1. Chapter 56 Principles for Prescribing Antiinfectives

2. Terms and Definitions • Antibiotic • The product of a living organism that kills or inhibits the growth of microorganisms • Antimicrobial • Any naturally occurring or synthetic substance that kills or inhibits growth of microorganisms • Bacteriostatic • The ability to inhibit the growth and replication of bacteria

3. Terms and Definitions • Bactericidal • The ability to kill bacteria independent of the immune system • Minimum Inhibitory Concentration (MIC) • The lowest concentration of an antimicrobial agent necessary to inhibit the growth of an organism • Minimum Bactericidal Concentration (MBC) • The lowest concentration of an antimicrobial agent necessary to kill an organism

4. Terms and Definitions • Intracellular Bacteria • Retain the ability to reside and replicate within cells • Examples: Salmonella typhi, Legionella spp,mycobacteria, chlamydiae • Extracellular Bacteria • Reside and replicate outside cells • Examples:streptococci, staphylococci, most gram (–) enteric rods and Pseudomonas spp

5. Terms and Definitions • Spectrum of Activity • Narrow spectrum • Effective against a limited number of organisms • Examples: Gram (+) and gram (–) anaerobes • Unlikely to disrupt normal flora • Broad spectrum • Effective against multiple organisms from more than a single class • Examples: Gram (+) and gram (–) anaerobes

6. Gram Positive vs. Gram Negative • Identification Helps Clinician Choose an Antibiotic That Will Be Effective Against a Specific Organism • Gram Stain Reflects Basic Differences in Cell Wall Composition • Gram positive: Retain red staining dye and appear deep violet in the microscope • Gram negative: Do not retain the red staining dye and appear red in the microscope

7. Gram Positive vs. Gram Negative • Gram-Positive Cell Walls Are Low in Lipids • Gram-Negative Cell Walls Are High in Lipids • Many Antibiotics Exert Their Effects Through Actions on Cell Walls • Cell wall difference determines whether certain antibiotics will be effective

8. Resistance to Antibiotics • Patterns of Resistance Differ from One Community to the Next and Change Rapidly • Consider Patient’s Exposure and What the Patient’s Treatment Behavior Has Been • Culture and Identify Organism When Possible • Monitor Culture Results and Share Information with Colleagues

9. Resistance to Antibiotics • Mechanisms of Resistance • Mutations occur in the gene that encodes the target proteins, so it no longer binds to the drug • Random events; does not require previous exposure to the drug • Examples of resistance through mutation: • Mycobacterium tuberculosis, Escherichia coli, Staphylococcus aureus

10. Resistance to Antibiotics • Mechanisms of Resistance (cont’d) • Transduction occurs when a virus that contains DNA infects bacteria that contain genes for various functions, including one that provides drug resistance • Incorporation of this bacterial DNA makes the newly infected bacterial cell resistant and capable of passing on the trait • Example: Staphylococcus aureus

11. Resistance to Antibiotics • Mechanisms of Resistance (cont’d) • Transformation involves transferring into the bacteria DNA that is free in the environment • Examples: Penicillin resistance in pneumococci and Neisseria • Conjugation is transfer of DNA from one organism to another during mating • Occurs predominantly among gram-negative bacilli • Examples: Enterobacteriaceae and Shigella flexneri

12. Mechanism of Action • Bacteriostatic vs. Bactericidal • Inhibit cell wall synthesis • Direct action on the cell membrane to alter permeability and cause leakage of intracellular compounds • Affect ribosomal subunits to inhibit protein synthesis • Bind ribosome subunits to alter protein synthesis and cause cell death

13. Mechanism of Action • Bacteriostatic vs. Bactericidal (cont’d) • Changes in nucleic acid metabolism • Blockage of specific essential metabolic steps by antimetabolites • Inhibition of viral enzymes essential for DNA synthesis through nucleic acid analogs

14. Treatment Principles • Standardized Guidelines • Infectious Diseases Society of America • www.idSociety.org • Cardinal Points of Treatment • Treat only if bacterial infection is present • Select according to most effective, narrowest spectrum, lowest toxicity, least potential for allergy, and most cost-effective

15. Treatment Principles • Prophylaxis • Selection of Antibiotic • Treatment is tailored to each patient according to patient and drug characteristics • Drug characteristics • Host factors

16. Treatment Principles • Administer Antibiotic According to Accepted Guidelines • Duration of Treatment

17. Classification of Common Pathogens • Gram (+) Cocci (Aerobic) • Staphylococcus aureus, S. epidermidis • Streptococcus pneumoniae • Group A, β-hemolytic (pyogenes) • Group B, group D • Gram (+) Bacilli (Aerobic) • Bacillus spp, diphtheroids

18. Classification of Common Pathogens • Gram (–) Bacilli (Aerobic) • Haemophilus influenzae; Campylobacter spp; Helicobacter pylori; Legionella spp

19. Classification of Common Pathogens • Gram (–) Cocci (Aerobic) • Enterobacteriaceae: Enterobacter spp; E. coli; Klebsiella spp; Proteus spp; Salmonella spp; Serratia spp; Shigella spp • Non–lactase fermenters: Pseudomonas aeruginosa

20. Classification of Common Pathogens • Gram (+) Cocci (Anaerobic) • Peptostreptococccus spp • Gram (+) Bacilli (Anaerobic) • Clostridium spp • Gram (–) Bacilli (Anaerobic) • Bacteroides fragilis group

21. Classification of Common Pathogens • Chlamydiae • Chlamydia trachomatis, C. pneumoniae, C. psittaci • Mycoplasmas • Mycoplasma pneumoniae • Not a true bacterium: Lacks a cell wall

22. Classification of Common Pathogens • Spirochetes • Treponema pallidum (syphilis); Borrelia burgdorferi (Lyme disease) • Fungi • Candida spp; Cryptococcus neoformans; Aspergillus spp