inhibits but does not kill; lowers the threshold aka bacteria stops growing; MBC >>> than MIC (concentration that kills will be higher than concentration that inhibits)

1. required second dosages 2. cost 3. toxicities

Microbiology Lecture I Flashcards by Chase Thompson

Antimicrobials on human life expectancy … added

a. 8-10 years
b. 20-22 years
c. 10-12 years

A. 8-10 years

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Infectious disease accounts for 10%/15%/20% of deaths worldwide?

10%

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25%/50% of deaths in low income countries are due to infectious disease while only 7% in high income countries.

50%

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Antibacterials are classified by their mechanisms of action. What are the four main mechanisms of actions?

Cell wall synthesis
Membrane structure
DNA synthesis
Protein synthesis

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minimum inhibitory concentration (MIC)

the lowest drug concentration required to inhibit the visual growth of a bacteria

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minimum bactericidal concentration (MBC)

the concentration of drug required to kill all bacteria

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bactericidal

kills bacteria; MBC will be approximately MIC

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bacteriostatic

inhibits but does not kill; lowers the threshold aka bacteria stops growing; MBC&raquo_space;> than MIC (concentration that kills will be higher than concentration that inhibits)

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methods to determine microbial susceptibility/resistance

disk diffusion, E-test, PCR/sequencing

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efficacy definition

the ability to produce a desired or intended result

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efficacy of antimicrobial drugs in limited by

mechanism of action
susceptibility of the target organism
side effects on the host
pharmacodynamics
cost
patient compliance

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Cmax

peak concentration, maximum concentration of drug

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AUC

area under the curve, total concentration of the drug that has accumulated in the patients body over a certain period of time

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time-dependent killing (TDK)

antibiotic that is suppose to maximize the time above the MIC

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concentration-dependent killing (CDK)

maximize Cmax and AUC

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post antibiotic effect (PAE)

the time it takes for bacteria to return to log-phase growth following removal of antibiotic

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how does TDK affect PAE

short PAE

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how does CDK affect PAE

long PAE

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longer PAES reduce

required second dosages
cost
toxicities

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rocephin

Class: B-lactam
Subclass: cephalosporin
Generic: ceftriaxone

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gram-negative

stains red because pores allow flow; thinner layer of peptidoglycan, inner and outer membranes, lipopolysaccharide (LPS) on outer membrane

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gram-positive

stains purple/blue; thick peptidoglycan, lipoteichoic acid (LTA)

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peptidoglycan

peptides and sugars (N-acetylmuramic acid NAM and N-acetylgucosamine NAG)

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N-acetylmuramic acid NAM

has the four peptides for transpeptidase

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B-lactam antibiotics interact with peptidoglycan by...

affecting transpeptidation so rows of NAM-NAGS cannot form; B-lactam ex. penicillin superimposes on D-ala-D-ala (last two amino acids attached to NAM) and bind to transpeptidase and inhibit formation; transpeptidation reaction that is essential for petidoglycan synthesis

B-lactam works better on gram +/gram - until there were alterations on penicillin

gram + because pepitdoglycan is exposed

B-Lactam subclasses

penicillin, cephalosporin, monobactams, and carbapenems

enzymatically inactivate drugs example, importance, and where they are found

ex. B-lactamases antibiotic resistance mchanism often on mobile genetic elements

how antibiotic resistance mechanisms can alter drug target

mutation and can occur via horizontal exchange

how antibiotic resistance mechanisms can alter drug exposure

decrease uptake or increase efflux

two important types of B-lactamases

1. extended spectrum B-lactamases (ESBL) | 2. metal-dependent

how do B-lactamases work?

cleave the ring on B-lactams

clavulanic acid

inhibits b-lactamases

b-lactam block

penicillin binding proteins

glycoprotein works by

inhibiting transglycosylase by covering d-ala-d-ala amino acid chains on peptidoglycan

glycoprotein example

vancomycin

bacterial resistance to glycoproteins

makes enzyme to change d-ala-d-ala to d-ala-d-lac and then antibiotic cannot bind but this is energy expensive and causes the bacteria to be more susceptible to other attacks

antibiotics that attack cell wall

b-lactam, glycoprotein, bacitracin, phosphomycin, and cycloserine

mycobacterium species

mycolic acid waxy outer wall | ex. M. tuberculosis and M. leprae

agents that act on mycobacterial cell walls

isoniazid and ethamnutol

isoniazid mechanism of action

inhibits mycolic acid synthesis

ethambutol mechanism of action

thought to inhibit arabinotransferases

lipopeptides

disrupts the cell membrane of G+ bacteria ; cannot disrupt the G- bacteria because the molecule is too large to fit through porins

how are lipopeptides selective for bacteria and not eukaryotic membranes?

bind to phosphatidylglycerol which is abundant in bacterial cell membranes but rare in eukaryotic cell membranes

lipopeptide antibiotic example

daptomycin

where in the human body is phosphatidylglycerol abundant?

lungs

Why would we not use daptomycin or any lipopetides to treat pneumonia?

would kill normal cells and not just bacterial cells because there is high amounts of phosphotidylglycerol present in the lungs

synergy

each drug works better in the presence of the other drug

TDK two types of mechanisms

cell inhibitors and protein inhibitors

TDK cell wall inhibitor examples

penicillins and cephalosporins

TDK protein synthesis inhibitors

macrolide and clindamycin

CDK two types of mechanisms

protein synthesis inhibitors and DNA inhibitors

CDK example of DNA inhibitors

fluoroquinolones

CDK example of protein inhibitors

aminoglycosides

Penicillins, cephalosporins, macrolides, and clindamycin have minimal-moderate/prolonged PAE

minimal-moderate they are TDK antibiotics

Fluoroquilolones and aminoglycosides have minimal-moderate/prolonged PAE

prolonged because they are CDK antibiotics

sulfonamides

inhibit folate synthesis (folate is used in DNA synthesis), bacteriostatic on their own ex. sulfamethoxazole

trimethoprim

affects DHFR (enzyme that converts folate), bactericidal, synergetic with sulfamethoxazole

quinolones/fluoroquinolones

inhibit prokaryotic DNA synthesis via gyrase (prokaryotes topoisomerase II) and topoisomerase IV, bactericidal ex. ciprofloxacin

ciprofloxacin

quinolone, can cause ruptured tendons

rifamycins

inhibit mRNA synthesis, bactericidal or bacteriostatic, bind to DNA-dependent- RNA- polymerase, not used often as a monotherapy because mutations occur rapidly (mutations in RNA polymerase)

rifampin class

rifamycin

nitroimidazoles

damage DNA, bactericidal and anaerobic

nitroimidazole subclass

metronidazole

prodrug

must be converted by microbial enzyme to active form