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Flashcards in cephalosporins 67 Deck (35):

Cefazolin (generic, Ancef) - parenteral

First Generation (Older) Cephalosporin
*drug of choice for surgical prophylaxis*
-activity against staph and some G- enterics
-SE: disulfiram-like rxn, anticoagulation (kill off vitamin K- methlythiotetrazole group in the R2 position)


Cephalexin (Keflex), cephalexin HCl monohydrate (Keftab) - oral

First Generation (Older) Cephalosporin


Cefaclor (Ceclor) -oral

Second Generation Cephalosporin
-good for sinusitis and OM (S. pneumoniae, H. influenzae, M. Catarrhalis, S. Pyogenes)
-more commonly implicated in causing serum-sickness like reactions: erythema multiforme or maculopapular pruritic rash or urticaria accompanied by arthritis, arthalgia and fever.


Cefoxitin (Mefoxin) - parenteral

Second Generation Cephalosporin
*activity against B. fragilis (anaerobe)*


Cefuroxime Axetil (Ceftin) –oral; Cefuroxime (Zinacef) - parenteral

Second Generation Cephalosporin
-good for sinusitis and OM (S. pneumoniae, H. influenzae, M. Catarrhalis, S. Pyogenes)
-coverage against S. pneumo, B-lactamase producing H. flu and Kleb – Making it useful for CAP


Cefprozil (Cefzil) – oral

Second Generation Cephalosporin
-good for sinusitis and OM (S. pneumoniae, H. influenzae, M. Catarrhalis, S. Pyogenes)


Ceftriaxone (Rocephin) - parenteral

Third Generation Cephalosporin
-longest half life (8 hrs)
-enter the CNS, can be used for meningitis
-eliminated via bile, not need to adjust for renal failure
-1st line for tx Gonorrhea
-neurologic complications of lyme disease


Cefixime (Suprax) - oral

Third Generation Cephalosporin


Cefotaxime (Claforan) - parenteral

Third Generation Cephalosporin


Ceftazidime (Fortaz, Tazidime) – parenteral

Third Generation Cephalosporin
*activity against Pseudomonas*, use combo with amino glycoside to tx pseudomonal meningitis


Cefepime (Maxipime) - parenteral

Fourth Generation Cephalosporin
*useful for enterobacter infections (UTI)*


Ceftaroline fosamil (Teflaro) – parenteral

Fifth Generation Cephalosporin


Ceph structure

similar in structure to penicillins and have a beta-lactam ring structure
derivative of 7.amino cephalosporonic acid (7-ACA)
(Chemical modifications at the 7 position of the beta-lactam ring (R1) are associated with changes in antibacterial activity, changes in the 3 position (R2) of the dihydrothiazine ring are associated with changes in metab/pharmko props


Ceph MOA

interfere with bacterial cell wall synthesis and are bactericidal
-split in the B-lactam ring structure destroys the activity


1st gen all have PH in their name

To know the first generation
cephalosporins you must have a PH.D. in Pharmacology:

exceptions – *cefazolin* and cefadroxil are first generation drugs without a Ph in their name but don’t let
that Faze you its just a fad.
(others: cephalothin, cephapirin, cephradine)


2nd gen mnemonic

have a fam, fa, fur, fox, tea in their names. After you get your Ph.D. your family will want to celebrate – The FAMily is gathered, some wearing FUR coats, and your FOXy cousin is drinking TE(A) and taking PROzac while driving her CAR.
It's NICe to have METlife insurance


3rd gen mnemonic

Most of the third generation drugs have a T in their name and T is for TRI and
after you drive your car you might have to FIX it.
exceptions – cefoperazone, cefpodoxime, Cefdinir


Note – cefote(a)tan has a t but it is a second generation drug because your foxy cousin is drinking tea and cefmetazole is a second generation (cause you need METlife insurance)


Ceph 1/2 life

absorption can be decreased by ??

most have half-lives in range of 1-3 hrs
*Ceftriaxone has longest 1/2 life of 8 hours : 1-2x day possible

-antacids (cefaclor), H2 antagonists (cefdoxime, cefuroxime)


Ceph tissue distr.

*1st and 2nd gen Cephs tend not to have good penetration into the CNS even if inflamed meninges, not used for meningitis
*EXCEPT Cefuroxime (2nd) does penetrate CNS, but less active against bac that cause meningitis compared to 3rd gen cephs, NOT typically used


ceph 3rd gen advantages

penetrate CNS and can be used for meningitis: Ceftriaxone, Cefotaxime, Ceftazidime

4th gen: Cefepime: enters CNS and can be used for meningitis
5th gen: Ceftaroline: experimentally can be used for meningitis


ceph elimination

most via renal excretion by glom. filt. and tubular secretion (organic acid. sec. mech)

adjust w. renal failure
probenicid slows sec. of most ceps
excretion of 3rd ten : *Ceftriazone is mainly via bile, not nec. to adjust for renal failure*


ceph toxic effects

90% of pts allergic to PCNs may be able to take cephs
5-10% cross-allergenicity

-if pt has sev. immediate rxn (anaphylaxis) to PCN: should NOT get ceph
-if mild rxn to PCN, can cautiously take ceph
-no skin test to predict allergic rxns
-T1 hypersensitivity: urticaria, pruritis, angioedema, bronchospasm, maculopapular rash, fever, eosinophilia, rarely severe anaphylaxis and death


ceph SEs

intolerance of etOH, disulfiram-like rxn via inhibition of aldehyde dehydrogenase--> accumulation of acetaldehyde
-flushing ha, N/V, hypotension
-avoid ingestion of etOH while taking and 24-72 hrs after drug
-*Cefazolin* more effect: methylthiotetrazole group in R2


ceph adverse: bleeding disorders

PT deficiency, thrombocytopenia, dec. in platelets, platelet dysfunc.
-kills off vit. K producing bac in GIT
-vit. K confers biol. activity upon PT and factors 7,9, 10
-administer vit K (10mg 2x/wk)


other ceph adverse

-Nephrotoxicity: renal tubular necrosis, synergistic nephrotoxic effect w. co-admin of loop diuretic/aminoglycoside (esp. oldies and renal disease pts)
-seizures in pts w. renal impairment (if dose not lowered)
-oral admin: N/V/D
-Superinfection with opportunistic microorganisms (e.g. pseudomembranous colitis caused by clostridium difficult)
-pregnancy category B: safety not established, appear to be safe


resistance to cephs

The most important resistance mechanism to cephalosporins is destruction of the beta-lactam ring.
1st gens are inactivated by B-lactamase.
in general, subsequent gens. are more resistant to breakdown by B-lactamases
*Cefaclor is a susceptible 2nd gen drug
-The best way to minimize resistance to the cephalosporins is to limit or restrict the usage of the drug.


Cephalosporins are classified into Generations (1-4) based on Antimicrobial activity

First gen ceph have good activity against G+ and S. pneumo, and modest activity against G-
2nd gen: less S. pneumo,
3rd gen: less G+ coverage

4th and 5th?
5th: coverage against MRSA and Enterococcus


1st gen

G+ EXCEPT Enterococci, MRSA, MRSE (S. epidermidis)
-activity against oral cavity anaerobes: peptostrp, (B. fragilis is resistant)
-some G- enterics: Proteus mirabilis, E. coli, Kleb (PEK)


1st gen uses

-NOT for serious systemic infections
-staph and strep infections in pts w. *mild allergic rxns to PCNs*
-oral agents for UTIs, minor staph infections, minor polymicrobial infections (cellulitis, ST abscess)


2nd gen activity

G+ : less activity than 1st gen
G-: MORE activity than 1st gen (H. flu, M. cat)
-use for *RTIs (1st gens are NOT)
anaerobes, i.e. Cefoxitin activity against B. fragilis
-NOT active against pseudomonas
-do have activity against enterobacter, but not used here clinically (due to B-lactamase induction)


2nd gen uses

oral: sinusitis, OM, CAP
-activity against Strep, H. flu, M. cat, Kleb
-mixed anaerobic infections (peritonitis, diverticulitis)
-skin/ST, UTIs
*not for meningitis


3rd gen drugs

-much more active against G- than 2nd, useful against G- bacilli resistant to other ceps, PCNs, aminoglycosides
-Broader spectrum because they are resistant to B-lactamases
-less active than 1st gen against G+
-in vitro activity against enterobacter species but should not be used clinically since mutants that express a chromosomal β-lactamase emerge rapidly during


3rd gen uses

-serious inf. resistant to other drugs
*1st line for tx Gonorrhea (N. ton) (*Ceftriaxone IM, Cefixime)
-penetrate CNS, used to tx meningitis (S. pneumo, H. flu, enteric G- rods)
-what if Listeria? Amp
-what if highly PCN resistant? vanco
-empiric sepsis tx
-sepsis, RTIs, UTIs, skin/ST, bone/jt


4th gen

-extended spectrum compated to 3rd gen
-more resistant to breakdown by plasmid and chromosomal B-lactamases
-against G- resistant to 3rd gen (pseudomenas, enterobacteriaceae)
-PCN resistant Strep
-uses similar to 3rd gen (UTIs, skin/ST, pneumonia, complicated intro-abd. inf.)
-used for meningitis, penetrates CSF


5th gen

-increased binding to PBP, responsible for methicillin-resistance so: *ACTIVITY AGAINST MRSA*
-some activity against Enterococci
used for:
-CAP: Strep pneumo, Staph (needs to be MSSA if respiratory), H. flu, Kleb, E. coli
skin infections: *MRSA*, strep pyogenes, strep agalactiae, E. coli, Kleb