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
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
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
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
5
Q
What are the First Generations Cephalosporins that are used?
A
- Cafazolin, Caphalexin
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
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 (-)
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]
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 (-)
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
11
Q
What are the Fourth Generation Cephalosporins that are used?
A
- Cefepime
Poor Inducer of AmpC
12
Q
What is the spectrum of activity for the Fourth Generation Cephalosporins?
A
- Gram (+): PRSP
- Gram (-): “HENPECKSSS” + Pseudomonas Aeruginosa
13
Q
What is the Anti-MRSA Cephalosporin?
A
- Ceftaroline
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
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
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
17
Q
What is the spectrum of activity for Ceftolozane-Tazobactam?
A
- Gram (+): Strep
- Gram (-): “HENPECKSSS” + Pseudomonas Aeruginosa [Super active toward]
18
Q
What is the spectrum of activity for Ceftazidime-Avibactam?
A
- Gram (+): Strep
- Gram (-): “HENPECKSSS” + Pseudomonas Aeruginosa [Super active toward]
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
20
Q
What is the Pharmacodynamic Priniple for the Cephalosporins>
A
- Time-dependent; T>MIC
21
Q
How are the Cephalosporins distributed in the Body?
A
- Into Tissues and Fluids; Pleural, Synovial, Bone, Bile, Placenta, Pericardial, Humor
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
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
What is the Half Life for the Cephalosporins?
- ~2 hours
- **EXCEPT** Ceftriaxone ~8 hours [making it dosed once daily]
26
What are some of the Clinical Used for the First Generation Cephalosporins/
- **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
What is the Clinical Uses of the Second Generation Cephalosporins?
- Oral agents good for; Pharyngitis, Tonsillitis, Sinusitis, Otits Media, Bronchitis, Pneumonia
- **NOT recommended for Meningitis**
- **Cephamycins, Cefoitin, Cefotetan, Cefmetazole** good in Bacteroids fragilis
28
What is the Clinical use of the Third Generations Cephalosporins?
- 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
What is the clinical use of Fourth Generation Cephalosporins?
- Pneumonia, Bacteremia, UTI, Skin, Soft Tissue...
- **Antipseudomonal Activity**
- NO to anaerbos so add Metronidazole
29
What is the Clinical use of the Anti-MRSA Cephalosporins?
- Skin and Soft tissue from **MRSA**
- **NOT Pseudomonas Aeruginous**
30
What is the Clinical Use of Cefiderocol?
- UTI [Pyelonephritis], HABP, VABP
- **VERY $$$**
31
What is the clinical use of Cephalosporin-B-Lactamase inhibitor combinations?
- UTI, IAI [with Metronidazole], HABP/VABP
32
What are some of the adverse effects of the Cephalosporins?
- Hypersensitivity [Rash, hives, itching...]
- Issues with 5-NMTT side chain
- GI [N, V, **Pseudomembranous Colitis**; Biliary Sludging
33
What is important to know about the cross-reactivity within Cephalosporins?
- Rate is ~1-5 % with 1st Generations being ~10% [except Cafazolin b/c of unique R1 group]
34
What is important to know about the 5-NMTT side chain within the Cephalosporins?
- Might cuase **Hypoprothrombinemia or Disulfiram Reaction**
- Found in **Cefamandole, Cefotetan, cefmetazole, Cefoperazone, Moxalactam**
35
What is the structural difference in the Carbapenems compared to the Cephalosporins?
- HAVE 5-member ring BUT theres a **Sulfur** group
36
What is the mechanism of action for the Carbapenems?
- Binds to PBPs that help with Cell Wall synthesis
- **Bactericidal**
| Similar to the other B-lactams
37
What are the Mechanism of resistance for the Carbapenem?
- Alteration in Porins [effects **Pseudomonoas Aeruginosa**
- Hydrolysis by **b-lactamase or Carbapenemase**
- **Alteration of PBP** [NO MRSA or PRSP]
38
What is the spectrum of activity for the Carbapenems?
- **VERY broad spectrum**
39
What Gram (+) do the Carbapenems affect and which are the best for it?
- **Imipenem & Doripenem**
- Group/Viridan Strep, PSSP, E. Faecalis, **MSSA** [NEVER 1st line]
40
What Gram (-) do the Carbapenems affect and which are the best for it?
- **Doripenem & Meropenem**
- "HECK YES Ma'aM" or "HENPECKSSS"
- **DOC** for ESBL, AmpC,
- **Acinetobacter sp., Pseudomonas Aeruginosa** not good with **Ertapenem**
41
What Anaerobes are the Carbapenems good for?
- Gram (+): Peptostreptococcus, Clostridium
- Gram (-): ALL Bacteroides
42
What organisms are NOT active against Carbapenem?
- **MRSA**
- **VRE**
- **C. Diff**
- **Stenotrophomonas Maltophilia**
43
What is the pharmacodynamic prinicples of carbapenems?
- Time-dependent ; **T>MIC**
- They are **Bactericidal**; only Bacteriostatic for Enterococcus
44
What is important to know about the distribution of Carbapenems?
- In body tissue and fluids [saliva, sputum, humor, skin, soft tissue, bone, bile, endometrium...]
- **CSF??** only **Meropenem goes into the CSF**
45
What is important to know about the Elimination of the Carbapenems?
- **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
What is important to know about the half life of the Carbapenems?
- Imipenem, Meropenem, Doripenem = 1 hour
- **Ertapenem = 4 hours**
47
What are the clinical uses of the Carbapenems?
- **Polymicrobial or Nosocomial Infections**
- **Ertapenem =/= Pseudomonas Aeruginosa**
- Gram (-) that make ESBLs, AmpC [**DOC**]
48
What are the Adverse Effects of the Carbapenems?
- 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
What is the main sturctual feature of a monbactam?
- Just a square brother
50
What is the mechanism of action for the Monobactams?
- Inhibits cell wall synthesis by inhibiting PBPs BUT...
- Bind to **PBP-3 helping be active to Gram (-)**
51
What is the Monobatacm that is used?
- Aztreonam
52
What is the spectrum of activity for the Monobactams/
- **ONLY good for Gram (-)**
- HENPECKSSS + **Pseudomonas Aeruginosa** [60% of strains]
53
What is important to know about the Pharmacodynamic principles of Aztronam?
- **T>MIC**
- Distrubtion: Body Tissues and Fluids; **DOES go into CSF**
- Elimination: **Kidneys** & removed via Hemodialysis
54
What is the Clinical use of Aztreonam?
- Gram (-) infections [**EVEN Pseudomonas Aeruginosa**]
- For those that have a Penicillin allergy
| **little to no Cross-reactivity**
