Antibiotics and Antimicrobial Therapy

1
Antibiotics and Antimicrobial Therapy

• Gerianne R. Bliss, M.D.
• Chuck Hensley, R.Ph., M.BA.

2
Basics of Therapy

• Classification and selection
• Based on the principle of selective toxicity

3
Which type of organism

• Antibacterial
• Antifungal
• Antiviral
• Antiparasitic

4
Site and Mechanism of Action
Inhibitors of

• Cell wall synthesis
• Protein synthesis
• Metabolic/protein synthesis
• Cell membrane synthesis

5
Antimicrobial Activity

• -cidal versus -static

6
Spectrum

• Narrow
• Extended
• Broad

7
Sensitivity and Resistance

• MIC minimum inhibitory conc
• CDKR conc dependent killing rate
• PAE postantibiotic effect

8
Sensitivity and Resistance

• Susceptibility
• Intermediate sensitivity
• Resistance patterns
• Mutation and selection
• Transferable resistance

9
Resistance- Mechanisms

• Inactivation
• Decreased accumulation
• Reduced affinity

10
Selection of Antimicrobial Drugs

• HOST FACTORS
• Allergies
• Age
• Immune Status
• Renal Impairment
• Hepatic Insufficiency
• Abscesses
• Indwelling Catheters

11
Drug Characteristics

• Antimicrobial Activity
• Pharmacokinetic Principles
• Adverse Effect Profile
• Cost and Convenience

12
Combination Drug Therapy
Relationship/effect may be

• Antagonistic
• Additive
• Synergistic
• Indifferent

13
Prevention

• Invasive procedures
• Prevent disease transmission

Refer to The Sanford Guide to Antimicrobial
Therapy 2002
14
Antibacterial Classification

• Inhibitors of Cell Wall Synthesis
• Inhibitors of Bacterial Protein Synthesis

15
Inhibitors of Cell Wall Synthesis
Inhibition of cell wall synthesis is bactericidal

• Gram positive negative have cytoplasmic
  membrane and cell wall
• Gram negative has outer membrane with porins

16
Site of Drug Action

• Beta-lactam drugs bind to penicillin-binding
  proteins and disrupt functions of the cell wall

• Other inhibitors block synthesis of the cell wall

17
Beta-Lactam Antibiotics

• Includes following
• penicillins
• beta-lactamase inhibitors
• cephalosporins
• monobactams
• carbapenems

18
Penicillins

• Narrow Spectrum
• Penicillinase Resistant
• Extended Spectrum
• Beta-Lactamase Inhibitors

19
Drug Properties

• Synthetic vs. semi synthetic
• Acid stable vs. acid labile
• Spectrum and indications
• Hypersensitivity reactions

20
Beta-Lactamase Inhibitors

• Beta-lactamases inactivate beta-lactam antibiotic
• Suicide inhibitors surrogate substitute
• Clavulanate, sulbactam, tazabactam
• Given with beta-lactam antibiotic to prevent
  degradation by bacteria

21
Cephalosporins

• Four generations
• Greater resistance to beta-lactamases
• Wider range of antimicrobial activity
• Little toxicity to host
• Some cross-reactivity with penicillins
• Can cause platelet dysfunction

22
Monobactams

• Aztreonam
• For gram negative organisms
• IV only
• Bone marrow suspression

23
Carbapenems

• Wide range of bacteria both gram and
• Can cause hematologic reactions

24
Other Cell Wall Inhibitors

• Vancomycin
• Bacitracin
• Cycloserine
• Fosfomycin

25
Inhibitors of Bacterial Protein Synthesis

• Selective blocking of protein synthesis at the
  ribosome
• Bacteriostatic

26
30s Ribosomal Subunit Antibiotics

• Aminoglycosides
• Given parenterally
• Not metabolized
• Renal excretion
• Peak and trough levels to avoid toxicity
• Gram neg spectrum
• Nephrotoxicity and ototoxicity

27
Tetracyclines

• Broad-spectrum
• Widespread resistance-R factors
• Avoid in pregnant women and children less than 8
  years
• Renal, liver, and skin toxicity
• Bind calcium, aluminum and iron

28
Spectinomycin

• Can be use to treat gonorrhea
• Causes nausea and pain at site of injection

29
50s Ribosomal Subunit Antibiotics

• Macrolides
• Erythromycin and semi-synthetic derivatives
• Upper and lower respiratory tract infections
• Remember
• GI upset
• Cholestatic jaundice

30
Other 50s ribosomal antibiotics

• Clindamycin
• Good for gram pos cocci
• Increased incidence of pseudomembranous colitis
• Chloramphenicol
• - anemia
• Quinupristin-Dalfopristin
• - streptogramin-new class

31
Mupirocin

• Structurally unrelated to all other antibiotics
• Inhibits protein synthesis through unique
  mechanism
• No cross-resistance
• Topically active against Staph and Strep