Synercid, Linezolid, Daptomycin, And Rifampin

Front 1

synercid consists of

Back 1

quinupristin
dalfopristin

Front 2

what abx are cidal vs entercoccus?

Back 2

none

Front 3

moa of synercid

Back 3

- protein synthesis inhibitor
Irreversibly binds to different sites on the 50S bacterial ribosomal subunit

Front 4

quinupristin moa

Back 4

Inhibits late phase (polypeptide chain elongation) and early termination of protein synthesis

Front 5

dalfopristin moa

Back 5

binds at a sequential site on 50S ribosomal subunit
- Directly interferes with early phase (peptidyl transferase inhibition, resulting in a conformational
change in the 50S subunit of the bacterial ribosome)
- Synergistically enhances binding of quinupristin

Front 6

synercid resistance moa

Back 6

- ribosome modification
-drug inactivation (q +d)
-active transport : effux pumps (d)

Front 7

synercid spectrum of activity

Back 7

Gram (+): Enterococcus faecium (including VRE) but NOT E. faecalis
- Staph aureus (including MRSA, VISA), Staph epidermidis (including MRSE)
- Strep pneumoniae (including PCN-R), Strep pyogenes, agalactiae, Viridans group Strep
- Corynebacterium jeikeum

Anaerobes: Clostridium sp., Peptostreptococcus, Fusobacterium

Others: Legionella pneumophila, Mycoplasma pneumoniae, Chlamydophila pneumoniae, Moraxella
catarrhalis, Neisseria gonorrheae, Listeria monocytogenes

Front 8

synercid covers enterococcus faecium or e faecalis

Back 8

faceium

-faceium- resistant
-faecalis- common

Front 9

synercid
basteristatic vs
bactericidal vs

Back 9

static- enterococcus
cidal- staph, strep

Front 10

synercid covers gram neg ?

Back 10

yes

Front 11

which is cheaper vanco or synercid

Back 11

vanco

Front 12

synercid

which is dosed more frequently vaco resistance e faceium or complicated skin and soft tissue infections

Back 12

- vre: q8h, tx more aggressively
- skin infections: q 12 hrs

Front 13

synercid is absorbed orally?

Back 13

no, not orally absorbed

Front 14

synercid metabolism

Back 14

- hepatic metabolism

Front 15

synercid inhibts what cyps

Back 15

cyp 3a4

Front 16

synercid elimination

Back 16

Elimination
- Biliary and fecal: 80%; Renal: 15-19%

-mostly hepatic

Front 17

explain synercid pae effect

Back 17

prolonged post antibiotic effect (hrs)

Front 18

when do you dose adjust for synercid

Back 18

-NO dosage adjustment in renal disease or hemodialysis
-Patients with liver impairment may require a dose adjustment

Front 19

t/f
dialysis patients need dosage adj for synercid

Back 19

false bc mostly hepatic elimination, need dosage adj for hepatic metab

Front 20

synercid is infused in peripheral or central line?

Back 20

it is infused in a central line

Front 21

synercid adr (3 mains ones)

Back 21

Infusion-related
- Inflammation (42%)
- Pain (40%)
- Edema (17%)

- Hyperbilirubinemia (up to 35%)

-Arthralgia, myalgia (~ 10%): more likely in patients with hepatic insufficiency and may be due to
accumulation of metabolites, therefore it is recommended that the frequency be decreased to Q12H

Front 22

main drug interaction w/ synercid

Back 22

Potent CYP3A4 - inhibitor

other
Non-Nucleoside Reverse Transcriptase Inhibitors, Protease inhibitors
Calcium channel blockers, HMG-CoA reductase inhibitors
Cyclosporine, tacrolimus
Warfarin
Carbamazepine.... and more !!!

Front 23

synercid is administered how?

Back 23

iv only!!!
Prefer infusion via central venous catheter

Front 24

iv bag compatability of synercid

compatible w/?
incompatible w/?

Back 24

incompatable w= saline and heparin

compatable w= dextrose

Front 25

how long do u infuse synercid

Back 25

60 mins

Front 26

synercid should be reserved for

Back 26

reatment of serious infections
caused by multiple-drug-resistant gram-positive organisms (ie VRE) !!

-mrsa

Front 27

linezolid belongs to what class

Back 27

oxazolidinone class

Front 28

brand name of linezolid

Back 28

zyvox

Front 29

linezolid is avail

Back 29

- iv
-po

Front 30

linezolid moa

Back 30

- Protein synthesis inhibitor
- Binds to 23S subunit of the 50S subunit preventing formation of
the 70S ribosome complex that initiates protein synthesis

Front 31

linezolid mech of resistance

Back 31

In vitro
- Point mutations in 23S ribosomal RNA of 50S ribosomal subunit
- More difficult to generate E. faecium resistant to linezolid than Synercid
- Unique chemical structure makes cross resistance with other antibiotics unlikely

Acquired resistance
- Slow development and infrequent
- Case reports of VRE. faecium becoming resistant to linezolid during its clinical use
- When antibiotic-resistant organisms are encountered in the hospital, it is important to emphasize
infection control policies

Front 32

linezolid vs synercid moa (main diff)

Back 32

linezolid covers both: Enterococcus faecium (including VRE)
- Enterococcus faecalis (including VRE)
(has both l and e, so covers faceium, and facalis)

synercid only covers faceium
(only has an e)

Front 33

linezolid spectrum of activity

Back 33

Gram (+)
- Enterococcus faecium (including VRE)
- Enterococcus faecalis (including VRE)
- Streptococcus pneumoniae (including penicillin-resistant strains)
- Streptococcus agalactiae, Streptococcus pyogenes, Viridans group streptococci
- S. aureus (including MRSA, VISA)
- Staph epidermidis (including MRSE)

Anaerobes
Prevotella sp, Peptostreptococcus
Fusobacterium spp
Cl. perfringens (NOT C. difficile)
Bacteroides spp (poor activity)

Others
M. pneumoniae, M.TB
Corynebacterium spp, Bacillus spp
Nocardia spp, Listeria monocytogenes
Measurable in vitro activity against Moraxella, H. influenzae, Legionella, Neisseria, Bordatella, but
unclear clinical significance

Front 34

linezolid
statis vs
cidal vs

Back 34

static vs: enterococcus, staph
cidal vs: strep spp (gram +)

Front 35

linezolid absorption

- po absorption?
- affected by food?
- bioavail: po, iv
- formulations avail

Back 35

-Rapid and complete
- NOT affected by food
- Bioavailability: IV=PO
- Available as oral suspension, tablets, and IV

Front 36

linezolid metabolism
- metabolised by cyp 450?
- dosage adjustment?

Back 36

- Not metabolized by CYP450
- No inhibition or induction of major CYP450 isoforms
- NO dosage adjustment in mild-mod hepatic disease

Front 37

comp synercid metab and linezolid

Back 37

-synercid needs hepatic dosage adj, does not need dosage adj after dialysis
- linezolid requires no dosage adj in mild-mod hepatic disease or renal insuff and is not a cyp 450 inhibitor, need to schedule medication after dialysis because hemodialysis removed drug

Front 38

dosing for linezolid

Back 38

- adults q 12 hrs
-peds: birth-11: q 8 hrs
12 += q 12 hrs

Front 39

can you give synercid to kids ?

Back 39

no, not approved for ages 16 and under

Front 40

adr of linezolid

Back 40

-
- Tongue discoloration
- Taste perversion

-Headache

-Peripheral and optic neuropathy = vision changes

-Myelosuppression
- Usually occurs after 2 weeks of therapy, but may occur before then.
- Thrombocytopenia
- Anemia
- Leukopenia
- Pancytopenia

Front 41

main adr of linezolid

Back 41

myelosuppression

Front 42

what would you monitor for in a patient on linezolid therapy

Back 42

- visual changes
- blood work values changes: hb/hct
- inc bleeding or brusing
- routine labs

Front 43

drug interactions w/ linezolid

Back 43

-NO effect on cytochrome P450 system

-Reversible MAO-Inhibitor
- Seretonergic agents: SSRI antidepressants

- Adrenergic agents: pseudoephedrine, phenylpropanolamine, foods containing high
content of tyramine ( ≥ 100 mg per meal)

Front 44

food that contain tyramine

Back 44

- cheese
- fermented/ air dried meats
- soy sauce
-beer
-wine

Front 45

what would you monitor for a patient receiving linezolid and dopamine in the icu?

Back 45

pressor response- monitor bp, hemodynamics

Front 46

What potential clinical manifestations may occur if a patient received linezolid and prozac?

Back 46

-seratonin syndrom: fever, inc bp, happy drunk, agitated state

Front 47

patient education of zyvox

Back 47

- Check with your prescriber or pharmacist before taking any non-prescription medicines while on this antibiotic
- Do not treat yourself for coughs, colds, or allergies
- Do not take any medications for weight loss
- Some ingredients in these products may increase possible side effects

Linezolid can interact with certain foods that contain significant amounts of tyramine to produce severe headaches, a rise in blood pressure, or irregular heart beat.
- Aged cheeses; smoked, pickled, or processed foods such as bologna, pepperoni, salami, sausage;
beer and ale; wine (especially red); sherry; hard liquor; liqueurs; avocados; bananas; figs; raisins;
soy sauce; miso soup; yeast/protein extracts; bean curd
- inc bleeding bc it causes mylosuppression
- vision changes
- tongue discoloration
-taste perversion

Front 48

zyvox should be reserved for ?

Back 48

treatment of serious infections
caused by multiple-drug-resistant gram-positive organisms (ie VRE) !!

0r mrsa, people who have failed vanco

Front 49

daptomycin brand name

Back 49

cubicin

Front 50

daptomycin is in what class

Back 50

lipopeptides

Front 51

daptomycin moa

Back 51

-unique
-Acts at the cytoplasmic membrane
-Binds to bacterial cell membrane via calcium-dependent insertion of its lipid tail forming an ion-conduction structure
Hypothesized to rapidly depolarize the cell membrane via an efflux of potassium (and possibly other
ions) destroying the ion-concentration gradient
Disruption of DNA, RNA, and protein synthesis Cell death

Front 52

daptomycin is static or cidal?

Back 52

bactericidal

Front 53

daptomycin spectrum of activity

Back 53

only gram + bacteria

S. aureus (including MRSA), S. pyogenes, S. agalactiae,
E. faecalis (vancomycin-susceptible strains only)

Front 54

pk of daptomycin
- half life
-protein binding
-tissue distrubtion
- renal excretion
-not extensively metabolized

Back 54

Half-life = 8.1 hours
Protein binding = 92%
Poor lung penetration do NOT use in pneumonia
Renal excretion = ~78%
Not extensively metabolized

Front 55

can u use daptomycin in pneumonia

Back 55

no, bc has poor lung penetration

Front 56

daptomycin dosing
- what are the 2 indication for dosing
- what the specific dosages

Back 56

- skin and skin structure infections
- bacteremia/right sided endocarditis

skin and skin structure infections
>30 ml/min = 4mg/kg q24h
<30 ml/min= 4 mg/kg q48 h

bacteremia/right sided endocarditis
>30 ml/min = 6mg/kg q24h
<30 ml/min= 6 mg/kg q48 h

Front 57

daptomycin requires dosage adj for?

Back 57

Hepatic impairment
- Mild to moderate: no dose adjustment recommended
- No data for patients with severe hepatic dysfunction

Front 58

daptomycin use in kids?

Back 58

no,
Pediatrics: safety and efficacy of daptomycin have not been established

Front 59

adr of daptomycin

Back 59

- gi: nausea, constipation, diarrhea, and vomiting
- injection site rxn, rash
- fever,headache, insomnia, dizziness
- elevated lfts
-signs and syx of neuropathhy, mainly peripheral neuropathy (rare)
-elevated cpk levels

Front 60

daptomycin adr is elevated cpk levels, is a imp paramets bc

Back 60

-Monitor for unexplained muscle pain and weakness
- Serum CPK levels should be monitored weekly
- Daptomycin should be discontinued if
1. (+) s/sx of myopathy and CPK levels of 5X upper normal limit (UNL = 200 U/L)
2. (-) s/sx of myopathy but CPK levels > than 10X UNL

Front 61

daptomycin drug interactions

Back 61

-Does not inhibit or induce cytochrome P450 isoenzymes 1A2, 2A6, 2C9, 2C19, 2D6, 3A4

- Tobramycin
- When tobramycin 1mg/kg was given with daptomycin 2 mg/kg decrease in Cmax and AUC
of tobramycin by 10.7% and 6.6% respectively
- However, daptomycin is normally dosed 4mg/kg... therefore, tobramycin levels should be
monitored closely if given concomitantly

HMG-CoA reductase inhibitors temporarily discontinue agents associated with rhabdomyolysis; if
used concomitantly, monitor CPK levels more frequently

Front 62

daptomycin admin
- what iv is compatablie?

Back 62

Mix in 0.9% sodium chloride over 30 minutes
Not compatible with dextrose containing solutions

Front 63

damptomycin and dextrose?

Back 63

-No
-incompatible w/ dextose
-only compatable with saline

Front 64

daptomycin is reserved for

Back 64

Reserve for use in patients with MRSA skin and skin-structure infections
or bacteremia or right-sided endocarditis
not responding to other antimicrobial therapies.

-Treatment option to consider for MRSA bacteremia when isolates are at the upper limit of what is considered “susceptible”.

Front 65

rifampin appears what color

Back 65

- reddish brown power

Front 66

rifampin is avail what formulations

Back 66

-iv
-po

Front 67

moa of rifampin

Back 67

- RNA synthesis inhibitor
-Binds to the beta-subunit of bacterial DNA-dependent RNA polymerase and inhibits RNA synthesis
-Rifampin does not bind to RNA polymerase in humans
-Readily penetrates most tissues and into phagocytic cells

Front 68

moa of rifampin

Back 68

rna synthesis inhibitor

Front 69

can you give rifamin monothrapy?

Back 69

no, will get resistanc. active infection give in combo tx purpsoe never alone

Front 70

spectrum of actiivty for rifampin

Back 70

- Gram (+): S. aureus (including MRSA)
S. epidermidis

Gram (-): PEcK
N. meningitides
H. influenzae

Others: Mycobacteria spp
Legionella pneumophila

Front 71

rifampin absorption?

Back 71

-Well absorbed after oral administration
-Food may decrease absorption
formulations : iv, po

Front 72

rifampin elimination

Back 72

- Excreted mainly through the liver into bile where it undergoes enterohepatic recirculation
Widely distributed in body fluids and tissues
High protein binding
Primarily excreted in feces via biliary elimination and a small amount is excreted in the urine

Front 73

rifampin adr

Back 73

Harmless orange discoloration to bodily fluids (urine, sweat, tears, soft contact lenses may be
permanently stained)
Rashes
Thrombocytopenia
Nephritis, proteinuria
Hepatic
- Increased LFTs (up to 14%)
- Cholestatic jaundice
- Hepatitis (rare)

Front 74

rifaminpin di

Back 74

-INH: additive hepatotoxicity
-Bactrim: may increase rifampin levels
-Antacids: may decrease its absorption
-Cytochrome P450 inducer

Front 75

elimination
synercid
linezolid
daptomycin
rafampin

Back 75

syn= hepatic
linezolid=hepatic
daptomycin=renal
rafampin=hepatic