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PHRM 865: Theraputics V > Lecture 8: Cephalosporins, Carbapenems, Monobactams > Flashcards

Lecture 8: Cephalosporins, Carbapenems, Monobactams Flashcards

Erdman's Section

1
Q

How are the Cephalosporins strucutrally different than the Penicilins?

A
  • They have 6-membered dihydrothiazine; helps with stability against B-lactamase
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2
Q

What is the Mechanism of Action for the Cephalosporins?

A
  • Same as Penicillins
  • Inhibits Cell Wall synthesis by binding to PBPs [Transpeptidase] leading to lysis
  • Bactericidial
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3
Q

What are the ways that Cephalosporins have resistance?

Mechanisms?

A
  • Productions of B-lactamases; they hydrolyze the amide bond breaking the ring
  • Alterations in PBPs
  • Altered Porins
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4
Q

What is the interesting scheme that Cephalosporins follow in terms of the Generations?

A
  • 1st to 4th Gen: LOSE Gram (+) Activity and GAIN Gram (-) & B-lactamase activity
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5
Q

What are the First Generations Cephalosporins that are used?

A
  • Cafazolin, Caphalexin
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6
Q

What is the spectrum of activity for the First Generation Cephalosporins?

A
  • GOOD to Gram (+); Best in Cephalosporins [Group/Viridan Strep, PSSP, MSSA
  • Gram (-): “PEK” –> P. Mirabilis, E. Coli, K. Pneumoniae
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7
Q

What are the Second Generation Cephalosporins that are used?

A
  • Cefuroxime, Cefprozil, Cefoxitin [Cephamycin]

Less active to Gram (+) and More Active to Gram (-)

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8
Q

What is the spectrum of activity for the Second Generation Cephalosporins?

A
  • Gram (+): Group/Viridan Strep, MSSA
  • Gram (-): “HENPEK” –> H. Influenzae, Enterobacter sp., Neissera sp., P. Mirabilis, E. Coli, K. Pneumoniae
  • Anaerobes: B. Fragilis [use Cefoxitin, Cefotetan, Cefmetazole]
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9
Q

What are the Third Generation Cephalosporins used?

A
  • Cefraxone, Ceftazidime, Cefpodoxime

Less active in Gram (+) than 1st and 2nd gen & good aginat Gram (-)

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10
Q

What is the Spectrum of Activity for the Thrid Generation Cephalosproins?

A
  • Gram (+): PRSP - Use Ceftriaxone & Cefotaxime
  • Gram (-): “HENPECKSSS”–> H.Fluenzae, Enterobacter, Neisseria, P. Mirabilis, E. Coli, Citerbacter, K. Pneumoniae, S. Marcescen, Salmonella, Shigella
  • Pseudomonas Aeruginosa [ONLY Ceftazidime & Cefoperazone

CEFTRIAXONE DONT COVER PSEUDO

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11
Q

What are the Fourth Generation Cephalosporins that are used?

A
  • Cefepime

Poor Inducer of AmpC

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12
Q

What is the spectrum of activity for the Fourth Generation Cephalosporins?

A
  • Gram (+): PRSP
  • Gram (-): “HENPECKSSS” + Pseudomonas Aeruginosa
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13
Q

What is the Anti-MRSA Cephalosporin?

A
  • Ceftaroline
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14
Q

What is the Spectrum of Activity for the Anti-MRSA Cephalosporin?

A
  • Gram (+): Strep & Staph [PRSP] & MRSA [maybe like 4th line tho]
  • Gram (-): “HENPECKSSS” with NO Pseudomonas Aeruginoas
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15
Q

What is Cefidercol and how does it work?

A
  • Binds to Free Iron, with the help of porins, transport the antibiotic into the cell
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16
Q

What is the spectrum of activity of Cefiderocol?

A
  • Gram (+): No real activity
  • Gram (-): Enterobacterales, P. Aeruginoas, A. Baumannii, S. Maltophilia some MDR [ESBLs, AmpC, Carbapenemases
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17
Q

What is the spectrum of activity for Ceftolozane-Tazobactam?

A
  • Gram (+): Strep
  • Gram (-): “HENPECKSSS” + Pseudomonas Aeruginosa [Super active toward]
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18
Q

What is the spectrum of activity for Ceftazidime-Avibactam?

A
  • Gram (+): Strep
  • Gram (-): “HENPECKSSS” + Pseudomonas Aeruginosa [Super active toward]
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19
Q

What is an overall thing to keep in mind regarding the Spectrum of Activity for Cephalosporins/

A
  • NOT ACTIVE toward MRSA [except Ceftaroline] Entercoccus sp., & Legionella Pneumophilia
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20
Q

What is the Pharmacodynamic Priniple for the Cephalosporins>

A
  • Time-dependent; T>MIC
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21
Q

How are the Cephalosporins distributed in the Body?

A
  • Into Tissues and Fluids; Pleural, Synovial, Bone, Bile, Placenta, Pericardial, Humor
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22
Q

Are Cephalosporins able to go into the CSF?

A
  • NO with most 1st and 2nd Generations
  • Parenteral Cefuroxime, 3rd & 4th Generations are able to go into CSF
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23
Q

How are the Cephalosporins Eliminiated from the Body?

A
  • Kidneys via Glomerular filration and Tubular Secretion
  • EXCEPT Ceftriaxone & Cefoperazone [Bile & Liver]
24
Q

Are Cephalosporins removed from Hemodialysis?

A
  • Most of them are EXCEPT Ceftriaxone
25
Q

What is the Half Life for the Cephalosporins?

A
  • ~2 hours
  • EXCEPT Ceftriaxone ~8 hours [making it dosed once daily]
26
Q

What are some of the Clinical Used for the First Generation Cephalosporins/

A
  • MSSA, Group/Viridan Strep [Skin/Soft Tissue, Septic Arthritis, Osteomyelitis, Endocaraditis]
  • Cefazolin is THE DOC for Surgical Proghylaxis
  • Gram (-): PEK
  • NOT for Meningitis [NOT into CSF]
27
Q

What is the Clinical Uses of the Second Generation Cephalosporins?

A
  • Oral agents good for; Pharyngitis, Tonsillitis, Sinusitis, Otits Media, Bronchitis, Pneumonia
  • NOT recommended for Meningitis
  • Cephamycins, Cefoitin, Cefotetan, Cefmetazole good in Bacteroids fragilis
28
Q

What is the Clinical use of the Third Generations Cephalosporins?

A
  • Gram (-) Bacterias [UTI, Bone/joint, Meningitis…]
  • Pseudomonas Aeruginosa use Ceftazidme or Cefoperzone
  • Ceftriaxime = Uncomplicated Gonorrhea
  • Cefotaxime & Ceftiaxone = Gram (+); Group/Viridan Strep [Endocarditis] & PRSP [Meningitis]
28
Q

What is the clinical use of Fourth Generation Cephalosporins?

A
  • Pneumonia, Bacteremia, UTI, Skin, Soft Tissue…
  • Antipseudomonal Activity
  • NO to anaerbos so add Metronidazole
29
Q

What is the Clinical use of the Anti-MRSA Cephalosporins?

A
  • Skin and Soft tissue from MRSA
  • NOT Pseudomonas Aeruginous
30
Q

What is the Clinical Use of Cefiderocol?

A
  • UTI [Pyelonephritis], HABP, VABP
  • VERY $$$
31
Q

What is the clinical use of Cephalosporin-B-Lactamase inhibitor combinations?

A
  • UTI, IAI [with Metronidazole], HABP/VABP
32
Q

What are some of the adverse effects of the Cephalosporins?

A
  • Hypersensitivity [Rash, hives, itching…]
  • Issues with 5-NMTT side chain
  • GI [N, V, Pseudomembranous Colitis; Biliary Sludging
33
Q

What is important to know about the cross-reactivity within Cephalosporins?

A
  • Rate is ~1-5 % with 1st Generations being ~10% [except Cafazolin b/c of unique R1 group]
34
Q

What is important to know about the 5-NMTT side chain within the Cephalosporins?

A
  • Might cuase Hypoprothrombinemia or Disulfiram Reaction
  • Found in Cefamandole, Cefotetan, cefmetazole, Cefoperazone, Moxalactam
35
Q

What is the structural difference in the Carbapenems compared to the Cephalosporins?

A
  • HAVE 5-member ring BUT theres a Sulfur group
36
Q

What is the mechanism of action for the Carbapenems?

A
  • Binds to PBPs that help with Cell Wall synthesis
  • Bactericidal

Similar to the other B-lactams

37
Q

What are the Mechanism of resistance for the Carbapenem?

A
  • Alteration in Porins [effects Pseudomonoas Aeruginosa
  • Hydrolysis by b-lactamase or Carbapenemase
  • Alteration of PBP [NO MRSA or PRSP]
38
Q

What is the spectrum of activity for the Carbapenems?

A
  • VERY broad spectrum
39
Q

What Gram (+) do the Carbapenems affect and which are the best for it?

A
  • Imipenem & Doripenem
  • Group/Viridan Strep, PSSP, E. Faecalis, MSSA [NEVER 1st line]
40
Q

What Gram (-) do the Carbapenems affect and which are the best for it?

A
  • Doripenem & Meropenem
  • “HECK YES Ma’aM” or “HENPECKSSS”
  • DOC for ESBL, AmpC,
  • Acinetobacter sp., Pseudomonas Aeruginosa not good with Ertapenem
41
Q

What Anaerobes are the Carbapenems good for?

A
  • Gram (+): Peptostreptococcus, Clostridium
  • Gram (-): ALL Bacteroides
42
Q

What organisms are NOT active against Carbapenem?

A
  • MRSA
  • VRE
  • C. Diff
  • Stenotrophomonas Maltophilia
43
Q

What is the pharmacodynamic prinicples of carbapenems?

A
  • Time-dependent ; T>MIC
  • They are Bactericidal; only Bacteriostatic for Enterococcus
44
Q

What is important to know about the distribution of Carbapenems?

A
  • In body tissue and fluids [saliva, sputum, humor, skin, soft tissue, bone, bile, endometrium…]
  • CSF?? only Meropenem goes into the CSF
45
Q

What is important to know about the Elimination of the Carbapenems?

A
  • Kidney via Glomerular or Tubular
  • Imipenem has DHP inactive it; so give with Cilastatin [protects from break down and helps with nephrotoxicity]
  • ALL Carbapenems NEED DOSAGE ADJUSTMENTS
46
Q

What is important to know about the half life of the Carbapenems?

A
  • Imipenem, Meropenem, Doripenem = 1 hour
  • Ertapenem = 4 hours
47
Q

What are the clinical uses of the Carbapenems?

A
  • Polymicrobial or Nosocomial Infections
  • Ertapenem =/= Pseudomonas Aeruginosa
  • Gram (-) that make ESBLs, AmpC [DOC]
48
Q

What are the Adverse Effects of the Carbapenems?

A
  • Hypersensitivity [Rash, hives, itching…]
  • GI: N, V, D, C. Diff
  • CNS - DIRECT TOXIC EFFECT [Insomina, agitation, confusion, dizziness, Seizures (from previous seizures or high doses)]
49
Q

What is the main sturctual feature of a monbactam?

A
  • Just a square brother
50
Q

What is the mechanism of action for the Monobactams?

A
  • Inhibits cell wall synthesis by inhibiting PBPs BUT…
  • Bind to PBP-3 helping be active to Gram (-)
51
Q

What is the Monobatacm that is used?

A
  • Aztreonam
52
Q

What is the spectrum of activity for the Monobactams/

A
  • ONLY good for Gram (-)
  • HENPECKSSS + Pseudomonas Aeruginosa [60% of strains]
53
Q

What is important to know about the Pharmacodynamic principles of Aztronam?

A
  • T>MIC
  • Distrubtion: Body Tissues and Fluids; DOES go into CSF
  • Elimination: Kidneys & removed via Hemodialysis
54
Q

What is the Clinical use of Aztreonam?

A
  • Gram (-) infections [EVEN Pseudomonas Aeruginosa]
  • For those that have a Penicillin allergy

little to no Cross-reactivity

PHRM 865: Theraputics V (42 decks)

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