PC 2 mod 2.2 lec 5-6

base structure of carbapenem is ____-membered carbon ring fused to _____

- 5

- beta-lactam

modifications at ____ and ____ of carbapenem improve stability, spectrum of activity, and lower epileptogenic potential

C3

C4

3 types of carbapenem

imipenem

meropenem

doripenem

imipenem is vulnerable to renal ____ and _____ potential due to ___ group

DHP-1

epileptogenic

H

meropenem has ___ on C__ to allow it to be stable to ____, less ____ potential and increased ____ activity

- CH3

- C4

- DHP1

- epileptogenic

- gram-negative

spectrum of activity of carbapenem depends on varying affinity to ____

PBP

meropenem brand name...

merrem

imipenem/cilastatin brand name

primaxin

does meropenem or imipenem/cilastatin have lower protein binding?

meropenem

can carbapenems penetrate CSF

yes, better with inflammation

carbapenems have SHORTEST/LONGEST T/MIC requirement

shortest

which of the following gram + do meropenem and imipenem/cilastatin have activity against?

a. streptococcus spp.

b. s. pneumoniae

c. viridans strep

d. MSSA/MSSE

e. MRSA/MRSE

f. E. faecalis

g. E. faecium

a. streptococcus spp.

b. s. pneumoniae

c. viridans strep

d. MSSA/MSSE

f. e. faecalis

which gram - do meropenem and imipenem/cilastatin have activity against?

ALL

do meropenem and imipenem/cilastatin have activity against anaerobe?

yes, oral and gut (b. fragilis)

meropenem and imipenem/cilastatin are stable against ____ and ____ resistance genes

- ESBL

- AmpC

meropenem and imipenem/cilastatin have are ACTIVE/INACTIVE against mycobacterium (non-TB) but ACTIVE/INACTIVE against s. maltophilic

- active

- inactive

if meropenem and imipenem/cilastatin are overused, they have a strong propensity for selecting resistant organisms like ______

carbapenem resistant enterobacterales (CRE)

meropenem and imipenem/cilastatin should be last line therapy, only used if know ____-producing bacteria and gram _____ resistant to other _____

- ESBL

- negative

- beta-lactams or other agent

ertapenem has CATIONIC/ANIONIC character, resulting in decreased penetration into _____ found in ______, but increased ______ and ______

- anionic

- porin channels

- pseudomonas

- protein binding

- half life

ertapenem PK

--> SHORT/LONG t1/2

--> renal elimination?

--> HIGH/LOW protein binding

- LONG

- yes

- high

which of the following gram + does ertapenem have activity against?

a. streptococcus spp.

b. s. pneumoniae

c. viridans strep

d. MSSA/MSSE

e. MRSA/MRSE

f. E. faecalis

g. E. faecium

a. streptococcus spp.

b. s. pneumoniae

c. viridans strep

d. MSSA/MSSE

which of the following gram- do ertampenem have activity against? (pt1)

a. neisseria spp.

b. H. influenzae

c. M. catarrhalis

d. e. coli

e. klebsiella

f. p. mirabilis

all

which of the following gram- do ertampenem have activity against? (pt2)

a. morganella spp

b. enterobacter spp

c. citrobacter spp

d. serratia spp

e. p. paeruginosa

f. acinetobacter

a. morganella spp

b. enterobacter spp

c. citrobacter spp

d. serratia spp

do ertapenems cover anaerobes?

yes, oral and gut (b.fragilis)

ertapenems are stable against ____ and ____ resistance

- ESBL

- AmpC

are ertapenems ACTIVE/INACTIVE against s. maltophilia

inactive

ertapenem is administed ___x daily

1x (ease transition)

ertapenem can be used in...

--> ______ infection

--> ______ and structure

--> community-aquired ______

--> ______

--> _____

--> prophylaxis in ______ surgery

- intra-abdominal

- skin

- pneumonia

- UTI

- pelvis

- colorectal

_______ is used for surgical prophylaxis in colorectal surgery

ertapenem

utilization for ertapenem is driven by organism ______ and need for ______

- susceptibility

- once daily dosing

which 3 organisms can cause resistance to carbapenems...

- enterobacterales

- acinetobacter

- pseudomonas

enterobacterales/acinetobacter can cause carbapenem resistance by _______ enzymes

carbapenem-hydrolyzing

pseudomonas can cause carbapenem resistance by decreasing _______ and adding ______

- permeability (porin channels)

- efflux

_______ produce carbapenem resistance by inactivating carbapenem-hydrolyzing enzymes

enterobacterales/acinetobacter

_______ produce carbapenem resistance by decreased outer membrane permeability and active efflux

pseudomonas

if one carbapenem is resistant, are all of them?

no

meropenem can be combined with ______ to increase coverage

vaborbactam

imipenem/cilastatin can be combined with _____ to increase coverage

relebactam

addition of vaborbactam to meropenem increased activity against ____, but does not enhance activity against pseudomonas or acitenobacter resistant due to _______ or _______ mutations

- CRE (KPC)

- efflux

- porin

relebactam addition to imipenem cilastatin expands activity against _______ and carbapenem resistant ______

- CRE (KPS+OXA)

- pseudomonas

_______ combination may have activity against nonTB mycobacterium

imipenem/cilastatin/relebactam

_______ is expanded to carbapenem-resistant pseudonomas

imipenem/cilastat/relebactam

which carbapenem has high epileptogenic potential?

imipenem/cilastatin

carbapenems have an effect on _______ and can reduce these concentrations by ____%, resulting in loss of _____ control

- valproic acid

- 50%

- seizure

______ interferes with tubular secretion of all carbapenems

probenecid

______ is a monobactam

aztreonam

aztreonam is a ______

monobactam

_____ group of monobactam enhanced pseudomonas activity

carboxy

aztreonam has high affinity for _____, which gives it gram POSITIVE/NEGATIVE, but lack affinity for _____ which gives it no gram POSITIVE/NEGATIVE

- PBP3

- gram negative

- PBP 1 or 2

- gram positive

two formulation of aztreonam + brand name

- IV/IM: azactam

- inhalation: cayston

PBP-3 is a ______ peptidoglycan transpeptidase contributing to _______

- septum

- cell division

aztreonam PK

--> LONG/SHORT T1/2

--> elimination?

--> renal adjustment?

- short

- renal

- yes

what are the 2 gram- that aztreonam does not have activity against

acinetobacter and neiserria

does aztreoname have activity against gram+

no

aztreonam has activity against _____ beta-lactamase, which is _____ resistant

- metall-beta-lactamase

- carbapenem

______ has activity against metalla-beta-lactamase

aztreonam

aztreonam is STABLE/UNSTABLE against ESBL and AmpC

unstable

aztreonam is stable against ______ resistance and unstable against (3)

- metallo-beta-lactamase

- ESBL, KPC, AmpC

which antibiotic is stable against metallo-beta-lactamse

aztreonam

can aztreonam penetrate into CNS?

poor without inflammation

common indications of aztreonam (4)

- UTI

- bacteremia

- pneumonia

- febrile neutropenia

place in therapy of aztreonam is for patient allergic to ______ since it is structurally dissimilar

beta-lactams

possible cross reactivity of aztreonam with _______ and ______ due to same R1 side chain

- ceftazidime

- cefiderocol

aztreonam is active against metallo-beta-lactamase producing ______, but may not be active against metallo-beta-lactamase producing _______

- enterobacterales

- pseudomonas

modification at C3 and C4 of carbapenems improve _______, ______ and lower ______

- stability

- spectrum of activity

- epileptogenic potential

doripenem has less ______ side chain at position 3, so more meropenem resistant psuedomonas activity (but not used)

alkaline

meropenem and imipenem/cilastin have miscellaneous activity against...

non-TB mycobacterium

transhydroxyethyl part of ertapenem contributes to ______

B-lactamase stability

1-B methyl group protects against _______ in ertapenem

hydrolysis

________ group substitution causes ertapenem to be anionic

meta-substituted benzoic acid

meropenem and imipenem/cilastin have activity against (3), while ertapenem does not

- e. facialus

- pseudomonas

- acinetobacter

addition of vabrobactam to meropenam does not increase activity against _______ or _______, only increases _______

- psuedomonas

- acinetobacter

- enterobacterales (CRE)

probenecid has drug-drug interactions with _______ and ______

- cephalosporins

- carbapenems

resistance mechanisms to aztreonam include ______, outer membrane _______ and ______

- beta-lactamase (ESBL, AmpC, etc)

- porin

- efflux

does aztreonam have anaerobic coverage?

no

possible cross rxn of ________ with ceftazidine or cefiderocol

aztreonam

are ertopenems stable against ESBL or AmpC?

yes

addition of ______ expands activity to KPC, OXA or pseudomonas

relebactam

_______ is does once daily

ertapenem

doripenem has less alkaline side chain at position 6, so more activity against ________

meropenem resistant pseudomonas

______ of ertapenem contributes to b-lactamase stability

tran-hydroxy ethyl

_______ of ertapenem contributes against hydrolysis

1-beta methyl

meta-substituted benzoic acid changes charge of molecule in _______ and anionic activity makes it difficult to enter _______

ertapenem

pseudomonas

_______ is anionic, resulting in decreased penetration into porins found in pseudomonas but increase half life and protein binding

ertapenem

______ has trans-hydroxy ethyl group and 1-beta methyl group

ertopenem