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selective toxicity
selectively finding & destroying pathogens w/o damaging host
chemotherapy
use of chemicals to treat a disease
antibiotic
substance produced by a microbe that inhibits another microbe
antimicrobial drugs
synthetic substance that interfere with growth of microbes
narrow spectrum of microbial activity
drugs that affect a narrow range of microbial types
broad spectrum antibiotics
affect a broad range of gram(+) or gram(-) bacteria
when would you use broad vs narrow spectrum antibiotics
use broad when infection is unknown; use narrow when infection is identified
Bactericidal
kill microbes directly
Bacteriostatic
prevent microbes from growing (no killing)
Name the 5 major actions of antibacterial drugs
1. inhibit cell wall synthesis
2. inhibit protein synthesis
3. injure plasma membrane
4. inhibit nucleic acid synthesis
5. inhibit synthesis of essential metabolites
Antibiotics that inhibit cell wall synthesis (4)
1. penicillin
2. cephalosporins
3. bacitracin
4. vancomycin
how does penicillin inhibit cell wall synthesis
prevent peptidoglycan synthesis
Antibiotics that inhibit protein synthesis (4)
1. chloramphenicol
2. erythromycin
3. streptomycin
4. tetracyclines
how do antibiotics inhibit protein synthesis
target 70S ribosomes
Antibiotic that injure plasma membrane(1)
Polymyxin B
how do antibiotics injure plasma membrane (2)
1. change membrane permeability
2. antifungal drugs combine with membrane sterols
Antibiotics that inhibit nucleic acid synthesis (2)
1. Quinolones
2, rifampin
how do antibiotics inhibit nucleic acid synthesis
interfere with DNA replication & transcription
Antibiotics that inhibit synthesis of essential metabolites (2)
1. Sulfanilamide
2. trimethoprim
how do antibiotics inhibit synthesis of essential metabolites (2)
1. compete with normal substrates for an enzyme
2. sulfanilmide competes with para-aminobenzoic acid (PABA) -> stops synthesis of folic acid
Penicillin essential part
b-lactam ring (no ring = no penicillin)
Penicillin G vs Penicillin V
G - injected, higher blood retention
V - taken orally, lower blood retension
What inactivates penicillin (developed by bacteria)
Penicillinase
What are actions that can extend the life of antibiotics (4)
1. penicillinase-resistant penicillins
2. extended-spectrum penicillins
3. penicillins plus b-lactamase inhibitors
4. cephalosporins
antibiotics with penicillinase-resistant penicillins (2)
methicillin
oxacillin
what does extended-spectrum penicillins imply
effectiveness against gram (-) and gram (+)
antibiotics with an extended-spectrum penicillins (2)
ampicillin
amoxicillin
(both are types of aminopenicillins)
what causes a b-lactamase inhibitor
clavulanic acid; a noncompetitive inhibitor of penicillinase
cephalosporins compared to penicillin
work similar to penicillin, but with a different b-lactamase ring (grouped by generation of development
Name the 3 ways to test for microbial susceptibility to chemotherapeutic agents
disk diffusion method
e test
broth dilution test
explain the disk diffusion method
- antibiotic on paper disk placed on lawn of bacteria
- clear spaces around the disk form if the antibiotic is effective against the bacteria
explain the e-test
- take a strip of antibiotic of differing gradients and leave in agar plate
- test where bacteria stops growing -> lowest gradient = the MIC
explain broth dilution test
- wells with dif concentrations of antibiotics (obtained by dilution series)
- grow bacteria on wells -> cloudiness forms for growth (no cloudiness means no growth)
- lowest concentration well with no growth is MIC
- concentration well plated onto agar with no growth is MBC
- if plated and bacteria grows, bacteria is inhibited, not killed
3 types of resistances to antibiotics
persister cells
superbugs
enterobacteriaceae (resistance to nearly all antibodies)
persister cells
microbes with genetic characteristics allowing for their survival when exposed to an antibiotic
(dormant when exposed, normal when free)
superbugs
bacteria that are resistant to large numbers of antibiotics (trait spread horizontally via conjugation/transduction)
mechanisms of resistance to antibiotics (5)
enzymatic destruction/inactivation of the drug
prevention of penetration to target site within microbe (mutate membrane)
alteration of drug's target site (mutate ribosomal protein)
rapid efflux of drug
variations of mechanisms of resistance
describe development of antibiotic-resistant mutant during antibiotic therapy
1. sensitive cells killed with antibiotic
2. cell population dips; slightly resistant cells die via further exposure
3. cells that are resistant to antibiotic spread the trait
4. trait is passed on and cell population increases
6 possible antibiotic misuses
1. outdated/weakened antibiotics
2. antibiotics for common cold & other inappropriate conditions
3. antibiotics in animal feed
4. someone else's leftover prescription
5. wrong combination of antibiotics
6. failing to complete the prescribed regimen
4 antibiotic safety notices
1. therapeutic index (risk vs benefit)
2. reactions of antibiotics with other drugs
3. damage to organs
4. risk to the fetus
synergism
effect of 2 drugs together > effect of either alone
antagonism
effect of 2 drugs together < effect of either alone
8 possible futures for antibiotics
1. target virulence factors
2. sequester iron, which feeds pathogens
3. seeks drugs that combat dormant persister cells
4. more drugs that target gram (-) bacteria
5. ways to test the antimicrobial safety of nonculturable bacteria
6. antimicrobial peptide production
7. bacteriocins
8. phage therapy
phage therapy
using bacteriophage to treat infections
bacteriocins
antimicrobial peptides prod. by bacteria
where do antimicrobial peptides come from
various organisms