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Pharm > Gram Positive Antibiotics > Flashcards

Gram Positive Antibiotics Flashcards

1
Q

Vancomycin: MOA

A

Inhibits bacterial cell wall synthesis at a site different than b-lactams by binding to D-alanyl-D-alanine portion of cell wall precursors.

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2
Q

Vancomycin: MOR

A

Resistance in VRE and VRSA due to modification of D-alanyl-D-alanine binding site of peptidoglycan

v. 3 phenotypes seen in VRE - vanA, vanB, vanC
a. vanA resistance to vancomycin and teicoplanin with inducible exposure
b. vanB inducible by vancomycin but may be susceptible to teicoplanin (lower level resistance)
c. vanC least important, constitutive resistance to vancomycin only

VISA- thickened cell wall

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3
Q

Vancomycin: Spectrum of activity

A

i. Gram-positive bacteria - MSSA AND MRSA, coagulase-negative staphylococci, strep. pneumo (including PRSP), S. viridans, Group streptococcus, Enterococcus spp.
iii. Corynebacterium, Bacillus. Listeria, Actinomyces, Clostridium spp. (including C. difficile*), Peptococcus, Peptostreptococcus

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4
Q

Vancomycin: Indications

A
  1. MRSA bacteremia, empyema, endocarditis, peritonitis, pneumonia, skin and soft tissue infections, osteomyelitis, and meningitis
  2. Serious gram-positive infections in b-lactam allergic patients
  3. Infections caused by multidrug resistant bacteria (PRSP)
  4. Endocarditis or surgical prophylaxis in select cases
  5. Oral vancomycin for moderate to severe C. difficile colitis
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5
Q

Vancomycin: Adverse effects

A
  1. Red-Man Syndrome
    Flushing - 5 to 15 minutes of starting infusion due to histamine release, related to rate of IV infusion. Slow down infusion and they’ll be fine.
  2. Nephrotoxicity and Ototoxicity
    Rare with vancomycin monotherapy, more common when administered with other nephro- or ototoxins , such as aminoglycosides.
    Risk factors include renal impairment, prolonged therapy, high doses, high serum concentrations, use of other nephro- or ototoxins
  3. Hematologic - neutropenia and thrombocytopenia with prolonged therapy
  4. Thrombophlebitis (painful clot in vein) – related to rate of infusion. Recommend slow infusion at least over 60 minutes.
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6
Q

Dalbavancin: MOA

A

binds to C terminal D-ala-D ala interfering with cross-linkage and polymerization. It can attach to the cell membrane from its lipophilic moiety, making it more portent than vancomycin.

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7
Q

Dalbavancin: Spectrum of activity

A

Spectrum is sim. to vanc.

Has activity against VISA and Linezolid resistant SA as well as 1 of 2 VRSA strains

Activity against VRE with vanB and vanC genes, but not vanA

Streptococcus, including PRSP

Gram positive anaerobes, Corynebacterium.

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8
Q

Dalbavancin: indications

A

Skin and skin structure infections due to MRSA and other drug resistant Gram positive organisms, including some resistant to vancomycin

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9
Q

Dalbavancin: Serious adverse effects

A

Nausea, vomiting
Pruritus, anaphylaxis, skin reactions
Increased ALT
Flushing with rapid infusion

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10
Q

Can vancomycin treat gram negative infections?

A

No

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11
Q

Can dalbavancin treat gram negative infections?

A

No

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12
Q

Does vancomycin have good bioavailability?

A

No

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13
Q

Do vanc and dalbavancin act against anaerobes?

A

Yes, so long as they’re gram-positive

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14
Q

How long is dalbavancin’s half-life?

A

9 to 12 days

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15
Q

Mech. of Action: Linezolid

A

Binds to the 50S ribosomal subunit near the surface interface of 30S subunit – causes inhibition of 70S initiation complex (unique binding site), which inhibits protein synthesis

Bacteriostatic (bactericidal against Strep pneumoniae)

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16
Q

Mech. of Resistance: Linezolid

A
  • Alterations in ribosomal binding sites - rare

* Cross-resistance with other protein synthesis inhibitors is unlikely

17
Q

Spectrum of Activity: Linezolid

A 
a. Gram-Positive Bacteria:
MSSA, MRSA and VRSA
Coag-negative Staph
Strep pneumo (including PRSP*)
S. viridans, Group streptococcus
E. faecium AND faecalis (including VRE)*
Bacillus. Listeria, Clostridium spp. (except C. difficile),
Peptostreptococcus, P. acnes

b. Some activity against atypicals + mycobacteria

18
Q

Indications: Linezolid

A

reserved for serious/complicated infections caused by resistant gram-positive bacteria:

a. VRE bacteremia, NOT urinary tract infections
b. Complicated skin and soft tissue infections due to MSSA, MRSA or Strep pyogenes
c. Nosocomial pneumonia due to MRSA

19
Q

Adverse Effects: Linezolid

A

a. GI – nausea, vomiting, diarrhea (6 to 8 %)
b. Headache – 6.5%
c. Peripheral neuropathy - irreversible
d. Bone marrow suppression –> leading to Thrombocytopenia or anemia: > 2-4%.
Most often with treatment > 10- 14 days
After therapy discontinued – counts will return to
normal
e. Optic neuropathy possibly due to mitochondrial toxicity
f. lactic acidosis possibly due to mitochondrial toxicity

20
Q

Can linezolid act against C. difficile?

A

No

21
Q

When would you use tedizolid instead of linezolid?

A

If the patient is taking SSRIs/MAOIs, tedizolid is a good alternative

22
Q

Mech. of Action: Daptomycin

A

a. Binds to bacterial membranes → rapid depolarization of membrane potential → inhibition of protein, DNA, and RNA synthesis
b. Concentration-dependent bactericidal activity

23
Q

Mech. of Resistant: Daptomycin

A

Unknown

24
Q

Spectrum of Coverage: Daptomycin

A

MSSA, MRSA + VRSA
Coagulase-negative staphylococci

Streptococcus pneumonia (including PRSP*),
Strep viridans
Group strep

E. faecium AND faecalis (including VRE)*

25
Q

Daptomycin Indications

A

Resistant bacteria:
 Complicated skin and soft tissue infections due to MSSA, MRSA, or S. pyogenes
 Bacteremia, including endocarditis, due to S. aureus

26
Q

Daptomycin Adverse Effects

A

a. Gastrointestinal – nausea, diarrhea
b. Headache
c. Injection site reactions
d. Rash
e. Myopathy and CPK elevation –(2.8-10%). Must follow CK levels while on this drug.
f. Eosinophilic pneumonia, usually in patients older than 60

27
Q

Rundown on Quinupristin-Dalfopristin (MOA, Spec, Elim.)

A

Protein synthesis inhibition (static) activity of both drugs makes the combination -cidal. Dalfopristin enhances binding of quinupristin.

Activity against Staphylococcus and VRE faecium

Cleared in the liver

28
Q

Which drugs interact with linezolid?

A

SSRIs and MAOIs

Pharm (22 decks)

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