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Infectious Disease 1 > JITT Beta Lactams > Flashcards

JITT Beta Lactams Flashcards

1
Q

What do beta lactams do?

A

They inhibit transpeptidases and carboxypeptidases (PBPs!), thereby killing bacteria as they try to grow and divide

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2
Q

What does transpeptidase do? Carboxypeptidase?

A

Cleaves D-ala to D-ala in the NAM sections of the peptidoglycan, Releases ATP

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3
Q

What are the main kinds of beta lactams?

A

Penicillins, beta-lactamase inhibitors, cephalosporins, monobactams, carbepenems

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4
Q

What are penicillin binding proteins?

A

PBPs are transpeptidases and carboxypeptidases - targets of beta-lactams!

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5
Q

What are the 3 determinants of antibiotic activity?

A
  1. Can it get to its target (permeability)?
  2. Can it bind to its target (affinity)?
  3. Will it be destroyed first (stability)?
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6
Q

How do gram + and gram - bacteria try to decrease permeability?

A

Gram +: thick peptidoglycan layer; Gram -: small peptidoglycan layer w/ porin (porin size is very important to permeability; it’s harder for many beta lactams to get into gram negs than gram positives)

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7
Q

How do beta-lactamases differ in gram positives vs gram negatives?

A

Gram +: release beta-lactamases into the environment (hoping to kill antibiotic before it gets to the cell wall); gram -: more like an ambush - concentrated in the periplasmic space (more efficient)

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8
Q

What are the key beta-lacatamase examples?

A

Penicillin ashes, cephalosporin ashes, extended-spectrum beta-lactamases, ampC beta-lactams she’s, carbepenemases

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9
Q

What makes MRSA resistant?

A

PBP-2a

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10
Q

What antibiotics can you use in MRSA?

A

Non-beta-lactams like linezolid, vancomycin, daptomycin

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11
Q

How is s. Pneumoniae developing resistance and to what?

A

Acquires alterations in its PBPs, resulting in resistance to penicillins (and in rare cases cephalosporins)

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12
Q

What are the basics of pharmacology in beta-lactams?

A

Short half-lives (often have to dose every 4-6h), excellent penetration into bodily fluids (sometimes CSF), most are renally excreted (so they require dose adjustment in renally impaired patients)

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13
Q

What are general side effects of beta lactams?

A

seizures, diarrhea, C. Difficile colitis, renal toxicity (particularly interstitial nephritis), immune-mediated cytopenias

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14
Q

What can you use if patient has penicillin allergy?

A

Aztreonam

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15
Q

What are rare cross-reactive beta lactams if patient has allergy to penicillin?

A

Cephalosporins and carbepenams

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16
Q

What is penicillin G? How is it active?

A

Acts against: gram positive cocci, streptococci, enterococcus, staphylococci (note: many staph and strep are now penicillin-resistant); treatment of choice for syphilis, n. Meningitidis, strep pyogenes, dental infections, IUD infections

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17
Q

What are the different common penicillins and how are they given?

A

Penicillin G: IV; Benzathine penicillin: IM; Penicillin G procaine: IM; Penicillin VK: oral

18
Q

How can anti-staphylococcal penicillins fight beta-lactamases?

A

Bulky side chain - steric hindrance - BUT they can’t enter gram-negatives

19
Q

What are the anti-staphylococcal penicillins?

A

Don’t “NOD” off now! Nafcillin, oxacillin, dicloxacillin; NOTE they undergo biliary excretion (negligible renal clearance)

20
Q

What are amino-penicillins?

A

Penicillins w/ -NH3 group, can get through porins giving them better GNR coverage (strep and enterococci); have to add beta-lactamase inhibitor to some b/c it will prevent the antibiotic from being killed in the periplasmic space

21
Q

What are common amino-penicillins and what are added to them?

A

Ampicillin, amoxicillin; ampicillin-sulbactam, amoxicillin-clavulanate

22
Q

What are the side effects of beta-lactamase inhibitors?

A

GI (diarrhea, vomiting, pain)! Amoxicillin has better absorption than ampicillin b/c it has an -OH that makes it stable in stomach acid

23
Q

What are anti-pseudo only penicillins?

A

Piperacillin-tazobactam (aka Zosyn) - broad spectrum of action, beta-lactamase inhibitor, given for HAI and VAP; NOT treatment of choice for bacteria w/ AmpCs

24
Q

What are beta lactams?

A

Antibiotics that inhibit the bacterial cell wall; bactericidal; the beta lactam nucleus must be intact for the antibiotic to be active; side chains give different pharmacodynamic properties

25
Q

What are first generation cephalosporins?

A

Cephalexin (PO), cefezolin (IV); used in Gram +s, streptococci, staphylococci, Gram -s (E coli, klebsiella, proteus); particularly helpful for skin and soft tissue infections or in the OR as perioperative prophylaxis to prevent surgical site infections

26
Q

What should you NOT use first generation cephalosporins for?

A

Enterococci, MRSA, resistant GNs, gut anaerobes (aka bacteroides)

27
Q

What are the differences between cephalosporins?

A

Cephalosporin nucleus can be modified in many places, yielding different drugs

28
Q

What are 2nd gen cephalosporins?

A

Increased GN activity, decreased GP activity; Cefuroxime - h influenza epidemic, community acquired respiratory tract infections; cefoxitin, cefotetan: increased anaerobic coverage and against beta-lactams she bacteroides - used in gut and pelvic surgery

29
Q

What are 3rd gen cephalosporins?

A

Better GN coverage, great for pneumococcus that is resistant to penicillin; ceftriaxone and cefotaxime have excellent CNS penetration and are frequently used to treat meningitis (Ax in the Head); used to treat gonorrhea

30
Q

What are 4th gen cephalosporins?

A

Broadest cephalosporin; used for gram positives and gram negatives (including pseudomonas), excellent CNS penetration; Cefepime

31
Q

What are 5th gen cephalosporins?

A

Ceftaroline - very new, similar to non-pseudomonas 3rd gen cephalosporins, increased affinity for PBP2a (MRSA), not currently used without ID consult

32
Q

What is aztreonam?

A

Used for GN infections in severely PCN allergic patients

33
Q

What is carbepenemases?

A

SUPER BROAD SPECTRUM - gram positive (but not MRSA), gram-negative (even if ESBL or ampC); excellent CNS penetration

34
Q

When should you not use carbapenem?

A

MRSA, E. Fascism, listeria, stenotrophomonas, burkholderia

35
Q

What is the key side effect of carbepenams?

A

May cause seizures in high doses/cases of renal insufficiency

36
Q

What are the key beta-lactamases?

A

TEM-1 and TEM-2

37
Q

What are the organisms w/ ampC beta-lactamases?

A

SPACE organisms (Serratus, pseudomonas indole, acinetobacter, vitro cater, enterobacter)

38
Q

What is vancomycin?

A

Glycopeptide antibiotic (NOT a beta-lactam); only active against gram-positive bacteria (like MRSA) - use in MRSA, resistant s. Pneumonia do, enterococci, listeria, bacillus, clostridium species

39
Q

How does vancomycin work?

A

Binds to the terminus and prevents PBPs from cross-linking the cell walls

40
Q

How should vancomycin be given for C. difficile?

A

Orally or rectally

41
Q

What is Redman syndrome?

A

If vancomycin runs in quickly, then histamine is released (face gets red, patient is itchy) - may have renal toxicity

42
Q

What is the relevant pharmacology of vancomycin?

A

> 90% eliminated by kidney (so has to be dose adjusted for those w/ renal insufficiency); dosed by weight; have to monitor trough levels to ensure adequate serum concentrations and prevent toxicity

Infectious Disease 1 (10 decks)

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