39 terms

micro chapt 12

STUDY
PLAY
chemotherapy
treatment of disease with chemicals
antibiotic
substance produced by
microorganisms that inhibits other microorganisms

Alexander Fleming accidentally discovered penicillin
Steptomyces
More than 1⁄2 of natural antibiotics are produced by filamentous, soil bacteria
failed drugs
• Destroyed during digestion
• Cannot penetrate into tissues/cells
• Is not stable for long periods of time in the body. Degrades/ excreted too quickly or too slowly.
• Harmful side-effects
• Is not selectively toxic
• Microbes are already resistant to it
• Interacts with other common drugs
ideal drugs
• selectively toxic to the microbe but nontoxic to host
• microbicidal rather than microbistatic
• soluble; functions in dilute body fluids
• remains potent long enough to act and it isn't broken down prematurely
• doesn't lead to antimicrobial resistance
• inexpensive
• doesn't cause allergic reactions
•helps with host's defenses
selective toxicity
drug will only harm pathogen of interest and not the human body as well ("magic bullet")
chemotherapeutic drug
any chemical used in the treatment, relief, or prophylaxis of a disease
prophylaxis
use of a drug to prevent imminent infection of a person at risk
narrow spectrum
antimicrobials effective against a limited narrow range of microbial types- for example, a drug effective mainly on gram-positive bacteria
broad spectrum
antimicrobials effective against a wide variety of microbial- for example a drug effective against both gram-positive and gram-negative bacteria

- Pro: treat unknown bacterial disease
- Con: kills normal microbiota
antimicrobial chemotherapy
the use of chemotherapeutic drugs to control infection
antimicrobials
all-inclusive term for any antimicrobial drug, regardless of what type of microorganism it targets
antibiotics
substances produced by the natural metabolic processes of some microorganisms that can inhibit or destroy microorganisms
semisynthetic drugs
drugs that are chemically modified in the laboratory after being isolated from natural sources
synthetic drugs
drugs produced entirely by chemical reactions within a laboratory setting
before starting a treatment, the doctor should...
1) Identify microbe causing infection

2) Assess degree of susceptibility (sensitivity) to drugs

3) Consider specific patient to be treated (age, other drug use, allergies, pregnancy, etc.)
zone of inhibition
mm of space where there is no bacterial growth around antibiotic carrier disc (Kirby Bauer disc diffusion test to determine drug susceptibility of microorganisms)

Resistance (there is growth) vs. Susceptibility (inhibited growth)

Greater zone of inhibition = greater susceptibility to antibiotic
disc
antibiotic carrier imprinted with abbreviation (ENR) and the concentration (5)
Kirby-Bauer method
test method for antibiotic sensitivity:
-discs laid on bacterial lawn
-during incubation, antibiotics diffuse from disks into agar
-bacterial specimen is sensitive to antibiotics, growth will be inhibited
-Larger zone (mm) = greater susceptibility to antibiotic; determine resistance, susceptibility, or intermediate result
E-test
-Advanced diffusion method
-use strip with antibiotic gradient
-gives an estimate of MIC
MIC
Minimum inhibitory concentration; lowest antibiotic concentration that inhibits bacterial growth; smallest inhibitory dose. It tells us how susceptible the organism is to the antibiotics. They care about the therapeutic index- the ratio of the toxic does to the therapeutic dose.
MBC
minimum bactericidal concentration (lowest concentration that still kills bacteria)
What is clinical significance of the MIC? How does the MIC affect treatment with antibiotics?
To pick the best antibiotic that has the most effect on the microbes, while picking the lowest concentration; we have to maintain the MIC within the tissues

Clinically, the minimum inhibitory concentrations are used not only to determine the amount of antibiotic that the patient will receive but also the type of antibiotic used, which in turn lowers the opportunity for microbial resistance to specific antimicrobial agents.
5 actions of antimicrobial drugs
inhibition of:

1) cell wall
2) protein synthesis
3) metabolite synthesis
4) plasma membrane
5) nucleic acid replication and transcription
Cell wall inhibitors
Block synthesis and repair; Drugs that are cell wall active usually target synthesis processes; only effective against actively growing cells:

-Penicillins
-Cephalosporins
-Carbapenems
-Bacitracin
-Vancomycin: fight MRSA
-Isoniazid: mycolic acid synthesis; for mycobacteria
β-lactam antibiotics
Penicillins- are susceptible to penicillinases (β-lactamases*) that cleave β-lactam ring

Cephalosporins- usually administered IV/IM; used for MRSA and penicillin-resistant bacteria

Carbapenems- Reserved for in-hospital when
other drugs aren't working
β- lactamases
Many bacteria possess a beta-lactamase enzyme that cleaves the beta-lactam ring of an antibiotic, and so the organism has produced antibiotic resistance! We have made a beta-lactamase inhibitor to prevent the organism from degrading the antibiotic

Penicillins are susceptible to penicillinases (β-lactamases) that cleave β-lactam ring. β-lactamase inhibitors (ex. clavulanic acidid*) are often combined with β-lactam antibiotics to improve effectiveness
Protein synthesis inhibitors
Chloramphenicol suppresses bone marrow activity

Aminoglycosides can cause hearing and kidney damage

Tetracyclines Very broad spectrum, but disrupts GI tract and normal microbiota too

Erythromycin
Metabolic pathways inhibitors
Sulfonamides sulfamethoxazole (competitive inhibitor); SXT
DNA/RNA inhibitors
Fluoroquinolones inhibit DNA unwinding helicases, stopping DNA replication and transcription

Rifamycins limit transcription, used to treat tuberculosis
Plasma membrane inhibitors
Polymyxins - insertion into membrane,
distortion of cell surface and leakage of cytoplasm; Toxicity to kidneys, limited use, an.bio.c topical ointments
therapeutic index
dose of drug that is toxic to humans lowest ÷ therapeutic dose (MIC)

Low TI = potentially toxic drug reactions in human High TI = larger margin of safety

Ex; since only bacteria have peptidoglycan cell wall, inhibiting cell wall synthesis is non-toxic to humans; high TI
therapeutic dose
drug level required for clinical treatment
toxic dose
drug level at which drug becomes too toxic for patient (i.e., produces side effects)
antimycobacterial antibiotics
Isoniazid
synergistic effect
the effects of a combination of antibiotics are greater than the sum of the effects of the individual antibiotics; Sulfonamides and Trimethoprim result in synergistic killing of bacteria
antifungal drugs
low TI and high toxicity

easier to treat superficial mycoses than systemic infections or subcutaneous infection

Azoles can inhibit ergosterol synthesis, disrupt membrane stability
antiviral drugs
Harder to target because viruses USE HOST MACHINERY!

Cannot target extracellular viruses or proviruses

Main modes of action are:
- Prevent penetration of virus
- Block transcription/translation of viruses
- Prevent maturation of viral particles
antiprotozoal drug
quinine drugs - malaria
• suppress protozoan reproduction in red blood cells
YOU MIGHT ALSO LIKE...