Antimicrobial Agents Flashcards
What 4 classes of antibiotics cover primarily one gram class?
“GLAM”
glycopeptides +
lincosamides +
aminoglycosides -
macrolides +
the rest cover both gram negative and positive
amiNOglycosides = gram Negative
Sulfonamides Mechanism
SulFOnamides inhibit Folate synthesis
Fluoroquinolones Mechanism
fluoroQUINolones– think of QUIN as quintuplets… multiple “replicated” babies
so fluoroquinoloes inhibit DNA replication
block both topoisomerase IV and DNA gyrase
usually for bacterial infections of the skin, sinuses, kidneys, bladder, and also used for bacterial infections causing bronchitis or pneumonia
Classes that Inhibit Protein Synthesis
“MALT”
macrolides (50S)
aminoglycosides (30S)
lincosamides
tetracyclines (30S)
aminoglycosides: blocks translation (streptomycin)
tetracyclines: block tRNA attachment
Macrolides: prevent continuation of protein synthesis after binding 50S ribosome (chloramphenicol)
Classes that inhibit cell wall synthesis
“Giant Cats Crush Peptidoglycan”
glycopeptides
cephalosporins
carbapenems
penicillins
Synergistic Drug Combination
action of one drug enhances the other
an agent that damages the cell wall can increase entry of another agent that isn’t normally allowed into the cell
Antagonistic Drug Combination
activity of one drug interferes with another
ex. an agent that needs cell growth is used with a bacteriostatic agent
Different Mechanisms of Antibacterial Drugs
- inhibit cell wall synthesis
- inhibit protein synthesis
- inhibit nucleic acid synthesis
- injury to plasma membrane
- inhibit synthesis of essential metabolites
Name the beta-lactam antibiotics and describe their mechanism
Cell wall, bactericidal, require cell growth
“MP triple-C”
monobactams penicillins cephalosporins cephamycins carbapenems
Tpase recognizes the beta lactam ring C-N bond and binds it to attach it to peptidoglycan, thinking it is D-ala-D-ala. This complex cannot be broken, so Tpase is irreversibly inactivated
Transpeptidase function and antibiotics targeting transpeptidase
Tpase crosslinks glycan strands in peptidoglycan
beta-lactams inhibit Tpase, so glycan strand cannot be joined
Penicillin Binding Proteins (PBPs)
Beta lactams target PBPs
PBPs include:
- transpeptidases (Tpase)
- carboxypeptidases
- endopeptidases
- all are involved in the later stages of peptidoglycan synthesis and reshaping the cell wall during growth and cell division
Penicillin G
First beta lactam antibiotic
only gram positive
acid and alkali-labile
inactivated by beta-lactamases (penicillinases)
6-aminopenicillanic acid (6-APA)
can produce penicillins synthetically starting with 6-APA as a precursor
Penicillins that are improvements over Penicillin G
better acid stability: amoxicillin and cloxacillin
broader spectrum (includes gram negative): ampicillin, amoxicillin, carbenicillin
increased bioavailability: ampicillin, pivampicillin
resistance to beta-lactamases: methicillin, cloxacillin
Beta Lactamase Inhibitors
clavulanic acid, sulbactam, tazobactam
can overcome beta lactamase resistance by using a beta lactam drug in combination with a beta lactamase inhibitor
Popular combinations:
- amoxicillin and clavulanate (augmentin)
- ampicillin and sulbactam (unasyn)
Carbapenems (Important General Info)
beta lactams
combine features of penicillins and cephalosporins
used to treat infections by multi drug-resistant bacteria (MDR bacteria)
excellent activity against a broad spectrum of gram positive and gram negative
ESBLs do NOT inactivate carbapenems
Thienamycin
carbapenem
penetrates easily through the outer membrane of gram negative bacteria through porins
resistant to ESBLs (like all carbapenems)
Monobactams
narrow spectrum targeting aerobic gram negative
useful for people with penicillin allergies
ex. aztreonam (azactam)
Bacitracin
non beta lactam cell wall inhibitor
polypeptide antibiotic
interferes with lipid carrier that takes peptidoglycan monomers across the cell membrane
side effect: can interfere with sterol biosynthesis in humans, so it is used ONLY TOPICALLY
Neosporin Contents
Polymyxin B: gram negative rods
Bacitracin zinc: gram positive
Neomycin sulfate: broad spectrum
** only used for broad spectrum topical use
Vancomycin
glycopeptide
non beta lactam cell wall inhibitor
gram positive, bactericidal
important in methicillin and cephalosporin resistant organisms
vancomycin binds D-ala-D-ala at the end of the peptidoglycan precursor so that transpeptidase “cannot reach” to make the bond
Streptomycin
amino glycoside
bactericidal, broad spectrum
NOT effective against anaerobes or intracellular bacteria
can cause kidney and/or 8th CN damage
** gentamicin, amikacin, and tobramycin have extended spectra, including activity against pseudomonas
Tetracyclines
tetracycline, minocycline, doxycycline
bacteristatic broad spectrum
includes mycoplasma, rickettsia, chlamydia
block acceptor site so that aminoacyl-tRNA cannot bind
can cause permanent discoloration of teeth and enamel hypoplasia when given during tooth development– do not give to pregnant women or children under 8 years old
Erythromycin
macrolide (50S)
bacteriostatic
gram positive, mycoplasma, chlamydia
bind 2 sites on 50S ribosome causing dissociation of tRNA and termination of peptide linking
stomach acid hydrolyzes erythromycin and the metabolites irritate the stomach.
azithromycin and clairithromycin are more acid stable so you have more time between doeses
14- membered lactone ring
