Antibiotics Flashcards
Mupirocin: Class? Action? Bacteriostatic/cidal? Species range? Applications?
Translation inhibitor
Binds isoleucyl-tRNA synthetase, so no charged ile-tRNA available
Bacteriostatic at low concentrations, cidal at higher (with topical administration)
Used in surgeons to prevent transmission of MRSA from nasal cavity
Ciprofloxacin: Class? Action? Bacteriostatic/cidal? Species range? Applications?
Fluoroquinolone (DNA replication inhibitor)
Inhibits DNA gyrase and thus DNA synthesis
Bacteriocidal
Broad spectrum: Gm- enterics, G+ cocci, Pseudomonas
Resistance emerging
Not for kids or pregnant women
Moxifloxacin: Class? Action? Bacteriostatic/cidal? Species range? Applications?
Fluoroquinolone (DNA replication inhibitor)
Inhibits DNA gyrase AND topoisomerase activity (less susceptible to resistance)
Bacteriocidal
Broad spectrum: Gm- enterics, G+ cocci, Pseudomonas, MRSA
Not for kids or pregnant women
Metronidazole: Class? Action? Bacteriostatic/cidal? Species range? Applications?
Nitroimidazole (DNA replication inhibitor)
Activated form (in anaerobic conditions) binds DNA and fragments it
Bacteriocidal
Useful against anaerobic bacterial, protozoa
Rifampin: Class? Action? Bacteriostatic/cidal? Species range? Applications?
RNA synthesis inhibitor
Binds beta subunit of RNA pol, inhibiting transcription
Bacteriocidal
Broad spectrum
Effective prophylactic against N. menigitidis b/c secreted in saliva
Resistance develops rapidly, used in combo
Example of antagonistic combined antibiotic action
Penicillin (requires growth) given with bacteriostatic agent (tetracycline)
Ethambutol and pyrazinamide: Class? Action? Bacteriostatic/cidal? Species range? Applications?
Anti TB drugs Unknown mechanism of action E- static, P- cidal once activated Narrow spectrum (TB)
Example of synergistic combined antibiotic action
Agent which damages cell wall/membrane with cidal agent taken up poorly by bacterium
Indications for combined use of antibiotics (5)
Synergistic activity expected Pathogen requires more than one agent Likelihood of resistance reduced Dosage of toxic drug can be reduced Polymicrobial infection requires use of more than one agent
Disadvantages of combined antibiotics (4)
Increased risk of side effects
Increased risk of superinfections
Possible antagonism
Increased cost
4 general reasons for antibiotic inactivity
- Enzyme inactivation: antibiotic is inactivated (extracellular, intracellular, both)
- Altered membrane permeability/antibiotic efflux: antibiotic can’t enter cell or is actively pumped out
- Alteration of ribosomal/cell wall precursor/enzyme targets: bacterial cell contains altered enzyme that resists action of antibiotic
- Bypass pathways: antibiotic enters cell but drug-binding target site is replaced
Mechanisms of resistance to trimethoprim
Plasmid-coded, trimethoprim-resistant dihydrofolate reductase
Mechanisms of resistance to penicillins (3)
Hydrolysis of beta-lactam ring by beta-lactamase
Decreased cephalosporins permeability of bacteria
Altered penicillin binding proteins
Mechanisms of resistance to methicillin
Altered penicillin binding proteins
Beta-lactamase resistant
Mechanisms of resistance to aminoglycosides (3)
Enzymatic modification of drug by plasmid-coded enzyme
Decreased permeability to antibiotic
Altered antibiotic binding site
Mechanisms of resistance to tetracyclines
Interference with transport of drug into cell
Mechanisms of resistance to chloramphenicol
Detoxification of drug by acetylation of hydroxyl
Mechanisms of resistance to erythromycin
Enzymatic methylation of 23S ribosomal RNA
Mechanisms of resistance to ciprofloxacin/rifampin
Altered target enzymes (gyrase, RNAP)
Mechanisms of resistance to vancomycin
Alteration of cell wall precursor target
Characteristics of an ideal antibiotic (4)
Target one or more bacterial species with no toxicity or allergy
Persist long enough to destroy target
Not lose effectiveness due to bacterial resistance
Achieve effective concentrations in sites of infection
Define bacteriostatic
Stops growth of bacteria for a time
Define bacteriocidal
Kills bacteria
What is the Kiby-Bauer disc diffusion method? How does it work?
Allows you to test the sensitivity of multiple antibiotics against a given strain
Plate purified bacteria on agar plate
-> Add filter paper discs with antibiotic onto the surface
-> Measure circular zones of inhibition of bacterial growth around each disc
(inhibition = sensitivity, growth = insensitivity)
How can you test for beta-lactamase production?
Plate bacteria on nitrocefin, which is chromogenic and has a beta-lactam ring sensitive to hydrolysis
What is the MIC? How can you test for it?
MIC = minimum inhibitory concentration
Inoculate tubes with same amount of bacteria
Add serial dilution of antibiotic
MIC= lowest amount of antibiotic needed to inhibit growth
What is MBC? How can you test for it?
MBC = minimum bacteriocidal concentration
Perform MIC test, then plate bacteria in absence of antbiotic to see if they grow or if they were killed by antibiotic
Define antimetabolite.
Interferes with the synthesis or function of a substance involved in normal cell metabolism
Often structurally similar to the natural substance
Sulfonilamide: Class? Action? Bacteriostatic/cidal? Species range? Application?
Sulfonamide (antimetabolite) Inhibits synthesis of folic acid -> lack of DNA synthesis Bacteriostatic Broad range of species Used for UTIs (concentrated in urine)
Trimethoprim: Class? Action? Bacteriostatic/cidal? Application?
Antimetabolite
Inhibits later step in folic acid metabolism (dihydrofolate reductase = present in humans, but much higher affinity for bacterial enzyme)
Bacteriostatic
Used for UTIs
Bactrim: Class? Action? Bacteriostatic/cidal? Application?
Antimetabolite
Combination of sulfamethoxazole and trimethoprim for a synergistic effect
Bacteriostatic
Used for UTIs
Isoniazid: Class? Action? Bacteriostatic/cidal? Species range?
Antimetabolite
Inhibits synthesis of mycolic acid, found in the cell walls of mycobacteria
Bacteriocidal
Narrow - specific to M tuberculosis
Efficient cellular penetration (intracellular)
Penicillins: why the large difference in sensitivity between bacterial and animal cells?
Bacteriostatic or bacteriocidal?
What conditions are required?
Difference in sensitivity because there is no cell wall in animal cells
Bacteriocidal
Growth is essential for action - inhibit peptidoglycan synthesis
Basic structure of penicillins. What are they sensitive to? (2 things)
Have beta-lactam and thiazolidine rings
Sensitive to hydrolysis by stomach acids and beta-lactamases
Mechanism of action of penicillins
Beta-lactam = structural analog of peptidoglycan pentapeptide - bind to and inactive penicillin-binding proteins (PBPs): transpeptidases that are responsible for cross-linking (the final step in cell wall assembly)
Penicillin G: Class? Action? Bacteriostatic/cidal? Species range? Application? Sensitivity?
Penicillin (cell wall synthesis inhibitor) Inhibits penicillin-binding proteins Bacteriocidal Ineffective against Gm- enterics Acid-labile - cannot be taken orally Sensitive to beta-lactamases
Penicillin V: Class? Action? Bacteriostatic/cidal? Species range? Application? Sensitivity?
Penicillin (cell wall synthesis inhibitor) Inhibits penicillin-binding proteins Bacteriocidal Ineffective against Gm- enterics Resist acid hydrolysis - can take orally Sensitive to beta-lactamases
Ampicillin/amoxicillin: Class? Action? Bacteriostatic/cidal? Species range? Application? Sensitivity?
Penicillin (cell wall synthesis inhibitor)
Inhibits penicillin-binding proteins
Bacteriocidal
Broader spectrum: effective against Gm- enterics
Resist acid hydrolysis - can take orally
Sensitive to beta-lactamases
Amoxicillin = higher serum levels
Tricarcillin: Class? Action? Bacteriostatic/cidal? Species range? Application? Sensitivity?
Penicillin (cell wall synthesis inhibitor)
Inhibits penicillin-binding proteins
Bacteriocidal
Extended spectrum - effective against Gm- enterics and Pseudomonas aeruginosa
Sensitive to beta-lactamases
Piperacillin: Class? Action? Bacteriostatic/cidal? Species range? Application? Sensitivity?
Penicillin (cell wall synthesis inhibitor)
Inhibits penicillin-binding proteins
Bacteriocidal
Extended spectrum - the most active penicillin against Gm- enterics and Pseudomonas aeruginosa
Sensitive to beta-lactamases
Methicillin: Class? Action? Bacteriostatic/cidal? Species range? Application? Sensitivity?
Penicillin (cell wall synthesis inhibitor)
Inhibits penicillin-binding proteins
Bacteriocidal
Narrow spectrum - antistaphylococcal! for resistant staph
Resistant to beta-lactamases
Acid-labile - cannot be taken orally
Oxacillin: Class? Action? Bacteriostatic/cidal? Species range? Application? Sensitivity?
Penicillin (cell wall synthesis inhibitor)
Inhibits penicillin-binding proteins
Bacteriocidal
Narrow spectrum - antistaphylococcal! for resistant staph
Resistant to beta-lactamases
Resist acid hydrolysis - can take orally
Cefazolin: Class? Action? Bacteriostatic/cidal? Species range?
Cephalosporin (beta-lactam antibiotic, cell wall synthesis inhibitor)
Inhibits penicillin-binding proteins
Bacteriocidal
Most active versus Gm+ cocci and some Gm- enterics
Cefuroxime: Class? Action? Bacteriostatic/cidal? Species range?
Cephalosporin (beta-lactam antibiotic, cell wall synthesis inhibitor)
Inhibits penicillin-binding proteins
Bacteriocidal
Most active versus Gm- enterics, less effective against Gm+
Ceftriaxone/ceftazidime: Class? Action? Bacteriostatic/cidal? Species range? Sensitivity?
Cephalosporin (beta-lactam antibiotic, cell wall synthesis inhibitor)
Inhibits penicillin-binding proteins
Bacteriocidal
Very broad spectrum, active against P. aeruginosa
Increased beta-lactamase resistance
Differences between cephalosporins and penicillins (5, 2 similarities)
Both have beta-lactam rings
Both bacteriocidal
Cephalosporins:
Have dihydrothiazine vs thiazolidine ring
Generally broader spectrum
Greater acid stability
Resist some beta-lactamases
Good for penicillin allergies (antigenically dissimilar)
Aztreonam: Class? Action? Bacteriostatic/cidal? Species range? Sensitivity?
Monobactam (cell wall synthesis inhibitor)
Inhibits penicillin-binding proteins
Bacteriocidal
Specific to Gm- aerobes including P. aeruginosa
Resistant to beta-lactamases
Minimal cross-immunogenicity with other beta-lactams
Imipenem: Class? Action? Bacteriostatic/cidal? Species range? Sensitivity?
Carbapenem (cell wall synthesis inhibitor) Inhibits penicillin-binding proteins Bacteriocidal Broadest spectrum Resistant to beta-lactamases Susceptible to renal dispeptidase
What s a beta-lactamase inhibitor? Name two.
Beta-lactams which have minimal activity as antibiotics but extend the use of beta-lactam antibiotics
Clavulanic acid (used with amoxicillin -> augmentin) Sulbactam
Vancomycin: Class? Action? Bacteriostatic/cidal? Species range? Applications?
Glycopeptide cell wall synthesis inhibitor
Binds R-D-Ala-D-Ala - blocks peptidoglycan precursor transfer
Bacteriocidal
Restricted to Gm+
Toxic - used for MRSA and multiply resistant enterococcus
VRSA now identified
Cycloserine: Class? Action? Bacteriostatic/cidal? Species range?
Cell wall synthesis inhibitor
Inhibits D-alanine steps
Bacteriocidal
Secondary tuberculosis drug
Bacitracin: Class? Action? Bacteriostatic/cidal? Species range? Applications?
Cell wall synthesis inhibitor Inhibits lipid carrier step Bacteriocidal Restricted to Gm+ Toxic - used for topical therapy
Polymyxin B: Class? Action? Bacteriostatic/cidal? Species range? Applications?
Cell membrane permeabilizer
Bind LPS, then membrane phospholipids, leading to membrane leakage
Bacteriocidal (does NOT require growth)
Selective for Gm- enteric rods, esp. Pseudomonas
Toxic, so topical only
Streptomycin: Class? Action? Bacteriostatic/cidal? Species range? Applications?
Aminoglycoside (translation inhibitor)
Binds 30S subunit, distorts acceptor site -> misreading -> bad proteins -> leaky membranes
Bacteriocidal due to membrane effects
Inhibited by anaerobic or acidic conditions
Not good for urine
Toxic!
Gentamicin: Class? Action? Bacteriostatic/cidal? Species range? Applications?
Aminoglycoside (translation inhibitor)
Binds multiple sites on the 30S subunit (less resistance) -> leaky membranes
Bacteriocidal due to membrane effects
Inhibited by anaerobic or acidic conditions
Toxic!
Tetracycline/doxycycline/minocycline: Class? Action? Bacteriostatic/cidal? Species range? Applications?
Tetracyclines (translation inhibitors) Block binding of aminoacyl tRNA to 30S Bacteriostatic Broad spectrum, also useful for intracellular parasites Not used for pregnancy or young children Wipe out normal flora
Erythromycin: Class? Action? Bacteriostatic/cidal? Species range? Applications?
Macrolide (translation inhibitor) Blocks chain elongation Bacteriostatic Broad spectrum, includes mycoplasma and chlamydia Widely used
Azithromycin: Class? Action? Bacteriostatic/cidal? Species range? Applications?
Macrolide (translation inhibitor) Blocks chain elongation, but higher tissue concentrations than erythromycin Bacteriostatic Slightly larger range than erythromycin Widely used
Chloramphenicol: Class? Action? Bacteriostatic/cidal? Species range? Applications?
Translation inhibitor
Blocks chain elongation
Bacteriostatic, can be cidal
Used for anaerobes, particularly enterics
Not widely used because of toxicity (lethal aplastic anemia)
Clindamycin: Class? Action? Bacteriostatic/cidal? Species range? Applications?
Translation inhibitor
Inhibits peptidyl transfer
Bacteriostatic
Active against Gm+, especially active against anaerobes
Dalfopristin/quinupristin [Synergin] Class? Action? Bacteriostatic/cidal? Species range? Applications?
Streptogramins (translation inhibitors)
Bind to 50S subunit
Bacteriostatic
Useful against resistant bacteria, especially because of synergistic combination
Linezolid (Zyvox): Class? Action? Bacteriostatic/cidal? Species range? Applications?
Oxazolidinone (translation inhibitor)
Interacts with 16S and 23S rRNA, inhibit tRNA translocation
Bacteriostatic
Useful against resistant bacteria
