Lecture 2 - Diagnosing infection, Cephalosporins, Carbapenems, & Monobactam Flashcards
Signs & Symptoms of Infection: General
Fever = > 100.4
1F Rectal > oral > 1F axillary
Inc WBC, HR, BP
Signs & Symptoms of Infection: Site Specific
Local signs of pain and inflammation
Swelling, erythema, tenderness, purulent drainage
Imaging
Signs & Symptoms of Infection: Labs + Tests
ESR
CRP
Cephalosporins MOA
- Bind to PBPs
2. Inhibit cross-linking of peptidoglycan in the cell wall
1st Gen Cephalosporins
Cefazolin (IV)
Cephalexin (PO)
Cefadroxil (PO)
2nd Gen Cephalosporins
Cefuroxime (IV/PO) Cefprozil (PO) Cefaclor (PO) Cefotetan (IV) Cefoxitin (IV)
3rd Gen Cephalosporins
Ceftriaxone (IV) Cefotaxime (IV) Ceftazidime (IV) Cefdinir (PO) Cefditoren (PO) Cefixime (PO) Cefpodoxime (PO) Ceftibuten (PO)
4th Gen Cephalosporins
Cefepime
5th Gen Cephalosporins
Ceftaroline
Advanced Gen Cephalosporins
Cefiderocol
Ceftazidime-avibactam
Ceftolozane-tazobactam
1st & 2nd Gen Cephalosporins Spectrum of Activity Gram +
No enterococcal activity
1st gen Cefazolin = txm of choice for MSSA…maybe better than nafcillin
Not effective against MRSA
Great activity against all Strep spp.
3rd & 4th Gen Cephalosporins Spectrum of Activity Gram +
Less active than 1st/2nd gen in general
no enterococcus activity
Limited activity against MSSA
Not active against MRSA
Great activity against all Strep spp.
Ceftriaxone treatment of choice against….
Invasive Streptococcal infections (Penicillin-I or -R)
Ceftriaxone exception…
used in combo with Ampicillin for synergy in E.faecalis endocarditis
5th gen Cephalosporins Spectrum of activity Gram +
Best gram + of all gen
no Enterococcus activity
** Great against Step Aureus, MSSA, MRSA **
Great activity against all Strep spp.
Which Cephalosporins are used as Salvage therapy in combo with vanc or dapto for synergy?
5th gen
Advanced Gen Cephalosporins Spectrum of activity
Designed for Gram -
Gram + isn’t as good
No activity against S. aureus or Enterococcus
Ceftolozane-tazobactam + Ceftazidime-avibactam active against Streptococcus spp.
Cefiderocol has some activity against Streptococcus, less than other beta-lactams
1st & 2nd Gen Cephalosporins Spectrum of Activity Gram -
No activity against non-fermenters
Limited Gram - activity overall
Active against susceptible E.Coli, K pneumoniae, P.mirabilis
2nd gene more activity than 1st
2nd gen activty agisnst H.influenzae + M. catarrhalis (used in CAP for children)
3rd + 4th Gen Cephalosporins Spectrum of Activity Gram -
3rd gen (Ceftriaxone) txm of choice for E.coli, K.pneum, H.influenzae
3rd gen don’t have activity against non fermenters
4th gen have broader activity against Gram -
Which 3rd gen Cephalosporin has activity against non-fermenters?
Ceftazidime
Pseudomonas aeruginosa 4th gen Cephalosporin that is drug of choice?
Cefepime
3rd gen would be Ceftazidime
5th Gen Cephalosporins Spectrum of Activity Gram -
Limited Gram - activity similar to 2nd gene
No activity against non-fermenters
Advanced Gen Cephalosporins Spectrum of activity Gram -
Very broad Gram - coverage
Expanded coverage against multi-drug resistant organisms
Ceftazidime-avibactam is active against…..
carbapenemase-producing organisms (commonly via KPC enzyme)
Ceftolozane-tazobactam has expanded coverage against…
MDR P. aeruginosa
Cefiderocol has activity against….
MDR Acinetobacter, MBL producing Enterobacterales, along with all the other stuff
Cephalosporins Anaerobes Spectrum of activity
overall not that great
Most have activity against Peptostreptococcus
** Cefoxitin + Cefotetan ** have best activity
Cephalosporins Spectrum of activity for Atypical?
none
Cephalosporins M & E
Few are extensively metabolized
Oral prep stable in Acid/ GI tract
None of the oral achieve therapeutic conc in CSF
Most excreted in kidney, 1/2 life 1-2hrs, some up to 3-8hrs allowing for 12-24hr dosing intervals (ceftriaxone)
Cephalosporins ADR
GI - Obstructive biliary toxicity (ceftriaxone)
Hepatic
CNS - Encephalopathy, seizures (cefepime)
Hypersensitivity = less than penicillins
Cephalosporins Drug Interactions
Interact w/ warfarin and increase inhibition of Vit K reductase, increased risk of bleeding
Probenecid = inc plasma lvls of cephalosporins
Using Ceftriaxone in MSSA?
nah, not preferred because MICs can be intermediate and treatment failure can be seen
Non-Pseudomonal Carbapenem
Ertapenem
Pseudomonal Carbapenems
Imipenem
Meropenem
Carbapenem + Beta-lactamase inhibitor
Meropenem-vaborbactam
Imipenem-relebactam
Carbapenems Spectrum of Activity Gram +
Limited Enterococcal activity
Active against MSSA but not MRSA
Active against all Strep spp.
Imipenem considered active against E.faecalis if…
its a Penicillin-susceptible one
Carbapenems Spectrum of Activity Gram -
Broad Gram - activity
No activity against Stenotrophomonas maltophilia
Ertapenem will not cover against which gram -
non-fermentors
Carbapenems active against Pseudomonas aeruginosa…..
Meropenem and Imipenem
Carbapenems are often used for….
ESBL producing strains
Carbapenems + Beta-lactamase inhibitor combo spectrum of activity is…
extended against carbapenemase-producing organisms (commonly via KPC enzyme)
active but not as helpful against MDR Acinetobacter or Pseudomonas
no activity against Stenotrophomonas maltophilia
Reserved for MDR gram - usually
Carbapenems Spectrum of activity for Anaerobes
Great activity against both Gram -/+ anaerobes
Used for polymicrobial infections that include anaerobes
Carbapenems Spectrum of activity for Atypicals
none
Carbapenems DI
Valproic acid = avoid combo
Probenecid = avoided, increase plasma levels
Carbapenems ADR
GI = N,V,D CNS = Seizures ( Imipenem>meropenem>ertapenem) Hypersensitivity = low cross reactivity w/ penicillin < 1%
Carbapenems M & E
Imipenem subject to degradation by DHP-1, made w/ something to prevent its breakdown
all distribute well, CNS too
Imi/Mero dosed every 6-8hr (1hr 1/life)
erta dosed every 24hrs (4hr 1/2life
all have renal elim, so need dose adjustment
Aztreonam MOA
Binding ot PBPs, specifically high affinity for PBP3
Inhibit cross-linking of peptidoglycan in cell wall
Aztreonam Spectrum of activity
Gram + = 0
Anaerobes = 0
Atypical = 0
Aztreonam Spectrum of Activity Gram -
Active against E.Coli, K. Pneumoniae, P. mirabilis
Not active against ESBL or KPC organisms
Active against MBLs
No activity against other nonfermentors (only P.aeruginosa)
Aztreonam is considered treatment of choice against….
Pseudomonas aeruginosa,
in patients who are beta-lactam intolerant/allergic
Aztreonam M & E
not extensively metabolized and not absorbed in GI tract
Distributes well into tissues + fluids, CNS too
1.7hrs 1/2life, prolonged in renal dysfunction
Monobactam drug
Aztreonam
Aztreonam ADR
GI = N,V,D Derm = rash
Aztreonam DI
no significant DI
