PC 2 Mod 2.2 lec 1-2 (penicillins)

base pieces of penicillin structure are the ______ and _______ that are the nucleus and required for biological activity

- beta-lactam

- thiazolidine ring

______ can break down base ring of penicillin

beta-lactamase

_____ modifications to penicillin can change spectrum of activity, stability to enzymes and PK

acyl side chain

acyl side chain of penicillin structure can change ______, stability to ______ and ______ properties

- spectrum of activity

- enzymes

- PK

_____ function to synthesize peptidoglycan, maintain cell shape, and cause septum formation

penicillin binding proteins (PBP)

PBPs are _______ that cause the crosslinking of _____peptides

- transpeptidases

- NAM

in _______ bacteria, PEN inhibits TP responsible for cross-linking peptide chains resulting in a dysfunctional cell wall and autolysis

ACTIVELY dividing

in actively dividing bacteria, penicillin inhibits _____ responsible for ______ peptide chains resulting in a dysfunctional cell wall and autolysis

- PBP (TP)

- crosslinking

penicillin's ability to ______ the cell wall and ______ for PBP determine activity

- penetrate

- affinity

first agents in the penicillin class were _____ penicillins

natural

originally penicillin G was given orally, IV, and IM, but challenge of this was rapid _____, susceptibility to ______ and ______ activity

- acid degradation

- beta-lactamases

- narrow spectrum

which penicillin is IV and IM?

penicillin G

which penicillin is oral?

penicillin VK (stable in gastric acid)

should penicillin be taken on an empty stomach or with food?

EMPTY (better absorption, less acid)

penicillin

--> SHORT/LONG T1/2

--> route of elimination?

--> short

--> renal

beta-lactams rely on ____/MIC to determine bactericidal activity

time/MIC

is the % time over MIC for penicillin the same as cephalosporins and carbapemens?

no (50%)

which of the following gram + do natural penicillins 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*

e. e. faecalis

do natural penicillins have activity against MSSA/MRSA? why or why not?

no

--> staph aureus produces penicillinase to block

do natural penicillins have activity against anaerobes?

yes, oral

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

a. neisseria spp.

b. H. influenzae

c. M. catarrhalis

d. e. coli

e. klebsiella

f. p. mirabilis

a. neusseria spp

which gram- do natural penicillins have activity against?

ONLY neusseria

miscellaneous bacteria natural penicillins are active against (2)

- T. pallidum (syphilis)

- b. burgdorferi (lyme)

narrow spectrum of activity of natural penicillins mainly cover which indications (2)

- strep

- syphilis

______ were developed in response to natural penicillins having short half-lives and poor oral absorption

long-acting parenteral agents

all long-acting parenteral penicillin agents are administered _____

IM

why are long-acting parenteral penicillin agents not administered IV?

risk of cardiac arrest

3 long-acting parenteral penicillin agents (brand+generic)

- penicillin G procaine

- penicillin G benzathine (bicillin L-A)

- penicillin G benzathine and procaine (bicillin C-R)

_______ long-acting parenteral penicillin absorbs slowly with max conc. in 2-4 hours and detectable for 24h so once daily dosing

penicillin G procaine

penicillin G procaine can be dosed ______ and challenges include drug-resistant _______

- once daily

- neisseria

______ long-acting parenteral penicillin has prolonged serum concentrations for up to 4 weeks and is what should be used for syphilis

bicillin LA

bicillin LA produces serum conc. for up to ______ and should be used for ______, but does cause _____

- 4 weeks

- syphilis

- pain

should bicillin LA or bicillin CR be given for syphilis?

bicillin LA

positive of bicillin CR is less _____ than LA

painful

3 penicillinase resistant penicillins

- nafcillin

- oxacillin

- dicloxacillin

nafcillin is IV/ORAL

oxacillin is IV/ORAL

dicloxacillin is IV/ORAL

- IV

- IV

- oral

why was methicillin (first penicillinase-resistant penicillin) removed from the market?

high incidence of interstitial nephritis

which of the following gram + do penicillinase resistance penicillins 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

do penicillinase resistant penicillins cover any gram -?

no

penicillinase resistant penicillins lose coverage of _____ and ______ compared with natural penicillins, but gain _____

- e. faecalis

- neisseria

- MSSA/MSSE

do you need renal dose adjustment for natural penicillins?

do you need renal dose adjustment for penicillinase resistant penicillins?

yes

no

penicillinase resistant penicillins

--> GOOD/POOR oral BA

--> SHORT/LONG T1/2

--> route of elimination?

- poor

- short

- hepatic biliary

penicillinase resistant penicillins main use is for _____ therapy of _____

- definitive

- MSSA

dicloxacillin has increased bioavailability and is HIGH/LOW protein bound, but has to be dosed frequently due to ______

- low

- short half life

dicloxacillin has ______ group that mitigates penicillinase and gastric acid breakdown

isoxazolyl

dixcloxacillin is used to treat _______ infections

mild bacterial skin/skin structure

resistance mechanisms against penicillins for streptococcus, neisseria, and enterococcus are by alterations in _____

PBPs

resistance mechanisms for staph aureus against penicillins are production of ______ and ______ resistance through altered ____

- penicillinase

- oxacillin/methicillin (MRSA)

- PBP2a

hepatic adverse effects of penicillins are more common with...

oxacillin/nafcillin

adverse effect of penicillin G is potential _____ overload

sodium

penicillins are well tolerated, but monitor for which adverse effects (4)

- neurologic

- hematologic

- renal

- GI

2 extended spectrum penicillins

aminopenicillins

ureidopenicillins

why where extended spectrum penicillins created?

--> ______ antimicrobials

--> improved ______ activity

--> higher affinity for ______

- safe

- gram-negative

- PBP

two types of aminopenicillins

- ampicillin

- amoxicillin

amplicillin has enhanced cell was penetration in part due to being ______ at a neutral pH

zwitterion

zwitterions are able to rapidly penetrate through _____ within the cell membrane

porins

amplicillin availble IV/ORAL?

both

amplicillin

--> SHORT/LONG T1/2

--> what type of elimination?

--> where can it penetrate?

- short

- renal

- lungs, bone, CNS (w/inflammation)

ampicillin has ______ absorption, meaning increasing the dose does not result linear increase of conc., but does result in _______

- saturable

- diarrhea

difference between ampicillin and amoxicillin is...

amoxillicin is oral formulation only (better BA)

amoxicillin has reduced frequency of ______ compared to ampicillin

diarrhea

primary use for amoxicillin is for ______ due to activity against ________

- upper resiratory infection

- s. pneumonaie

primary use for _______ is for upper respiratory infections due to activity against s. pneumonaie

amoxicillin

which of the following gram + do aminopenicillins (amoxicillin/ampcillin) 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. pneumonaie

c. viridans strep

f. e. faecalis

g. e. faecium

which of the following gram- do aminopenicillins (amoxicillin/ampicillin) have activity against? (pt1)

a. neisseria spp.

b. H. influenzae

c. M. catarrhalis

d. e. coli

e. klebsiella

f. p. mirabilis

g. morganella

a. neisseria

b. h. influenzae

d. e. coli

f. p. mirabilis

do aminopenicillins have activity against anaerobes?

yes, oral

miscellaneous activity of aminopenicillins (4)

- l. moncytogenes (lysteria)

- h. pylori

- salmonella

- shigella

______ is drug of choice for e. faecalis

ampicillin

ampicillin is drug of choice for _______

e. faecalis

do aminopenicillins have activity against MSSA/MRSA?

no

4 common indications for empiric therapy aminopenicillins

- streptococcal pharyngitis

- s. pneumoniae

- h. pylori

- listeria (amp)

high dose amoxicillin can be used empirically for...

s. pneumoniae

_____ is drug of choice for empiric therapy against listeria infections, especially CNS infections

ampicillins

ampicillins is drug of choice for empiric therapy against _____, especially _____

- listeria

- CNS

3 common indications for definitive therapy for aminopenicillins

- enterococcus

- s. pneumonaie

- h. influenzae (if beta-lactamase negative)

ampicillin can be combined with _____ and brand name is _____

--> is it IV or PO?

- sulbactam

- unasyn

- IV

sulbactam is a ______, meaning it permanently inactivates beta-lactamase and cannot be reused/recycled and it has minor _____ properties

suicide inhibitor

PBP inhibitory

_______ is a suicide inhibitor, meaning it permanently inactivate _______ and cannot be _______

- sulbactam

- beta-lactamase

- reused

spectrum of enzymes sulbactam inhibits includes... (3)

- penicillinase

- cephalosporinase

- other beta-lactamase

sulbactam alone has weak activity against... (2)

neisseria and acinetobacter

ampicillin/sulbactam PK

--> SHORT/LONG T1/2

--> POOR/GOOD BA

--> path of elimination?

- short

- poor

- renal (needs adjustment)

does ampicillin/sulbactam need renal dose adjustment

yes

ratio of ampicillin to sulbactam is...

2 ampicillin: 1 sulbactam

where does sulbactam penetrate? (3)

- CSF

- lung

- bone

amoxicillin can be combined with ______ and brand name is ______ and this is ORAL/IV

- clavulanate

- augmentin

- oral

is clavulanate a suicide inhibitor?

yes

clavulanate extends spectrum of activity through inhibition of ....

beta-lactamases

does clavulanate have activity against acinetobacter?

no

difference between sulbactam and clavulanate is sulbactam has activity against...

acitenobacter

should augmentin be taken with food?

yes

amoxicillin/clavulanate PK

--> POOR/GOOD BA

--> SHORT/LONG T1/2

--> elimination?

- better

- short

- renal (amoxicillin), renal +hepatic (clavulanate)

adverse effect of amoxicillin clavulanate is mainly...

diarrhea (less with new formulation)

only penicillin without any renal excretion

nafcillin/oxacillin

which of the following gram + do aminopenicillins plus inhibitor 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

g. E. faecium

do augmentin and unasym have activity against MSSA?

yes (have inhibitor)

which of the following gram- do aminopenicillins (amoxicillin/ampicillin) + INHIBITOR 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

do aminopenicillins + inhibitor have activity against anaerobes?

yes, oral AND gut

miscellaneous activity of aminopenicillins + inhibitor

similar to ampicillin

--> l. monocytogenes, h.pylori, salmonella spp, shigella spp.

ampicillin/sulbactam is used EMPIRICALLY for...

--> surgery prophylaxis for patients undergoing _____ surgery

--> _____ infections involving oral cavity

--> _____ infections

- intra-abdominal

- head and neck

- sinus

ampicillin/sulbactam is used DEFINITEVELY for...

--> ______ infections

--> ______ infection

--> ______ infections

--> infections caused by ______ species

- intra-abdominal

- gynecologic

- head and neck

- acinetobacter