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Immuno mikro eng > Pharmacology: General principles and Beta-lactams > Flashcards

Pharmacology: General principles and Beta-lactams Flashcards

1
Q

Are enterococcus gram negative or gram positive?

A

Gram positive

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2
Q

What are the major enteric gram negatives?

A

PEK: Proteus spp., E. coli, Klebsiella pneumoniae

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3
Q

What are the “nasty” gram negatives?

A

Pseudomonas aeruginosa, Acetinobacter baumanii

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4
Q

What is empiric versus definitive therapy?

A

Empiric - probability-based therapy used before causative organism is known for sure
Definitive - therapy used once organism is cultured and antibiotic sensitivity is known

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5
Q

What is bactericidal versus bacteriostatic? When is this relevant?

A

Bactericidal - number of bacteria decrease
Bacteriostatic - number of bacteria stay the same for innate immune clearance

Relevant in immunocompromised patients who will not be able to clear an infection from bacteriostatic antibiotics, or in serious infections of immune-compromised places like meningitis or endocarditis

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6
Q

What is pharmacokinetics?

A

Kinetics - What the body does to the drug, including absorption, distribution, metabolism, and secretion

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7
Q

What is pharmacodynamics?

A

Dynamics - What the drug does to the body, or the bug at the site of action
Includes concentration-dependent or time-dependent killing

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8
Q

What is MIC?

A

Minimum inhibitory concentration

The lowest concentration of the antimicrobial which inhibits growth (bacteriostatic) in a test tube

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9
Q

What is defined as susceptible for antimicrobials?

A

The PK/PD targets are achievable and you would expect common doses of the antimicrobial to lead to clinical success of organism clearance

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10
Q

What is defined as intermediate susceptibility for antimicrobials?

A

MICs are elevated, but one MIGHT see clinical success with optimal dose-optimization strategies like continuous IV drug infusion

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11
Q

What is defined as resistant for antimicrobials?

A

PK/PD targets are not obtainable, and clinical success would not be expected with the agent

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12
Q

What are the “time dependent” antimicrobials and what does this mean?

A

Amount of time > MIC is the only thing that matters

  1. Beta-lactams
  2. Macrolides
  3. Oxazolidinones
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13
Q

What is an AUC antimicrobial and what drugs full in this class?

A

Area under the curve matters, a combination of dosage and time

Most drugs fall in this class

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14
Q

What antimicrobials are concentration-max dependent?

A

Aminoglycosides

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15
Q

What is the most common site of action for antimicrobials?

A

Ribosomes

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16
Q

What are the major mechanisms of resistance to antimicrobials?

A
  1. Modify the antimicrobial enzymatically
  2. Alter the target site
  3. Decrease its concentration in the cell (efflux pumps or downregulation of porins which transport the drug into the cell)
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17
Q

What is the mechanism of action of beta-lactams?

A

Inhibit the transpeptidation enzymes (penicillin-binding proteins) which catalyze the last step of cell wall synthesis - cross-linking of peptidoglycan

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18
Q

What is penicillin used for?

A

1st line treatment for Streptococci and E. Faecalis, as well as syphillis

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19
Q

What type of penicillin is used to treat syphillis?

A

Benzathine penicillin - long-acting and low level of drugs (only extremely susceptible bugs can be treated this way)

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20
Q

What is the difference between penicillin, cephalosporins, carbapenams, and monobactims?

A

The beta-lactam structure (number of ring and its members)

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21
Q

How does beta-lactamase work? What is one called?

A

Hydrolyzes the beta-lactam ring, opening it up so it cannot bind PBP anymore

I.e. penicillinases, cephalosporinases, carbapenemases

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22
Q

Are beta-lactamases more common in gram negative or gram positive and why?

A

Gram negative -> enzyme can be held in periplasmic space rather than secreted into extracellular space

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23
Q

Why is penicillin important for dentists?

A

It has good streptococcal dental coverage to prevent endocarditis associated with this microbes

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24
Q

What are the two clinically important 2nd generation penicillins? How is the second generation different?

A
  1. Nafcillin - IV
  2. Dicloxacillin - PO

Second generation is pencillinase resistant

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25
Q

What are antistaphylococcal penicillins? When can they be used?

A

Nafcillin - given IV for treatment of MSSA. Naf for Staph

Not usable against MRSA
- methicillin is a second generation that indicates susceptibility

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26
Q

What is the orally given second generation penicillin?

A

Dicloxacillin

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27
Q

How does staph resist second generation penicillins?

A

Make PBPs with decreased affinity for Beta-lactams, which can carry out cross-linking

This confers resistance to all beta-lactams

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28
Q

What are the two types of aminopenicillins and how are they given?

A

Ampicillin - IV

AmOxicillin - PO, better oral bioavailability

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29
Q

What spectrum do aminopenicillins?

A 
HELPS bugs
H - Haemophilus influenzae
E - Enterococcus faecalis
L - Listeria monocytogenes
P - Proteus mirabalis
S - Salmonella and Shigella
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30
Q

What is the problem with treating enterococcus infections with aminopenicillins?

A

Only static vs faecalis, and minimal activity vs faecium

For serious infections, need combination therapy with gentamicin (aminoglycoside) and ceftriaxone (cephalosporin)

31
Q

When are aminopenicillins used to treat meningitis?

A

High does ampicillin when concern for listeria

32
Q

Can aminopenicillins be used to treat streptococcal infections?

A

Yes, most of them are still susceptible

33
Q

What drug expands ampicillin coverage to P. aeruginosa? Route of delivery?

A

Piperacillin, IV only

34
Q

What are two clinical pearls about piperacillin?

A

Pearl 1 - if enterococcus is susceptible to ampicillin, it is susceptible to piperacillin

Pearl 2 - combination therapy with tazobactam is not more effective

35
Q

How did we get around beta-lactamases produced by Gram (-) bacilli and anaerobes?

A

Beta-lactam / beta-lactamase inhibitor combinations

36
Q

What are the three beta-lactam / beta-lactamase inhibitors?

A
  1. Clavulanic acid
  2. Sulbactam - poop
  3. Tazobactam
37
Q

What is Augmentin? Route?

A

Amoxicillin / Clavulanic Acid - PO (amoxicillin is PO)

38
Q

What is Unasyn? Route?

A

Ampicillin / Sulbactam - IV (ampicillin is IV)

“unison”

39
Q

What is Zosyn? Route? What is it used for?

A

Piperacillin / Tazobactam - IV (Piperacillin, IV)

Used for broad spectrum nosocomial infections (anti-PA) VITAMIN Z baby

40
Q

What do beta-lactamase inhibitors bring to the table?

A

Greater gram negative and anaerobic coverage
More MSSA

Good option for community based respiratory infections

41
Q

What is one bug which beta-lactamase inhibitors alone have significant activity against?

A

Acetinobacter - although Unasyn is given because sulbactam is not sold alone

42
Q

What is the most common side effect of penicillins?

A

Allergic reactions, question of whether it is due to the Beta-lactam ring or the side chains

43
Q

What penicillin class has the highest chance of kidney damage, and what symptoms are associated?

A

Can be seen with all penicillins, but methicillin most common. Cause:
Acute interstitial nephritis

Triad: Fever, Rash, Eosinophilia which can lead to renal failure

44
Q

What are three other rare side effects of penicillin?

A
  1. Bone marrow suppression, i.e. neutropenia or thrombocytopenia
  2. Seizures, especially in epileptics with compromised kidney clearance
  3. Contact dermatitis, especially with ampicillin (IV)
45
Q

In general, what are cephalosporins used and not used for treating?

A

Used: Gram + coverage

Not used: Enterococcus (no activity, use Augmentin instead)

46
Q

What are the first generation cephalosporins? Routes?

A
  1. Cephalexin (Keflex) - PO
  2. Cefazolin - IV
  3. Cefadroxil
47
Q

What is 1st generation cephalosporin’s gram + coverage?

A

Really good for MSSA, and potentially safer than Nafcillin (AKI risk)
Good versus streptococcus (minus pneumoniae), and nice skin coverage minus MRSA

48
Q

What is 1st generation cephalosporin coverage vs gram - and anaerobic?

A

Gram negative - narrow spectrum, activity against PEK (mild, not for empiric treatment) and mild-moderate UTI (Keflex for UTI)

Anaerobic - Lack clinically significant activity

49
Q

What is the best respiratory second generation cephalosporin and what is it active against?

A

Cefuroxime

Better gram + coverage than first gen (S. pneumoniae)

Gram negative - Slightly better for PEK

Anaerobic and PA - still no activity

50
Q

What is the clinical utility of Cefuroxime?

A

Respiratory tract infections, due to activity against S. pneumoniae, H. influenzae, and Moraxella cattarhalis

51
Q

What is the most commonly used GI second generation cephalosporin, and what is its major utility?

A

Cefoxitin - Good anaerobic activity and PEK activity

Used for community acquired GI infections + surgical anaphylaxis

52
Q

What are the names and routes of two common 3rd gen cephalosporins?

A

CefTRIaxone (IV) - 3rd gen

CefPOdoxime (PO) - taken orally

53
Q

What is changed about the gram + and gram - activity of 3rd gen cephalosporins?

A

Gram + - Enhanced S. pneumoniae activity (good against Community-acquired pneumonia and bacterial meningitis), but worse MSSA activity (use first class)

Gram - - Good against nosocomial gram negative (PEK), but no Pseudomonas coverage

54
Q

What is the last 3rd generation cephalosporin and what is its appeal?

A

Ceftazidime - Less staph and strep activity, but actually good against P. aeruginosa

55
Q

Why might we not want to use Ceftazidime alot?

A

Induces resistance mechanisms, also not good against respiratory infections other than PA

56
Q

Other than respiratory infections + meningitis, why might Ceftriaxone be used?

A

Intra-abdominal infections (Rather than second gen)

UTIs (rather than first gen)

57
Q

Why are ceftriaxone and ceftazidime good for meningitis?

A

They penetrate the meninges / BBB the best

58
Q

What are SPICE organisms?

A 
Serratia
Providencia
Indole-positive Proteus
Citrobacter
Enterobacter**
59
Q

Why do we worry about SPICE organisms when treatment with 3rd generation cephalosporins? What should we do instead?

A

All have a beta lactamase which can be selected for during therapy, so against these it is best to use cefepime or carbapenems for invasive / critically ill infections

60
Q

What is the 4th generation cephalosporin and what is it used for?

A

Cefepime

Used primarily against nosocomial organisms as it is great against SPICE organisms and P aeruginosa.

61
Q

What is the newest and coolest cephalosporin? How does it work? What is it used for?

A

Ceftaroline - binds PBP2A - the thing that makes MRSA resistant.

Has okay gram negative activity (almost as good as 3rd generation), but mainly used for MRSA when vancomycin isn’t an option. NOT PA-active

62
Q

What does Avibactam do?

A

It is a non-betalactam b-lactamase inhibitor which can restore ceftazidime activity against organisms which produce b-lactamases and carbapenemases

63
Q

List the antipseudomonal antibiotics

A 
Piperacillin
Piperacillin/tazobactam
Ceftazidime
Cefepime
Imipenem, meropenem, doripenem (carbapenems)
Aztreonam (monobactam)
64
Q

What is the most common side effect of cephalosporins?

A

Similar to penicillins -> hypersensitivites

65
Q

What is the important side effect of ceftriaxone?

A

Can cause biliary sludging (binding calcium, gall stones), which can mess with liver function tests / pancreatic enzymes

DO NOT GIVE TO NEONATES - can cause death

66
Q

What is the cross-reactivity of penicillin allergy with cephalosporin allergy?

A

5-15%

67
Q

What is the general activity of carbapenems?

A

Broadest spectrum we have
All Gram +, except MRSA
All Gram Negative
All Anaerobes not C. Difficile

68
Q

What is the group 1 carbapenem and why is it important?

A

Ertapenem

More narrow spectrum, holes are APE: Acinetobacter, pseudomonas, enterococcus

Drug of choice for ESBL producing organisms (less selective pressure on P. aeruginosa)

69
Q

What are ESBLs?

A

Extended Spectrum B-laactamases

Most commonly seen in Enterobacters like E. coli and K. pneumoniae

Can hydrolyze all Beta-lactams, except carbapenems

70
Q

What are Group 2 Carbapenems and when are they used?

A

Impinem, Meropenem, Doripenem

Used against ESBL organisms, especially gram negative, including Pseudomonas and Acetinobacter

Used against MDR organisms

71
Q

What is the major side effects of carbapenems?

A

Seizures, especially imipenem

72
Q

What is the only monobactam and what is its claim to fame?

A

Aztreonam (beta-lactam with no side chain)

Used for empiric nosocomial gram negative coverage in patient with penicillin allergy (zero cross-reactivity)

Covers P. aeruginosa but NO ESBL (not quite carbapenem)

73
Q

What is used to fight an Acetinobacter baumannii infection?

A

Ampicillin / Sulbactam (Unasyn)
Carbapenems minus ertapenem

Both are limited

74
Q

What are the only Beta-lactams which are not renally cleared and thus you don’t have to think about dosing?

A
  1. Ceftriaxone
  2. Penicillinase-resistant penicillins - i.e. Nafcillin

Have a major contribution of biliary secretion

Immuno mikro eng (56 decks)

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