cephalosporins 67 Flashcards
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
- gonorrhea*
Cefixime (Suprax) - oral
Third Generation Cephalosporin
gonorrhea
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:
cephalexin
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 cefamandole *cefaclor *cefuroxime *cefoxitin cefote(a)tan *cefprozil loracarbef cefmetazole cefonicid
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
- ceftriaxone
- ceftazidime
- cefotaxime
- cefixime
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
- Cefazolin*
- 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
treatment
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
