Beta Lactam Abx and cell wall synthesis inhibitor 2 - Fitzpatrick Flashcards
Cephalosporins have MOA and resistance similar to _
other beta lactams.
- variable degradation by beta lactamase
- clearance by renal excretions
All Gen1-3 cephalosproins are ineffective and lack activity against which pathogens?
- Listeria monocytogenes
- Legionella
- Atypical mycoplasma
- MRSA
- Enteroccoci
what are the 1st gen cephalosporins
Cefazolin and cephalexin
Which 1st gen cephalosporin can be given IV/IM; which one can be given PO? what are their distinctive indication?
- Cefazolin = Parenteral, IV, IM = penetrates well into bone
- Cephalexin = PO = 2x daily for pharyngitis
1st gen cephalosporins is useful against which agents? Not useful against?
- Gram (+) cocci, strep and staph aureus.
Not active against: MRSA, MRSE, enterococci
what is the main clinical use of 1st gen cephalosporin?
Surgical prophylaxis if skin flora are likely pathogens; soft tissue and skin infection due to s. aureus, s pyogenes
What are the main 2nd gen cephlosporins?
- Cefoxitin (IV, IM) ( active against anaerobes e.g. b fragilis)
- Cefotetan (IV, IM) ( active against anaerobes e.g. b fragilis)
- Cefaclor (PO) - serum sickness in kids
- Cefuroxime axetil (PO)- poor substrate for beta lactamase
What is the main distinction between 1st gen and 2nd gen cephlosporins?
2nd gen is less active than 1st gen agents vs gram(+) organisms; enhanced activity against gram (-) e.g. ecoli, klebsiella, h influenza, moraxella cattharalis, proteus
what is the main clinical use of 2nd gen?
if facultative gram (-) bacteria and anaerobes are likely pathogens, e.g. Intra-abdominal and gynocological sepsis, surgical prophylaxis for intra-abdominal and colorectal surgery
What are the main 3rd gen cephlosporins?
- Ceftriaxone
- Cefotaxime
- Cetazidime
- Cefaperazone
What distinctions do the 3rd gen cephalosprins have?
ALL Parenteral
- Ceftriaxone: penetrates CSF and bone. used for Gonorrhea. Biliary clearance
- Cefotaxime: enters CSF; useful fo rmeningitis due to H influenza, s pneumonia, N meningitidis
- Cetazidime: active vs pseudomonas aeruginosa
- Cefaperazone: disulfiram like alcohol intolerance; active against pseudomonas
How do 1st gen and 3rd gen cephalosporins compare?
3rd gen is comparable to 1st gen vs S.aureus, s pneumonia, s pyogens.
- 3rd gen is enhanced activity against gram (-) rods, enteric organism
Because Ceftriaxone (3rd gen cephalosporin) has excellent distribution into CNS, It is recommended for therapy of _
Peinicillin-resistant gonorrhea, Lyme disease involving CNS or joints, meningitis due to ampicillin-resistant H. influenza, and meningitis in kids
- cleared via biliary excretion
Becuase cefotaxime has excellent CNS distribution, it is useful against _
bacterial meningitis frmo covered organism- H. influenza, s pneumonia, N meningitis and gram (-) enteric bacterial.
- Cleared via renal tubular secretion
Ceftazidime is particularly active against _ when the first line abx for this infection is resistant. Must be given in combo with _
pseudomonas. Ceftazidime is given in combo with an amyiinoglycoside (tobramycin) for treatment of serious P.aeruginosa
Anti-pseudomonas is first line. If infection is resistant to those abx and/or if pt is allergic to penicillin then use this.
What are some distinctive characteristics of 4th gen cephlosporins like cefepime?
- Activity is greater or equal to cefotaxime vs gram(-), H influenza, N gonorrhea, N meningitidis
- Excellent penetration into CSF
- Activity is comparable to ceftazidime for pseudomonas
If 1st line, and cetazidime are both resistant to pseudomonas what can be given?
Cefepime (4th gen cephalosporin)
What AE are associated with 4th gen cephalosporins?
- Hypersensitivity (immediate type I anaphylaxis or delayed type IV rash)
- disulfiram- like reaction (nausea, flushing, HA w/alcohol consumption)
Cephalosporins should not be used in pts with recent _
severe hypersensitivity rxn to a penicllin
The disulfiram-like reaction seen as an AE to cehlosporins results from an inhibition of what enzyme? Causes build up of what product?
Aldehyde dehydrogenase. builds up acetaldehyde
due to the methylthiotetrazole side chain of cefotetan and cefaperazole, these should be avoided in pts taking what other drug?
warfarin or pts with coagulation abnormalities.
MTT causes reduction in Vit K producing bacteria in GI tract–> hypoprothrombinemia and bleeding
Name a monobactam drug
aztreonam
Aztreonam is useful against what organisms?
- ONLY active against Gram (-) rods such as Klebsiella, psudomonas, serratia.
NOT useful for gram+ or anaerobes
What are some distincive characteristics of aztreonam?
- MOA: binds to PBP 3 of gram(-) rods
- substitute for extended spectrum penicillin or gen 3/4 cephalosporins if these are contraindicated cuz of hypersenstivity
- safe alternative for aminoglycosides in elderly or renal impairment
- synergistic with aminoglycosides parenteral IV, IM
A severely ill hospitalized pts needs empirical abx for several bacteria, including gram (-) and (=), and MRSA. what is a good option?
Cabapenems such as Imipenem/cilatatin. These guys are THE BROADEST spectrum abx available.
Can treat gram(+) like enterocococus faecalis and listeria; Gram (-) like H influenza, gonorrhea, enterobacteriacease and pseudomonas); anaeroboes like B fragilis. NOT degrade d by beta lactamase
- Given IV with excellent penetration into tisues and fluid including CNS with inflamed meninges.
What AE are associated with carbapenems?
- Hypersensitivity and rahs (caution in pts with penicillin allergy)
- CNS tox - seizures, confusion
- NEPHROTOXICITY - imipenem.
Imipenem is a nephrotoxin and thus is always used with _
Cilastatin which is a renal dipeptidase inhibitor, NOT a beta lactamase inhibitor
Vancomycin is used under what condition?
- penicillin hypersensitivity
- Narrow spectrum: gram+ cocci including MRSA, PRSP (pen resistant strep pneumo)
Erythromycin is used under what conditioin?
- Penicillin hypersensitivity
2. Narrow spectrum: gram + and beta lactamase secreting staph aureus for BUT NOT MRSA or PRSP
Under what condition is clindamycin used?
Used with penicillin to decrease toxin synthesis in life threatening streptococcal toxic shock and necrotizing fasciitis
When is Tigecycline used?
Broad spectrum including: MRSA and VRE (vanco resistant enterococcus)
when is Linezolid used?
- VRSA and VRE
