PC2 MOD 3.3

glycopeptides

VANCO

missipi mud

VANCO MOA

inh cell wall synthesis

VANCO spec

has coverage until E. facieum

vanco PO can be given for C.diff

VANCO dosing

critically ill pts w/serious MRSA = LOADING DOSE 20-35 mg/kg

TDM VANCO

goal trough 10-20 mcg/mL

AUC/MIC

RATIO 400-600 CLINICAL EFFICACY (SAFETY)

TWO SAMPLES: PEAK= 1-2 HRS after infusion ends TROUGH= 30 min prior to next dose

VANCO AEs

nephrotoxicity seen with >4 g/day and in higher troughs & when using aminoglycosides or zozyn

ototoxicity

infusion reaction= histamine mediated

resistance in VANCO

enterococcus: VanA gene

• VRE

s. aureus: VanA gene

• VRSA

VANCO targets for MRSA

AUC/MIC 400-600

SERIOUS infection: trough 15-20 mg/L

low inoculum infections: trough 10-15 mg/L

VANCO dosing considerations

infusion times: at least one hour per G of vanco to reduce risk of infusion rxn

VANCO nomogram limitations

used for initial regimen selection, NOT FOR ADJUSTING once VANCO concentrations are available

lipoglycopeptides

telavancin

dalbavancin

oritavancin (orbactiv & kimyrsa)

LIPOGLYCO spec of activity

they cover up until VRE

unlike vanco it only covers up to E.facieum

lipoglyco resistance

VRE- harboring VanB resistance

poor activity against species w/VanA

telavancin (LIPOGLYCO)

MOA- interferes w/cell wall synthesis & binding to cell membranes, increased membrane permeability

telavancin AEs

soapy taste/metallic

caution in use w/pts that have renal dysfunction

telavancin drug interactions

co-administration w/heparin is contraindicated because we cant measure the effect of heparin accurately, tela interferes w/heparin monitoring measurements

LONG ACTING LIPOGLYCO

DALBAVANCIN

ORITAVANCIN BOTH FORMS

ORITAVANCIN LONG ACTING LIPOGLYCO

improves activity agains VSE & VRE

potent activity against MSSA, MRSA, VSE, VRE, & streptococcus sp

REMAINS ACTIVE AGAINST VanA VRE

also contraindicated with heparin for the same reason as telavancin

KEY POINTS FOR LIPOGLYCO

long half life

better spec of activity against G+, MRSA, and ENTEROCOCCUS

GLYCO MED CHEM

5 points of H bonding on peptide backbone that will bind to transpeptidase

sugar moieties

telavancin med chem

lipophilic side chain= more potency (better anchoring)

phosphonomethyl aminomethyl= more potency (ADME)

LIPOPEPTIDE MED CHEM

MOA= binds & depolarizes cell membranes

DAPTO SPEC of activity

covers until VRE

DAPTO AEs

myopathy & rhabdomyolsis

monitor CPK & serum creatinine

eosinophilic pneumonia

dapto resistance

diversion & repulsion

DAPTO SYNERGY W/B-LACTAMS

beta lactam exposure increases negative charge of cell surface leading to an increase in dapto binding

KEY POINT FOR DAPTO

DAPTO CANNOT BE USED TO TREAT PNEUMONIA BC IT IS INACTIVATED BY PULMONARY SURFACTANTS

linezolid oxalazidones

MOA= protein synthesis inh binding to the V domain of 23S RNA of 50s ribosomal unit

linezolid spec

until VRE

3 anerobes= prevotella, fusobacterium, clostridium sp

linezolid AEs

thrombocytopenia (hematological effects)

linezolid DDI

linezolid +SSRI/SNRI= serotogenic effect DO NOT USE TOGETHER

resistance LINEZOLID

mutations of the 23S RNA

cfr gene

alterations in ribosomal protein

tedezolid

active against CFR + strains

active against linezolid resistance MRSA

thrombocytopenia similar to linezolid

tetracyclines

MOA- inh bacterial protein synthesis by bind to 30s ribsomal unit

resistance- tet genes, efflux pumps,

tetracyclines spec of activity

none cover pseudo aeruginosa

only tige,erava, & omadacycline cover the resistant strains and up to enterococci &VRE

doxy & mino only cover up to MRSA

think SPIROCHETES & RICKETTSIAE & MYCOBACTERIUM & NORCARDIA

Tetracycline clinical uses

respiratory infections, genitourinary infections, complicated intrabdominal infections

WARNINGS TETRACYCLINE

TIGE should never be used as monotherapy

ERAVA is not indicated for the treatment of complicated UTI

PILL ESOPHAGITIS W/ DOXY

PHOTOSENSITIVITY & HYPERPIGMENTATION

BLUE BLACK DISCOLORATION OF GUMS

TEETH & BONE

AVOIDED IN PREGANCY

AVOID ADMIN W/ FOOD OR SUPPLEMENTS THAT CONTAIN CATION TRI/DIVALENT ION

COUNSELING POINTS TETRA

take on empty stomach for tetra

doxy/mino can be w/or w/out food

take at least 8oz of water sit upright to avoid esophagus irritation

wear sunscreen

watch for DDI and drug food interactions

2nd gen tetracyclines lead to better drugs

less toxic

macrolides med chem

bind to 50s to inhibit protein synthesis diff from aminoglycosides/tetracylines bc these bind to the 30s

macrolides med chem

desoamine sugar critical for binding to ribosomal unit

erythromycin loses activity in acid

macrolides with increased acid stability

clarithromycin & azithromycin

macrolide spec of activity

DO NOT COVER MRSA, ENTEROCOCCI, ENTERBACTERACEA, P.AERU

MACROLIDE RESISTANCE

ERM GENE

msr gene= staph spp

mef gene= strepto spp

erythromycin uses

gastroparesis off label

diptheria= only approvide macrolide for indication

not used for respiratory tract infections bc azithromycin dominates

erythromycin AEs

cardiac toxicity QT prolongation

GI effects

hepatotoxicity

MACROLIDE DDI

ERYTHRO & CLARITHRO= strongly inhibit CYP 3A4

azithro= less extent

clinda= lincoasmide

moa= binding reversibly to 50s ribsomal unit

clinda spec of activity

only up till MRSA

covers anaerobes like bacteroids, prevotella, fusobacterium, clostridum

D TEST

D= inducibly resistant D test used to rule out inducible resistance

msrA gene & erm gene

if D test is + then erm gene is present

clinda uses

pneumocystis jirovecii & toxoplasma gondii

clinda AEs

may cause C.diff

metro spec of activity

anaerobes like: bacteroids, prevotella spp, fusobacterium, clostridium

metro AEs

peripheral neuropathy CNS AEs

metro resistance

nim gene