microbio ch 8

Ehrlich

made ehrlich’s magic bullets (compound 6060)

compound 606

targeted bacterium treponema pallidum

what did compound 606 cure

syphilis in rabbits and humans

first antimicrobial agent

compound 606

prontosil (synthetic dye) was used to treat?

streptococcal and staphylococcal infections in mice

first natural antibiotic

penicillin

alexander fleming

discovered penicillin in 1928

how was penicillin discovered

old plates of staphylococci had mold growth, but was inhibited by penicillin on one plate by penicillin

penicillin is antibacterial against

streptococci, meningococci, and corynebacterium diphtheriae

chemotherapy

use of drugs to treat a disease

three types of chemotherapeutic agents

antibiotics, semi-synthetic antibiotics, and synthetic drugs

antibiotics

natural products

semi-synthetic antibiotics

modified natural products

synthetic drugs

not naturally made

selective toxicity

should be toxic for microorganism, not for the host

antimicrobial spectrum

the drug should be able to destroy or inhibit many kinds of pathogenic microorganisms

no side effects

the drug should not produce any undesirable side effects

no killing effect on normal flora

the drug should not destroy the normal flora of the body

no inactivation

when the drug is given orally, it should not be inactivated by stomach acids

solubility in body fluids

must have solubility in body fluids

sufficient concentration of the drug in target tissues

the drug must be able to reach sufficiently in high concentration in the tissues or the blood of the patient

low breakdown rate of drug

breakdown rate of drug must be low so that it will remain in the tissues long enough to exert its effects

availablity

easily available at affordable cost or prices

antibiotic definition

chemical substances produced by microorganisms that selectively kill or inhibit the growth of another microorganism(s)

antimicrobial agent

chemical that kills or inhibits the growth of microorganisms

bacterialcidal

work to directly kill existing bacteria

bacteriostatic

works to inhibit/ slow further growth, ultimately causing the bacteria to die

superinfection

secondary infection in a patient having a preexisting infection

what is the risk of broad-spectrum antimicrobials targeting broad spectrums of microbiota

superinfection

examples of superinfection

yeast infections, pseudomembranous colitis

combinations of antibiotics can be

synergistic or antagonistic

synergistic drugs

have greater effectiveness when used together (combined effect > additive effect)

antagonistic drugs

interfere with each other and decrease effectiveness

dosage

amount of medication given during a certain time interval

therapeutic dose

minimum dose per kg of body weight that stops growth

toxic dose

maximum dose tolerated by the patient

chemotherapeutic index

ratio of the toxic dose to the therapeutic dose

higher chemotherapeutic index=

safer drug

highest concentration of drug with fastest response time

intravenous

2nd highest concentration of drug with fastest response time

intramuscular

3rd highest concentration of drug with fastest response time

oral

drug to bacteria relationship

pharmacodynamics (PD)

bacteria to drug relationship

resistance

host to bacteria relationship

host defense

bacteria to host relationship

infection

drug to host relationship

toxicity

host to drug relationship

pharmacokinetics (PK)

B-Lactams

cidal, inhibits bacteria cell wall biosynthesis

aminoglycosides

cidal, inhibit synthesis of proteins by bacteria

glycopeptides

cidal, inhibit bacteria cell wall biosynthesis

ansamycins

cidal, inhibit the synthesis of RNA by bacteria

quinolones

cidal, interfere with bacteria DNA replication and transcription

streptogramins

cidal, inhibit synthesis of proteins by bacteria

lipopeptides

cidal, disrupt multiple cell membrane functions

sulfonamides

static, prevent bacteria growth and multiplication

chloramphenicol

static, inhibit synthesis of proteins

tetracyclines

static, inhibit synthesis of proteins by bacteria

macrolides

static, inhibit protein synthesis by bacteria

oxazolidinones

static, inhibits synthesis of proteins by bacteria

inhibition of cell wall biosynthesis

blocks biosynthesis of peptidoglycan, beta- lactam antibiotics, penicillin and related antibiotics bind to them

penicillin-binding proteins

enzymes that produce peptide cross-links in peptidoglycan

cephalosporin examples

cefalexin, cefuroxime, cefotaxime, and ceftriaxone

carbapenem examples

meropenem, imipenem, doripenem, and ertapenem

penicillin narrow spectrum examples

benzylpenicillin, phenoxymethylpenicillin, and flucloxacillin

broad spectrum penecillin examples

amoxicillin, ampicillin, and piperacillin

cell wall composition

beta-lactam ring and organic acid, natural and semi-synthetic, bactericidal (binds to penicillin binding protein and interferes with the transpeptidation reaction)

toxicity

allergy, anaphylaxis, and diarrhea

polypeptide antibiotics

bacitracin and vancomycin

bacitracin

topical application, used against gram positive

vancomycin

glycopeptide, important last line against S. aureus

antibiotics used against mycobacteria

isoniazid and ethambutol

inhibition of protein biosynthesis

broad spectrum, toxicity problems

examples of protein synthesis antibiotics

chloramphenicol, aminoglycosides, tetracyclines, and macrolides

inhibition of membrane function

poking holes in bacterial cytoplasmic membrane (gramicidin and polymyxin)

detergent action (platensimycin)

inhibits fatty acid synthesis

quinolones and flouroquinolones

inhibit DNA synthesis by blocking the action of DNA gyrase, preventing bacteria from regulating supercoiling

inhibition of metabolic pathways

sulfonamides and timethoprim

sulfonamides

inhibit folic acid synthesis, broad spectrum

trimethoprim

antimetabolite within same folic acid synthesis pathway as sulfonamides

polyenes

disrupt membrane integrity

polyene examples

nystatin, amphotericin B

azoles

interferes with ergosterol synthesis

azole examples

imidazole, triazoles

allylamines

interferes with ergosterol synthesis

allyamine examples

terbinafine, lamisil

echinocandins

block fungal cell wall synthesis

echinocandin example

caspofungin

griseofulvin

blocks cell division

flucytosine

inhibits DNA synthesis