8. Those that inhibit cell wall synthesis:
Isoniazid; pyrizinamide: Mycolic acid synthesis inhibitors
Ethambutol: Inhibits MA incorporation to cell wall
Those that affect nucleic acid metabolism:
Rifampin; rifabutin: DNA dependent RNA polymerase
inhibitors
Clofazimine: Binds to DNA and inhibits the template function
of DNA
Those that inhibits intermediary metabolism:
Dapsone; sulfoxone: The same as that of sulfonamides.
11. Ability of an antibiotic to destroy target cells without
damaging host cells
Differences between microbes and host
Prokaryotic vs Eukaryotic
Cell wall
Inhibition of microbial enzymes
Disruption of bacterial protein synthesis
12. Host defense (immune system, skin)
Site of infection
BBB, vascularity, heart valves, abscess
Age
Pregnancy & Lactation
Previous Allergic Reaction
Genetic
Host defense mechanism: A chemotherapeutic regimen that
is perfectly adequate for immuno-competent patient
may be totally ineffective for immuno-incompetent
patient. Immuno-incompetence may be due to
deficiencies in Immunoglobulin, phagocytic cells and
cellular immune system.
13. Hepatic function: Erythromycin, clindamycin, rifampin,
Chloramphenicol depend on liver metabolisms for
the inactivation of antimicrobial mechanisms.
Patients with impaired liver function may accumulate
in the body active form of the drugs to a toxic level
if the dosage adjustment is not made.
Kidney function: Normal kidney function is essential for
disposal of -lactams, aminoglycosides, vancomycin,
Active form of these drugs may accumulate in the
patient with renal diseases.
15. MIC: Minimum inhibitory concentration if drug does not
get the concentration, then drug is ineffective
Mechanisms
Drug inactivating enzymes
Cease uptake of drug
Change in bacterial receptors
Synthesize drug antagonists
Acquisition
Spontaneous mutation – single resistance
Conjugation –multiple drug resistance
16. Natural (Inherent)
Lack target or transport
Acquired
Mutation
Horizontal transfer
Vertical
Horizontal
Transformation
Transduction
Conjugation
20. Use of antibiotics to treat viral infections
Inadequate pathogen coverage
Excessive use of broad spectrum agents
Sub-optimal dosing
Retaining unfinished antibiotic for later use
21. Increased rate of treatment failure
Poor patient compliance
Increased mortality
Need for combination therapy
Increased cost of treatment