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Cephalosporins lecture Flashcards

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1
Q

cephalosporins are closely related to what antibiotic group due to presence of what structure

A

Cephalosporins are similar to the PCN family

Both have beta lactam ring structure

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2
Q

what makes cephalosporins unique and what does this feature do

A

cephalosporins are unique in that they have a 7 methyl group that increases their resistance to Beta-lactamase compared to PCNs

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3
Q

List the features of 1st generation cephalosporins

A

good activity against G+ and moderate against G-
most MSSA G+ cocci susceptible,
good alternative for people with PCN allergy,
some are acid resistant,
increased B-lactamase resistance,
Renal excretion

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4
Q

what is the drug of choice for surgical prophylaxis?

A

Cefazolin (kefzol, ancef) - IV, IM

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5
Q

what are all the 1st generation cephalosporins and their route of administration

A

Cefazolin (kefzol, ancef) - IV, IM
Cephalothin Sodium (Keflin) - IV, IM
Cephalexin (keflex) - ORAL

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6
Q

List the features of the 2nd generation cephalosporins

A
  • they are the same as first generation except have more gram - and less gam + activity
    (e. g. no antipseudomonal activity, increase B-lactamase resistance, some acid resistant, most Renal excretion)
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7
Q

Name the second generation cephalosporins and their route of administration

A

Cefaclor (ceclor) - oral
Cefprozil (cefzil) - oral
Cefuroxime (Zinacef) - IV, IM

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8
Q

Describe the activity of third generation cephalosporins

A
  • less G+ cocci activity
  • more activity against enterobacteriaceae (incl PCNase producing strains)
  • some pseudomonas aeruginosa activity (comb. with aminoglycosides)
  • some are acid resistant
  • increased B-lactamase activity
  • mostly renal excretion (cefoperazone - hepatic secretion)
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9
Q

name the DOC for N. gonorrhoeae and when it should not be used

A

DOC N gonorrheoeae = Ceftriaxone

avoid use in neonates, bilirubin displacement

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10
Q

list all the 3rd gen cephalosporins and their activity

A
  1. Ceftriaxone (Rocephin), CNS penetration, Neisseria
  2. Cefotaxime Sodium (Claforan), CNS penetration
  3. Cefoperazone (Cefobid), CNS penetration, P aeruginosa (metab by liver!!)
  4. Ceftazidime (Fortaz) P. aeruginosa
  5. Cefixime (Suprax) - ORAL
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11
Q

what makes the 3rd generation cephalosporins unique

A

they have CNS penetration and some pseudomonas resistance

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12
Q

List the activity of the 4th generation cephalosporins

A

Similar to 3rd generation, more resistant to some B lactamases, *antipseudomonal, better G+ coverage, renal excretion, broadest coverage**: enterobacteriaceae, MSSA, Pseudomonas, empirical therapy, particularly when resistance to B lactamase are anticipated

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13
Q

how does is the 4th generation of cephalosporins break the pattern of 1st to 3rd generation

A

1st to 3rd have progressing gram- activity and decreasing gram+ activity whereas 4th generation has increased G+ coverage

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14
Q

Name the one 4th generation cephalosporins and what it is used for

A

Cefepime (maxipime) IV is the only fourth generation cephalosporin

It has the broadest coverage (enterobacteriaceae, MSSA, Pseudomonas) so it is used in empirical therapy esp. when resistance to B lactamases are anticipated

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15
Q

Name the characteristics and drug of the “unnamed” generation cephalosporins

A

Unnamed:Ceftaroline fosamil (teflaro) - IV
approved by FDA 2010
no antipseudomonal but DOES cover MRSA and VRSA (this is the only beta lactam active against VRSA)
G+, G- activity, approved for CABG
Renal excretion

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16
Q

Describe the mechanism which the unnamed cephalosporin (Ceftaroline fosamil (teflaro) - IV) acts

A

ceftaroline fosamil (teflaro)-IV can bind PBP2A with very high affinity; PBP2A is the mutated PBP other beta lactamases cannot bind to

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17
Q

DOC Moraxella catarrhalis infection

A

second or third generation cephalosporin

2nd: Cefaclor, Cefprozil, Cefuroxime
3rd: Ceftriaxone, Cefotaxime, Cefoperazone, Ceftazidime, Cefixime

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18
Q

DOC Neisseria gonorrhoeae

A

Ceftriaxone (Rocephin)
Cefixime (Suprax) -oral

*both are third generation cephalosporins

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19
Q

DOC e. coli, Klebsiella, Proteus (these are Gram -)

A

first or second generation cephalosporin

1st: Cefazolin, Cephalothin Sodium, Cephalexin
2nd: Cefaclor, Cefprozil, Cefuroxime

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20
Q

DOC salmonella

A

third generation cephalosporins

3rd: ceftriaxone, cefotaxime, cefoperazone, ceftazidime, cefixime

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21
Q

DOC PCN resistant S. pneumonoiae

A

ceftriaxone (rocephin)

*this is a third generation cephalosporin

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22
Q

DOC B. burgdorferi

A

Ceftriaxone (rocephin)
(late disease)
*this is third gen cephalosporin

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23
Q

Describe the toxicity of cephalosporins

A

~fairly safe, 10% cross sensitivity with PCN (rash, hives, fever, eosinophilia)
~superinfection (enterococci, G-bacilli, Pseudomembranous colitis or candida)
~direct and indirect positive Coomb’s tests
~GI - anorexia, N/V, diarrhea
~dose dep renal tubular necrosis *works syngergistically with aminoglycosides –> nephrotoxicity

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24
Q

what is the therapeutic advantage of Cefazolin (Kefzol, ancef) - IV, IM and what generation does this cephalosporin belong to

A

Cefazolin (kefzol, ancef) is a first generation ceph
advantage: good bone penetration; parenteral med has long duration of action and similar spectrum of action compared to the other first gen cephalosporins (Cephalothin sodium (Keflin) - IV,IM; Cephalexin (Keflex) -oral

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25
What is the therapeutic advantage of Cephalexin (Keflex)- oral and what gen does this ceph belong to?
Cephalexin (Keflex)-oral belongs to 1st gen ceph | advantage: prototype of 1st gen oral cephalosporins, PO 2x/day effective against pharyngitis
26
What is the therapeutic disadvantage of Cefaclor (Ceclor) - oral
Cefaclor (ceclor) -oral is a second generation cephalosporin associated with serum sickness
27
What is the generation and therapeutic advantage of Cefuroxime (Zinacef) -IV,IM
Cefuroxime (zinacef) IV, IM is a second generation cephalosporin advantage: prototype Parenteral 2nd gen cephalosporin w/ longer t1/2 life than similar agents, can cross BBB and can be used for community acquired bronchitis or pneumonia in elderly and for immunocompromised
28
What is the Therapeutic advantage and generation of Cefixime (Suprax) - oral
Cefixime (Suprax) - oral is a 3rd gen cephalosporin | advantage: PO 1x/day
29
What is the therapeutic advantage and generation of cefotaxime (claforan) - IV, IM
``` Cefotaxime Sodium (Claforan) - IV, IM is a 3rd generation cephalosporin Advantage: good CSF penetration ```
30
What is the therapeutic advantage and generation of Ceftazidime (fortaz, tazidime) IM, IV?
Ceftazidime (tazidime) IV, IM is a 3rd gen ceph | Advantage: active against P aeruginosa
31
What is the therapeutic advantage and generation of Ceftriaxone (rocephin) IM, IV
Ceftriaxone (Rocephin) IM, IV is a 3rd gen ceph Advantage: longest half life of ceph (6-8 hr) allows once a day dosing. High levels can be achieved in blood and CSF. Effective against genital, anal and pharyngeal PCN-resistant N gonorrhoeae. May use in pt with renal insufficiency bc excreted in bile. Good bone penetration
32
Name the one monobactam
Aztreonam (Azactam)
33
What is the activity of the monobactam class and what drug comprises this class?
Only monobactam = Aztreonam (Azactam) *has monocyclic beta lactam ring *relatively B lactamase resistant *acitve ONLY against AEROBIC G- rods (pseudomonas, serratia, klebsielle, proteus) no G+ or anaerobe activity parenteral admin few side effects (phlebitis, rash, abn liver func) *no cross sensitivity with other B lactams thus good if pt has PCN allergy
34
List the carbapenems
1. Imipenem; Cilastatin (primaxin) 2. Meropenem (merrem) 3. Ertapenem (invanz)
35
What must imipenem (primaxin) be given with and why? What overall group does imipenem belong to?
Imipenem (Primaxin) is a Carbapenem. Must be given with cilastatin, a dihydropeptidase inhibitor bc it is rapidly inactivated by renal tubule dihydropeptidases
36
Imipenem (primaxin), a carbapenem, is inactivated by renal tubule dihydropeptidase and must be admin with cilastatin. What is another carbapenem (not ertapenem) and does it need any special protection
The other carbapenem besides Imipenem (primaxin) and ertapenem (invanz) = Meropenem (merrem). Meropenem is not inactivated by dihydropeptidases
37
What is the activity of Imipenem (primaxin), Meropenem (merrem) and what class do they fall under
Imipenem (primaxin) and Meropenum (Merren) are Carbapenems (IV admin) * broad spectrum activity - anaerobes, G+/- (good for mixed infections) * B lactamase resistant * Good idea to combo with an aminoglycoside bc Pseudomonas can dev resistance
38
What is a risk of taking the carbapenem, Imipenem (Primaxin) at high levels?
Seizures; use cautiously if renal failure, brain lesion, head trauma, or hx of CNS disorders
39
which is more likely to cause a seizure... Meropenum (Merrem) or Imipenem (Primaxin)
Imipenem (primaxin) has the seizure risk *caution if renal failure, brain lesion, head trauma, hx CNS disorders ie seizure
40
What is the DOC for B lactamase producing enterobacter infections
Imipenem (Primaxin) and Meropenem (Merrem) *these are carbapenems
41
Detail the route and activity/qualities of Ertapenem (Invanz)
Ertapenem (invanz) -IV, IM is a carbapenem * highly stable against B lactamase * wide variety of G+/- and anerobic (Enterobacteriaceae) * less active against Pseudomonas (don't use) IV,IM 95% protein binding, renal elim
42
What class of drugs is generally the class that is susceptible to B lactamase producing bacteria?
PCNs
43
What is the mechanism of action of Vancomycin (vancocin)
Vancomycin (vancocin) is an ICWS but is NOT a B-lactam | *it DOES prevent transpeptidation of peptidoglycan chain by binding to the terminal D-ala-D-ala
44
Why is vancomycin (vancocin) useful
Vancomycin (vancocin) is good against PCN and MRSA infections!!, & for G+ infections in PCN allergic pt (IV)... ONLY G+
45
Oral vancomycin (vancocin) is used for...
treating superinfections caused by staphylococcus and C diff | *note that first choice for C diff is METRONIDAZOL
46
Why should vancomycin (vancocin) be drug of last resort
bc of emerging VRE (vancomycin resistant enterococci) and need for alt. MRSA tx
47
What are some of the adverse side effects of Vancomycin (Vancocin)
risk of thrombophlebitis (if IV injection) Ototoxic* Nephrotoxic* "red man" syndrome (from histamine release)
48
Fosfomycin (Monurol) - mechanism?
Fosfomycin (monurol) is an ICWS at early step in peptidoglycan synthesis by acting as analog of PEP to prevent NAG ==> NAM reduction. *Structurally unrelated to other drugs
49
Activity of Fosfomycin (Monurol).. admin, excretion, use?
G+/G- admin Orally, excreted by kidney Use: uncomplicated low UTI *combo with B-lactam, aminoglycoside, or fluoroquinolone for synergistic effect
50
Bacitracin (AK-tracin) Inhibits CWS how?
interferes with final dephos step in PL carrier cycle --> can't transport NAG-NAM across inner membrane thus can't assemble cell wall
51
What is/are the route(s) for Bacitracin (AK-tracin) and what is it's activity?
Bacitracin (AK-tracin) is admin parenterally rarely (bc nephrotoxicity risk), usu topical polypeptide antibiotic (NEOSPORIN) to prevent superficial skin/eye infections G+ G- when combo w/ neomycin and polymyxin
52
What is the MOA of cycloserine (seromycin)
Cycloserine (seromycin) ICWS by preventing D-ala from being incorportated into Peptidoglycan pentapeptide
53
What is cycloserine (seromycin) used for
cycloserine (seromycin) is used as 2nd line, broad spectrum antibiotic to treat activit pulmonary and extrapulmonary TB and UTI's *can be bactericidal or bacteriostatis)
54
what are the adverse effects of cyclserine (seromycin) therapy
CNS side effects (HA, depression, psychosis) are the adverse side effects assoc with cycloserine (seromycin) tx
55
MOA: vancomycin, B-lactams, Bacitracin, Cycloserine, Fosfomycin *all ICWS
Vancomycin: Prevents elongation of Peptidoglycan and cross lining of peptide chains by binding to D-ala-D-ala and inhibits transpeptidation B lactams: interfere with PBP, prevents structurally strong cell wall Bacitracin: Maintains lipid carrier in phosphorylated state so can't transport NAG-NAM across membrane to assemble cell wall Cycloserine: prevents D-ala from being incorportated into peptidoglycan pentapeptide (don't make proper peptide chain) Fosfomycin: acts as PEP analog in the early phase of peptidoglycan synthesis preventing NAG --> NAM reduction
56
What is DOC for M. Catarrhalis (G- cocci aerobe)
2nd/3rd gen cephalosporin 2nd: Cefaclor (Ceclor) -ORAL, Cefprozil (Cefzil) -ORAL, Cefuroxime (Zinacef) -IV,IM 3rd: Ceftriaxone (Rocephin), Cefotaxime sodium (claforan), Cefoperazone (Cefobid), Ceftazidime (Tazidime) **ALL 3rd gen = IV/IM except Cefixime (suprax) - ORAL
57
DOC N gonorrhoeae (G- bacilli aerobe)
Cefriaxone (Rocephin) - 2nd gen | Cefpodoxime
58
DOC Enterobacter, Citrobacter, Serratia (G- bacilli aerobe)
Carbapenem: Imipenem (Primaxin), Meropenem (Merrem) - Ertapenem (invanz)?? not sure if this carbapenem is included as DOC
59
DOC MRSA (G+cocci)
vancomycin (vancocin)
60
DOC Bacillus species (non anthracis)? (G+ bacilli aerobe)
vancomycin (vancocin)
61
DOC salmonella (G- bacilli, aerobe)
Cephalosporin 3rd gen 1. Ceftriaxone (rocephin), 2. Cefotaxime sodium (clarforan), 3. Cefoperazone (cefobid), 4. Ceftazidime (tazidime) * all above are IV, IM 5. Cefixime (suprax) - ORAL
62
DOC B. burgdorferi (spirochetes) - Lyme disease
late stages: Ceftriaxone

Pharm - Final exam (3 decks)

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