PC2 2.2.3 1st-3rd Gen Cephalosporins

What three structural components make up a cephalosporin?

b-lactam ring

dihydrothiazine ring

acyl side chain

What structural modifications can occur & how does this impact the antibiotic? (2)

C3 (on dihydrothiazine) - PK

C7 (acyl side chain) - spectrum activity

What is the MOA?

inh. transpeptidase -> autolysis

The relationship between gram positive bacteria & the generations of cephalosporins is __________. As generations improved, gram positive coverage _________.

inverse

decreased

List the three 1st gen meds & their ROA

cefazolin - IV

cephalexin, cefadroxil - PO

The 1st gen & 2nd gen meds are excreted _________

renally

List the 3 indications for 1st gen cephs

1) skin infections (MSSA)

2) surgical prophylaxis

3) uti

Treatment for MSSA is considered _________ therapy. Some examples of MSSA infections include: blood stream infections, ________, & __________.

definitive

endocarditis

osteomyelitis

List the 2nd gen cephs & their ROA (5)

cefprozil, cefaclor, cefuroxime - PO

cefoxitin, cefotetan - IV

Which of the 2nd gen cephs has the worst bioavailability?

cefuroxime

Which of the 2nd gen cephs has the longest half-life?

cefotetan

The 2nd gen cephs taken orally are also known as _________________ agents.

respiratory

The 2nd gen cephs that are IV only are also known as ______________.

cephamycins

Cephamycins cover most (aerobes/anaerobes), including B. fragilis.

anaerobes

List the indications for 2nd gen cephs (3)

1) respiratory

2) otitis media

3) UTI

List the indications that cephamycins are definitive therapy for (3)

1) intra-ab

2) mycobacterial - cefoxitin

3) surgical prophylaxis

Third gen cephs have the _________ bioavailability.

lowest

List the 3rd gen cephs & their ROA (5)

cefixime, cefdinir, cefpodoxime - PO

ceftriaxone, cefotaxime - IM/IV

Cefixime, cefdinir, & cefpodoxime have long half-lives, but ____________ has the longest within the 3rd gen ceph group.

ceftriaxone

Aside from having the longest half-life, what else makes ceftriaxone unique?

works in CNS

What is the dosing of ceftriaxone for meningitis?

2g q12h

How are 3rd gen cephs eliminated? (2)

renal

biliary

What are the disadvantages of using 3rd gen cephs? (2)

1) can induce AmpC in enterobacterales

2) overuse causes inc. risk of infection by ESBL orgs

What are the indications 3rd gen cephs can be used for? (7, CROUBIS)

1) CNS

2) respiratory

3) otitis media

4) UTI

5) bone & joint

6) intra-ab

7)) skin & soft tissue

_____________ can be used for neisseria associated gonorrhea.

cefixime

What are the resistance mechanisms & what generations do they affect? (3)

1) AmpC b-lactamases - all gens

2) ESBL - all gens

3) alterations in target binding for gram pos. cocci

What are the 3 rare drug interactions that occur with 3rd gen cephs & what do they cause?

1) probenecid - block tubluar secretion

2) iron supplements - binds to AB -> dec. AB absorption

3) ceftriaxone + Ca2+ -> kidney stones