Intro to Antimicrobials Flashcards

1
Q

Prophylactic Therapy

A

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.

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2
Q

Preemptive Therapy

A

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.

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3
Q

Empiric Therapy

A

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.

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4
Q

Definitive Therapy

A

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.

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5
Q

Post-Treatment Suppressive Therapy

A

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.

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6
Q

Most valuable, time tested method for immediate ID of bacteria

A

gram stain

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7
Q

Minimum Inhibitory concentration (MIC)

A

lowest concentration of drug required to inhibit growth

Breakpoints established by Clinical and Laboratory Standards Institute (CLSI)

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8
Q

Types of susceptibility tests

A

Dilution Tests
Disk Diffusion
Optical Diffusion

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9
Q

Dilution Tests

A

broth dilution method for measuring minimum inhibitory concentration of antibiotics

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10
Q

Antibacterial Spectrum

A

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

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11
Q

Bacteriostatic

A

arrests growth and replication of bacteria (limits spread of infection)

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12
Q

Bactericidal: 2 different kinds

A

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

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13
Q

Bacteriostatic vs. Bactericidal

A

This concept is relative

Certain drugs are –cidal against specific bacteria while –static against others

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14
Q

Drug-drug enhancement or synergism– one particular example

A

Gentamicin – ineffective against enterococci in the absence of a cell-wall inhibitor
Combining penicillin with gentamicin leads to bactericidal activity

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15
Q

Antimicrobial Classification

A

Antimicrobials classified based on:
Class and spectrum of microorganisms it kills
Biochemical pathway it interferes with
Chemical structure

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16
Q

Beta Lactams

A

Penicillins
Cephalosporins
Monobactam
Carbapenems

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17
Q

β-Lactam Mechanism of Action

A

Time-dependent; structural analogs of D-Ala-D-Ala; covalently bind penicillin-binding proteins (PBPs), inhibit the last transpeptidation step in cell wall synthesis

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18
Q

penicillin G

A

Natural penicillin

Narrow; gram-positive cocci; primarily streptococci

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19
Q

nafcillin

A

Anti-staphylococcal

Narrow; gram-positive cocci; primarily staphylococci

Naf rhymes with staph

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20
Q

ampicillin, amoxicillin

A

aminopenicillin

Extended; gram-positive and gram-negative (H. influenzae, E. coli, P. mirabilis), Listeria, enterococci
HELPS kill enterococci

21
Q

Penicillins: Adverse effects:

A

Allergic reactions (0.7-10%)
Anaphylaxis (0.004-0.04%)
Nausea, vomiting, mild to severe diarrhea
Pseudomembranous colitis

22
Q

cephalexin

A

gram-positive coverage in general

First generation

23
Q

ceftriaxone

A

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 ***

24
Q

Cephalosporins Adverse Effects

A

1% risk of cross-reactivity to penicillins

Diarrhea

25
Q

β-Lactamase Inhibitors

A

Claulanic acid, e.g.

MOA: prevent destruction of B-lactam antibiotics (penicillins, for example)

26
Q

Vancomycin

A

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

27
Q

What is the mechanism of action of the penicillin class of drugs?

A

anti cell wall –> cell lysis

Bacteriocidal

Narrow spectrum: naficillin and penicillin G

extended spectrum: amoxicillin and ampicillin (aminopenicillins)

broad spectrum: antipsudomonals

28
Q

How are cephalosporins and penicillins similar?

A

all have the beta lactam ring

results in a similar mechanism of action for those drugs

29
Q

If a patient is allergic to penicillin, can he safely be given a cephalosporin?

A

just a rash/ upset stomach? fine.

true anaphylaxis? not a great idea.

30
Q

Second and third generation cephalosporins are more effective against __________ and are less effective against __________ compared to the first generation agents?

A

gram negative

gram positive

31
Q

Fluoroquinolone Mechanism of Action

A

Concentration-dependent, targets bacterial DNA gyrase & topoisomerase IV. Prevents relaxation of positive supercoils

32
Q

Ciprofloxacin

A

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

33
Q

What is the mechanism of action of fluoroquinolones?

A

targets DNA replication (DNA gyrase, topoisomerase)

broad gram-negative spectrum

34
Q

Inhibitors of Protein Synthesis- targets

A

Formation of initiation complex
Amino-acid incorporation
Formation of peptide bond
Translocation

35
Q

gentamicin

A

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

36
Q

doxycycline

A

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!

37
Q

azithromycin

A

macrolide (along with other -mycins)

binds 50S ribosomal subunit

adverse effects: arrhythmia, QT prolongation

38
Q

clindamycin

A

binds 50S ribosomal subunit

adverse effects; pseudomembranous colitis (.01-10%)

39
Q

Protein Synthesis Inhibitors review of the details

A

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

40
Q

aminoglycosides characteristic spectrum

A

gram negative, aerobic

41
Q

Why are aminoglycosides bactericidal while other protein synthesis inhibitors are –static?

A

misreading of mRNA leads to synthesis of abnormal proteins –> increased permeability/ lysis. Directly kill bacteria, vs. arresting growth by others.

42
Q

Metronidazole

A

cause DNA damage

spectrum: anaerobes, clostridium difficile, giardiasis

adverse effects: disulfiram-effect

not to take with alcohol!

43
Q
Please describe one characteristic toxicity of the following agents:
Doxycycline
Clarithromycin
Clindamycin
Metronidazole
A

doxyclicline- teeth discoloration
clarithromycin- arrhythmia, QT prolongation
clindamycin- pseudomembranous colitis
metronidazole- terrible hangover

44
Q

Acyclovir Mechanism of Action

A

Competes with deoxyGTP for DNA polymerase; causes DNA chain termination

45
Q

Antifungal Mechanisms

A

Azoles
Reduce production of ergosterol

Amphotericin B
Forms pores in cell membrane

46
Q

Amphpotericin B adverse effects

A

amphoterrible!

infusion related (fever, chills, vomiting, headache) and cumulative toxicity

47
Q

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
A

Clindamycin

48
Q

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

A

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

49
Q

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
A

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!