–building ability of bacteria when they divide
Indication
Treatment of infection caused by susceptible bacteria
Pharmacokinetics
Well absorbed from the GI tract
Metabolized in the liver, excreted in the urine
Contraindications
Allergies to cephalosporins or penicillin
Adverse effect
GI tract
Drug-to-drug interactions
Aminoglycosides, oral anticoagulants, and ETOH
Fluoroquinolones
Relatively new class of antibiotics with a broad spectrum of activity
Indications: treat infections caused by susceptible strains of gram-negative bacteria, including urinary tract, respiratory tract, and skin infections
Actions: interferes with DNA replication in susceptible gram-negative bacteria, preventing cell reproduction
Pharmacokinetics
Absorbed in the GI tract
Metabolized in the liver
Excreted in the urine and feces
Contraindications
Known allergy, pregnancy, and lactation
Adverse effects
Headache, dizziness, and GI upset
Drug-to-drug interactions
Antacids, quinidine, and theophylline
Macrolides
Antibiotics that interfere with protein synthesis in susceptible bacteria
Indications: treatment of respiratory, dermatologic, urinary tract, and GI infections caused by susceptible strains of bacteria
Actions: bind to cell membranes causing a change in protein function and cell death; can be bacteriostatic or bactericidal
Pharmacokinetics
Absorbed from the GI tract
Metabolized in the liver, excreted in the bile to feces
Contraindications
Allergy and hepatic dysfunction
Adverse effects
GI symptoms
Drug-to-drug interactions
Digoxin, oral anticoagulants, theophylline, and corticosteroids
Lincosamides
Similar to macrolides but more toxic
Action
Similar to macrolides
Indications
Severe infections
Pharmacokinetics
Well absorbed from the GI tract or IM
Metabolized in the liver and excreted in the urine and feces
Contraindications
Hepatic or renal impairment
Adverse effects
GI reactions
Monobactams
Unique structure with little cross-resistance
Action
Disrupts bacteria cell wall synthesis, which promotes the leakage of cellular content and cell death
Indications
Treatment of infections caused by susceptible bacteria; UTI, skin, intra-abdominal, and gynecologic infections
Pharmacokinetics
Well absorbed from the IM injection
Excreted unchanged in the urine
Contraindications
Allergy
Adverse effects
GI and hepatic enzyme elevation
Penicillins
First antibiotics introduced for clinical use
Action
Inhibit synthesis of the cell wall in susceptible bacteria, causing cell death
Indications
Treatment of infections caused by streptococcal, pneumococcal, staphylococcal, and other susceptible bacteria
Pharmacokinetics
Well absorbed from the GI tract
Excreted unchanged in the urine
Contraindications
Allergy
Caution in patients with renal disease
Adverse effects
GI effects
Drug-to-drug interactions
Tetracyclines and aminoglycosides
Sulfonamides
Drugs that inhibit folic acid synthesis
Action
Interfere with the cell-wall–building ability of dividing bacteria
Indications
Treatment of infections caused by gram-negative and gram positive-bacteria
Pharmacokinetics
Well absorbed from the GI tract
Metabolized in the liver and excreted in the urine
Contraindications
Allergy and pregnancy
Adverse effects
GI symptoms and renal effects related to the filtration of the drug
Drug-to-drug interactions
Cross sensitivity with thiazide diuretics
Sulfonylureas
Tetracyclines
Developed as semisynthetic antibiotics based on the structure of a common soil mold
Action
Inhibit protein synthesis in susceptible bacteria, preventing cell replication
Indications
Treatment of various infections caused by susceptible strains of bacteria and acne, and when penicillin is contraindicated for eradication of susceptible organisms
Pharmacokinetics
Adequately absorbed from the GI tract
Concentrated in the liver and excreted unchanged in the urine
Contraindications
Allergy, pregnancy, and lactation
Adverse effects
GI, skeletal: damage to bones and teeth
Drug-to-drug interactions
Penicillin G, oral contraceptive therapy, methoxyflurane, and digoxin
Antimycobacterials
Contain pathogens causing tuberculosis and leprosy
Action
Act on the DNA of the bacteria, leading to lack of growth and eventual bacterial death
Indication
Treatment of acid-fast bacteria
Pharmacokinetics
Well absorbed from the GI tract
Metabolized in the liver and excreted in the urine
Contraindications
Allergy and renal or hepatic failure
Adverse effects
CNS effects and GI irritation
Drug-to-drug interactions
Rifampin and INH can cause liver toxicity
Antibiotic Use Across the Lifespan
Pediatric population
Adult population
Geriatric population
Comparison of Prototype Antibiotics
Drug/ Classification
Indication
Action
Route
Onset
Peak
Pharmacokinetics
Adverse Effects
Gentamicin/ Aminoglycosides
Treatment of serious infections caused by susceptible bacteria
Inhibits protein synthesis in susceptible strains of gram negative bacteria
IM
Rapid
30-90 min
T½ – 2-3 h
Sinusitis, dizziness, rash, fever, risk of nephrotoxicity
IV
Metabolized in the liver,
excreted in the urine
Cefaclor/ Cephalosporins
Treatment of respiratory, dermatological, urinary tract, and middle ear infections
Inhibits synthesis of bacteria cell wall
Oral
30-60 min
8-10 h
T ½ 30-60 min
Nausea, vomiting, diarrhea, rash, superinfections, bone marrow suppression, risk for pseudomembranous colitis
Excreted unchanged in the urine
Ciprofloxacin/ Fluoroquinolones
Treatment of respiratory, dermatological, urinary tract, ear, eye, bone, and joint infections
Interferes with DNA replication in susceptible gram negative bacteria
Oral
Varies
4-5 h
T ½ – 3.5-4 h
Headache, dizziness, hypotension, nausea, vomiting, diarrhea, fever, and rash
IV
10 min
4-5 h
Metabolized in the liver,
excreted in bile and urine
Erythromycin/ Macrolides
Treatment of respiratory, dermatological, urinary tract, and GI infections
Binds to cell membrane causing change in protein function and cell death
Oral
1-2 h
1-4 h
T ½ – 3-5 h
Abdominal cramping, vomiting, diarrhea, rash, superinfections, liver toxicity, potential for hearing loss
IV
Rapid
1h
Metabolized in the liver,
CONTINUED ON NEXT SLIDE
excreted in bile and urine
Treatment of serious infections caused by susceptible strains of bacteria
Inhibits protein synthesis in susceptible bacteria
Paul Ehrlich worked on developing a synthetic chemical effective against infection-causing cells only
Scientists discovered penicillin in a mold sample
1935
The sulfonamides were introduced
Mechanisms of Action
Interfere with biosynthesis of the bacterial cell wall
Prevent the cells of the invading organism from using substances essential to their growth and development
Interfere with steps involved in protein synthesis
Interfere with DNA synthesis
Alter the permeability of the cell membrane to allow essential cellular components to leak out
Mechanism of Anti-infective Agents
Mechanism of Anti infective Agents
Anti-infective Activity
Anti-infectives vary in their effectiveness against invading organisms
Some are selective: they are effective only for a small number of organisms
Bactericidal: kill the cell
Bacteriostatic: prevent reproduction of the cell
Narrow Spectrum vs Broad Spectrum
Narrow spectrum of activity
Effective against only a few microorganisms with a very specific metabolic pathway or enzyme
Broad spectrum of activity
Useful in treating a wide variety of infections
Human Immune Response
Goal of anti-infective therapy is reduction of the population of the invading organism
Drugs that eliminate all traces of any invading pathogen might be toxic to the host as well
Immune response is a complex process involving chemical mediators, leukocytes, lymphocytes, antibodies, and locally released enzymes and chemicals
Problems With Treating Infections in Immunosuppressed Patients
Anti-infective drugs cannot totally eliminate the pathogen without causing severe toxicity in the host
These patients do not have the immune response in place to deal with even a few invading organisms
Resistance
Anti-infectives act on a specific enzyme system or biological process; many microorganisms that do not act on a specific system are not affected by the particular drug
This is considered natural or intrinsic resistance to that drug
Acquired Resistance
Microorganisms that were once sensitive to the particular drug have begun to develop acquired resistance
This results in serious clinical problems
Ways Resistance Develops
Producing an enzyme that deactivates the antimicrobial drug
Changing cellular permeability to prevent the drug from entering the cell
Altering transport systems to exclude the drug from active transport into the cell
Altering binding sites on the membranes or ribosomes, which then no longer accept the drug
Producing a chemical that acts as an antagonist to the drug
Preventing Resistance
Limit the use of antimicrobial agents to the treatment of specific pathogens sensitive to the drug being used
Make sure doses are high enough, and the duration of drug therapy long enough
Be cautious about the indiscriminate use of anti-infectives
Identification of the Pathogen
Identification of the infecting pathogen is done by culture
A culture of a tissue sample from the infected area is done
A swab of infected tissue is allowed to grow on an agar plate
Staining techniques and microscopic examination identify the bacterium
Stool can be examined for ova and parasites
Sensitivity of Pathogen
Shows which drugs are capable of controlling the particular microorganism
Important to be done for microorganisms that have known resistant strains
Along with a culture, identifies the pathogen and appropriate drug for treatment
