Intro to Antimicrobials Flashcards
Prophylactic Therapy
Prevent infection or prevent dangerous disease in those already infected
An 18 yo female is admitted to the hospital with a diagnosis of meningococcal meningitis. She lives in the dorms and is only one month into her freshman year of college. Her roommate is considered a “close contact” and must receive antibiotic therapy to prevent infection.
Preemptive Therapy
Early, targeted therapy in high risk patients who are asymptomatic but have become infected
An 8 yo male presents to the ED with a perforated appendix. Antibiotics are initiated pre-operatively to reduce risk of intra-abdominal abscess and surgical wound infection.
Empiric Therapy
Provide therapy to a symptomatic patient without identification of infecting organism
A 50 yo male presents to his PCP with dyspnea, fever, and cough. Community-acquired pneumonia is suspected and his physician initiates appropriate therapy to cover the most likely infecting organisms.
Definitive Therapy
Infecting organism now known. Antibiotics streamlined based on susceptibility. Duration of therapy limited to appropriate length.
A 45 yo female, undergoing 3x weekly dialysis, presents with fever and fatigue. Blood cultures reveal gram-positive cocci on gram stain and Staphylococcus is suspected. After sensitivity determined, antibiotics are appropriately adjusted to the most narrow-spectrum coverage.
Post-Treatment Suppressive Therapy
Antimicrobial coverage at lower dose when infection has not been completely eradicated
A 75 yo male presents to his PCP for follow-up of prosthetic hip joint infection. Review of his drug list reveals continued low dose antimicrobial therapy. Hip prosthesis was unable to be removed and replaced during hospitalization.
Most valuable, time tested method for immediate ID of bacteria
gram stain
Minimum Inhibitory concentration (MIC)
lowest concentration of drug required to inhibit growth
Breakpoints established by Clinical and Laboratory Standards Institute (CLSI)
Types of susceptibility tests
Dilution Tests
Disk Diffusion
Optical Diffusion
Dilution Tests
broth dilution method for measuring minimum inhibitory concentration of antibiotics
Antibacterial Spectrum
Narrow-spectrum:
Act on a single or a limited group of microorganisms
Extended-spectrum:
Active against gram-positive bacteria but also against significant number of gram-negative bacteria
Broad-spectrum:
Act on a wide variety of bacterial species, including both gram-positive and gram-negative
Bacteriostatic
arrests growth and replication of bacteria (limits spread of infection)
Bactericidal: 2 different kinds
kills bacterial
Concentration-dependent killing: rate and extent of killing increase with increasing drug concentrations
Time-dependent killing: activity continues as long as serum concentration above minimum bactericidal concentration
Bacteriostatic vs. Bactericidal
This concept is relative
Certain drugs are –cidal against specific bacteria while –static against others
Drug-drug enhancement or synergism– one particular example
Gentamicin – ineffective against enterococci in the absence of a cell-wall inhibitor
Combining penicillin with gentamicin leads to bactericidal activity
Antimicrobial Classification
Antimicrobials classified based on:
Class and spectrum of microorganisms it kills
Biochemical pathway it interferes with
Chemical structure
Beta Lactams
Penicillins
Cephalosporins
Monobactam
Carbapenems
β-Lactam Mechanism of Action
Time-dependent; structural analogs of D-Ala-D-Ala; covalently bind penicillin-binding proteins (PBPs), inhibit the last transpeptidation step in cell wall synthesis
penicillin G
Natural penicillin
Narrow; gram-positive cocci; primarily streptococci
nafcillin
Anti-staphylococcal
Narrow; gram-positive cocci; primarily staphylococci
Naf rhymes with staph
ampicillin, amoxicillin
aminopenicillin
Extended; gram-positive and gram-negative (H. influenzae, E. coli, P. mirabilis), Listeria, enterococci
HELPS kill enterococci
Penicillins: Adverse effects:
Allergic reactions (0.7-10%)
Anaphylaxis (0.004-0.04%)
Nausea, vomiting, mild to severe diarrhea
Pseudomembranous colitis
cephalexin
gram-positive coverage in general
First generation
ceftriaxone
second generation cephalosporin
Less active against gram-positive; good activity against gram-negative infections (Klebsiella, Enterobacter, Proteus, Serratia, Haemophilus), ceftriaxone drug of choice for gonorrhea ***
Cephalosporins Adverse Effects
1% risk of cross-reactivity to penicillins
Diarrhea
β-Lactamase Inhibitors
Claulanic acid, e.g.
MOA: prevent destruction of B-lactam antibiotics (penicillins, for example)
Vancomycin
MOA: inhibits cell wall synthesis binding with high affinity to D-Ala-D-Ala terminal of cell wall precursor units
Spectrum: broad gram-positive (including resistant organisms); Clostridium difficile
Adverse effects: red-man syndrome (histamine release), ototoxicity, nephrotoxicity
What is the mechanism of action of the penicillin class of drugs?
anti cell wall –> cell lysis
Bacteriocidal
Narrow spectrum: naficillin and penicillin G
extended spectrum: amoxicillin and ampicillin (aminopenicillins)
broad spectrum: antipsudomonals
How are cephalosporins and penicillins similar?
all have the beta lactam ring
results in a similar mechanism of action for those drugs
If a patient is allergic to penicillin, can he safely be given a cephalosporin?
just a rash/ upset stomach? fine.
true anaphylaxis? not a great idea.
Second and third generation cephalosporins are more effective against __________ and are less effective against __________ compared to the first generation agents?
gram negative
gram positive
Fluoroquinolone Mechanism of Action
Concentration-dependent, targets bacterial DNA gyrase & topoisomerase IV. Prevents relaxation of positive supercoils
Ciprofloxacin
fluoroquinolone
broad gram-negative
S. aureus (not MRSA), limited coverage of Streptococcus spp [exception – covered by “respiratory FQ’s” (levofloxacin, moxifloxacin)]
Adverse effects: GI distress, CNS, * photosensitivity, Achilles tendon rupture*
so don’t use in kids except if there is cystic fibrosis because benefit might outweigh risk
What is the mechanism of action of fluoroquinolones?
targets DNA replication (DNA gyrase, topoisomerase)
broad gram-negative spectrum
Inhibitors of Protein Synthesis- targets
Formation of initiation complex
Amino-acid incorporation
Formation of peptide bond
Translocation
gentamicin
aminoglycoside
MOA: concentration-dependent; binds 30S RIBOSOMAL SUBUNIT; interferes with initiation of protein synthesis; causes misreading of mRNA
Spectrum: AEROBIC GRAM-NEGATIVE BACTERIA
Adverse effects: ototoxicity, nephrotoxicity
doxycycline
Tetracycline
MOA: bacteriostatic; binds 30S RIBOSOMAL SUBUNIT; prevents access of aminoacyl tRNA to acceptor (A) site
Spectrum: broad gram-positive and –negative; RICKETTSIA, Coxiella burnetii, Borrelia burgdorferi (LYME disease)
Adverse effects: PHOTOSENSITIVITY, TEETH DISCOLORATION
not for kids!
azithromycin
macrolide (along with other -mycins)
binds 50S ribosomal subunit
adverse effects: arrhythmia, QT prolongation
clindamycin
binds 50S ribosomal subunit
adverse effects; pseudomembranous colitis (.01-10%)
Protein Synthesis Inhibitors review of the details
Aminoglycosides (gentamicin)
Bind 30S subunit; prevents formation of initiation complex; causes misreading
Tetracyclines (doxycycline)
Binds 30S subunit; prevents access of aminoacyl tRNA to A site
Macrolides (azithromycin)
Binds 50S subunit; inhibits translocation
Clindamycin
Binds 50S subunit; inhibits translocation
aminoglycosides characteristic spectrum
gram negative, aerobic
Why are aminoglycosides bactericidal while other protein synthesis inhibitors are –static?
misreading of mRNA leads to synthesis of abnormal proteins –> increased permeability/ lysis. Directly kill bacteria, vs. arresting growth by others.
Metronidazole
cause DNA damage
spectrum: anaerobes, clostridium difficile, giardiasis
adverse effects: disulfiram-effect
not to take with alcohol!
Please describe one characteristic toxicity of the following agents: Doxycycline Clarithromycin Clindamycin Metronidazole
doxyclicline- teeth discoloration
clarithromycin- arrhythmia, QT prolongation
clindamycin- pseudomembranous colitis
metronidazole- terrible hangover
Acyclovir Mechanism of Action
Competes with deoxyGTP for DNA polymerase; causes DNA chain termination
Antifungal Mechanisms
Azoles
Reduce production of ergosterol
Amphotericin B
Forms pores in cell membrane
Amphpotericin B adverse effects
amphoterrible!
infusion related (fever, chills, vomiting, headache) and cumulative toxicity
A 75 yo female presents to her PCP with persistent, foul smelling, watery diarrhea. She was recently treated for a dental abscess with an antibiotic that inhibits the 50S ribosomal subunit, preventing translocation. Which of the following antimicrobials was most likely prescribed?
Clindamycin Gentamicin Metronidazole Nafcillin Vancomycin
Clindamycin
A 24 yo female presents to her PCP for follow-up of her acne. At her last visit, an antibiotic agent was initiated. She is complaining of severe sunburns she believes are due to the new medication. What is the mechanism of action of the drug most likely prescribed?
A. Binds D-Ala-D-Ala terminal of cell wall precursor unit
B. Free radicals damage DNA
Inhibits 30S ribosomal subunit
C. Inhibits final transpeptidation step of cell wall synthesis
D. Reduces production of ergosterol
tetracyclines and fluoroquinolones would cause photosensitivity.
A describes Vancomycin B describes Metronidazole C. describes aminoglycosides, doxycycline is one of them D. Cephalexin E. ?
The answer is C
A 46 yo immunocompromised, female is receiving treatment for invasive aspergillosis in the ICU. An infusion is begun and she begins experiencing fever, chills, vomiting, and headache. Which antimicrobial was most likely prescribed?
A. Acyclovir B. Amphotericin B C. Fluconazole D. Levofloxacin E. Vancomycin
aspergillis is a fungal infection
Vancomycin could case an infusion related problem but is not anti-fungal
Acyclovir can also be eliminated because anti-viral
Levofloxacin is a fluoroquinolone, primarily anti-bacterial
Amphoterrible is the likely candidate!
