Antibiotics Flashcards
What aspects of bacterial machinery can be inhibited by abx?
Cell wall synthesis Protein synthesis DNA/RNA synthesis Folate synthesis Membrane integrity
Cell wall synthesis inhibitors
Beta-lactams (penicillin, cephalosporin, carbapenems, monobactams)
Glycopeptides and lipoglycopeptides
How do glycopeptides and lipoglycopeptides differ mechanistically from the beta lactams?
Beta lactams bind to and inhibit transpeptidase while glycopeptides and lipoglycopeptides bind to cell wall precursors and prevent cross linking/extension
Which abx relies on renal dipeptidase inhibitor celastatin?
Imipenem
What differentiates second generation cephalosporins from cephamycins?
The bacterial spectrum
Cephamycins are active against B.fragilis and some Serratia spp. and the purely second generation cephalosporins (cefaclor, cefprozil, and cefuroxime) are not
What is the general spectrum of coverage for the monobactam aztreonam
Gram-negative aerobes
What are the protein synthesis inhibitors that bind the 50s ribosomal subunit?
Oxazolidinones
Macrolides and ketolides
Streptogramins
What are the protein synthesis inhibitors that bind the 30s ribosomal subunit?
Tetracyclines
Aminoglycosides
Glycylcyclines
What is the difference in MOA between oxazolidinones and streptogramins?
Oxazolidinones bind to P site on ribosome and prevent initiation of protein synth
Streptogramins have 2 headed mechanism as they are given in combined ratio — quinupristin inhibits polypeptide elongation and induces early termination of protein synth; dalfopristin impedes polypeptide chain formation and induces conformational change in 50S ribosomal subunit that enhances quinupristin binding
Why are macrolides grouped with the ketolides? What distinguishes a macrolide from a ketolide?
Grouped together bc similar MOAs, chemical structure, and adverse effects
Their bacterial coverage differs; ketolides can be active in macrolide resistant strains
What antibiotic acts as a DNA/RNA synthesis inhibitor?
Fluoroquinolones
What proteins do fluoroquinolones inhibit?
Topoisomerase II (DNA gyrase) and topoisomerase IV
What are some side effects of fluoroquinolones?
Abdominal discomfort, nausea, vomiting, C.diff induced colitis, HA, dizziness
Achilles tendon rupture
QT prolongation (moxifloxacin)
What are the 2 folate synthesis inhibitors?
Sulfonamides
Benzylpyrimidines
What is the antibiotic that works as a membrane integrity inhibitor?
Polymyxins
Why are sulfonamides and benzylpyrimidines synergistic?
Trimethoprim and sulfamethoxazole inhibit subsequent steps in THF biosynthetic pathway
Are polymyxins active against gram positive bacteria? Why?
No, because they do not have an outer membrane
Major mechanisms of antibiotic synergism
Blockade of sequential steps in metabolic sequence (TMP/SMX)
Inhibition of enzymatic inactivation (beta-lactamase inhibitors)
Enhancement of antimicrobial agent uptake (penicillins and vancomycin can increase uptake of aminoglycosides)
Major mechanisms of antibiotic antagonism
Inhibition of cidal activity by static agents (tetracyclines and penicillins)
Induction of enzymatic inactivation (P.aeruginosa and some other bacteria possess inducible beta-lactamases; some beta lactam abx are potent inducers of beta-lactamase production — imipenem, cefoxitin, ampicillin)
Which of the following is a mechanism underlying the resistance of strains of S.pneumoniae to fluoroquinolones?
A. Reduced topoisomerase sensitivity to inhibitors
B. Increased synthesis of PABA
C. Formation of methyltransferases that change receptor structure
D. Structural changes in porins
E. Formation of drug-inactivating hydrolases
A. Reduced topoisomerase sensitivity to inhibitors
What is the most likely mechanism of resistance for MRSA to methicillin?
A. Methylation of the binding site
B. Active efflux of drug from bacteria
C. Beta-lactamase production
D. Phosphorylation of the drug by bacterial enzymes
E. Structural modifications of transpeptidase
E. Structural modifications of transpeptidase
37 y/o female presents to clinic with low grade fever and sore throat. PE reveals tonsillar exudate and gram stain reveals high number of bacteria. A dx is made and penicillin G is prescribed because the identified tonsillar exudate has been shown to be sensitive to penicillin G.
Which of the following bacteria is most likely to be causing this patient’s infection?
A. Klebsiella pneumoniae B. Clostridium difficile C. Staphylococcus aureus D. Streptococcus pyogenes E. Pseudomonas aeruginosa
D. Streptococcus pyogenes
67 y/o woman presents to ED with nausea, vomiting, fever, and altered consciousness. Her vitals are BP 90/50 mm Hg, pulse 115 bpm, respirations 20/min and temp 103.6 F. PE reveals pt in distress with nuchal rigidity. Empirical IV therapy is initiated with ampicillin, ceftriaxone, and vancomycin.
Which of the following best explains the common mechanism of action that all 3 of these drugs possess?
A. Inhibition of THF synthesis B. Misreading of mRNA template code C. Inhibition of peptidoglycan synthesis D. Blockade of peptidyl-transfer RNA translocation E. Enhancement of DNA gyrase activity
C. Inhibition of peptidoglycan synthesis
A 5 y/o boy presents with ear pain despite being tx with amoxicillin. Your pediatrician partner suggests changing the pt’s prescription to amoxicillin + potassium clavulanate.
Which of the following best explains the advantage of this proposed drug combo over amoxicillin monotherapy?
A. Extended antibacterial spectrum against P.aeruginosa
B. Inhibition of bacterial inactivation of amoxicillin
C. Inhibition of renal excretion of amoxicillin
D. Increased influx of amoxicillin into bacteria
E. Decreased amoxicillin hypersensitivity
B. Inhibition of bacterial inactivation of amoxicillin
Female presents with leg pain and blood cultures reveal MRSA. Treatment is initiated with antibiotic that binds to P site on 50S ribosomal subunit and prevents the formation of ribosomal n-formylmethionine tRNA complex.
Which of the following drugs was most likely given?
A. Linezolid B. Tigecycline C. Gentamicin D. Imipenem E. Tetracycline
A. Linezolid
70 y/o male presents with c/o HA, nausea, vomiting, vertigo, tinnitus, and progressive hearing loss. Medical hx reveals that pt had been receiving an antibiotic for 2 weeks to treat a UTI d/t serratia marcescens.
The drug used was most likely a member of which of the following abx classes?
A. Cephalosporins B. Polymyxins C. Tetracyclines D. Aminoglycosides E. Glycopeptides
D. Aminoglycosides
A 42 y/o female presents with c/o dysuria. Medical hx reveals recurrent UTIs and congenital long QT syndrome. Analysis of clean-catch midstream urine sample shows many gram-negative rods.
Which of the following abx would be contraindicated in this pt?
A. Moxifloxacin B. Aztreonam C. TMP/SMX D. Ceftriaxone E. Meropenem
A. Moxifloxacin
Which drug class does the following list belong to:
Penicillin G
Penicillin
Which drug class does the following list belong to:
Ampicillin
Amoxicillin
Aminopenicillins
Which drug class does the following list belong to:
Methicillin
Nafcillin
Oxacillin
Dicloxacillin
Penicillinase-resistant penicillins
Which drug class does the following list belong to:
Ticarcillin
Carbenicillin
Piperacillin
Mezlocillin
Anti-pseudomonal penicillins
Which drug class does the following list belong to:
Cefazolin
Cephalexin
First generation cephalosporins
Which drug class does the following list belong to:
Cefuroxime
Cefaclor
Cefprozil
Second generation cephalosporins
Which drug class does the following list belong to:
Cefotetan
Cefoxitin
Cephamycins
Which drug class does the following list belong to:
Cefotaxime Cefixime Cefdinir Ceftibuten Ceftazidime Ceftriaxone Cefpodoxime proxetil Cefditoren pivoxil
Third generation cephalosporins
Which drug class does the following list belong to:
Cefepime
Fourth generation cephalosporin
Which drug class does the following list belong to:
Ceftaroline fasamil
Ceftolozane
Fifth generation cephalosporins
Which drug class does the following list belong to:
Imipenem
Meropenem
Doripenem
Ertapenem
Carbapenems
Which drug class does the following list belong to:
Aztreonam
Monobactam
Which drug class does the following list belong to:
Vancomycin
Glycopeptides
Which drug class does the following list belong to:
Telavancin
Dalbavancin
Oritavancin
Lipoglycopeptides
Which drug class does the following list belong to:
Clavulanic acid
Sulbactam
Tazobactam
Beta-lactamase inhibitors
Which drug class does the following list belong to:
Linozolid
Tedizolid
Oxazolidinones
Which drug class does the following list belong to:
Erythromycin
Clarithromycin
Azithromycin
Fidaxomicin
Macrolides
Which drug class does the following list belong to:
Telithromycin
Ketolides
Which drug class does the following list belong to:
Quinupristin
Dalfopristin
Streptogramins
Which drug class does the following list belong to:
Doxycycline
Tetracycline
Minocycline
Demeclocycline
Tetracyclines
Which drug class does the following list belong to:
Tigecycline
Glycylcylines
Which drug class does the following list belong to:
Streptomycin Gentamycin Tobramycin Amikacin Neomycin Paromomycin Kanamycin Netilmicin
Aminoglycosides
Which drug class does the following list belong to:
Moxifloxacin Ciprofloxacin Enoxacin Ofloxacin Pefloxacin Gatifloxacin Gemifloxacin Levofloxacin
Fluoroquinolones
Which drug class does the following list belong to:
Sulfamethoxazole
Sulfonamides
Which drug class does the following list belong to:
Trimethoprim
Benzylpyrimidines
Which drug class does the following list belong to:
Polymyxin B
Colistin
Polymyxins
MOA of penicillins
Inhibit growth of bacteria by interfering with transpeptidation reaction - thus inhibiting bacterial cell wall synthesis
___ = gateway for penicillin to access cell wall in gram- bacteria
Porins
Penicillin G fights what bacteria?
Gram+ cocci = S.pneumo, S.pyogenes, S.viridans
Certain gram-negative cocci = N.meningiditis
Spirochetes like T.pallidum
C.perfringens
Adverse effects of penicillin G
Anaphylaxis (d/t HSR to beta lactam ring)
Nausea, vomiting, diarrhea
Bacteria killed by aminopenicillins
E.coli
Proteus
Salmonella
Shigella
With beta lactamase inhibitors, can fight H.influenzae, E.coli, Klebsiella spp., proteus spp., and B.fragilis
What bacteria are penicillinase resistant penicillins effective against
S.aureus
S.epidermidis
Major mechanism of abx resistance to anti-pseudomonal penicillins
Beta-lactamase production
What bacteria are anti-pseudomonal penicillins effective against?
P.aeruginosa Klebsiella pneumoniae E.coli H.influenzae B.fragilis
T/F: cephalosporins have an almost identical MOA to penicillins
True
Mechanisms of bacterial resistance to cephalosporins
Beta-lactamase production
Altering porins
Altering transpeptidase
Upregulation of efflux pumps
First gen cephalosporins generally have better coverage against gram ____ organisms, while third generation have better coverage against gram ____ organisms
Positive; negative
[note that second gen fall somewhere in the middle with 50/50 +/- coverage]
Most common side effect to cephalosporin use
HSR to beta lactam ring = maculopapular rash several days after therapy; sometimes accompanied by eosinophilia and fever
Only 3rd gen cephalosporin effective against p.aeruginosa
Ceftazidime
______ is an abx that may displace bilirubin d/t its high affinity for serum albumin. This can potentially lead to jaundice in neonates, thus, ____ is the preferred agent
Ceftriaxone; cefotaxime
Due to its high affinity for Ca, ceftriaxone can lead to ____
Biliary pseudolithiasis (gallstones)
Which generation cephalosporin fights p.aeruginosa as well as provides excellent coverage against enterobacter spp, but has POOR activity against B.fragilis?
Fourth gen cephalosporin (cefepime)
Which 5th gen cephalosporin is active against MRSA since it has increased binding to transpeptidase?
Ceftaroline
[this drug also effective against pseudomonas spp. - hard to tx! — note this one has gram+ coverage]
T/F: all carbapenems require combination with a renal dipeptidase inhibitor: celastatin
False; only imipenem requires this
MOA of carbapenems
Inhibition of transpeptidase - inhibiting cell wall synth (same as cephalosporins and penicillin)
T/F: like penicillin and cephalosporins, carbapenems have the issue of abx-resistance d/t degradation by beta-lactamases
False
Mechanisms of abx resistance to carbapenems
Porin alteration
Upregulation of enzymes toxic to carbapenems
Carbapenems as a class are good agents for targeting gram ___ bacteria
Negative
Adverse rxns to carbapenems
Reactions at infusion site Skin rash Diarrhea Vomiting Nausea Renal failure Seizures
MOA of monobactams
Binds and inhibits gram-negative specific sub-type of transpeptidase —> cell wall loses its rigidity
T/F: aztreonam has no activity against gram positives or anaerobes
True
T/F: penicillin allergic pts are able to tolerate aztreonam
True
Aztreonam should not be given to pts allergic to what drug?
Ceftazidime
Adverse effects of aztreonam
Hepatotoxicity
Skin rash
MOA of glycopeptides
Bind D-alanyl-D-alanine terminus of cell wall precursor units with very high affinity —> prevents peptidoglycan synth
Primary glycopeptide resistant strain of enterococci
E.faecium
How must vancomycin be administered?
IV
Vancomycin is effective against what?
Many gram+ bacteria
[Almost all gram negative bacilli and mycobacteria are RESISTANT to vancomycin]
Adverse effects of vancomycin
Hypotension
Tachycardia
Flushing (“red man syndrome”)
Nephrotoxicity
MOA of oxazolidinones
Bind P site on 50S ribosomal subunit, preventing initiation of protein synth by preventing formation of n-fMet tRNA complex
Primarily bacteriostatic, but bactericidal against streptococci!
Mechanisms of resistance to Oxazolidinones
Point mutations on 23S rRNA that makes up Oxa. binding site on 50S subunit
Oxazolidinones are acitve against a large majority of what type of bacteria
Gram+
[they have poor coverage of gram-neg]
Adverse effects of oxazolidinones
Myelosuppression, thrombocytopenia, lactic acidosis, optic neuritis, peripheral neuropathy (mitochondrial toxicity), drug-drug interactions (MAOs, SSRIs)
MOA of macrolides and ketolides
Bind reversibly to 50S subunit of bacterial ribosome, preventing translocation of tRNA from A site to P site, thus halting protein synth
They can also elicit conformational change in bacterial ribosome which can result in indirect inhibition of transpeptidation
Lastly, they can inhibit the formation of the 50S subunit
Bacteriostatic!
4 main mechanisms of resistance to macrolides and ketolides
Drug efflux
Production of methylase
Degradation
Mutations in 50S ribosomal subunit
