Antibacterial Agents Flashcards
Penicillins used in combination with tetracyclines produce additive or antagonistic effects?
antagonistic effects
Which antimicrobial agents act through inhibition of bacterial cell-wall synthesis?
penicillins, cephalosporins, imipenem/ meropenem, aztreonam, vancomycin
Which antimicrobial agents inhibit bacterial protein synthesis?
aminoglycosides, chloramphenicol, macrolides, tetracyclines, streptogramins, linezolid
What antimicrobials act through the inhibition of nucleic acid synthesis?
fluoroquinolone, rifampin
What antimicrobials act through inhibition of folic acid synthesis?
sulfonamides, trimethoprim, pyrimethamine
Primary mechanism of resistance for pens and cephalosporins?
production of beta-lactamases, which cleave the beta-lactam ring structure; change in penicillin-binding proteins; change in porins
Primary mechanisms of resistance to aminoglycosides?
formation of enzymes that inactivate drugs
Primary mechanism of resistance to macrolides?
formation of methyltransferases that alter drug binding sites of 50S ribosomal subunit, and active transport out of cells.
Primary mechanism of resistance to tetracycline drugs?
increased activity of transport systems that “pump” drugs out of the cell
Primary mechanism of resistance to sulfonamide drugs?
change in sensitivity to inhibition of target enzyme;
increased formation of PABA;
use of exogenous folic acid
What are the primary mechanisms of resistance in evading fluoroquinolone action?
change in sensitivity to inhibition of target enzymes;
increased acitivity of transport systems that promote drug efflux
What are primary mechanisms of microbials when trying to confer resistance in response to treatment with chloramphenicol?
formation of inactivating acetyltransferases
PBP stands for what?
penicillin binding proteins
Penicillin MOA
pens interact with cytoplasmic membrane binding proteins PBPs to inhibit transpeptidation involved in cross-linking the final steps in cell-wall synthesis
What are the drugs considered antistaph pens?
nafcillin
oxacillin
methicillin
Are antistaph pens beta lactamase sensitive or resistant?
resistant
What spectrum of organisms are antistaph pens effective against?
very narrow: staphylococci (not MRSA)
Name the natural Pens and what organisms the are useful against?
Pen G and Pen V
Narrow spectrum:
streptococci, pneumococci, treponema
Are natural pens beta lactamase resistant or sensitive?
beta lactam sensitive
Name some aminopenicillin drugs, their spectrum and organisms they are useful against?
Amoxicillin
Ampicillin
Broad spectrum
Gram (+) cocci, Listeria, E. coli, Borrelia, H. pylori
Are aminopenicillins beta lactase sensitive or resistant?
sensitive
What is the spectrum of action for antipseudomonal penicillins?
very broad
gram (+) cocci, gram (-) rods, pseudomonas
Are antipseudomonal pens beta lactamase sensitive or resistant?
sensitive
Which drugs act by enhancing the activity of pens because they inhibit betalactamase?
clavulanic acid, sulbactam
Pens have synergistic effects with what drugs to act against pseudomanal and enterococcal species?
aminoglycosides
Which HSR is IgE mediated: rapid onset; anaphylaxis, angioedema, laryngospasm?
Type I HSR
Which HSR is IgM and IgG antibody fixed to cells; vasculitis, neutropenia, positive Coombs test?
HSR II
Which HSR is linked to immune complex formation, vasculitis, serum sickness, interstitial nephritis?
HSR III
Which HSR is linked to T-cell mediated urticarial and maculopapular rashes, SJS?
HSR IV
What is a S/E reaction that is evidenced with use of pens when treating syphillis?
Jarisch-Herxheimer rxn
Ampicillin is mostly excreted by which organ?
kidney
Nafcillin and oxacillin are largely eliminated where?
in the bile
MOA and resistance of cephalosporins?
similar to pens
Name the 1st generation cephalosporins?
cefazolin, cephalexin
ph 1st
What are the spectrum of organisms 1st generation cephalosporins can treat?
gram-positive cocci (not MRSA), E. coli, Klebsiella pneumoniae, and some proteus specieis
Indication for use of many 1st generation cephalosporins?
surgical prohylaxis
Name some second generation cephaloposporins.
cefotetan, cefaclor, cefuroxime, cefoxitin
What spectrum of microbials can second generation cephalosporins act on?
more gram neg coverage including some aneaerobes
Name some third gerneration cephalosporins.
ceftriaxzone (IM) and cefotaxime (parenteral), cefdinir and cefixime (oral)
What is the spectrum of antibiotic that third generation cephalosporins are useful against?
all of the above covered organisms by previous generations, bacteria resistant to other beta lactams,
gram positive and gram negative cocci (Neisseria gonorrhea) plus many gram - rods
In comparison to 1st and 2nd cephalosporins can 3rd gen cross the CNS?
yes
Can fourth generation cephalosporins cross the CNS?
yes
Are most fourth generation cephalosporins resistant to beta-lactamases?
yes
Name a fourth generation cephalosporin.
cefepime (IV)
Probenecid can block active tubular secretion of which antimicrobials mainly?
pens and cephalosporin
Because there is cross-allergenicity between pens and cephalosporins what are other antimicrobial agents that suggested instead?
consider macrolides for gram positive organisms
consider aztreonam for gram negative rods
Imipenem and meropenem MOA?
same as pens and cephalosporins
Is meropenem resistant to beta-lactamase?
yes
Spectrum of drug coverage for imipenem and meropenem?
gram + cocci, gram - rods and anaerobes
What drug inhibits imipenems metabolism to a nephrotoxic metabolite? What is this drugs MOA?
cilastatin; a renal dehydropeptidase inhibitor
Use for Aztreonam? also ROA?
IV drug mainly active vs gram negative rods
MOA of vancomycin?
binding at the D-ala-D-ala muramyl pentapeptide to sterically hinder the transglycosylation rxns (and indirectly prevent transpeptidation involved in elongation of peptidoglycan chains.
What is the spectrum of microbial that vancomycin can treat?
MRSA, enterococci, Clostridium difficile (backup drug)
How is there resistance to vancomycin? (explain the mechanism)
enterococcal resiste innobles change in the muramyl pentapeptid target such that terminal D-ala I replaced bh D-lactate
Can vancomycin enter the CNS?
no
How is vancomycin eliminated?
renal filtration
S/E of use of vancomycin?
“red man syndrome” (histamine release)
ototoxicity (usually permanent, additive with other drugs
nephrotoxicity
Which category of protein synthesis inhibition drugs act on the 30 S ribosome?
aminoglycosides, tetracyclines
Which categories of protein synthesis inhibitions drugs act on the 50 S ribosomes?
Linezolid
Pristins dalfopristin/ quinupristin
chloramphenicol
macrolides and clindamycin
Which drugs that inhibit protein synthesis of the cell wall inhibit formation of initiation complex?
aminoglycosides
linezolid
Which drugs inhibit amino acid incorporation? (block attachment of aminoacyl tRNA to acceptor site (static) (protein synthesis inhibitors)
tetracyclines
Dalfopristin/ quinupristin
Which drugs inhibit formation of peptide bond? (protein synthesis inhibitor drugs)
chloramphenicol
Which drug inhibit translocation? (protein synthesis inhibitors)
macrolides and clindamycin
Which protein synthesis inhibitors are the only ones which are bactericidal?
aminoglycosides
MOA aminoglycosides and Linezolid.
interfere with initiation of codon functions-block association of 50S ribosomal subunit with mRNA -30S (static)
Misreading of code, incorporation of wrong amino acid (cidal) aminoglycosides only
MOA tetracyclines and the pristine?
block the attachment of aminoacyl tRNA to acceptor site (static)
What is the MOA of chloramphenicol?
inhibit the activity of peptidyltransferase (static)
MOA macros and clindamycin?
inhibit translocation of peptide tRNA from acceptor to donorr site (static
Which antimicrobials shouldn’t be used in pregnancy?
aminoglycosides, fluoroquinolone, sulfonamides, tetracyclines
Which type of organisms are aminoglycosides useful in the treatment of? (What are some names of aminoglycoside agents)
gram-negative rods; gentamicin, tobramycin, amikacin
Which aminoglycoside is the DOC for bubonic plague and tularemia?
stremtopmycin
Side effects of aminoglycosides? Way to remember certain major characteristics of this drug class.
AmiNOglycosides
NO, NO, NO
Needs O2
Neg Organisms
Nephrotoxic and ototoxic
also neuromuscular blockade with dec release of ACh release
Way to remember what Tetracyclines are the DOC for?
tets for Ticks
(rickettsia) RMSF, (Borrelia burgdoferi) Lyme disease, as well as chlamydial and mycoplasma species, H. pylori, brucella, vibirio, and treponema (back up drug)
What are the names of tetracycline antibiotics?
doxycycline, minocycline, Tigecycline
Use for Doxycycline? (specifically where can this drugs reach high levels in the body?)
prostates because reaches high levels in prostatic fluid
Use for minocycline?
used in meningococcal carrier states
What is the use for Tigecycline and why is the use good for this type of tetracycline?
used in complicated skin, soft tissue, and intestinal infections because can act on resistant gram pos. (MRSA, VREF, gram neg organisms, and anaerobes)
VREF - Vancomycin-resistant Enterococcus faecium
How are most tetracyclines eliminated?
via the kidneys
How is doxycycline eliminated?
liver
Tetracylcines can bind what found in the body?
divalent cations Ca2+, Mg2+, Fe2+
Which antimicrobials are known to be phototoxic?
tetracyclines
sulfonamides
quinolones
Indications for chloramphenicol?
currently backup drug for infection due to salmonella typhi, B. fragilis, Rickettsia, and possibly bacterial meningitis
Side effects of chloramphenicol
dose dependent bone marrow suppression common; aplastic anemia rare
“gray baby” syndrome in neonates (they have dec levels of glucuronosyltransferase)
Indication for use of macrolides?
wide spectrum antibiotics
Gram- positive cocci (not MRSA)
Atypical organisms (chlamydia, mycoplasma, and ureaplasma species)
Legionella pneumophila
campylobacter jejunii
mycobacterium avium intracellular (MAC) Mac for Mac
H. pylori
What are the most common organisms associated with community acquired pneumonia?
M. pneumonia, C. pneumonia, and viruses
Smokers: pneumococcus
M = mycoplasma
C= chlamydia
Which drugs are commonly used in the treatment of community acquired pneumonia?
macrolides
What is telithromycin used for?
a ketolide active against macrolide- resistant S. pneumonia
S/E of using macrolides.
GI distress erythromycin, azithromycin > clarithromycin) due to stimulation of motion receptors
reversible deafness at high doses
increase QT interval
MACROS
Motility Issues GI
Arrythmias (QT prolongation)
Cholestatic hepatitis
Rash
eosinOphilia
MOA clindamycin?
not a macrolide but same MOA and resistance
What organisms can clindamycin be used to treat against?
narrow spectrum: gram positive cocci (including community-acquired MRSA) and anaerobes, including B. fragilis (back up drug)
S/E clindamycin use?
pseudomembranous colitis (most likely cause)
What is the MOA of Linezolid? (specifically)
inhibits initiation compl.ex in bacterial translation systems by preventing formation of N-formylmethionyl - tRNA- ribosome- mRNA ternary complex
What is the spectrum of bacteria Linezolid can act against?
VRSA, VRE, and drug resistant pneumococci
S/E Linezolid use?
bone marrow suppression (platelets), MAO-A and B inhibitor
MOA Quinupristin-Dalfopristin.
Binding to sides one 50S ribosomal subunit they prentent integration of amino-acyl-tRNA with acceptor site and stimulate its dissociation from the ternary complex
What is the spectrum of bugs quinupristin can act against?
vancomycin resistant staphylococci (VRSA) and other drugs resistant gram + cocci
What are the streptogramins?
drugs ending in pristin
Which enterococci can linezolid treat in comparison to streptogramins?
Streptogramins for E. faecium, including VRE faecium, but not for E. faecalis
Linezolid for both
