Intro to Antimicrobials - Ported from yr I PBD decks. Flashcards

1
Q

Ok, so we are going to run through the drug list, shall we begin?

What are the broad categories of drugs we were presented?

For example, the first one was Natural Penicillins.

Now, you try!

(there are a lot. Just try to get the 15 bolded ones. These categories have drugs in them that Dr. Kinder listed in RED as must knows)

A
  1. Natural penicillins
  2. ›Anti-staphylococcal Penicillins
  3. Aminopenicillins
  4. Anti-pseudomonal Penicillins
  5. First Gen Cephalosporins
  6. Second gen cephalosporins
  7. Third gen cephalosporins
  8. Fourth gen cephalosporins
  9. Carbapenems
  10. Monobactams
  11. B-Lactamase inhibitors
  12. Glycopeptides
  13. Lipopeptides
  14. Fluoroquinolones
  15. Aminoglycosides
  16. Tetracyclines/glycyclines
  17. Macrolides/Ketolides
  18. Lincosamides
  19. Oxazolidinones
  20. Metronidazole
  21. Sulfonamides/Trimethoprim
  22. Antivirals
  23. Antifungals
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the natural penicillin we must know?

A

Penicillin G

›(IV, IM)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the anti-staphylococcal penicillin we must know?

A

Nafcillin
›(IV, IM)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the aminopenicillins (2) we must know?

A

›Ampicillin (PO, IV, IM)
›Amoxicillin (PO)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What first gen. cephalosporin must we know?

A

›Cephalexin [Keflex] (PO)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What 3rd gen cephalosporin must we know?

A

›Ceftriaxone [Rocephin] (IV, IM)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Which Beta-lactamase inhibitors must we know?

A

›Amoxicillin-clavulanic acid [Augmentin] (PO)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What glycopeptide drug must we know?

A

›Vancomycin (PO, IV)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Which fluoroquinolone must we know?

A

›Ciprofloxacin [Cipro] (PO, IV, topical)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What aminoglycoside must we know?

A

›Gentamicin (IV, IM, topical)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What Tetracyclines/Glycylcyclines do we need to know?

A

Doxycycline
›(PO, IV)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What macrolide/ketolide must we know?

A

›Azithromycin [Zithromax, Z-pak] (PO, IV, topical)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What lincosamide must we know?

A

›Clindamycin [Cleocin] (PO, IV, IM, topical)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the trade name for metronidazole?

A

Flagyl

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What antiviral do we need to know?

A

›Acyclovir (PO, IV, topical)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What antifungals must we know? (2)

A

›Fluconazole [Diflucan] (PO, IV)

›Amphotericin B (IV)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Via what route of administration would you use vancomycin to treat a C. diff infection?

A

Oral administration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Over use of antimicrobials has proven a major problem. When considering wether to use antimicrobial therapy, what are six questions you should consider before prescribing?

A
  1. ›Is an antimicrobial indicated based on clinical findings?
  2. ›Have appropriate cultures been obtained?
  3. ›What is the most likely causative organism?
  4. ›What must be done to prevent secondary exposure?
  5. ›Is there clinical evidence or established guidelines that have determined antimicrobial therapy provides a clinical benefit?
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are the five types of therapy we can employ using antimicrobials?

A
  1. ›Prophylactic Therapy
  2. ›Preemptive Therapy
  3. ›Empiric Therapy
  4. ›Definitive Therapy
  5. ›Post-Treatment Suppressive Therapy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Describe the purpose of prophylactic therapy.

A

›Prevent infection or prevent dangerous disease in those already infected.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Describe preemptive antimicrobial therapy

A

›Early, targeted therapy in high risk patients who are asymptomatic but have become infected

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Describe empiric therapy

A

›Provide therapy to a symptomatic patient without identification of infecting organism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is definitive therapy?

A

›Infecting organism now known. Antibiotics streamlined based on susceptibility. Duration of therapy limited to appropriate length.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Describe ›Post-Treatment Suppressive Therapy.

A

›Antimicrobial coverage at lower dose when infection has not been completely eradicated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Name the type of therapy appropriate in this situation.

›A 50 yo male presents to his PCP with dyspnea, fever, and cough. Community-acquired pneumonia is suspected.

A

Empiric therapy - The physician shoul initiate the appropriate therapy to cover the most likely infecting organisms.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

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.

What kind of therapeutic approach is appropriate for maintaining the health of any close contacts she might have, including her roommate?

A

Prophylactic therapy: ›Her roommate and other “close contacts” must receive antibiotic therapy to prevent infection.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What kind of therapy is best suited to this scenario?

›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. Sensitivity tests are performed with clear results.

A

Definitive therapy: At this point the organism is identified and the appropriate antibiotics are determined, the physician can narrow the spectrum of coverage.

28
Q

What type of therapy is called for in this situation?

›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.

A

This patient should be on post-treatment suppressive therapy

29
Q

›An 8 yo male presents to the ED with a perforated appendix. What kind of antimicrobial therapy is appropriate for this patient?

A

Preemptive therapy: Antibiotics are initiated pre-operatively to reduce risk of intra-abdominal abscess and surgical wound infection.

30
Q

What is the most valuable, time tested method for immediate ID of bacteria

A

Gram stain

31
Q

In gram negative bacteria, what connects the outer membrane to the peptidoglycan layers?

A

Lipoprotein

32
Q

What chemical feature gives peptidoglycan its rigid stability?

What enzyme is involved in its creation?

why is this important clinically?

A

terminal D-alanine cross linking

transpeptidase

it is the target of B-lactam antibiotics

33
Q

Which layer is LPS found in?

Which layer is transpeptidase found in?

A

Gram Negative

Outer membrane

inner membrane

34
Q

What is a Minimum Inhibitory Concentration?

How do we use this data between various species?

A

(MIC): lowest concentration of drug required to inhibit VISIBLE growth

MICs are not directly compared between species.
›Breakpoints established by CLSI are used to classify degree of susceptibility/resistance, and this is compared.

35
Q

Describe the serial dilution testing.

What is it for?

Why is it done?

A

Susceptibility testing

36
Q

Describe the disk diffusion testing.

What is it for?

​Why is it done?

A

Susceptibility Testing

39
Q

What is an “Antibiogram”, and how can it help you, clinically?

A

Institutions keep tabs on the susceptibility & resistance patterns of local pathogenic strains.

Will help you decide which antibiotics to use based on these local patterns

40
Q

What is this graph showing?

A

time dependent killing

41
Q

what is this graph showing?

A

concentration dependent killing

42
Q

What is the difference between “broad-spectrum” and “extended-spectrum”

A

Both cover gram positive and negative, but “broad-spectrum” has more coverage of gram negatives than “extended spectrum” does

43
Q

Describe the two general types of bacteriocidal agents

A

›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

45
Q

What are the sites of action of antibacterial drugs?

A

›Cell wall synthesis
›Cell membrane synthesis
›Protein synthesis
›Nucleic acid metabolism
›Function of topoisomerases
›Folate synthesis

47
Q

What is the mechanism of action for B lactam antibiotics?

A

Time-dependent
structural analogs of D-Alanine
covalently bind transpeptidases (AKA penicillin-binding proteins)
inhibit the last transpeptidation step in cell wall synthesis

48
Q

what is an example of antibiotic synergy we should be aware of?

A

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

49
Q

Are protein synthesis inhibitors generally bacteriocidal or bacteriostatic?

A

bacteriostatic

50
Q

Why is antibiotic selective toxicity important?

A

This property is what allows us to use toxic agents medicinally - they are much more toxic to bacteria than they are to us.

52
Q

What are the B lactam antibiotic groups?

A

›Penicillins
›Cephalosporins
›Monobactam
›Carbapenems

Kinder says focus on Penicillins & ›Cephalosporins

54
Q

Ok so now for the really hard cards not the childs play we have seen before.

What natural penicillin do we have to know and what does it treat?

What is a narrow spectrum penicillin that treats staph?

A

Penicillin G, treats strep and is narrow spectrum

Nafcillin

55
Q

Ampicillin and amoxicillin treat what?

+

A

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

56
Q

What is the MOA of fluoroquinolone?

Is it time or concentration dependant?

A

targets bacterial DNA gyrase & topoisomerase IV. Prevents relaxation of positive supercoils

Concentration

57
Q

What are some adverse effects of penicillins?

When can no B-lactam be given?

A

›Allergic reactions (0.7-10%)
›Anaphylaxis (0.004-0.04%)
›Nausea, vomiting, mild to severe diarrhea
›Pseudomembranous colitis
If anaphylaxis occurs no B-lactam can be given

58
Q

What is a first gen cephalosporin that covers gram positives?

What is a good third gen cephalospirin and what does it hit?

A

Cephalexin

Ceftriaxone-
›Less active against gram-positive; good activity against gram-negative infections (Klebsiella, Enterobacter, Proteus, Serratia, Haemophilus), ceftriaxone drug of choice for gonorrhea

59
Q

What are some adverse effects of cephalosporins?

A

Diarrhea

1% cross reactivity with penicillins.

60
Q

Why do we give B-lactamase inhibitors?

give an example of one.

A

Because some organisms destroy B-lactam rings so to make the drug effective that must be inhibited

Clavulonic acid

61
Q

What is the MOA of vancomyocin?

Spectrum?

A

›inhibits cell wall synthesis binding with high affinity to D-Ala-D-Ala terminal of cell wall precursor units

›broad gram-positive (including resistant organisms); Clostridium difficile, with what stipulation?

62
Q

What adverse effects can vanco have, what should you do if they appear?

A

›Adverse effects: red-man syndrome (histamine release), ototoxicity, nephrotoxicity
Slow down rate of drug

64
Q

What is a fluoroquinolone we should know?

Spectrum?

Why is it contraindiated in children?

A

›Ciprofloxacin,
›Spectrum: broad gram-negative, S. aureus (not MRSA), limited coverage of Streptococcus spp [exception – covered by “respiratory FQ’s” (levofloxacin, moxifloxacin)]

Because of achilles tendon rupture, also see other adverse effects
›GI distress, CNS, photosensitivity

65
Q

What is the MOA of acyclovir?

What is it against?

A

Competes with deoxyGTP for DNA polymerase; causes DNA chain termination

Viruses

66
Q

Ok so we have azoles and Ampotericin B as antifungals, what are their MOAs

A

Azoles

•Reduce production of ergosterol

Amphotericin B

•Forms pores in cell membrane

67
Q

Gentamicin is a aminoglycoside, what is its MOA

Spectrum (What else can it kill if combined with what drug)

aDVERSE effects?

What is a requirement of the drug?

A

Concentration dependent, binds 30S ribosomal subunit, interferes with initiation of protein syn,causes misreading of nRNA (this by the way makes it not only a syn inhibitor but also cidal)

aerobic gram neg bacteria (will kill gram pos in the presence of a B-lactam)

ototoxicity, nephrotoxicity

Require oxygen and energy to be transported into bacteria

68
Q

Name a tetracyclin you should know?

MOA

Spectrum

A

Doxycycline

bacteriostatic; binds 30S ribosomal subunit; prevents access of aminoacyl tRNA to acceptor (A) site

›broad gram-positive and –negative; Rickettsia, Coxiella burnetii, Borrelia burgdorferi (Lyme’s disease)

69
Q

Tetracyclines have what adverse effects?

This makes them contraindicated for what group?

A

photosensitivity, teeth discoloration

Children- because of the kelation of Ca ions (teeth)

70
Q

Name a good macrolide?

MOA

Spectrum

Adverse effects

A

azithromycin

›bacteriostatic; binds 50S ribosomal subunit; inhibits translocation

›aerobic gram-positive, some gram-negative

Arrhythmia, QT prolongation (important)

71
Q

What is the MOA of clinamycin?

Spectrum

Adverse effects?

A

›binds 50S ribosomal subunit; inhibits translocation

pneumococci, S. pyogenes, viridans Streptococci, MSSA, anaerobes (B. fragilis)

pseudomembranous colitis (0.01-10%)

72
Q

So to sum up run through the protein syn inhibitors again on your own

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

73
Q

What is the MOA of metronidazole?

Spectrum

Adverse effects

A

›nitro radical anions interact with DNA; cause DNA damage

anaerobes; Clostridium difficile, trichomoniasis, amebiasis, giardiasis

›Adverse effects: disulfiram-effect- this means you will be really sick if you drink alcohol while taking this drug

76
Q

Amphotericin B does have some adverse effects, what are they?

A

Amphotericin B adverse effects: infusion related (fever, chills, vomiting, headache) and cumulative toxicity