Ch 3: Antimicrobial Agents Flashcards
What is differential toxicity?
Drugs are more toxic to infecting organism than to the host
What are some traits of the ideal antimicrobial?
- *appropriate spectrum of activity for the clinical setting
- *no toxicity to host, be well tolerated
- wont develop resistance
- wont induce hypersensitivities
- long half life
- rapid and extensive tissue distribution
- easy to administer
- inexpensive
Who developed the idea of selective toxicity?
Paul Ehrich
Who discovered that Penicillium notatum, a common mold, had destroyed staphylococcus bacteria in culture, discovering penicillin?
Sir Alexander Fleming
What is minimum inhibitory concentration (MIC)?
Minimum concentration of antibiotics required to inhibit the growth of test organism
What is minimum bactericidal concentration (MBC)?
Minimum concentration of antibiotic required to kill the test organism
What is the difference between treatment and prophylaxis?
Prophylaxis is when antimicrobials are used (usually in life threatening infections) to prevent infection, while treatment are used to cure existing infections
Which one is NOT a beta lactam?
A) penicillin
B) monobactams
C) carbapenems
D) teicoplanin
D) teicoplanin
ToF: Penicillins are strong inhibitors of Gram negative organisms
F: act on bacterial cell walls especially in Gram positive organisms
ToF: Penicillins are toxic to animal cells
F: not toxic, only work on organisms with a cell wall
Beta lactams are produced by:
A) fungi
B) ascomycetes
C) actinomycetes
D) all of the above
D) all of the above
What is the mode of action of penicillins?
beta lactam ring binds to penicillin binding protein (PBP) and PBP is unable to cross link peptidoglycan chains. Consequently, bacteria is unable to synthesize a stable cell wall, bacteria is lysed
Which of these would be effective against Staphylococcus?
A) Penicillin G
B) Synthetic penicillins
C) Cloxacillin
D) Piperacillin
C) Cloxacillin
Which of the following would be effective against Pseudomonas?
A) Piperacillin
B) Penicillin V
C) Methicillin
D) Cloxacillin
A) Piperacillin
ToF: Pencillin G/V is effective against gram negative bacteria.
F: not effective against gram negatives or anaerobic bacteria
What compounds are prescribed along beta lactamic antibiotics?
Clavulanic acid, sulbactam, or tazobactam. These are beta lactamase inhibitors
What is the mode of action of Cephalosporins
Inhibit PBP (penicillin binding protein) and therefore cannot make cross links, unstable cell wall and cell lyses
How are Cephalosporins different to penicillin?
They have wider antibacterial spectrum, resistant to many beta-lactameses and have longer half lives
What generation of Cephalosporins is Ceftriaxone?
3rd: excellent gram negative, some gram positive
What is the name and generation of the Cephalosporins with excellent effectiveness with gram negative, and good gram positive bacteria?
4th generation, Cefepime
Which generation of Cephalosporins does Cefazolin belong to?
1st (mainly gram positive, some gram negative)
Which generation of Cephalosporins does Cefuroxime belong to?
2nd (weaker gram positive, better gram negative)
ToF: Monobactams have a broad spectrum of activity
F: narrow spectrum
Which beta-lactam has the most broad spectrum of activity of all antimicrobials?
Carbapenems
Which of these microbes is resistant to Carbapenems?
A) Enterococcus faceium
B) Stenotrophomonas maltophilia
C) Burkholderia cepacia
D) All of the above
D) all of the above
Which microbes are resistant to Carbapenems?
- Methicillin resistant S. aureus
- Methicillin resistant S. epidermis
- E. faecium
- S. maltophilia
- B. cepacia
What is the mode of action of glycopeptides?
Inhibit bacterial cell wall synthesis by binding to the D-alanine-D-alanine termini of the chain
Interfere with the formation of bridges between the peptidoglycan chains
Which of the following is a Glycopeptide?
A) Vancomycin
B) Penicillin
C) Monobactam
D) Erythromycin
A) Vancomycin
ToF: Glycopeptides can affect ONLY gram positive bacteria
T: they cannot cross the outer membrane of Gram negatives
ToF: Vancomycin is used as a ‘last resort’ drug in medicine
T: due to serious side effects
Glycopeptides are bactericidal, except for ______
Enterococcus
What is the mode of action of Macrolides?
Inhibit translocation by binding to 50S ribosomal subunit
=Bacteriostatic
What are examples of Macrolides?
Erythromycin, Clarithromycin, Azithromycin
Spectrum of activity of Macrolides
gram positive bacteria, Mycoplasma, Legionella
What is Chloramphenicol and Lincosamides mode of action?
Bind to the 50S ribosome and inhibit peptidyl transferase activity
ToF:Chloramphenicol has a broad range spectrum of activity
T
ToF: Lincomycin and Clindamycin have a broad range spectrum of activity
F: moderate spectrum, primarily active against gram positive bacteria, most anaerobic bacteria and some mycoplasma
ToF: Lincomycin and Clindamycin are effective against gram positive bacteria
T
When is Chloramphenicol used? What are the adverse effects?
Used for treatment of meningitis (life threatening)
It is toxic, causes rare anemia, and liver enzyme inhibition
Which of the following is an Aminoglycoside?
A) Tobramycin
B) Lincomycin
C) Erythromycin
D) Clarithromycin
A) Tobramycin
What are examples of Aminoglycosides?
Gentamicin, Tobramycin, Amikacin
What is the mode of action of Aminoglycosides?
Bind to the 30S subunit of ribosomes and inhibit transpeptidation and translocation processes resulting in premature detachment of incomplete polypeptides chains (bactericidal)
What is the spectrum of action of Aminoglycosides?
Excellent gram negative, moderate gram positive
What are examples of tetracylines?
Minocycline and Doxycycline
What is the mode of action of Tetracyclines?
Reversibly bind to 30S ribosome and inhibit binding of aminoacyl-t-RNA to the acceptor site on the 70S ribosome
ToF: Tetracyclines have a broad spectrum of activity
T: useful against intracellular bacteria
ToF: Tetracyclines have a broad spectrum of activity
T: useful against intracellular bacteria
What are the adverse effects of Tetracyclines?
- Destruction of the normal intestinal flora resulting in increased secondary infections
- Staining and impairment of the structure of bone and teeth
What is the mode of action and spectrum of activity of Streptogramins?
Irreversibly bind to the 50S ribosomal subunit
Narrow spectrum
_____ is an example of a Streptogramin
Virginiamycin (banned in the EU)
What is the mode of action of Oxazolididones?
Protein synthesis inhibitor on the ribosomal 50S subunit of the bacteria; blocks initiation
ToF: Linezolid is an Oxazolididone
T: useful for methicillin-resistant S. aureus, Vancomycin-resistant enterococci, and penicillin-resistant S. pneumoniae
ToF: Fluoroquinolones function by inhibiting nucleic acid synthesis
T: mode of action = bind to two essential enzymes required for DNA replication (DNA gyrase and topoisomerase IV)
Name examples of Fluoroquinolones
Nalidixic acid, ciprofloxacin, ofloxacin, levofloaxcin, sparfloxacin, norfloxacin, moxifloxacin
What is the spectrum of activity of Fluoroquinolones?
Gram positive cocci and urinary tract infections
What is the spectrum of activity for Ansamycins?
Treatment of tuberculosis and meningitis prophylaxis
ToF: Ansamycins do not have any serious adverse effects
F: the most serious adverse effect is hepatotoxicity
Name an example of an Ansamycin
Rifampin/Rifampicin
What is the mode of action of Ansamycins?
Enters neutrophils and macrophages and inhibits DNA-dependent RNA polymerases
ToF: Metronidazol works by inhibiting the production of the cell wall
F: works through inhibition of nucleic acid synthesis; reduce a nitro group in the molecule producing cytotoxic compounds which interfered with bacterial DNA
What type of treatment is Metronidazol used for?
Effective against anaerobic bacterial infections (periodontal infections)
What type of treatment is Metronidazol used for?
Effective against anaerobic bacterial infections (periodontal infections)
ToF: Metronidazol is active against aerobic or facultative bacteria
F: only anaerobic bacteria
What is the mode of action for Sulfonamides and Trimethoprim?
Sulfoamides competitively inhibit formation of dihydropteroic acid.
Trimetoprim binds to dihydrofolate reductive and inhibits formation of tetrahydrofolic acid
(Folic acid synthesis inhibition)
Which enzymes are blocked by Sulfonamides and Trimethoprim
Dihydrofolate synthetase is blocked by Sulfoamides
Dihydrofolate reductase is blocked by Trimethoprim
These enzymes are needed for folic acid synthesis
What is the spectrum of activity of Sulfonamides and Trimethoprim?
Broad range against both gram positive and negative; primarily urinary tract and Nocardia
ToF: Sulfonamides are used in combination with trimethoprim to block two steps in folic acid metabolism
T: prevents the emergence of resistant strains
ToF: Lipopeptides disrupt multiple aspects of bacterial cell membrane function
T
Which of the following is an example of a Lipopeptide?
A) Erythromycin
B) Daptomycin
C) Trimethoprim
D) Rifampin
B) Daptomycin
What is the range of spectrum of Lipopeptides?
Gram positive organisms
What is the mode of action of Polymyxins?
Binds to the lipid A portion of lipopolysaccharides and also to phospholipids, disrupting the outer membrane of gram negative
ToF: The spectrum of action of Polymyxins is gram negative
T: cell membrane is not exposed in gram positive
What is the main goal of combination therapy?
To prevent the emergence of resistance
(Also: to treat poly microbial infections)
Why do we not use combination therapy all the time?
Antagonism, cost, increased risk of side effects, may enhance resistance, drugs interaction of different classes and often is unnecessary
What influences the choice of antibiotics?
- activity of agent against proven or suspected organism
- site of infection
- mode of administration
- metabolism and excretion
- duration of treatment, frequency of dose
- toxicity/ cost
- local rates of resistance
