ID: Gram negative resistance
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ID: Gram negative resistance
ID Gram negative resistance
ID: Gram negative resistance
risk factors for GN resistance?
previous abx exposure
hosp admission >2 or more days in preceding 90d
residence NH, ECF
hepatic failiure and long term HD
ceftriaxone not working for pseudo is what kind of resistance? innate vs. developing
cefepime not working for pseudo is what kind of resistance? innate vs. developing
notorious resistant bugs? - ESKAPE
ESBL producing bacteria are?
which cephalo induces ESBL producing bacteria?
3rd gen cephalo
definition of MDR?
resistant to equal to or > 3 of the following classes
B lactam (cephalo, monobact, pcn, carba)
definition of pan-resistant?
resistant to ALL avail abx options
4 mechanisms of GN resistance
production of enzyme (destroy integrity of abx)
mutation at binding site (abx can't bind)
down regulate outer membrane protein (abx can't get into periplasmic space)
efflux pump (remove out abx)
if bacteria produce enzyme to resist abx, what can you use?
suicide substrate sulbactam can overcome!
mechanism of resistance of p.seudo?
: down regulate outer membrane protein (prevent abx from getting into periplasmic space); reduced permeability
: efflux pump
mechanism of resistance of imipenem?
loss of 54-kD outer membrane protein (OprD)
(mechanism #3) down regulate outer membrane protein (prevent abx from getting into periplasmic space) reduced permeability
which is better vs. bacteria resistance and why? imi vs. mero
imi doesn't work once OprD is lost (54kD outer membrane protein)
mero needs two steps (upregulation of MexAB-OprM efflux pump AND OprD loss)
mechanism of resistance of acinetobacter?
: efflux pump
need double cover abx
mech of resistance of FQ?
: binding site mutation
mutation of topoisomerase II (gyrA) and IV (parC)
this results in increase MIC
(gyrA mutation is most impt and occurs before parC mutation)
mech of resistance of AG? which is the weakest AG?
: production of enzyme
: acetyl-, adenyl-, and phophoryl-transferases
1) they chemically modify AG structure
2) interfere with drug transport
3) prevent AG from binding to 30S rib subunit
gent usu goes down first, then amik and tobra
most common and clincially sig resisstance mechanism displayed by ALL GN bacilli?
production of b-lactamase
how to b-lactamase work?
hydrolyze the b-lactam chem structure and inactivate the drug
4 categories of b-lactamases (bush-jacoby medeiros classification)
examples of ESBL (2a)? what do these do? how are they inhibited
they hydrolyze ESC
(chromosomally encoded or plasmid and transposon mediated)
inhibited by clavulanate
2 major machanism of resistance for ESBL (2a)?
selection of point mutant of
type plasmid-mediated b-lactamses
type enzymes thru horizontal gene transfer (CTX-M 15 is globally dominant strain)
how to you test ESBL resistance (2a)?
ceftazidime MIC >2ug/ml
confirmed if MIC changes upon clavulanic acid addition
to what abx is ESBL resistance (2a) resistant to? where is resistant mechanism carried on?
all cephalo (except cefoxitin and cefotetan - cephamycin)
pcn (except zosyn)
also FQ, bactrim, AG
mech carried on plasmid
DOC for ESBL (2a) treatment (e.coli and kleb)?
: erta, tige, AG, FQ (only for UTI)
can AmpC cephalosporinase (1) be inhibited by b-lactamase inhibitors, like clavulanic acid and tazobact?
what b-lactamase resistance does klebsiella have?
AmpC cephalosporinase (1)
what b-lactamase resistance does e.coli have?
to what abx is AmpC-cephalosporinase (1) resistant to?
all cephalo!!! (including cefoxitin, cefotetan - cephamycin)
also zosyn as well
what is the DOC and alt tx for AmpC-cephalosporinase (1) bugs?
action of AmpC cephalosporinase (1)?
loss of outer membrane porins and/or over expression of efflux pump
action of carbapenemase (2b)?
hydrolyze carbapenem and other b-lactam abx
basically ESBL resistance + carba
klebsiella with carbapenemase (2b) resistance. what to use?
pseudo with carbapenemase (2b) resistance. what to use?
(cannot use tige unlike klebsiella b/c innate resistance)
Acinetobacter with carbapenease (2b) resistance. what to use?
(highlighted = DOC)
examples of carbapenemase (2b)?
examples of metallo-b-lactamase (3) ?
what b-lactamase resistance does pseudomonas have?
what b-lactamase resistance does acinetobacter have?
innate cephalosporinase AmpC (1)
mutation in topoisomerase, AG modifying enzyme, reduced expression of outer membrane protein, efflux
3 organisms that have metallo-b-lactamase as resistance?
metallo-b-lactamase (3) is resistant to? this mechanism is carried on?
carried on integron (easily transferable)
metallo-b-lactamase (3) is sensitive to which abx?
aztreonam (for pseudo)
when you have ESBL, which abx class is most reliable?
carbapenem (slide 34)
which conditions/abx can fail to achieve PD target?
under dose (thus use high dose AG)
4 agents in which the MICs of drug increase up to 100 fold due to ESBL?
3 reasons for increased mortality in ESBL?
more serious or deep seated enterobacter spp infxn
higher organism burden
inadequate or delayed abx tx
what is NDM-1?
what abx can tx this?
new delhi metallo-b-lactamase
presence of carbapenem resistant gene
colistin, tige, maybe aztreonam
SE issue with imipenem/cilastatin?
(careful with dose)
which has more activity vs. pseudo?
mero and dori
which has more activity vs. acinetobacter?
which has no activity vs. pseudo nor acinetobacter?
which binds stronger to ribosome? tetracycline vs. tigecycline
tige binds 5x more
is tigecycline active vs. metallo-b-lactamase producing kleb and e.coli?
is tigecycline active vs. ESBL producing kleb and e.coli?
is tigecycline active vs. KPC producing kleb and e.coli?
but little data
is tigecycline active vs. acinetobacter?
only in vitro activity so cannot tell if S, I or R
which conditions is tige indicated?
IA (anaerobe, GN, MRSA)
CAP +/- bacteremia (but doesn't stay in blood long)
is tige active vs. pseudo?
is tige active vs. providencia
is tige active vs. morganella?
is tige active vs. proteus?
does tigecycline have high urine concentration?
nope, rapidly moves into tissues thus not in urine and blood (slide 44)
you can inc urinary conc of tige by using high dose (slide 48)
for VAP tx, which is better, carba vs. tige? (slide 44)
enterobactericiae is sensitive vs.? (put in order) slide 49
colistin is aka ___
polymixin E (slide 50)
polymixin is __ depedent and is it cidal or static?
actions of polymixin?
bind phospholipid in the outer membrane of GN
cell wall destabilize and cell death
is polymixin active vs. p.aeru?
is polymixin active vs. acinetobacter?
is polymixin active vs. k.pneumo?
is polymixin active vs. e.coli (MDR)?
is polymixin active vs. proteus?
is polymixin active vs. providencia?
is polymixin active vs. burkholderia?
is polymixin active vs. nesseria or serratia?
SE of polymixin? which has less SE (polymixin B vs. E)
nephro and neuro tox
colistin (E) has less
what to use to tx peritonitis with k.pneumoniae (ESBL)?
polymix B + amik + mero
does sulbactam have activity vs. acinetobacter?
how to tx severely ill pseudo empirically?
zosyn or ceftazidime + cipro or AG
(b-lactam + AG)
which is better to use for kleb pneumo?
carba mono vs. carba + polymix
carba + polymix
for KPC (2b), which is better?
polymix mono vs. AG+ polymix+ tige
combo is better
what's ME 1036?
what bug does it cover, not cover?
IV carba (phase I)
covers MRSA, VRE, ESBL e.coli and kleb
what's PZ-60? what bugs does it cover?
good vs. MRSA and GN
no pseudo and acineto
active vs. which bug?
IV and PO penem
good vs. ESBL enterobact, GP, anaerobe
what's tomopenem? active vs. which bug?
active vs. p.aeru
what's PTK-0796? what spectrum does it have?
IV and po aminomethylcycline
active vs. MRSA, VRE, some resistant GN patho (acineto)
what do metallo b-lactamase inhibit ME1071 (CP 3242) med cover?
pseudo and acineto
what's BAL 30376?
b-lactam b-lactamase inhibitor
b lactamase enterobacteriaceae
what does "squeezing the balloon phenomenon" mean?
may develop resistance elsewhere
how to prevent GN resistance? what abx to use?
third gen cephalo
acinetobacter surprives long time on surfaces. what can you do for ICU pts?
chlorhexidine skin disinfection to reduce skin contamination