18. Cefalosporins, monobactams and carbapenems Flashcards
Structure of cephalosporins
Penicillins - 5 member ring (thiazolidine ring), cephalosporins - 6 member ring -› not as easy can be inhibited by beta-lactamase
Mechanism of action of cephalosporins
Same as in penicillins
Mode of action of cephalosporins
BACTERIACIDAL, time-dependent
+ PAE (postantibiotic effect) - 1-4 hours
Drug list of cephalosporins:
1 generation:
- cefazolin
- cefapirin
- cefalexin
- cefalonium
- cefadroxil
2 generation:
- cefuroxime
3 generation:
- ceftiofur
- cefovecin
- cefoperazone
- ceftriaxone
- cefotaxime
- ceftazidime
4 generation:
- cefepime
- cefquinome
Resistance of bacteria against cephalosporins
Same as in penicillins:
- ab ovo
- beta-lactamase production
- PBP-mutation
Antibacterial spectrum of 1st generation of cephalosporins:
Similar to amoxicilin.
Good activity against Gram+ bacteria
Gram—: NOT against lactamase producers, not good against anaerobic bacteria
Antibacterial spectrum of 2nd generation of cephalosporins:
Worse than 1st generation against Gram+ bacteria
Gram—: active against several lactamase producers! (E. coli, Salmonella, Klebsiella …)
Anaerobic bacteria: rarely
Antibacterial spectrum of 3d generation of cephalosporins:
Weak against Gram+ bacteria
Gram—: active against most lactamase producers and fastidious and anaerobic bacteria
+ Pseudomonas aeruginosa (cefoperazone, ceftazidime)
Antibacterial spectrum of 4th generation of cephalosporins:
Almost perfect
Good activity against Gram+
Gram—: most lactamase producers
Also 4th generation cephalosporins are more active (MICs are lower)
Pharmacokinetics of cephalosporins :
Absorption:
1,2 gen. - orally/parenterally
3,4 gen. - parenteral
Distribution:
1,2: not very good
3,4: pretty good
Metabolism
cefovecin, ceftiofur (3) - veeeeery long half-life
Excretion: kidney (exc.: cefoperazone, ceftriaxone (3) - through bile)
Side effects of cephalosporins
- allergy (~5% cross allergy - 5% chance that if patient is allergic to penicillins it will be allergic to cephalosporins too)
- dysbacteriosis
- haematological (anaemia)
- tissue irritation (depending on drug)
- mild nephrotoxicity
Cefalexin
- 1st generation
- good against Staphylococcus
- skin soft tissue infections: dermatitis, mastitis (Gram+)
- orally
Cefazolin
- 1st generation
- main indication: pre- and postoperatic IV in case of long surgery (›1hour)
- parenteral administration
Cephapirin
- 1st generation
- Staphylococcus caused mastitis
- parenteral administration
Cefuroxime
- 2nd generation
- UTI, resp. Infections, otitis
- oral/parenteral administration
Cefoperazone
- 3d generation
- good against Gram— caused mastitis (e.g. Enterobacteria)
- good against Pseudomonas
- excreted via bile (!)
Ceftiofur
- 3d generation
- in large animals against almost everything - mastitis, resp. diseases, foot rot (Fusobacterium)
- covers anaerobic bacteria too
- long half-life
- parenteral administration
Cefovecin
- 3d generation
- oral cavity infections, UTI, dermatitis
- long half-life
Cefotaxime, ceftriaxone
- 3d generation
- can go through BBB -› meningitis, encephalitis, second choice in osteomyelitis (1 - clindamycin), second choice for Lyme-disease (1 - doxycyclin)
- ceftriaxone is excreted via bile
Cefquinome, cefepime
- 4th generation
- only for large animals
- work good against almost everything
General indications for cephalosporins
- mastitis/metritis
- dermatitis, soft tissue infections
- resp. Infections (best - 3/4 gen)
- UTI (if not excreted through bile like cefoperazone and ceftriaxone)
- meningitis, encephalitis
- preoperative, postoperative prophylaxis (cefazolin)
- osteomyelitis (1st choice is clindamycin)
What cephalosporins are effective against Pseudomonas aeruginosa
- cefoperazone
- ceftazidime
Cephasporins ‹-› AMEG classification
3d and 4th gen. -› category B: restrict - CIA highest priority
1st and 2nd gen. -› category C: caution
Monobactams
- excellent activity against gram-
- primary UTI
Aztreonam (parental)
Tigemonam (p.o)
category A (AMEG)
Carbapenems
Meropenem
Imipenem
last resort antibiotics, highly active against all important known pathogenic bacteria
Category A: avoid
