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Respiratory Medicine Midterm > Beta Lactam Abx & Cell Wall Synthesis Inhibitors - Fitzpatrick > Flashcards

Beta Lactam Abx & Cell Wall Synthesis Inhibitors - Fitzpatrick Flashcards

1
Q

Which natural penicillin can be given IV? PO?

A

IV or IM = pen G

PO = Pen V

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2
Q

which Anti-‘Staphylococcla’ can be given PO?

A
  • Oxacillin
  • Dicloxaillin
  • Nafcillin (IV is also available: notice it’s name does not have an ‘o’ so its not just for oral)
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3
Q

Which extended spectrum penicillin can be given IV? PO?

A 
IV = ampicillin
PO = amoxicillin (the one with 'o' in it's name can be give PO)
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4
Q

what are the two anti-psudomonal commonly used?

A

Ticarcillin (taken with the beta lactamase inhibitor Clavulanic acid)
Pipercillin (taken with beta lactamse inhibitor Tazobactam)

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5
Q

In the cell wall biosynthesis of gram(+) bacteria such as strep, staph, and enterococci what is cross linked to a string of glycines?

A

Dipeptide D-ala-D-ala

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6
Q

what do beta lactams such as penicillins inhibit?

A

Beta lactams resemble D-ala-D-ala and they inhibit cross-linking enzymes/transpeptidases; and related penicillin binding proteins (PBPs) irreversibly

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7
Q

like penicillin, cephalosproins, carbapenems, monolactams also inhibits _

A

Peptidoglycan cross linking transpeptidase PBPs)

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8
Q

Penicillin G is indicated for what infections?

A

Gram (+) cocci:
1. Strep. pneumoniae (pneumococal pneumonia)
2. Strep. pyogenes (e.g. pharyngitis, scarlet fever)
(and others, don’t need to know for this test)

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9
Q

Pen G or V can be distributed to CNS only if _

A

inflamed meninges. Pen G/V cannot cross intact BBB

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10
Q

How is Pen G/V eliminated?

A

Renal tubular secretion

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11
Q

What is the main AE associated with Penicillin G/V?

A

Hypersensitivity –> anaphylaxis. Penicillin “hapten” reacts with proteins and on 2nd exposure to hapten provokes allergy/anaphylaxis in sensitized host (Type IV hypersensitivity)

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12
Q

Organisms resistant to penicillin do so by _

A

producing beta-lactamase (penicilllinase).
- the beta-lactam ring in penicillin G/V and some related penicillin confers vulnerability to drug resistance cuz it can be cleaved by beta lactamase thus inactivating penicillin G

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13
Q

What abx can be inactivated by beta lactamase enzymes?

A
  • Natural penicillins such as G and V
  • Extended spectrum: ampicillin, amoxicillin
  • Anti-psudomonal: ticarcillin, piperacillin
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14
Q

What abx works well against organism that are resistant to penicillin G/V but sensitive to anti-spaphlococcal penicillins?

A

The anti-staph group of abx and they include: methicillin, nafcillin, oxacillin, and dicloxacillin (meth is not used anymore cuz it causes interstitial nephritis)

  • they have chemical appendages that make them penicillin poor substrates for beta lactase and thus have excellent activity against staph aureus (aka Methicillin-sensitive S. aureus (MSSA)
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15
Q

How is nafcillin cleared and what AE are associated with it?

A
  • Cleared via hepatic/biliary

- AE: hypersensitivity; increased P450 induction

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16
Q

How is oxacillin and dicloxicillin cleared and what are their AE?

A
  • both cleared via renal/biliary

- AE for both is hypersensitivity

17
Q

What is meant by MRSA and how is it acquired?

A
  • (MRSA = Methicillin Resistance S. Aureus)
  • Alteration of mec A gene and PBP 2 in S. aureus confers high level resistance to methicillin, oxacillin and other antistaph penicillins–despite the fact that they are not substrates for beta lactamase. This type of resistance is termed MRSA
18
Q

True or false: methicillin resistance is caused by beta lactamase enzyme leading to MRSA

A

False. MRSA is caused by alteration of PBPs (PBP2). not beta lactamse enzymes

19
Q

What is the drug of choice for MRSA?

A

vancomycin

20
Q

What four main organisms is vancomycin used against?

A
  1. methicillin resistant s. aureus (MRSA)
  2. Methicilin resistant S. epidermis (MRSE)
  3. Enterococci (E. faecalis, E. Faecium)
  4. C. Difficile (if metronidazole fails)
21
Q

what is the only time vancomycin is given orally?

A

To treat C. diff. All other times it’s given parenterally.
Vancomycin is NOT absorbed in the gut thus if given orally it will not treat infection in other other place besides the gut.

22
Q

Pt is shown to have s.aureus infection. what is the best first line therapy for this pt?

A
  • Anti-staphylococal penicillins such as nafcillin, oxacillin and dicloxacillin.
  • ONLY if the s. aureus is resistant those the above, or if the pt is allergic to the above THEN give vancomycin.

Vancomycin is not a replacement for MSSA

23
Q

what is the MOA of vancomycin?

A

vancomycin is a glycopeptide cell wall synthesis inhibitor. Glycopeptides abx such as vancoycin and teicoplanin, inhibit cell wall synthesis by binding the D-ala-D-ala and sterically hindering translycosylation and transpeptidation.

24
Q

Vancomysin is not used for what strain of bacteria?

A

gram negative

25
Q

what AE are associated with vancomysin?

A
  • erythroderma or shock (manage with antihistimine/steroid)
  • Nephrotoxicity and Ototoxicity (rare with monotherapy, more common when given with othe nephro or ototoxins (e.g. aminoglycosides, furosemide)
  • Dermatologic - rash
  • Phlebitis at injection site
26
Q

what are the two extended spectrum aminopenicillins? what makes them different from regular penicillin?

A
  • Ampicillin and amoxicillin
  • They have an amino-group attached to the penicillin. This makes them polar and water soluble thus they are able to pass through the porins of gram negative bacterial cell wall in order to bind to PBPs in the periplasm of gram(-) bacterias, and then disrupt cell wall integrity
27
Q

what are aminopenicillins used for?

A
  1. Gram +: Strep. pneumoniae and pyogenes ( respiratory infecitons - communicty acquired pneumonia, sinusitis, bronchitis, pharyngitis. Amoxicillin is active against penicillin sensitive s. pneumonia and often used for pharyngitis in kids cuz of taste ); Strep viridans; enterococci
  2. Gram + bacilli: listeria monocytogenes
  3. Gram (-): H. Influenza (e.g. bronchitis in COPD); E.coli (e.g otitis media); protein mirabilis (e.g. UTI)
28
Q

Because of resistance due to beta lactamase, amipicillin and amoxicillin are given in combo with beta lactamase inhibitors such as _.

A
  1. Ampicillin + Sulbactum (given IV)
  2. Amoxicillin+ clavulanic acid (given PO)

( to remember: longer word penicillin goes with longer beta lactamase inhibitor)

29
Q

Anti-psudomonal abx are given in combo with which beta lactamase inhibitor?

A
  1. Ticarcillin + clavulanic acid
  2. Pipericillin + tazobactam (extended)

(To remember: T does not go with T)

30
Q

How does beta lactamase inhibitors work?

A

irreversibly inactivate and deplete beta-lactamase enzyme. Beta lactamase inhibitors don’t have any intrinsic antibiotic effects alone

31
Q

Amoxicillin + clavulanic can be given orally, but why are they not good for GI infections such as shigella, salmonella?

A

They are almost 100% absorbed from the gut and so very little actually stays in the gut to have any effect

32
Q

What is ampi+sulbactam/ and amoxi+clavulanic acid commonly used for?

A

penicillin resistant/methicillin sensitive bacterias such as s. aurue; s. pneumonia; H. influenza; e.coli

33
Q

what pt population are at risk of pseudomonas infection?

A
  • burn victims
  • CF
  • IV drug users
  • Immunosuppressed
  • chronic lung disease such as COPD
34
Q

What organisms are covered under anti-pseudomonal abx?

A
  • Gram (-) rods: enterobacter; e.coli; proteus mirabilis; H. influenza) AND psudomonas aeruginosa.
35
Q

which anti pseudomonal (gram(-) rods ) penicillin is more potent?

A

Piperacillin

36
Q

How is resistance acquired in pseudomonas?

A
  • Altered PBPs (NOT meta lactamase)

- Porin deficit–> multi drug resistance (MDR)

37
Q

pseudomonas resistance is not mediated by beta lactamase, then why is a beta lactamase inhibitor usually given in combo with anti-pseudomonas?

A

Anti-pseudomonas are broad spectrum abx that happens to also cover pseudomonas. While pseudomonas resistance is not via beta lactamase, other organism that anti-pseudomonas come can be rendered resistant via beta lactamase thus you give it to cover your basis.
In other words, most are given as empirical therapy of serious infections when suspected organism are gram(-) and if pseudomonas is a concern. Some examples include: severe pneumonia in hospitalized patient with structural lung disease; neutropenic fever- sepsis; aspiration pneumonia in a hospitalized patient or stroke victim

Respiratory Medicine Midterm (7 decks)

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