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HDID - Bacteriology > Lecture 38 & 41 - Intro to Anti-Microbials + Cell Envelope Anti-Microbials > Flashcards

Lecture 38 & 41 - Intro to Anti-Microbials + Cell Envelope Anti-Microbials Flashcards

1
Q

Name the 2 Folate Anti-Metabolites

A

Sulfonamides

Trimethoprim

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2
Q

Sulfonamide:
Common Agent
Mechanism

A

Common Agent: Sulfamethoxazol

Mechanism: Analogous structure to PABA.
Inhibition of Dihydropteroate Synthetase

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3
Q

Trimethoprim:

Mechanism

A

Inhibition of DIhydrofolate Reductase

Bacteriostatic when used alone

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4
Q

TMP-SMX

  • What is it?
  • Spectrum/Clinical uses?
  • Is it bacterostatic or bacterocidal
A

Combination of Trimpethoprime + Sulfamethoxazole (1:5 ratio)

Spectrum:
-GN (but NOT pseudomonas)
- GP: Staphylococci;
Most Enterococci are resistant

Uses: UTI, GI, Respiratory

Bactericidal with Excellent Bioavailbility

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5
Q

TMP-SMX: Adverse Events

Drug interactions

A
  • All abx: alteration of the micro-biota
  • Common: Rash, Nausea, Vom, HA
    Uncommon: Hyperkalemia, hepatitis, pancreatitis
    Rare: Steven’s Johnson, aplastic anemia, thrombocytopoenia,

Drug Interxn: Displaces warfarin and Pehytoi from Albumin

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6
Q

Name the Classes of abx that are “DNA inhibitors”

A
  • Quinolones, Fluoroquinolones

- Nitrofurantoin

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7
Q

Quinolones, Fluoroquinolones:
- Common Agents and their Mechanisms

  • Adverse Effects
  • Bactericidal or Static?
  • Resistance Mechanisms for Quinolones
A

Common Agents:

Ciprofloxacin - DNA Gyrase (topoisomerase II) inhibitor

Moxifloxacin
- Topo II and Topo IV Inhibitor

Stabilization of the Double Stranded DNA breaks – leading to chromosomal fragmentation

Adverse Effects: Overall quite well tolerated

  • Common: N, V, abd, HA, dizziness
  • Serious: Prolonged QT Syndrome

Bactericidal

Mutation to the Target: GryA, ParC
Plasmids, Efflux pumps

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8
Q

Ciprofloxacin: Spectrum and Clinical uses

Moxifloxacin: Spectrum

A

Cipro Spectrum: GN, Atypicals
Clinical uses: UTIs

Moxi: GN, GP, anaerobic, atypicals
Poor penetration to the GU tract

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9
Q

Nitrofurantoin -
Mechanism

Clinical Uses:

Adverse Effects:

A

Mechanism: Unknown damage to the DNA; also binds RNA and interfers with Translation

Clinical Uses: Exclusively Used for UTIs

Adverse Effects: Nausea, Pulmonary Fibrosis with prolonged use

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10
Q

What abx are considered RNA inhbitors?

A

Rifamycins: Rifampin, Rifabutin, Rifaximin

Fidaxomicin

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11
Q

Rifamycins -
Mechanism
Bacteriostatic or Cidal?
Adverse Effects?

A

Mechanism: Inhibition of RNA Polymerase

Bacteriostatic

GI: N, V, D, abd pain
Heme: Thrombocytopenia, anemia, hepatitis

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12
Q

Spectrum In General:

Clinical Uses

What is different about Rifaximin

A

General: Broad Spectrum
- GP, GN, Mycobacterial

Clinical uses: Prophylaxis for N. meningitis, S. Aureus

Rifaximin: Not absorbed; only used GI (enteric) infections

Clinical uses: Traveler’s diarrhea

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13
Q 
Fidaxomicin: 
Mechanism 
Adverse Effects 
What's unique about it? 
Spectrum
Clinical uses
A

Mechanism: Blocks RNA polymerase; prevents formation of DNA complex

Adverse effects: None

Unique: Non-absorbed;

Spectrum: C. DIff Only; No GNs

Clinical use: Use for C. Diff. Only if relapse after Vanc therapy

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14
Q

What Abx Classes Attack the Cell-Envelope?

A

Beta Lactams: PCN and derivatives, Cephalosporins, Carbapenams, Monobactams

Glyocopeptides

Cyclic Lipopeptides

Other (Polymyxins, bacitracin, fosfomycin)

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15
Q

What is the General mechanism of Beta Lactam Agents

A

B-lactam ring
Resembles peptide
Mimics terminal D-ala-D-ala of peptidoglycan monomer (pentapeptide)
Penicillin binds to transpeptidases (PBPs) of bacterial cell – now these enzymes not available to from stabilizing cross-links
· Autolysins still break up cell wall – continual remodeling
· Weaker and weaker cell wall
Eventually leads to cell lysis from osmotic pressure – death

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16
Q

Mechanisms of Resistance Against Beta Lactam Agents?

A

B-lactamases (inactivate it and break it)
· Enzymes that hydrolyze the beta-lactam ring
Penicillinases, cephalosporinases, carbepenemases
Extended-spectrum beta-lactamases (ESBL)

Modified PBP’s
- MRSA, encoded by mecA gene

Decreased permeability/porins 
· Avoid it – don’t let it in 
Efflux pumps (MDR)
· Avoid it – pump it out
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17
Q

PCN (General)

  • Bactericidal or static?
  • Common Adverse Effects:
A
  • Bactericidal
  • Adverse Effects:
    hypersensitivity: Rash, hives, anaphylaxis, serum sickness, cytopenias, nephritis
  • Seizures are high doses
18
Q

PCN (G)
- Spectrum

  • Clinical uses
A

Gram negative: GN cocci only

Gram positive: cocci/anaerobes (good if resistance not present)

Infections caused by Streptococci
Dental abscesses/human bites (GP anaerobe)
Syphilis
IV Only

19
Q

PCN - SemiSynthetics:
-Common Agents

Mechanism:

Common Resistances: what gene causes this?

Spectrum

A

Nafcillin (IV)
Dicloxacillin (PO)
(Methicillin)

Penicillinase-resistant penicillins (pre-MRSA)
· Bulky “R” Group – can’t fit into many b-lactamases
· Still maintain b-lactam ring

Resistance due to altered PBP (new protein PBP2a) encoded by mecA gene
· MRSA

Spectrum:
Gram-positive ONLY
Cannot penetrate Gram-negative (thick OM)

20
Q

Amino-PCNs
- Common agents

  • Mechanistic change
  • Spectrum of Activity
A

Ampicillin (IV)
Amoxicillin (PO)

R-group more polar, allows penetration through some Gram-negative porins

GP: Strep and cocci
Some Gram-negative porins:
· H. flu, E. coli
· NOT Pseudomonas

21
Q

Anti-Pseudomonal penicillins

  • Common Agents
  • Resistances
  • Spectrum of activity:
A
  • Piperacillin (used with tazobactam)
  • Uses is limited by penicillinases
    Never used alone

Spectrum:
GP, but not MRSA
Some GN – Pseudomonas

22
Q

Beta Lactamase Inhibitors:

  • what do they do?
  • Common agents
  • Spectrum
A
  • Extend the activity of penicillins and overcome much of resistance
  • Ampicillin – sulbactam
    · Adds S. aureus (not MRSA), B-lactamase-producing GN and anaerobes
    Amoxicillin – clavulanic acid (augmentin)
    · Similar, but PO

Piperacillin-tazobactam
· Adds S. aureus (not MRSA), B-lactamase producing GN and anaerobes (including Pseudomonas)
· Becomes broad spectrum antibiotic

23
Q

Beta Lactam: Cephalosporins

  • Common Adverse Effects
  • General Spectrum
A

Common Adverse Effects:
Well tolerated; Some cross re-activity with PCN allergy

Spectrum:
Most have some GP coverage
Gram Negative coverage increases with generations 1 through 4

24
Q

First Generation Cephalosporins

  • Common agents
  • Spectrum
  • Clinical uses
A

Cefazolin (IV)
Cephalexin (PO)

Good Gram + activity

Surgical prophylaxis – prevent infections caused by pathogens at site surgery (i.e. common Strep/Staph get in through skin)
Skin/soft tissue infections (limited/resistance)

S. Pyogens - - Impetigo

25
Q

Second Generation Cephalosporins
- Common Agents:
Spectrum
Clinical uses

A

Cefoxitin (IV)

Some GP coverage
Increased Gram-negative activity
Excellent anaerobe activity (rare to see with cephalosporins)

Prophylaxis for intra-abdominal surgery
· GI tract: want to include Gram – and anaerobes

26
Q

Third Generation Cephalosporins

  • Common agents
    Spectrum
    which one covers pseudomonas ?
A

Ceftriaxone, IV (will see a lot)
Ceftazidime, IV

Excellent GN activity – but NOT pseudomonas

Ceftriaxone:
· Community-acquired pneumonia,
N. meningitis – can penetrate the CSF
· Many uses, serious infections

Ceftazidime
· Has activity against pseudomonas

27
Q

4th Generation Cephalosporins

  • Common Agents
  • Resistances
  • Spectrum
A

Cefepime, IV only

Highly resistant b-lactamases

Broad spectrum
· Gram-negative (excellent) – including pseudomonas
· Gram-positive

Serious or resistant infections

28
Q

5th Generation Cephalosporins

  • Common agent
  • what is unique about its coverage ?
  • Clinical uses
A

Ceftaroline, IV

Overcomes MRSA resistance, binds PBP2a

Broad spectrum
· Gram positive – only cephalosporin with MRSA activity
· Gram negative – some, NOT pseudomonas

29
Q

Beta Lactam: Carbapenem

  • Common Agents
  • Spectrum
  • what resistances are avoided
A

Imipenem
Meropenem
Ertapenem

  • Resistant to Beta Lactamases
VERY BROAD SPECTRUM
· Gram negative, including pseudomonas 
· Gram-positive 
· Anaerobes 
Ertapenem – NO activity against Pseudomonas/Acinetobacter

Empiric treatment for serious infections
Resistant infections

30
Q

Beta Lactam: MonoBactams

  • Common Agents;
  • Spectrum
  • When is it used?
A

Aztreonam (IV)

Spectrum: GN ONLY (including pseudomonas, but really a last resort)

Clinical Uses: Only when there is allergy to other beta lactams

31
Q

Glycopeptides:
Common Agent

Mechanism of Action -

Mechanism of Resistance

Bactericidal or Static ?

A

Vancomycin

Binds to terminal D-ala-D-ala (intermediate in cell wall synthesis)
Inhibits transglycosylase (new chains) 
Inhibits transpeptidase (cross-links)

Alteration of binding site
· VanA gene (D-ala D-lac can’t bind vancomycin)

Bactericidal

32
Q

Glycopeptide
Common Adverse Events?

Spectrum?

Clinical Uses

A

Red Man Syndrome - Infusion reaction; Not Hypersensitivity
Nephrotoxicity

Spectrum: GP ONLY
- Staph (including MRSA)
- Sterp, Entero,
C. diff

GNs are intrinsically resistant

Empiric therapy for severe infections
C. Diff Infection

33
Q

Cyclin Lipopeptides
Common Agent
Mechanism
Bactericidal or Static

A

Daptomycin: IV Only

Lipophilic tail inserts into cell membrane
Membrane depolarization/K+ efflux
Cessation of vital processes (i.e. ATP production)
Cell death (without lysis)

Bactericidal

34
Q

Cyclin Lipopeptides:
- Adverse Events

  • Spectrum
  • Clinical Uses
A 
GI Distress: 
Headaches 
Elevated CPK/rhabodmyolysis 
· Associated with BID dosing 
· Clinical/lab monitoring 
Avoid statins 
Spectrum: 
- Gram-positive ONLY
· Staphylococci (including MRSA) 
· Enterococci (including VRE) 
· GP anaerobes 
No gram-negative!

Clinical uses:
Complicated Gram + infections
· Skin/soft tissue
· Bacteremia/endocarditis

35
Q

Polymixins:

Common Agents:

A

Polymyxin B and Colistin

Common Adverse Events: Nephrotoxicity; Neurotoxicity; Bronchospams

Spectum: GN ONLY

used for Pseudomonas
Clinical Uses: Serious Resistant GN Infections
Inhaled - resistant GN PNA

36
Q

Bacitracin

Fosfomycin

A

Bacitracin: Topical; GP only

Fosfomycin: Oral, UTI only

37
Q

What drugs are Anti-Pseudomonal?

A

Piperacillin+tazobactam

3rd generation Cephalosporins

4th Generation cephalosporins

Ciprofloxacin

Amonoglycosides: Gentimycin, Amikacin

Polymixins –

monobactam: aztreonam

38
Q

For what condition should you never use daptomycin?

why?

A

Never use daptomycin for PNA

Daptomycin is inhibited by pulmonary surfactant

39
Q

what are the best drugs for MSSA?

po

iv

A

po -Dicloxacillin, cephalexin

iv - Nafcillin, Cefazolin

40
Q

What are the best drugs for MRSA?

iv

po

A

iv -
Linezolid, ceftaroline
Vancomycin, Daptomycin – high grade
bacteremia, endovascular infections of bone/joint.

po - 
Clindamycin 
TMP/SMX 
Doxycyclin
Linezolid

HDID - Bacteriology (21 decks)

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