Antimicrobial Agents in Pediatric Office Practice.ppt

Antimicrobial Agents in Pediatric Office Practice

1. Antimicrobial Drugs on
Pediatric Office Practice

2. Ehrlich’s Magic Bullets

3. Fleming and Penicillin

4. Chemotherapy
•The use of drugs to treat a disease
•Selective toxicity: A drug that kills
harmful microbes without damaging
the host

5. Antibiotic/Antimicrobial
•Antibiotic: Chemical produced
by a microorganismthat kills or
inhibits the growth of another
microorganism
•Antimicrobial agent: Chemical
that kills or inhibits the growth of
microorganisms

6. Microbial
Sources
of
Antibiotics

7. Antibiotic Spectrum of Activity
•No antibiotic is effective against all
microbes

8. Mechanisms of
Antimicrobial Action
•Bacteria have their own enzymes
for
–Cell wall formation
–Protein synthesis
–DNA replication
–RNA synthesis
–Synthesis of essential
metabolites

9. Mechanisms of
Antimicrobial Action
•Viruses use host enzymes inside
host cells
•Fungi and protozoa have own
eukaryotic enzymes
•The more similar the pathogen and
host enzymes, the more side
effectsthe antimicrobials will have

10. Modes of Antimicrobial Action

11. •Penicillin (over 50 compounds)
–Share 4-sided ring (blactam ring)
•Natural penicillins
•Narrow range of action
•Susceptible to penicillinase (b
lactamase)
Antibacterial Antibiotics
Inhibitors of Cell Wall Synthesis

12. Prokaryotic Cell Walls

13. Penicillins
Fig 20.6
Figure 20.6

14. Penicillinase (bLactamase)
Figure 20.8

15. •Penicilinase-resistant penicillins
•Carbapenems: very broad
spectrum
•Monobactam: Gram negative
•Extended-spectrum penicillins
•Penicillins + b-lactamase inhibitors
Semisynthetic Penicillins

16. •Cephalosporins
–2
nd
, 3
rd
, and
4
th
generations
more effective
against gram-
negatives
Other Inhibitors of Cell Wall
Synthesis
Figure 20.9

17. •Polypeptide antibiotics
–Bacitracin
•Topical application
•Against gram-positives
–Vancomycin
•Glycopeptide
•Important "last line" against
antibiotic resistant S. aureus
Other Inhibitors of Cell Wall
Synthesis

18. Other Inhibitors of Cell Wall
Synthesis
•Antibiotics
effective against
Mycobacteria:
interfere with
mycolic acid
synthesis or
incorporation
–Isoniazid (INH)
–Ethambutol

19. •Broad spectrum, toxicity problems
•Examples
–Chloramphenicol (bone marrow)
–Aminoglycosides: Streptomycin,
neomycin, gentamycin (hearing, kidneys)
–Tetracyclines (Rickettsias & Chlamydia;
GI tract)
–Macrolides: Erythromycin (gram +, used
in children)
Inhibitors of Protein Synthesis

20. •Polymyxin B (Gram negatives)
–Topical
–Combined with bacitracin and
neomycin (broad spectrum) in over-
the-counter preparation
Injury to the Plasma Membrane

21. •Rifamycin
–Inhibits RNA synthesis
–Antituberculosis
•Quinolones and fluoroquinolones
–Ciprofloxacin
–Inhibits DNA gyrase
–Urinary tract infections
Inhibitors of Nucleic Acid
Synthesis

22. –Sulfonamides (Sulfa drugs)
•Inhibit folic acid synthesis
•Broad spectrum
Competitive Inhibitors
Figure 5.7

23. Antifungal Drugs
•Fungi are
eukaryotes
•Have unique
sterols in their cell
walls
•Pathogenic fungi
are often outside
the body

24. Antiviral Drugs
•Viruses are composed of nucleic
acid, protein capsid, and host
membrane containing virus proteins
•Viruses live inside host cells and
use many host enzymes
•Some viruses have unique
enzymes for DNA/RNA synthesis or
protein cutting in virus assembly
Figure 20.16a

25. Antiviral Drugs
Nucleoside and Nucleotide Analogs
Figure 20.16a

26. Figure 20.16b, c
Analogs Block DNA Synthesis

27. •Inhibit assembly
–Indinavir (HIV)
•Inhibit attachment
–Zanamivir (Influenza)
•Inhibit uncoating
–Amantadine (Influenza)
Antiviral Drugs
Enzyme Inhibitors

28. •Interferonsprevent spread of viruses
to new cells (Viral hepatitis)
•Natural products of the immune
system in viral infections
Antiviral Drugs
Enzyme Inhibitors

29. Antiprotozoan Drugs
•Protozoa are
eukaryotic cells
•Many drugs are
experimental and
their mode of
action is unknown

30. Antihelminthic Drugs
•Helminths are
macroscopic
multicellular
eukaryotic
organisms:
tapeworms,
roundworms,
pinworms,
hookworms

31. •Prevent ATP generation (Tapeworms)
•Alters membrane permeability
(Flatworms)
•Neuromuscular block (Intestinal
roundworms)
•Inhibits nutrient absorption (Intestinal
roundworms)
•Paralyzes worm (Intestinal
roundworms)
Antihelminthic Drugs

32. Measuring Antimicrobial
Sensitivity
•E Test
•MIC: Minimal
inhibitory
concentration

33. Measuring Antimicrobial
Sensitivity: Disk Diffusion

34. Figure 20.20
Antibiotic Resistance

35. Antimicrobial Resistance
•Relative or complete lack of
effect of antimicrobial against a
previously susceptiblemicrobe
•Increase in MIC

36. •Enzymatic destruction
of drug
•Prevention of
penetration of drug
•Alteration of antibiotic
or target site
•Rapid ejection of the
drug
Mechanisms of Antibiotic
Resistance

37. Antibiotic Selection for
Resistant Bacteria

38. What Factors Promote
Antimicrobial Resistance?
•Exposure to sub-optimal levels
of antimicrobial
•Exposure to microbes carrying
resistance genes

39. Inappropriate Antimicrobial
Use
•Prescription not taken correctly
•Antibiotics for viral infections
•Antibiotics sold without medical
supervision
•Spread of resistant microbes in
hospitals due to lack of hygiene

40. Inappropriate Antimicrobial
Use
•Lack of quality control in
manufacture or outdated
antimicrobial
•Inadequate surveillance or
defective susceptibility assays
•Poverty or war
•Use of antibiotics in foods

41. Antibiotics in Foods
•Antibiotics are used in animal feeds
and sprayed on plants to prevent
infection and promote growth
•Multi drug-resistant Salmonella
typhihas been found in 4 states in
18 people who ate beef fed
antibiotics

42. Consequences of
Antimicrobial Resistance
•Infections
resistant to
available
antibiotics
•Increased
cost of
treatment

44. Multi-Drug Resistant TB

45. MRSA “mer-sah”
•Methicillin-Resistant
Staphylococcus aureus
•Most frequent nosocomial
(hospital-acquired) pathogen
•Usually resistant to several
other antibiotics

46. Vancomycin Resistant Enterococci

47. Vancomycin Use USA

48. Proposals to Combat
Antimicrobial Resistance
•Speed development of new
antibiotics
•Track resistance data nationwide
•Restrict antimicrobial use
•Direct observed dosing (TB)

49. Proposals to Combat
Antimicrobial Resistance
•Use more narrow spectrum
antibiotics
•Use antimicrobial cocktails

50. •Antimicrobial peptides
–Broad spectrum antibiotics from
plants and animals
•Squalamine (sharks)
•Protegrin (pigs)
•Magainin (frogs)
The Future of
Chemotherapeutic Agents

51. •Antisense agents
–Complementary DNA or peptide
nucleic acids that binds to a
pathogen's virulence gene(s) and
prevents transcription
The Future of
Chemotherapeutic Agents