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201 Cards in this Set

  • Front
  • Back
Where do protein synthesis inhibitors start to work?
From mRNA on
Steps in protein synthesis
Initiation
Elongation
Translocation
Termination
Parts of the initiation complex
30S + IFs + mRNA
AUG (start codon) + N-fMet-tRNA
50S
Direction that AA move in ribosome and description of each site
A - new tRNA
P - tRNA with peptide chain
E - torqued to pry tRNA from mRNA
Role of EF-Tu
delivers aa-tRNA to A site and gives energy for peptide bond formation
Role of EF-G
gives energy for translocation
Where do most drugs bind the ribosome?
at RNA (not protein)
Mupirocin - target
isoleucyl-tRNA-synthase
Mupirocin - MOA
prevents isoleucine-tRNA formation
Mupirocin - static or cidal
static
AG - synthetics
Amikacin (S)
Isepamicin (M)
Netilimicin (M)
Mupirocin - spectrum
Gram positive only (due to LPS on G-, large molecule)
Staph aureus
Strep pyogenes
Mupirocin - source
Pseudomonas fluorescens
Mupirocin - use
topical only (selective and non-toxic but esther is rapidly hydrolyzed)
nasal Staph carriers (HCW)
Aminoglycosides - drugs
Streptomycin
Kanamycin
Tobramycin
Neomycin
Amikacin
Gentamicin
Sisomicin
Isepamicin
Netilimicin
AG - Streptomyces sourced
Streptomycin
Kanamycin
Tobramycin
Neomycin
AG - Micromonospora sourced
Gentamicin
Sisomicin
How is Streptomycin different from other AGs?
no deoxystreptamine (2 sugars instead of three)
one-step resistance (change in S12 protein)
Streptomycin - target
16S rRNA on 30S (near interface)
S12 protein assisted (proofreading protein)
Streptomycin - static or cidal
cidal (irreversible binding and frame shift mutations)
Streptomycin - MOA
A-site blocked (fMet-tRNA cannot bind)
Blocks IF3 binding (mRNA cannot bind)
A-site distortion into error-prone 30S conformation (frame-shift mutations)
AG - general RNA binding mechanism
AG+ (NH)
RNA- (PO4)
AG - static or cidal
cidal (irreversible and misreading)
AG - MOA
protein synthesis inhibition by 30S binding (O2 and pH dependent)
- inhibit translocation
- premature peptide release
- misreading, faulty proteins
AG - spectrum
Enterobacteriacae
Pseudomonas aeruginosa
Acinetobacter spp.
Staphylococcus aureus
NO ANAEROBES
NO LOW pH
AG - mechanisms of resistance
Alteration in target site
Efflux pump
Impermeability (anaerobes)
Enzymatic (AGIEs) - major mechanism
Methylate 16S-rRNA (what producers do)
AG - spectrum of AGIE resistance (least to most)
Gentamicin
Tobramycin
Amikacin - resistant

(will not report Amikacin sensitivity if bug is Tobramycin S)
AG - AGIE names
AG acetyltransferases (AAC)
AG adenylytransferases (ANT-nucleotidyl)
AG phosphotransferases (APH)

numbers denote site of modification
AG - oral
yes, but poorly absorbed
GI infections only
bowel surgery
hepatic coma
Streptomycin - resistance mech
one-step chromosomal gene mutation of S12 protein (no cross-resistance with this change)
AGIEs (affect all AGs)
AG - injection
IV or IM, especially for systemic infection
Restricted to serious G-
- Pseudomonas (often w/ Pens)
- Proteus
- E. coli
- KES
AG - topical
large wounds
surgical bowel lavages
AG - volume of distribution
equal to ECF (body water)
0.25 L/kg
AG - increase drug dose
CHF
Peritonitis
Ascites
Edema
AG - decrease drug dose
Dehydration
AG - poor penetration
ocular fluid
CSF (intrathecal for meningitis)
adipose tissue
AG - good penetration
synovial fluid
peritoneal fluid
URINE (100x serum)
AG - route of elimination
excreted unchanged in urine
GFR estimator
AG - renal dysfunction
significant accumulation
AG - hepatic dysfunction
no effect
AG - dialysis
removes up to 50% of drug
AG - SE
ototoxicity
nephrotoxicity
neuromuscular blockade
hypersensitivity rxn
injection site rxn
AG - ototoxicity
8th cranial nerve damage from hair cell or vestibular apparatus damage
auditory = reversible, tinnitus
vestibular = irreversible, NVD, vertigo, nystagmus, difficulty walking
AG - nephrotoxicity
more common
usually reversible
acute tubular necrosis with accumulation in proximal tubular cells
occurs at >5 days of tx
gradual rise in BUN and SCr (monitor 2-3x week)
AG - nephrotoxicity risk factors
advanced age
renal dysfunction
liver dysfunction
duration of therapy
nephrotoxic drugs (amphotercin B, radiocontrast, furosemide)
obesity (tend to overdose)
volume depleted (tend to overdose)
shock/sepsis (decrease renal perfusion)
AG - neuromuscular blockade
rare
reverse w/ Ca gluconate
AG - neuromuscular blockade risk factors
anesthesia
myasthenia gravis
hypocalcemia
hypomagnesemia
CCBs
AG - target
multiple 30S sites
AG - Beta-lactams DI
synergy vs G+ and G- aerobes
- low dose for G+ (80 mg)
- high dose for G- (120 mg)
precipitates out in IV bag (ion pair)
inactivates Pen in bloodstream (amine attacks B-lactam)
pipercillin/tazobactam is Y-site compatible (EDTA)
AG - Vancomycin DI
synergy vs Enterococcus, Staphylococcus and Streptococcus
G+ so use low dose (80 mg)
AG - resistant to AGIEs
amikacin
netilmicin
(not resistant to all AGIEs)
AG - AGIE MOA
adenylate
aceylate
phosphorylate
AG - mechanism of AGIE resistance
block key amino group
- 2-OH-4-NH2-butyrate (amikacin)
- ethyl group (netilmicin)
Gentamicin - use
synergy for G+ and G-
inhalation for difficult respiratory infections
opthalmic ointment and solution
Tobramycin - use
synergy for G+ and G-
inhalation for difficult respiratory infections
opthalmic ointment and solution
Amikacin - use
synergy for G+ and G-
inhalation for difficult respiratory infections
opthalmic ointment and solution
Kanamycin - use
irrigation
Neomycin - use
oral bowel preparation
topical ointment
AG - traditional vs extended-interval
toxicities associated with number of doses per day, not peak level
uptake into hair cells and nephrons is saturable
can give much higher amounts (5-6x) with the same risk of toxicity
AG - monitor trough
prevent accumulation
prevent toxicity
AG - monitor PK and 12 hr
efficacy
ensuring bactericidal
AG - no levels
minimal effort
reducing cost
fine esp if short-term (3-5 days)
AG - random (8 h)
prevent low AUCs and drug accumulation
identifying pts with extreme levels
Tetracyclines - structure
napthacene carboxamide
not planar (first 3 rings are, 4th at right angle)
bottom part chelates metal, cannot be altered
right side also cannot be altered
Tetracyclines - drugs and generation
Chlortetracycline (1st)
Demeclocycline (1st)
Tetracycline (2nd)
Doxycycline (2nd)
Minocycline (2nd)
Tetracyclines - sources of instability
H+ (prolonged exposure)
OH- (don't expose to base, usually not a problem)
salt formation (HCl supersolution forms if stored for too long)
chelation (don't take w/ dairy, antacids, etc)
Tetracyclines - patient instructions
take 1 hr ac or 2 hr pc
do not take with dairy or antacids
take all of the drug
do not take out of date
take with a full glass of water
Tetracyclines - target/MOA
reversibly binds 30S at interface
chelates Mg to block A site
stops elongation
Tetracyclines - selectivity
binds to 30S (bug) and 40S (us)
TC carrier confers selectivity
Tetracyclines - mechanisms of resistance
block carrier (plasma-mediated antagonist)
ribosomal alteration to prevent binding - major mechanism
efflux pumps
Minocycline - uses
serious G+ skin infections
maybe MRSA?
Tetracyclines - efflux pumps
Tet(A) and Tet(D) translocases
TC/H+ antiporter
from Streptomyces
Tetracyclines - side effects
GI upset (N/V, anorexia, epigastric burning, caustic to mucosa)
superinfection
hepatotoxicity (esp in pregnancy, rare but fatal, more in tetra)
teeth/bone hypoplasia
mottling of teeth (mid-preg to 8 yo)
photosensitization
nephrotoxicity (Fanconi Syndrome, expired drug)
hypersensitivity (rare)
neurotoxic (not common)
Tetracyclines - Superinfection
done by bugs that are generally resistant

Candida
Staph (bloody diarrhea)
C. difficile (pseudomembranous colitis, watery diarrhea)

begins with the first dose but takes time for symptoms to appear
Tetracyclines - static or cidal
static
Tetracyclines - spectrum
G+ aerobes (MSSA, not Enterococcus)
G- aerobes (acquired resistance is common)
anaerobes (esp G-, Bact)
Mycoplasma, Chlamydia, Rickettsiae, B. burgdorferi
Tetracyclines - absorption
tetracycline = 60-80% (decreased by 50% with food)
doxy/mino = 90-100% (food does not effect)
Doxicycline - advantages over other tetracyclines
much lower dose needed (100 v 250)
longer half-life (QD v QID)
not as likely to mottle (weaker chelation)
can take with meals
very well absorbed (less GI flora disruption)
alpha-1 acid glycoprotein
binds drugs like albumin does
- macrolides
- clindamycin
- tetracyclines
fluctuates based on stress, infections, etc.
binding fluctuates also
probably not an issue except in severe legionella
Tetracyclines - protein binding
to alpha-1 acid glycoprotein
doxy 90%
mino 76%
tetracycline 65%
Tetracyclines - tissue penetration
poor CSF penetration
mino > doxy > tetra
Tetracyclines - routes of elimination
tetra = renal (6-12 hr)
doxy = feces (15-24 hr)
deme = renal/feces
mino = metabolism (not P450, 11-22 hr)
Tetracycline - pregnancy category
D
crosses placenta and enters breast milk
Tetracycline - drug interaction with cations
divalent and trivalent
decrease absorption
Ca, Mg, Al, Fe, Na Bicarb, cimetidine, milk
Tetracycline - drug interaction with penicillin/AGs
antagonism (cidal + static)
Tetracycline - drug interaction with oral contraceptives
lower effectiveness of OC
impaired bacterial hydrolysis of conjugated esters
Tetracycline - drug interaction with anesthesia
Methoxyflurane anesthesia
fatal nephrotoxicity
Doxycycline - drugs that increase metabolism
carbamazepine
phenytoin
barbiturates
Tetracycline - uses
Rickettsia infections
STDs (chlamydia)
Anthrax
Lyme disease (DOC for B. burgdorferi)

URTI and LRTI if pt cannot tolerate macrolides
Glycylcyclines - efflux pumps
substrate for uptake but not for efflux pump
Tetracycline - dosing
tetra - 250-500 mg po qid
doxy - 100 mg po/IV q12h
mino - 100 mg po/IV q12h

(could give 200 mg qd but increases GI upset)
Glycylcyclines - drugs
tigecycline (derived from minocycline)
Glycylcyclines - structural difference
glycine residue
Glycylcyclines - MOA
same as tetracycline (chelation of Mg on 30s subunit, blocks A site)
binding is 5x higher
Glycylcyclines - spectrum
G+ aerobes including MRSA, VRE
G- aerobes including ESBL and Acinetobacter, NOT P. aeruginosa
Anaerobes
Atypicals
Glycylcyclines - absorption
poor
IV only
Glycylcyclines - volume of distribution
large (10 L/kg)
Glycylcyclines - metabolism/elimination
hepatic metabolism (not P450)
billiary/fecal elimination
not for UTI's
36 hr
Glycylcyclines - dosing
100 mg LD with 50 mg IV q12h
(doesn't match t1/2, but GI AE to >90% at QD dosing)
Glycylcyclines - side effects
similar to TC (limited data)
GI (N/V/D, dose-dependent)
CNS
Glycylcyclines - uses
complicated skin/skin-structure infections
intra-abdominal infections
CAP (under study)
not for bloodstream or UTI's
Glycylcyclines - penetration
extremely good into tissue
very little left in blood
MIC = 0.5-2, Cmax = 0.87 (do not use in bloodstream infections)
Macrolides - 14-membered drugs
erythromycin
clarithromycin
dirithromycin
roxithromycin
Macrolides - 15-membered drugs
azithromycin
Macrolides - spectrum
G+ aerobes
- S. aureus (MSSA)
- S. pyogenes, S. pneumoniae
G- aerobes
- H. flu (not erythromycin)
- M. cat
- NOT: E. coli, Kleb, Enterobacter, P. aeruginosa, Acinetobacter
Intracellular organisms
- Chlamydia
- Mycoplasma (DOC)
- Legionella (DOC)
- Camphylobacter
Mycobacterium

No enterococcal or MRSA activity
Macrolides - source
Streptomyces erythreus (erythromycin)
Macrolides - instability
acid unstable
forms a hemi-ketal which inactivates drug and irritates stomach
deal with pain or enteric coat
Macrolides - target/MOA
binds 23S of 50S
blocks peptide exit tunnel
derails translocation
premature peptide release
Macrolides - specificity
does not bind mammalian ribosome
Macrolides - static or cidal
static (low conc) - generally static b/c reversible

cidal depends on
- high concentration at site
- organism
- inoculum size
Macrolides - mechanism of resistance
methylation of 23S rRNA
mutation of rRNA
esterases
efflux pumps
Macrolides - bacteriocidal combinations
Erythromycin
- S. pneumoniae
- S. pyogenes

Clarithromycin, Azithromycon
- H. influenzae
- S. pneumoniae
- S. pyogenes
Macrolides - methylation of 23S rRNA
by the ermB gene (erythromycin ribosome methylation)
N,N-dimethylation of Ad2058 (domain 5)
MLS resistance
common in European S. pneumo
Macrolides - efflux pump
more common US S. pneumo
mef, msr and vga (mefA primarily)
confers low-level resistance that can be overcome
Macrolides - distinguishing modes of resistance
clindamycin has the same target site but is not touched by the efflux pump
Macrolides - oral bioavailability drugs
Roxithromycin (72-85%, oral only)
Clarithromycin (55%, w/ or w/o food, oral only)
Azithromycin (37%, take w/o food, also IV)
Erythromycin (25-60%, also IV)
Dirithromycin (6-14%)

oral forms are stepdown therapy (do not give oral azithromycin to the elderly or hospitalized)
Macrolides - distribution
very lipophilic
large volume of distribution
high intracellular concentrations (esp macrophages, pump drug into other cells)
tissue and cellular conc > plasma
Macrolides - protein binding
alpha-1 acid glycoprotein
Macrolides - tissue penetration
does not penetrate BBB (not for meningitis, also static)
crosses the placenta
Macrolides - metabolism/elimination
eryth/clarith = P450 3A4 to active metabolites

azith = metabolized but not by P450 (fewer drug interactions)

dirith = metabolized by P450 but too slow to cause interactions
Macrolides - side effects
Clarithromycin and azithromycin are better tolerated and have fewer SE than erythromycin.

GI (most common, hemi-ketal, erythromycin)
hepatotoxicity (rare but serious, bile excretion, builds up in liver if already damaged)
ototoxicity (reversible)
thrombophletis (IV, esp erythromycin)
allergic rxns (rare)
QTc prolongation (clarithromycin and erythromycin)
Macrolide - drug interactions
TDP through 3A4 inhibition (CI)
- Astemizole (withdrawn)
- Cisapride (withdrawn)
- Ergotamine
- Terfenadine (withdrawn)

P450 inhibitors used in combination for mycobacterium
- rifampin
- rifabutin

inhibit the P-glycoprotein
Macrolides - uses
Mediterranean spotted fever (rickettsia)
Lyme disease (B. burgdorferi)
MAC
PUD (H. pylori)
STDs
Endocarditis prophylaxis (if pen allergic)
Skin and soft tissue (if pen allergic, less now with MRSA)
LRTI (CAP, COPD exacerbation)
URTI (improper, most are viral)
Clarithromycin - dosing
IR: 250-500 mg po bid
XL: 1 g qd (two tablets, must be taken together)
Azithromycin - dosing
Z-pak: 500 mg po day 1, 250 mg po qd for days 2-5 (URTI)
1 g x 1 day (?)
2 g x 1 day
500 mg po x 3 days
500 mg po or IV qd (500 mg po is the proper step down therapy, not a Zpak)
Dirithromycin - dosing
500 mg po qd
Clarithromycin - structure
-OCH3 prevents hemi-ketal
- more stable
- less GI irritation
- higher levels allow BID dosing

first-pass metabolism to active OH

same P450 issues
Clarithromycin - uses (v. Erythromycin)
more potent for G+
More potent for URTI (Strep, H. flu, Mycoplasma)
More potent for Chlamydia
Used for disseminated TB
Dirithromycin - structure
like erythromycin with a linker that makes it act like a depot formation
not a prodrug b/c linker decomposes spontaneously
major advantage: qd dosing
enteric coat
Amino erythromycin (NH2 replaces ketone)
no P450 issues (like azithromycin)
Azithromycin - structure
15-membered azilide
more lipohilic (replace ketone with NCH3)
- PML's pump into cells
- longer t1/2 (qd dosing)
- no P450 issues

enhanced G- (?)
Ketolides - structure vs. macrolides
also 14-membered
replace two OH's with carbamate
- blocks efflux pump
- tighter ribosomal binding (2 places)
remove one sugar and add a ketone
- enhanced with respiratory pathogens
- enhanced activity
- prevent MLS resistance
change OH to OR
- enhanced acid stability
Ketolides - target
23S rRNA
binds strongly to domain 5 AND domain 2
Ketolides - resistance v. macrolides
not a substrate for efflux pump
not effected by MLS resistance
DOES NOT INDUCE MLS RESISTANCE
Ketolides - drugs
telithromycin
Ketolides - spectrum
same as macrolides + multi-drug resistant S. pneumoniae
Ketolides - absorption
oral formulation only
57%
unaffected by food
Ketolides - distribution
large VD
60-70% protein bound
Ketolides - uses/indications
had most indications removed when black box was added
CAP
macrolide-resistant pneumococci
Ketolides - elimination
metabolism
P450 interactions
Ketolides - side effects
black box: CI in myasthenia gravis
liver damage (severe: transplants, fatalities)
vision problems (accommodation, esp in women <40 yo)
fainting
Ketolides - CI
hypersensitivity to telithromycin or macrolide
Cisapride (withdrawn)
Primozide (antipsychotic)
Ketolide - drug interactions
Statins
- atorvastatin
- lovastatin
- simvustatin

Antiarrhythmics
IA
- quinudine
- lidocaine
- procainamide
III
- amiodarone
- bretylium
- ibutilide
- sotalol
Ketolide - dosage
CAP: 800 mg qd for 7-10 days
Telithromycin - structure
long arm off of carbamate binds to domain 2
Lincomycin - source
Streptomyces lincolnensis
Clindamycin - source
semi-synthetic lincomycin
Clindamycin - structure vs. lincomycin
replace R with Cl (20x more lipophilic, better bacterial penetration)
Lincomycin/Clindamycin - target
23S rRNA of 50S
overlaps erythromycin site, but distinct (not domain 5)
blocks peptidyl transferase (peptide bond fools PTC)
Clindamycin - spectrum
G+ aerobes
- not enterococcus or MRSA
G+ and G- anaerobes
Protozoa

G- aerobes are resistant
Clindamycin - absorption
oral well absorbed w/ or w/o food
IM well absorbed
palmitate ester suspension well absorbed (hydrolyzed to active base)
Clindamycin - distribution
binds to alpha-1 acid glycoprotein (concentration dependent)
poor CSF penetration
good tissue penetration
Clindamycin - excretion
metabolized (85%)
eliminated in bile

not removed in HD or PD
no adjustment for renal dysfunction
Clindamycin - side effects
GI (most common)
- NVD
- metallic taste
- antibiotic-associated colitis (C. diff, potentially fatal)
hypersensitivity
transient LFT increase
hematologic
Clindamycin - uses
B. frag (and other PCN-resistant anaerobes outside CNS)
- abdominal
- PID
- pulmonary
C. diff (alternative to PCN)
alternative for Staph and Strep
acne vulgaris
community-acquired MRSA
toxoplasmosis and PCP in AIDS
Clindamycin - dosing
Oral
mild: 150-300 mg po qid (or tid for GI)
severe: 300-450 mg po qid

Parenteral
mild: 300-600 mg q8h
severe: 600-900 mg q8h
Clindamycin - resistance
MLS resistance (b/c target is close to macrolide binding site)
Chloramphenicol - source
Streptomyces venezuelae
Chloramphenicol - target
same as clindamycin

50S rRNA
inhibits peptidyl transferase (resembles peptide)
stops elongation
partial overlap with erythromycin
Chloramphenicol - uses/dosage
brain abscess: 100 mg/kg/day
meningitis: 100 mg/kg/day

typhoid fever: 50 mg/kg/day
rickettsial infection: 50 mg/kg/day (when tetracyclines and macrolides don't work/aren't tolerated)
Chloramphenicol - spectrum
G+ and G- aerobes
- Salmonella typhi (DOC)
G+ and G- anaerobes
- B. frag
Spirochetes
Rickettsia
Chlamydia
Mycoplasma

meningitis
- H. flu (was ampicillin, now vaccinate)
- Strep
- Neisseria
Chloramphenicol - side effects
Penetrates mitochondria, 70S rRNA
- blood dyscrasias
- dose-dependent BM suppression
- idiosyncratic aplastic anemia (1:25,000-40,000, fatal)
- hemolytic anemia (drug deposition?)

Gray Baby Syndrome
- lack glucuronidation, poor excretion
- cyanosis
- 40% fatal

Hemorrhage
- reduce Vit K (gut flora)
- inhibit P450 warfarin metabolism

CNS (penetrates BBB)
- optic/peripheral neuritis
- HA
- depression
- mental confusion
Chloramphenicol - resistance
enzymatic (acetylation)
not common
Chloramphenicol - absorption/formulations
suspension: palmitate ester
- hydrolyzed by lipases in small intestines

Capsule: free base
- does not need to be hydrolyzed

IV: succinate
- undergoes hydrolysis
Chloramphenicol - distribution
large Vd (~100 L, wide)
penetrates CSF
bound to albumin
lipophilic
Chloramphenicol - excretion
metabolized by glucuronidation
10-15% in urine (not for UTI)
half-life of 4-6h
monitor peak and trough
Polymixins - drugs
polymixin B
colistatin (polymixin E)
Colistin - formulations
sulfate: oral or topical
methane sulfate: IV (hydrolyzed to active)

sulfate is 4-8x more active
Polymixins - target
bacterial cell wall
Polymixins - static or cidal
static at low concentrations
cidal at high concentrations
Polymixins - spectrum
G- aerobes
- P. aeruginosa
- Acinetobacter baumannii

(respiratory)
Polymixins - distribution
poor into the following
- synovial
- pleural
- CSF
- adipose
Polymixins - excretion
renal (requires adjustment)
normal half-life: 6 h
anuric half-life: 2-3 d
not removed by HD (unlike AG)
Polymixins - side effects
not seen as often, maybe doing dosing better

nephrotoxicity (higher than AG)
- acute tubular necrosis
neurotoxicity
- in renal impaired
- can cause respiratory failure
injection site reaction
- fever
- rash
- pain
Polymixins - uses
G- negative infections, esp with MDR Pseudomonas and Acinetobacter
- pneumonia
- bacteremia
- wound infections
- UTI
Streptogramins - target
23S rRNA of 50S
Streptogramins - static or cidal
cidal (irreversible binding)
Streptogramins - structure
macrocyclic peptide
Streptogramins - source
Streptomyces graminofaciens
Linezolid - target
23S rRNA of 50S
bind initiation complex, cannot translocate

allows assembly but not procession
Streptogramins - drugs
Synercide (quinupristin/dalfopristin)
- synergistic 30:70 ratio (16x more potent)
Streptogramins - domain targets
dalfopristin: domain 5
quinupristin: domain 2

link together
Streptogramins - resistance
does not induce MLS resistance
susceptible to MLS resistance

blocks dalfopristin binding
quinupristin cannot link
Linezolid - static or cidal
Burgess: static

Davis: static (Enterococci) or cidal (Strep)
Streptogramins - spectrum
G+ only

Entercoccus faecium (vanco-resistant)
MRSA, MRSE
Streptococcus

Not active against E. feacalis!
Streptogramins - side effects
infusion site rxn (>30%)
thrombophlebitis
GI (NVD)
arthralgia and myalgia cause DC
Linezolid - resistance
no cross-resistance b/c a novel mechanism
23S rRNA mutation
- seen even in trials
- hospital-wide outbreaks of resistance
Streptogramins - dosing
7.5 mg/kg IV q8-12
central line preferred (thrombophlebitis)
infuse over 1 hr
D5W only (flush with D5W too)
only 5 hrs at room temp (54 in fridge)
Linezolid - spectrum
G+ aerobes
- MRSA
- VRE. faecium
- Entercoccus faecalis
Streptogramins - absorption
poor
IV only
Streptogramins - distribution
large Vd
Linezolid - absorption
excellent (100%)
IV or oral
Streptogramins - elimination
metabolized (not much P450)
fecal excretion

less than 1 hr t1/2
Streptogramins - uses
VRE (no longer 1st choice, 3rd or 4th)

Not used for any longer
- nosocomial pneumonia
- skin and skin structure
- CAP
Linezolid - distribution
40-50L (large)
31% bound (not much)
oxazolidinones - drugs
linezolid (Zyvox)
eperezolid (pending approval)
Linezolid - excretion
metabolized by oxidation
no P450 effects
half-life: 5-7 hr
no dosage adjustment for hepatic or renal dysfunction
Linezolid - side effects
overall, well tolerated

GI (NVD)

CNS
- HA
- insomnia
- serotonin syndrome (MAOI)
- peripheral and optic neuropathy

LFT increases

Reversible BM suppression (long-term, 10-4 days, monitor CBC)
Linezolid - drug interactions
significant pressor response (increase BP)
- tyramine
- pseudoephedrine
- phenylpropanolamine

MAOI interactions
Linezolid - uses
HAP and CAP
skin/skin-structure infections (uncomplicated and diabetic foot infections)
- better for MRSA than Vancomycin
VRE

Deep infections (surprising with a static drug)
- endocarditis
- bone and joint infections

NOT FOR CATHETER-RELATED INFECTIONS (use Vanc)
Linezolid - dosage
600 mg po or IV q12h
10 mg/kg IV or po q8h (peds)
Streptomycin - uses
Plague
TB (combo therapy)
Enterococcus

shortage issues b/c only one manufacturer