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Block 5 Drugs > Cephalosporins-Cell wall synthesis inhibitors > Flashcards

Cephalosporins-Cell wall synthesis inhibitors Flashcards

1
Q

What are the major types of bacterial cell wall synthesis inhibitors APART from penicillins?

A

1) Cephalosporins
2) Carbapenems
3) Monobactams

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2
Q

Cephalosporins are not active against which organisms?

A

Cephalosporins are not active against Enterococci and Listeria

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3
Q

How do first generation cephalosporins compare to later generations?

A

1st generation are more active vs gram positive organisms (e.g. staph, streptococci), while later drugs (2nd, 3rd, 4th gen) are more active vs gram negative aerobic organisms (e.g. E. coli, etc.)

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4
Q

What generation of cephalosporin is Cefazolin?

A

First generation cephalosporin

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5
Q

What is the mechanism of action of Cefazolin?

A

Binds to PBP’s, and thereby inhibits the assembly of the bacterial cell wall, leading to bactericidal action

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6
Q

What organisms are sensitive to Cefazolin?

A

Sensitive: most streptococci, most S aureus (MSSA), most oral anaerobes, some sensitive GNR like E. coli

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7
Q

What organisms are resistant to Cefazolin?

A

Resistant: MRSA (about 30% and growing), enterococcus, nosocomial GNRs, some pneumococcus, bowel anaerobes

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8
Q

How is Cefazolin usually administered?

A

Usually administered IV but can be given IM

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9
Q

What toxicity is associated with Cefazolin?

A

Contraindicated in serious Pen-allergic patients (cross-allergy); anemia, drug allergy especially rash, analphylaxis, antibiotic-associated colitis

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10
Q

What drug interactions should be considered with Cefazolin?

A

probenecid inhibits renal active tubular secretion, prolongs half-life

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11
Q

What are the indications for Cefazolin?

A

Soft tissue infections (strep and staph)

  • UTI
  • Patients with mild allergies (but not anaphylaxis) to penicillins
  • Surgical prophylaxis (e.g. just before appendectomy or hysterectomy)
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12
Q

What is the mechanism of action of Ceftriaxone (3rd generation cephalosporin)?

A

Binds to PBP’s, and thereby inhibits the assembly of the bacterial cell wall, leading to bactericidal action; more active against many GNRs which produce beta-lactamases

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13
Q

What organisms are sensitive to Ceftriaxone?

A

Sensitive: streptococci, most (>90%) pneumoccus, many S aureus (only MSSA), most oral anaerobes, Neisseria, Most gram negative rods, Lyme disease

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14
Q

What organisms are resistant to Ceftriaxone?

A

Resistant: MRSA (about 30% and growing), 5-10% pneumococcus, bowel anaerobes, enterococcus, nosocomial GNRs, bowel anaerobes, pseudomonas, and Listeria

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15
Q

How is Ceftriaxone generally administered?

A

Usually given IV, but can be given IM

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16
Q

What toxicity is associated with Ceftriaxone?

A

Contraindicated in serious Pen-allergic patients (cross-allergy); anemia, drug allergy especially rash, anaphylaxis, antibiotic-associated colitis

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17
Q

What drug interactions should be considered with Ceftriaxone?

A
  • Probenecid inhibits renal active tubular secretion - Synergistic with gentamicin against some gram negative rods
  • May enhance effects of warfarin
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18
Q

What are the indications for Ceftriaxone?

A

Meningitis, serious pneumonia, gonorrhea, otitis, sinusitis

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19
Q

To what generation of cephalosporin does Ceftazidime belong?

A

3rd generation cephalosporin

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20
Q

What is the mechanism of action of Ceftazidime?

A
  • Binds to PBP’s, and thereby inhibits the assembly of the bacterial cell wall, leading to bactericidal action
  • More active against many GNRs which produce beta-lactamases
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21
Q

What organisms are sensitive to Ceftazidime?

A

Sensitive: some streptococci, but most effective against many GNRs, including most PSEUDOMONAS strains

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22
Q

What organisms are resistant to Ceftazidime?

A

Resistant: large majority of staph, some pneumococcus, bowel anaerobes; good at inducing resistance

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23
Q

How is Ceftazidime usually administered?

A

IV but can be given IM

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24
Q

What toxicity is associated with Ceftazidime?

A

Contraindicated in serious Pen-allergic patients (cross-allergy); drug allergy especially rash, anaphylaxis, antibiotic-associated colitis

25
Q

What drug interactions should be considered with Ceftazidime use?

A
  • Synergistic with gentamicin against some GNR, especially Pseudomonas
  • May enhance effects of warfarin
26
Q

What are the indications for Ceftazidime?

A
  • Infections where resistant GNRs and Pseudomonas are likely
  • Meningitis or sepsis where GNR is likely pathogen
  • Bacteremia, UTI, urosepsis
  • Empiric Rx of febrile neutropenic pts
27
Q

To what generation of cephalosporin does Ceftaroline belong?

A
  • “5th generation” cephalosporin
  • Amazingly active against GNR (like the 3rd and 4th generation drugs), but also active against GPC like staph aureus, including both MSSA and MRSA
28
Q

What is the mechanism of action of Ceftaroline?

A

Binds to PBP’s, and thereby inhibits the assembly of the bacterial cell wall, leading to bactericidal action; more active against many GNRs which produce beta-lactamases

29
Q

What organisms are sensitive to Ceftaroline?

A

Sensitive: many GNR (E. coli, Klebsiella, H. influenza)

-Many GPC, including Str. pneumoniae, both MSSA and MRSA

30
Q

How is Ceftaroline generally administered?

A

IV but can be given IM

31
Q

What toxicity is associated with Ceftaroline?

A
  • Very well tolerated during testing
  • Can produce anaphylaxis and serious skin reactions
  • Watch out in patients allergic to other beta-lactam antibiotics
  • Can produce Clostridium difficile-associated diarrhea
  • 10% of patients convert to a positive direct Coombs test
32
Q

What is the indication for Ceftaroline?

A

Community acquired bacterial pneumonia, skin infections, but only for pathogens likely to be sensitive, and only when you need a drug this broad; IV use only

33
Q

What are the adverse side effect for all cephalosporins?

A

1) Allergic reactions, similar to penicillins

2) Super-infection can develop from GPC (MRSA, enterococcus) or fungi

34
Q

What antibiotics is MRSA resistant to?

A

1) Methicillin (no longer used due to nephrotoxicity)
2) Nafcillin, oxacillin, and dicloxacillin
3) Cefazolin and cephalexin (basically all Cephalosporins)

35
Q

What is the mechanism of action of Meropenem?

A

Binds to PBP’s, and thereby inhibits the assembly of the bacterial cell wall, leading to bactericidal action; more active against many GNRs which produce beta-lactamases

36
Q

What organisms are sensitive to Meropenem?

A

Sensitive: most GPC, most GNR (including pseumomonas), and all anaerobes

37
Q

What organisms are resistant to Meropenem?

A

Resistant: MRSA, rare pneumococcus, enterococcus; pseudomonas can develop resistance rapidly

38
Q

How is Meropenem usually administered?

A

IV

39
Q

What toxicity is associated with Meropenem?

A

Contraindicated in serious Pen-allergic patients (some risk of cross-allergy); antibiotic-associated colitis; seizures in patients prone to them

40
Q

What drug interactions should be considered with Meropenem?

A

Probenecid inhibits renal active tubular secretion; synergistic with gentamicin against some GNR; may enhance effects of warfarin

41
Q

What are the indications for Meropenem?

A
  • Mixed nosocomial infections with resistant gram negative rods
  • Complicated meningitis, peritonitis, serious pneumonia, sepsis
42
Q

What monobactam is used in the U.S.?

A

Aztreonam

43
Q

What is the indication for Aztreonam?

A
  • Active ONLY against aerobic GNR

- Often given in place of an aminoglycoside for narrow coverage of aerobic GNR like E. coli

44
Q

What is the mechanism of action of vancomycin?

A

Inhibits synthesis of cell wall peptidoglycan by binding to the free carboxyl (COOH) end of the D-Ala-D-Ala chain, thereby preventing cross linking

45
Q

What organisms are sensitive to Vancomycin?

A

Sensitive: virtually all GPC, including MSSA, MRSA, coag neg staph, enterococcus, Clostridium difficile (only time we give it po)

46
Q

What is the only case Vancomycin is given by mouth?

A

C. Difficile infection

47
Q

What organisms are resistant to Vancomycin?

A

All GNRs, anaerobes other than clostridia sp, very rare S. aureus and enterococcus (VRE)

48
Q

How is Vancomycin administered?

A

given IV and excreted unchanged

49
Q

What toxicity is associated with Vancomycin?

A

Nephrotoxicity, neutropenia, red man syndrome (related to rate of infusion)

50
Q

What drug interactions are associated with vancomycin?

A
  • Additive (possibly synergistic) nephrotoxicity if given with other nephrotoxic drugs, including aminoglycosides, amphotericin
  • Synergistic when given with gentamicin against staph aureus and enterococcus
51
Q

What are the indications for Vancomycin?

A
  • Empiric treatment of serious infections likely caused by GPC (e.g meningitis, sepsis, pneumonia, endocarditis) pending culture results
  • Treatment of serious infections caused by GPC resistant to other drugs (e.g. MRSA)
  • Oral treatment of C. difficile colitis
52
Q

How do enterococci and S. aureus become resistant to vancomycin?

A

Resistance develops in enterococci and S aureus by the bacteria learning to change their terminal D-Ala to D-lactate
- prevents vancomycin from binding as tightly, and this in turn results in loss of its ability to prevent cross-linking

53
Q

What is the mechanism of action of daptomycin?

A

Binds to the cell membrane, depolarizes the cell, which leads to inhibition of synthesis of protein, DNA, and RNA, leading to cell death; does not enter the cytoplasm itself

54
Q

What bacteria are sensitive to daptomycin?

A

Sensitive: most GPC

55
Q

What bacteria are resistant to daptomycin?

A

Resistant: All GNRs

56
Q

How is daptomycin administered?

A

Given IV; 80% excreted unchanged

57
Q

What toxicity is associated with daptomycin?

A

cardiac failure, pseudomembranous colitis, hypoglycemia

58
Q

What drug interactions should be considered with daptomycin?

A
  • Use cautiously with statins (may increase risk of myopathy- check CPK)
  • May alter levels of tobramycin
  • May alter response to warfarin
59
Q

What are the indications for Daptomycin?

A

Treatment of serious infections caused by resistant GPC (e.g. MRSA, VRE) such as bacteremia, endocarditis, skin and soft tissue infections

Block 5 Drugs (9 decks)

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