vancomycin, linezolid, and daptomycin Flashcards Preview

Pharm test #3 > vancomycin, linezolid, and daptomycin > Flashcards

Flashcards in vancomycin, linezolid, and daptomycin Deck (56):
1

vancomycin belongs in which family of drugs

glycopeptides

2

glycopeptides affect what types of bacteria

gram + aerobes and some anaerobes

3

how does vancomycin work

inhibits cell wall synthesis by binding D-alanyl-D-alanine portion of cell wall precursors to
prevent cross-linking and further elongation of peptidoglycan

4

how can cells confer resistance to vancomycin

i. Resistance in VRE and VRSA due to modification of D-alanyl-D-alanine
binding site of peptidoglycan
ii. Terminal D-alanine replaced by D-lactate
iii. Loss of critical hydrogen bond
iv. Loss of antibacterial activity
v. 3 phenotypes - vanA, vanB, vanC
vi. VISA – thickened cell wall

5

vancomycin spectrum of activity

i. Gram-positive bacteria - Methicillin-Susceptible AND MethicillinResistant
S. aureus and coagulase-negative staphylococci*
ii. Streptococcus pneumoniae (including PRSP*), viridans streptococcus, Group streptococcus, Enterococcus spp.
iii. Corynebacterium, Bacillus. Listeria, Actinomyces Clostridium spp. (including C. difficile*), Peptococcus, Peptostreptococcus
iv. No activity vs gram-negative organisms

6

clinical uses

i. Infections due to methicillin-resistant staph including bacteremia, empyema, endocarditis, peritonitis, pneumonia, skin and soft tissue
infections, osteomyelitis, meningitis
ii. Serious gram-positive infections in -lactam allergic patients
iii. Infections caused by multidrug resistant bacteria (PRSP)
iv. Endocarditis or surgical prophylaxis in select cases
v. Oral vancomycin for moderate to severe C. difficile colitis

7

when do you give vancomycin orally

for C. difficile (not absorbed well so it stays in the gut/colon)

8

Red-Man Syndrome

• due vancomycin administration
• Flushing, pruritus, erythematous rash on face, neck, and upper torso within 5 to 15 minutes of starting infusion due to Histamine release from mast cell degranulation;
• Related to RATE of intravenous infusion;
• Resolves spontaneously after discontinuation
• May lengthen infusion (over 2 to 3 hours) or pre-treat with antihistamines in some cases

9

Nephrotoxicity and Ototoxicity with vancomycin use

• 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

10

adverse effects of vancomycin use

• red man syndrom
• nephrotoxicity and ototoxicity
• Dermatologic - rash (later onset)
• Hematologic - neutropenia and thrombocytopenia with prolonged therapy
• Thrombophlebitis – related to rate of infusion. Recommend slow infusion at least over 60 minutes.
• interstitial nephritis

11

old name for vancomycin

mississippi mud - had a brown color - purification lead to less adverse effects

12

main uses for vancomycin

MRSA and PRSP

13

is vancomycin bactericidal or static

time dependent bactericidal except for enterococcus which it is bacteriostatic

14

timing of vancomycin effects

can take days after beginning therapy to see the effects clinically

15

vancomycin elimination

unchanged via the kidney
1/2 life depends on renal function normally 6-8 hr but can be very very long with renal disease

16

vancomycin absorption and distribution

slow - peak concentrations are measured 1 hr after infusion

not absorbed well orally

widely distributed to all tissues - variable CSF penetration but increased when inflamed (used for strep pneumo menigitis)

17

Dalbavancin belongs to which drug group

2nd generation gycopeptide

A semisythetic lipoglycopeptide.

18

Dalbavancin mechanism of action

binds to C terminal D-ala-D ala interfering with cross-linkage and polymerization.

•It can attach (anchors) to the cell membrane from its lipophilic moiety, making it more potent than vancomycin*

19

Dalbavancin is used against

resistant gram + bacteria
MRSA, VISA
VRE with the vanB or vanC gene
MRSE (epi), streptococcus

20

how is dalbavancin given?

via IV with once a week dosing
half life is 9-12 days

(decrease dose with renal insufficiency)

21

dalbavancin side effects

Hematologic, headaches
Pruritus, anaphylaxis, skin reactions
Increased ALT
Flushing with rapid infusion (red man syndrom)

22

telavancin is used for

MRSA and GPOs (resistant gram + organisms

SSSI, HAP, VAP (all S. aureus

23

telavancin toxicity

higher renal toxicity than vancomycin

shown to be teratogenic in animals

24

telavancin delivery

IV only

25

Oritavancin used for

MSSA, MRSA, enterocococcus, strep

possible some bacillus anthacis

26

oritavancin mechanism of action

disrupts cell membrane and cell well

27

oritavancin dosing

IV - single dose

28

oritavancin belongs to which group

semisynthetic glycopeptide (for GPOs)

29

what drug is an Oxazolidinones

Linezolid

30

Mechanism of Action of Linezolid

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)

31

Linezolid dosing

same given IV or orally
has a 100% bioavailability when given orally

32

linezolid is used for

• Methicillin-Susceptible, Methicillin-Resistant AND VancomycinResistant Staph aureus* and coagulase-negative staphylococci
• Streptococcus pneumoniae (including PRSP*), viridans streptococcus, Group streptococcus
• Enterococcus faecium AND faecalis (including VRE)*
• Bacillus. Listeria, Clostridium spp. (except C. difficile), Peptostreptococcus, P. acnes

no gram neg activity

33

linezolid elimination

both renal and non-renal
* adjustment is NOT needed for renal insufficiency

34

clinical uses for linezolid

VRE bacteriemia (NOT UTIs)
nosocomal pneumonia due to MRSA
comilicated skin and soft tissue infections due to MRSA, MSSA, or strep pyrogens

35

drug interactions with linezolid

interacts with adrenergic or serotonergic agents

enhances the pressor response to Epi and dopamine

* serotonin syndrome with SSRIs and MAOIs
-- hyperpyrexia, diarrhea, cognitive dysfunction, restlessness, seizures, coma (may need 2 week washout period before starting linezolid)

36

adverse effects of linezolid

GI- lactic acidosis
Headache
peripheral neuropathy
**Thrombocytopenia (platlets drop- most often after 10 days) or anemia

37

Tedizolid advantages

can be given IV or Oral, more potent than linezolid, no SSRI interaction**

38

Tedlizolid uses

Staph, strep, enterococcus, skin and skin structure infections

39

adverse effects of Tedlizolid

headache, dizzy
hematologic (similar to linezolid)
neuropathy (peripheral and optic) (linezolid)

40

Daptomycin belongs to which drug group

lipopeptides

41

Daptomycin struture

very large molecule

42

Daptomycin is used for

resistant gram +ives --VRE, MRSA, VISA

43

Mechanism of Action of daptomycin

Binds to bacterial membranes causing rapid depolarization of membrane potential, inhibition of protein, DNA, and RNA synthesis

concentration dependent bactericidal activity

44

daptomycin resistances

rare in VRE and MRSA but can be due to altered cell membrane binding

45

Daptomycin spectrum of activity

gram +
MRSA, VISA, VRE

46

daptomycin distribution

only available IV
distributed into well profused tissue

47

daptomycin elimination

mainly kidney - dose needs to be adjusted based on kidney function

48

daptomycin in inactivated by

surfactant - therefore do not give for pneumonia

49

MRSA pneumonia treatment

vancomycin or linezolid (NOT daptomycin)

50

adverse effects of daptomycin

GI
headache
injection site reaction
rash
**myopathy and CPK elevation

51

daptomycin drug interactions

HMG CoA-reductase inhibitors - may lead to increased incidence of myopathy

52

Quinupristin-Dalfopristin (aka synercid)

individually they are static but together they have a cidal effect on bacteria

53

Quinupristin-Dalfopristin (aka synercid) mechanism

• dalfopristin enhances binding of quinupristin. Inhibits peptidyltransferase
• quinupristin prevents elongation of the pp chain and coauses incomplete chain release

54

Quinupristin-Dalfopristin (aka synercid) elimination

cleared by the liver

55

Quinupristin-Dalfopristin (aka synercid) adverse effects

server GI intolerance -- not tolerated well

56

Quinupristin-Dalfopristin (aka synercid) spectrum of activity

gram positive resistant bacteria -- end of the line if nothing else works