Antiinfective Agents

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Antiinfective Agents

• By Jim Clarke

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Aerosolized Anti-infectives

• 2 occasionally used agents
• Pentamidine (NebuPent)
• Ribavirin (Virazole)

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Indications for Pentamidine

• History of one or more episodes of PCP
• A low CD4 lymphocyte count

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Rationale for Administration

• Aerosol administration delivers drug to area of
  lung most likely to be affected
• Parenteral administration has numerous side
  effects
• Aerosol administration produces higher blood
  levels than parenteral

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Side Effects of Aerosol Pentam

• Cough bronchial irritation
• SOB
• Bitter taste (burning in mouth)
• Bronchospasm wheezing
• Conjunctivitis

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Dosing Issues

• Use nebulizer designed for Pentam use
• Should produce particles in 1-2 micron range
• Should have one-way valves directing exhalation
  through filter
• Give tx in negative pressure booth or room

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Dosing Issues

• Pregnant or nursing mothers should avoid contact
• Use gloves, mask eyewear

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Ribavirin

• Classification
• Anti-viral agent that works against RSV
  (Respiratory Syncytial Virus), influenza herpes
  simplex
• Indications
• Given via inhalation to children suffering from
  RSV
• Only given if patient has severe bronchiolitis
  with moderate to severe hypoxemia

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Side Effects

• Pulmonary
• Deterioration of pulmonary function pneumothrax
  bacterial infection
• Cardiovascular
• Hypotension cardiac arrest
• Topical
• Rash eyelid erythema conjunctivitis

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Dosing Issues

• Virazole must be given with SPAG nebulizer
• Generally given via head-hood
• Can be given via ventilator

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Aerosolized Antibiotic Use

• In Cystic Fibrosis
• Has become a popular method for prevention of
  pneumonia
• Prevents outbreaks of Pseudomnas aeruginosa,
  Hemophilus influenzae Staphylococcus aureus
• Gentamicin

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Non-Aerosolized Antibiotics
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Definitions

• Antibiotic is a substance produced by
  microorganisms that is capable of inhibiting or
  killing bacteria and other microorganisms
• Mode of Action - how the antibiotic actually
  kills the targeted microorganisms

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Antibiotic Terms

• Bacteriostatic- a drug that inhibits the growth
  of a microorganism
• Bactericidal is a drug that kills the
  microorganism
• Broad Spectrum - a drug that works on a wide
  variety of organisms
• Narrow Spectrum - a drug that works only only a
  few organisms

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How Antibiotics Work
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Inhibition of Cell Wall Synthesis

• These antibiotics prevent normal cell wall
  formation
• Examples of these antibiotics
• Penicillans
• Bacitracin
• Cephalosporins
• Vancomycin

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Alteration of Cell Membrane Permeability

• Disruption of cell wall filtering causes cellular
  death
• Examples
• Polymyxin B

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Inhibition of Protein Synthesis

• Prevention of the ribosomes ability to make
  necessary proteins
• Examples
• Gentamicin
• Erthromycin
• Streptomycin
• Tetracyclines

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Inhibition of Nucleic Acid Synthesis

• Prevents DNA replication or formation of
  messenger RNA
• Examples
• Cipro
• Trimethoprim
• Sulfonamides
• Rifampin

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Antibiotic Sensitivity Resistance

• Sensitivity - measures how well the antibiotic
  inhibits or kills
• Resistance - describes an organisms ability to
  inactivate the antibiotic

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Penicillins

• Inhibit cell wall formation
• Numerous forms available - generic agents always
  end with cillin
• Numerous strains of Staph. Aureus, E. coli,
  Proteus and pseudomonas species are resistant to
  penicillans
• Nafcillan is now the only agent that generally
  works on Staph. Aureus
• Penicillans used to treat Strep., some Staph and
  Haemophilus influenzae infections

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Cephalosporins

• Broken into 3 categories
• First generation - active on gram organisms
• Second generation - more active on gram -
  organism
• Third generation - variable against gram
  more active against gram -

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Cephalosporins cont.

• Nephrotoxicity can occur causing renal necrosis

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Aminoglycosides

• Act by prevention of normal protein synthesis
• Used to treat many gram - pneumonias
• Examples
• Gentamicin, Tobramycin Amikacin
• Inhalation used in tx of Pseudomonas pneumonias
  in Cystic Fibrosis
• These agents can be extremely nephrotoxic

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Tetracyclines

• Act by interfering with protein synthesis
• Broad spectrum
• Used to treat atypical pneumonias
• Mycoplasma pneumoniae
• Cause GI irritation nausea, diarrhea
• Should not be used with children except for short
  periods - (tooth discoloration)

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Fluoroquinolones

• Broad Spectrum
• Inhibition of DNA synthesis
• Used widely in COPD Cystic Fibrosis
• Pseudomonas Aeruginosa
• Examples
• Cipro (Ciprofloxacin)
• Noroxin (Norfloxacin_

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Macrolides (Etythromycins)

• Inhibit protein synthesis
• Drug of choice for treatment of Mycoplasma
  Legionella infections
• Oral administration can cause GI upset
• Examples
• Biaxin
• Zithromax

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Sulfonamides

• Inhibit nucleic acid synthesis
• Not really an antibiotic!
• Used mainly to treat urinary some intestinal
  infections
• Trimethoprim-Sulfamethoxazole combination used to
  treat Pneumocystis carinii pneumonia

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Miscellaneous Antibiotics
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Vancomycin

• Reserved mainly for use in treating
  methicillin-resistant S. aureus (MRSA)
• Can be toxic to the kidneys ears
• There are now strains of Enterobacter that are
  resistant to Vancomycin (VRE)

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Chloramphenicol

• Very rarely used due to chances of causing
  aplastic anemia
• Only used in cases of life-threatening infections
  resistant to other antibiotics

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Flagyl

• Used as an antiprotozoal agent to treat GI
  infections most anaerobes

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Nitrofurantoin (Furadantin)

• Synthetic agent (not a true antibiotic)
• Broad Spectrum agent
• Used mainly in tx of urinary tract infections
• Can cause pulmonary side effects
• pleural effusions and infiltrates

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Antifungal Agents

• Amphotericin B
• Has severe toxic side effects - nephrotoxicity
  fever decreased BP
• Can cause metabolic acidosis!
• Nystatin
• Topical treatment for Candida albicans infections

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Anti-Tuberculosis Drugs
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End of this session