Antibiotics/Vaccines Flashcards
What is the general mechanism of fluroquinolone antibiotics?
Quinolones inhibit DNA gyrase; they prevent the separation of sister chromatids after DNA replication
What is the general mechanism of beta lactam antibiotics?
Beta lactam antibiotics inhibit bacterial wall synthesis by interfereing with peptidoglycan formation
What is the general mechanism of tetracycline antibiotics?
Inhibit the bacterial ribosome
What is the general mechanism of aminoglycoside antibiotics?
Inhibit protein synthesis by inhibiting the 30s ribosomal subunit
What is the general mechanism of macrolide antibiotics?
Inhibit the bacterial ribosome
What is the general mechanism of oxazolidinone antibiotics?
Inhibit the bacterial ribosome
What is the general mechanism of lincosamide antibiotics?
Inhibit the bacterial ribosome
What is the general mechanism of rifampin antibiotics?
Rifampin antibiotics inhibit RNA polymerase
What is the general mechanism of sulfonamide antibiotics?
Inhibit the folic acid pathway
Which antibiotic is generally used to treat Streptococus pyogenes?
Penicillin;
Most strains are susceptible
A patient is scheduled for throacic surgery. To prevent an incision site infection, the surgeon orders prophylactic antibiotics.
- What microbes are you worried about?
- What antibiotics would be appropriate?
- Gram (+) microbes
- Cephazolin (IV) or cephalexin (oral)
Which organisms are first-generation cephalosporins most effective against?
Gram (+) bacteria
Which organisms are later-generation cephalosporins most effective against?
Later generation cephalosporins provide broader coverage, especially for gram (-) organisms
What kind of antibiotic is amoxicillin-clavulanate?
Beta lactam + Beta lactamase inhibitor
Amoxicillin = beta lactam
Clavulanate = beta lactamase inhibitor
(Any -illin + something else is usually this combo)
What is a toxoid?
A chemically treated toxin that is no longer toxic but retains immunogenicity
Example: Diphtheria toxoid = vaccine that protects against diphtheria
What kind of antibiotic is trimethoprim/sulfamethoxazole?
A sulfonamide
Sulfonamides inhibit the folate synthesis pathway
What kind of antibiotics are -floxacins?
Fluoroquinolones;
They directly inhibit bacterial DNA synthesis
What kind of antibiotics are -mycins or -micins?
Aminoglycosides; inhibit the 30s subunit of the bacterial ribosome to inhibit protein synthesis
What kind of antibiotic is carbapenem?
A beta-lactam; interferes with peptidoglycan synthesis
What are the 4 major beta-lactam antibiotics?
Penicillins, Cephalosporins, Monobactams, Carbapenems
Which beta-lactam antibiotic is active against most gram negative bacteria?
Carbapenems
We want to “save” these; if a bacteria is resistant to carbapenem, we’re kind of screwed
What is empiric antibiotic therapy?
Choosing an antibiotic based on
- Guidelines for recommendations
- Knowledge of the organism that typically causes a certain infection
- Knowledge of the susceptibilities of organisms present in a certain setting
What is directed therapy?
Choosing an antibiotic based on knowledge of what organism is causing an infection and what antibiotics it is susceptible
(such as results from a wound culture)
What is an example of a broad spectrum beta-lactam with both gram-positive and gram-negative coverage?
Piperacillin-tazobactam
What is the mechanism of action of beta-lactams?
Binding and inhibiting PBPs, causing termination of peptidoglycan structure, interfering with synthesis of the cell wall and leading to cell death
What are the mechanisms of bacterial resistance to beta-lactams?
- Beta-lactamases: enzymes that destroy beta-lactam antibiotics (penicillinases: penicillin resistance in Staph aureus)
- Alteration of pencillin binding proteins (PBP2a of MRSA has low affinity for beta-lactams and renders MRSA resistant)
What groups of antibiotics are in the beta-lactam class?
- Penicillins
- Cephalosporins
- Monobactams
- Carbapenems
What is an example of a glycopeptide antibiotic?
Vancomycin
What is the mechanism of action of glycopeptides (vancomycin)?
Inhibiting bacteria cell wall synthesis by binding to D-alanyl-D-alanine terminus and blocking linkage to glycopeptide polymer
What are the mechanisms of bacterial resistance to glycopeptides (vancomycin)?
- Change in peptidoglycan with reduced binding to vancomycin (terminus altered to D-ala-D-lactate or D-ala-D-serine)
- Production of thick cell wall with increased or false targets for vancomycin
What is an example of a lincosamide antibiotic?
Clindamycin
What is the mechanism action of action of lincosamides (clindamycin)?
Inhibits protein synthesis by binding to the 50s subunit of the ribosome and blocking peptide bond formation
What are the mechanisms of bacterial resistance to lincosamides (clindamycin)?
- Methylation of the 50s subunit prevents clindamycin attachment
- Cross resistance with macrolides
What is an example of a folate antagonist antibiotic?
Trimethoprim-sulfamethoxazole
What is the mechanism of action of folate antagonist antibiotics (trimethoprim-sulfamethoxazole)?
Blocks sequential steps in folate metabolism (synergistic combo)
What are the mechanisms of bacterial resistance to folate antagonist antibiotics (trimethoprim-sulfamethoxazole)?
- Increased PABA concentration
- Enzymes with reduced affinity
- Loss of permeability
What is an example of an oxazolidinone?
Linezolid
What is the mechanism of action of oxazolidinones (linezolid)?
Inhibit protein synthesis by binding to the 23S portion of the 50S subunit and preventing formation of ribosomal complex
What is the mechanism of bacterial resistance to oxazolidinones (linezolid)?
Point mutation in 23S rRNA
What is an example of a lipopeptide antibiotic?
Daptomycin
What is the mechanism of action of lipopeptides (daptomycin)?
- Bind to cell membran
- Cause depolarization due to K+ efflux
- Depolarization disrupts cellular processes and leads to cell death
What is the mechanism of bacterial resistance to lipopeptides (daptomycin)?
Not characterized yet
Describe the differences among the generations of the cephalosporin classes
- There is increasing gram-negative coverage as you progress from the 1st through the 4th generations of cephalosporins
- Gram-positive coverage
- 1st and 4th generations have good streptococcal and staphylococcal coverage
- 2nd generation has poor coverage
- 3rd generation: ceftriaxone has good coverage but ceftazidime has no coverage
Name two agents from the beta-lactam class that have activity against both Gram-positive and Gram-negative organisms
Cefazolin
Imipenem
Others
Why would a clinician not want to use the broadest, most potent antibiotic in all circumstances?
Using unnecessarily broad antibiotics will
- Kill more of the normal flora
- Be more likely to select for future resistance
What are examples of fluoroquinolones?
- Ciprofloxacin
- Moxifloxacin
- Levofloxacin
What is the mechanism of action of fluoroquinolones (ciprofloxacin, moxifloxacin, levofloxacin)?
Disrupting DNA synthesis by interacting with DNA gyrase (topoisomerase II) and DNA topoisomeraise IV
Bacterial cell growth inhibiting by trapping the enzymes in a complex
Bacterial cell death due to DNA cleavage and inability to repair DNA
What is the function of DNA gyrase (DNA topoisomerase II) in bacteria?
Relaxes DNA supercoiling during transcription and replication
What is the function of DNA topoisomerase IV in bacteria?
Separates replicated DNA into daughter cells
What are the mechanisms of bacterial resistance to fluoroquinolones (ciprofloxacin, moxifloxacin, levofloxacin)?
- Point mutation in DNA gyrase or topoisomerase results in conformational change and inability of fluoroquinolones to bind
- Efflux pumps pump out fluoroquinolones
- Reduction in porin channels prevents fluoroquinolones from entering bacterial cell
What is an example of a nitrofuran antibiotic?
Nitrofurantoin
What is the mechanism of action of nitrofurantoin?
- Inhibits bacterial Acetyl-CoA, interfering with carbohydrate metabolism
- Disrupts bacterial cell wall formation
What are examples of aminoglycosides?
- Gentamicin
- Amikacin
- Tobramycin
- Streptomycin
- Neomycin
What is the mechanism of action of aminoglycosides?
Interfering with protein synthesis by binding to 30s ribosomal subunit
- Blocks formation of initiation complex between 50S and 30S subunits
- Misread mRNA leading to miscoded peptide chain
- Block translocation on mRNA
What are the mechanisms of bacterial resistance to aminoglycosides?
- Bacterial transferase enzyme inactivates aminoglycoside
- Fewer porin channels decrease drug entry into bacterial cells
- Conformational change in 30S subunit prevents binding
What is the minimum inhibitory concentration (MIC)?
Lowest concentration of an antibiotic that prevents visible growth of bacteria after 18-24 hours of incubation
What is the minimum bactericidal concentration (MBC)?
Lowest concentration of an antibiotic that results in complete killing of bacteria
What is the MIC breakpoint?
Antibiotic concentration that separates strains where there is a high likelihood of treatment success from those bacteria where treatment is more likely to fail
“clinical cut-off”
When can a drug be used while considering MIC and breakpoint?
When MIC is under the breakpoint
(ideally want MIC as far from breakpoint as possible)
When is a bacteria sensitive to an antibiotic?
When growth of the organism is inhibited by the antibiotic concentration lower than the breakpoint
Which is the best aminoglycoside to use?
Trick question! You need to have the MIC breakpoint to answer the question
What is the best aminoglycoside to use?
Why?
Amikacin
Amikacin MIC is two dilutions away from the breakpoint, which is a larger difference than tobramycin (MIC is one dilution away from the breakpoint) or gentamicin (MIC is at the breakpoint)
When is interpreting MICs most critical?
- For the sickest patients
- For multi-drug resistant organisms
Can you compare the absolute number of MICs between antibiotic classes or between antibiotics in the same class?
No. Cannot compare absolute number of MICs between antibiotic classes or between antibiotics within same class
Describe the difference between microbroth dilution, Kirby-Bauer test, and E-test
- All these methods determine MIC by evaluating what concentration of antibiotic effectively kills the bacteria being tested
- Microbroth dilution utilizes tubes or wells of antibiotics into which the bacteria are inoculated
- Kirby-Bauer test uses discs impregnated with antibiotic placed on an agar plate inoculated with bacteria
- E-test is a strip that has a gradient of antibiotic concentrations that is placed on an agar plate inoculated with bacteria
You are seeing a patient with community-acquired pneumonia. You remember you need to cover Streptococcus pneumoniae as well as atypical organisms such as Legionella pneumophila and Chlamydophila pneumoniae. Which agents would achieve intracellular penetration and be active against atypicals?
- Fluoroquinolones
- Tetracyclines (doxycycline)
- Macrolides (azithromycin)
What is the mechanism of action of tetracyclines?
Inhibiting protein synthesis by binding reversibly to the 30S ribosome
What are the mechanisms of bacterial resistance to tetracyclines?
- Impaired influx or increased efflux by an active transport protein pump
- Ribosome protection due to production of proteins that interfere with tetracycline binding to the ribosome
- Enzymatic inactivation
What are the uses/spectrum of tetracyclines?
- Gram-positive
- Gram-negative
- Anaerobic
- Atypical organisms (Chlamydiae, Mycoplasma, Legionella)
- Ricketssiae and Borreliae spp. (Rocky Mountain spotted fever, Lyme disease)
(distributed widely to tissues and fluids, good intracellular activity)
What is does it mean if an antibiotic acts by concentration-dependent killing?
The rate of bactericidal killing is mazimized at the peak concentration (Cmax) in the serum
For an antibiotic that acts by concentration-dependent killing, what occurs after drug concentrations decrease to levels below the MIC?
Persistent suppression of growth
due to post-antibiotic effect (PAE)
For an antibiotic that acts by concentration-dependent killing, why is there persistent suppression of growth after drug concentrations decrease to levels below the MIC?
Post-antibiotic effect
What is the relationship between drug concentration and the duration of post-antibiotic effect and residual bacterial population for an antibiotic that acts by concentration-dependent killing?
The higher the drug concentration, the longer the duration of the PAE and the smaller the residual bacterial population when the next dose is given
Which classes of antibiotics act by concentration-dependent killing?
- Aminoglycosides
- Fluoroquinolones
What does it mean if an antibiotic acts by time-dependent killing?
Bacterial killing occurs while serum concentrations remain above the MIC
Goal is to keep antibiotic concentrations higher than the MIC for as much of the dosing interval as possible (at least 40-50%)
For an antibiotic that acts by time-dependent killing, what do you want the antibiotic concentrations to be?
Goal is to keep antibiotic concentrations higher than the MIC for as much of the dosing interval as possible (at least 40-50%)