PC 2 mod 2.2 lec 3-4

cephalosporin base structure is cephem nucleus made of _____ linked to ______

- beta-lactam

- dihydrothiazide ring

modification of cephalosporin at ...

--> ____ alter pharmacokinetic

--> ____ alter spectrum of activity

- C3

- C7

C3 modifications of cephalosporin alter...

pharmacokinetics

C7 modifications of cephalosporins alter...

spectrum of activity

need to get through ______ of gram negative cell envelope to reach peptidoglycan

porin

MOA of cephalosporins is as a ...

beta-lactamase (interfere with PBP)

cephalosporins have the LONGEST/SHORTEST time>MIC requirement

longest

cephalosporin activity is based on ____/MIC

time

3 first generation cephalosporins

- cefazolin

- cephalexin

- cefadoxil

cefazolin has POOR/GOOD oral BA... IV/ORAL

cephalexin has POOR/GOOD oral BA... IV/ORAL

cefadroxil has POOR/GOOD oral BA... IV/ORAL

- poor --> IV

- good --> oral

- good --> oral

1st gen cephalosporins PK...

- SHORT/LONG T1/2

- eliminated...

- does it need renal dose adjustment?

- short

- renally

- yes

do 1st gen cephalosporins enter CSF well?

no

1st gen cephalosporins do not enter CSF because of _____ from BBB

efflux

1st gen cephalosporins have good penetration to...

- skin

- bone/joints

- urine

- lung

NO CEPHALOSPORINS COVER...

enterococcus

which of the following gram + do first gen cephalosporins 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. strep spp

c. viridans strep

d. MSSA/MSSE

do 1st gen cephalosporins have activity against MSSA/MSSE?

yes

which gram- bacteria do natural 1st gen cephalosporins have activity against?

a. neisseria spp.

b. H. influenzae

c. M. catarrhalis

d. e. coli

e. klebsiella

f. p. mirabilis

a. neisseria

d. e. coli

e. klebsiella

f. p. mirabilis

do 1st gen cephalosporins cover anaerobes?

yes, oral

1st gen cephalosporins are used for...

--> ______ infections with MSSA or s.pyogene

--> ______ infections with e.coli

--> ______ by cefazolin

--> definitive therapy for ______

- skin/structure

- UTI

- surgical prophylaxis (cefazolin)

- MSSA endocarditis or osteomyelitis

1st gen cephalosporin used for surgical prophylaxis is...

cefazolin

1st gen cephalosporin is used with ______ as drug of choice to treat severe MSSA infections

nafcillin/oxacillin

5 2nd generation cephalosporins

- cefprozil

- cefaclor

- cefuroxime

- cefotetan

- cefoxitin

cefotetan and cefoxitin are both ____ gen cephalosporins called ____

2nd

cephamycins

which 3 2nd gen cephalosporins have good BA and are given orally?

- cefprozil

- cefaclor

- cefuroxime

which 2 2nd gen cephalosporins have poor BA and are given IV?

- cefotetan

- cefoxitin

which 2nd gen cephalosporin has less renal elimination?

cefprozil

2nd gen cephalosporins PK

--> LONG/SHORT T1/2

--> elimination?

- short

- renal

which 3 2nd gen cephalosporins are used for respiratory infections?

- cefprozil

- cefaclor

- cefuroxime

which 2 2nd gen cephalosporins are used for intra-abdominal infections?

- cefotetan

- cefoxitin

2nd gen cephalosporins have good penetration into ... (5)

- skin

- bone/joint

- urine

- respiratory

- intra-abdominal

does 2nd gen cephalosporin have good CSF penetration?

variable, not used

which of the following gram + do 2nd gen cephalosporins (RESP) and cephamycins 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 gram- bacteria do natural 2nd gen cephalosporins (RESP) and cephamycins have activity against?

a. neisseria spp.

b. H. influenzae

c. M. catarrhalis

d. e. coli

e. klebsiella

f. p. mirabilis

g. morganella spp

ALL

do RESP 2nd gen cephalosporins have activity against anaerobes? cephamycins?

- yes, oral

- yes most anaerobes

some resistance is observed in ______ anaerobes against cephamycin

b. fragilis

place in therapy for 2nd gen cephalosporins (RESP) ... (3)

- otitis media

- UTI

- upper and lower resp

place in therapy for 2nd gen cephalosporins (cephamycins) ... (3)

- intra-abdmonial

- mycobacterial

- surgical prophylaxis

CEFOXITIN/CEFOTETAN cephamycin can treat mycobacterial infections as long as they are ______

- cefoxitin

- non TB

5 3rd generation cephalosporins...

- cefixime

- cefdinir

- cefpodoxime

- ceftriaxone

- cefotaxime

which 3rd gen cephalosporins are given orally (3)

- cefixime

- cefdinir

- cefpodoxime

which 3rd generation cephalosporins are give IM/IV only? (2)

- ceftriaxone

- cefotaxime

cefixime used for ______ and ______ and has LONG/SHORT t1/2 and is used as ______ dose

- neisseria

- ghonorrhea

- long

- once daily

ceftriaxone has LONG/SHORT t1/2 and is give as _____ dose but ____ dose for meningitis to overcome protein binding

- long

- 1x daily

- 2x daily

do you need to renally adjust ceftriaxone?

no

_______ and ______ are 3rd gen cephalosporins with lower renal elimination and more biliary

- cefixime

- ceftriaxone

ceftriaxone can be given with _______ to treat enterococcus fecalis endocarditis

ampicillin

ceftriaxone + ampicillin is given to treat _______

enterococcus faecalis endocarditis

PK for most 3rd gen cephalosporins

--> SHORT/LONG t1/2

--> elimination?

- short

- renal

where do 3rd gen cephalosporins penetrate? (6)

- skin

- bone/joints

- urine

- resp

- intra-abdominal

- CNS

which 2 3rd gen cephalosporins can be used for CNS infections?

ceftriaxone and cefotaxime (IV)

which is worst cephalosporin for MSSA? 1st, 2nd, 3rd

3rd

which of the following gram + do 3rd gen cephalosporins 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 gram- bacteria do natural 3rd gen cephalosporins have activity against? (pt1)

a. neisseria spp.

b. H. influenzae

c. M. catarrhalis

d. e. coli

e. klebsiella

f. p. mirabilis

g. morganella spp

ALL

which gram-bacteria do 3rd gen cephalosporins have activity against (pt2)

a. enterobacter spp

b. citrobacter spp

c. serratia

d. p. aeruginosa

e. acinetobacter app

a. enterobacter spp

b. citrobacter spp

c. serratia

can 3rd gen cephalosporins have activity against anaerobes?

yes, oral

3rd gen cephalosporins have no activity against _____ resistance and weak activity against _____ resistance

- ESBL

- ampC

do 3rd gen cephalosporins have activity against ESBL and ampC

no

7 places in therapy for 3rd gen cephalosporin

- upper and lower resp

- otitis media

- UTI

- CNS

- intra-abdominal

- skin and soft tissue

- bone and joint

common resistance of 1st, 2nd and 3rd gen cephalosporins are from _____ and _____, as well as altered target binding in gram POSITIVE/NEGATIVE cocci

- AmpC

- ESBL

- positive cocci

ampC beta-lactamases are inducible in _____ and can cause resistance of 1st/2nd/3rd gen during treatment

- enterobacter

- 3rd

ceftriaxone is contraindicated in ______ due to _______

neonates

_______ is contraindicated in neonates due to hyperbilirubinemia

ceftriaxone

avoid giving cephalosporins in patients with ______ allergies due to cross reactivity

penicillin

______ reaction could occur if cefotetan is taken with alcohol (not common)

disulfiram

disulfiram reaction could occur if _______ is taken with alcohol

cefotetan

cephalosporins interact with ________, as it blocks tubular secretion and increases serum conc/half life

probenecid

probenecid interacts with cephalosporins by blocking _______ to increase conc. and halfl life

tubular secretion

ceftriaxone interacts with...

calcium or calcium containing solutions

calcium or calcium containing solutions interact with...

ceftriaxone

ceftraixone binds to calcium forming ________ and this can cause ______ and _______

- insoluble precipitate

- biliary sludging

- nephrolithiasis

______ should be separated from cefdinir by 2 hrs before or after dose

iron supplements

iron supplements should be separated from ______ 2hrs before or after dose

cefdinir

2 antipsuedomonal cephalosporins

- ceftazidine

- cefepime

ceftazidine brand name...

fortaz

cefepime brand name

maxipime

ceftazidine is a ___ gen cephalosporin

3rd

structures of ceftazidime are...

--> ______ ring off position ____ increases activity against gram- bacilli

--> ______ group off position _____ confers stability against beta-lactamase and increases activity against pseudomonas

--> _____ group at position _____ enhances activity against pseudomonas and provides zwitterion properties

- aminothiadiazole --> 7

- carboxypropyl-oxyimino --> 7

- methyl-puridinium --> 3

structures of ceftazidime are...

--> aminothiadiazole ring off position C7 increases activity against _______

--> carboxypropyl-oxyimino group off position C7 confers stability against _______ and increases activity against ________

--> methyl-puridinium group at position C3 enhances activity against pseudomonas and provides ________ properties

- gram - bacilli

- beta-lactamase and pseudomonas

- zwitterion

ceftazidime is STABLE/UNSTABLE against ESBL, AmpC and carbapenamases

unstable

cefepime is a ___ gen cephalosporin

4th

structures of cefepime are

--> _____ at position ____ to provide PBP binding and stability against AmpC

--> _____ at position ______

- n-methylpyrollidine --> 3

- alkoxyimino group --> 7 (negative carboxyl)

structures of cefepime are

--> n-methylpyrollidine at position C3 to provide _____ binding and stability against _____

--> alkoxyimino group at position C7

- PBP

- AmpC

cefepime is a ______ at physiologic pH

zwitterion

is cefepime a zwitterion?

yes

ceftazidime and cefepime (antipseudomonal) PK

--> SHORT/LONG t1/2

--> POOR/GOOD BA

--> IV/ORAL

--> elimination?

--> renal dose adjustment?

- short

- poor

- IV/IM

- renal

- yes

can ceftazidime and cefepime penetrate CNS?

yes (w/inflammation)

which of the follow gram+ do ceftazidime 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

which gram- bacteria do ceftazidime have activity against? (pt1)

a. neisseria spp.

b. H. influenzae

c. M. catarrhalis

d. e. coli

e. klebsiella

f. p. mirabilis

g. morganella spp

all

which gram-bacteria do ceftazidime have activity against (pt2)

a. enterobacter spp

b. citrobacter spp

c. serratia

d. p. aeruginosa

e. acinetobacter app

a. enterobacter spp

b. citrobacter spp

c. serratia

d. p. aeruginosa

does ceftazidime have activity against anaerobes?

yes, oral

is ceftazidime stable against ESBLs and AmpC

no

is cefepime stable against AmpC?

yes (4th gen)

ceftazidime has miscellanous activity against _____ and ______, while cefepime has poor activity against these

- achromobacter

- stenotrophomona maltophilia

_______ has miscellaneous activity against achromobacter and stenotrophomonas, while _______ has poor activity against these

- ceftazidime

- cefepime

does ceftazidime cover MSSA?

no

which of the follow gram+ do cefepime 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 gram- bacteria do cefepime have activity against? (pt1)

a. neisseria spp.

b. H. influenzae

c. M. catarrhalis

d. e. coli

e. klebsiella

f. p. mirabilis

g. morganella spp

all

which gram-bacteria do cefepime have activity against (pt2)

a. enterobacter spp

b. citrobacter spp

c. serratia

d. p. aeruginosa

e. acinetobacter app

all

cefepime has activity against ______ gram- while ceftazidime does not

acinetobacter