Cephalosporins
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Cephalosporin MoA | bactericidal
cell wall active, inhibit cell wall synthesis leading to abnormal cell wall
bind to penicillin binding proteins (PBPs) & essential enzymes required to build cell wall
synergistic w/ aminoglycosides (G+/-)
additive w/ quinolones
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Mech of resistance to Cephs | Beta-lactamase including ESBL’s
Altered cell wall penetration limiting access to targets
PBP affinity alteration
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Gen SoA of Cephs | From 1st to 4th gen, you start with G+ and do pick up G-.
Do NOT work for enterococcus or Listeria!
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1st Gen Cephs | cefazolin (Ancef)
cephalexin (Keflex)/cephradine
cefadroxil
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1st Gen Cephs: SoA | Mainly G+ cocci, eg. Staphylococcus and Streptococcus
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Ancef (cefazolin) | frequently used IV as a pre-operative prophylaxis antibiotic against skin organisms or general penicillin or methicillin susceptible S. aureus
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Cephs PK | Cleared renally, requiring adjustment
Concentration INdependent (all b-lactams are)
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Ceftriaxone (Rosephin) doses | Gonorrhea: 125-250mg IM x 1 dose (w/ Azith for Chlamydia)
Meningitis: 2g BID IV
Pneumonia: 1-2g QD
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2nd Gen Cephs | cefaclor
cefprozil
cefuroxime
cefoxitin*
cefotetan*
*most freq used, these are cephamycins
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2nd Gen Cephs spectrum | Similar to 1st gen, but more activity against H. influenza, Enterobactericeae, N. gonorrhoeae
(don't use for MSSA, use 1st gen Cephs)
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Cephamycin (Cefotetan, Cefoxitin) SoA | enhanced activity for Enterobacteriaceae (E. Coli, Klebsiella) and anaerobic coverage for B. fragilis.
freq used for intra-abdomnial/pelvic infections/prophylaxis
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Cefotetan ADRs | MTT group in structure causes bleeding risk (not good for ptx with GI ulcers) & ETOH intolerance (not good for alcoholics!).
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Cefoxitin | Like Cefotetan (same SoA) except no bleeding risk or ETOH problem b/c lack of MTT group. However, less stable (shorter half-life)
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Cefuroxime | Classic true Ceph in 2nd gen
Must be taken with food for absorption!
for Strept. pneumonia & H. influenza
for upper RT infection
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3rd Gen Cephs (Good for penicillin intermediate/resistant Streptococcus pneumoniae & has good H. influenzae coverage thus is frequently used for CAP. Don't use for MSSA) | ceftriaxone
cefotaxime
ceftazidime
cefixime
cefpodoxime
cefditoren
ceftizoxime
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Ceftriaxone and cefotaxime mainly used for? (hint: NOT pseudomonas) | RT infection:
Strept pneumo (even the drug-resistant forms when PBP is altered!)
H. influenza
Also used for:
adult bacterial meningitis
gonorrhea
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Ceftriaxone ADR | biliary stones/sludge
(not good for babies or elderly with weak hepatic fxn)
Thus, Cefotaxime is better since it has identical SoA, but is cleared by the kidney & therefore, no biliary problems.
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Ceftazidime is used for meningitis, CAP, RT infection. Problem: may induce ESBL | The only ceph besides Cefepime that covers Pseudomonas Aeruginosa (thus, active for other G- such as H. flu). Also covers S. pneumo.
Tests for ESBL. If E. Coli, Klebsiella, or Acinetobacter are resistant to Ceftazidine, then they're ESBL producers.
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Cefixime | PO. Used in children's RT or ear infections.
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Which of the cephs are taken with food to increase absorption? | • Cefuroxime
• Cefditoren
• Cefpodoxime (Vantin)
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Cefpodoxime | like an oral cefotaxime.
Take with food.
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Cefditoren | Cefpodoxime is preferred b/c it has the same spectrum w/o 3 main issues of Cefditoren:
L-carnitine: caution in L-carnitine deficiency since Cefditoren increases its excretion
BA prob: needs high-fat meal for absorption
Caseinate (milk protein: al
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4th Gen Ceph | Cefepime
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Cefepime | Zwitterionic: rapid outer membrane passage of gram negative organisms
for Pseudomonas & S. pneumoniae
generally reserved for SPACE & ICU infections
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2 cephs for pseudomonas | Ceftazidine
Cefepime
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2 cephs for IAB infections | Cefoxitin
Cefotetan
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2 cephs for hospitalized patients with CAP (a bunch will cover RT) or meningitis | Ceftriaxone
Cefotaxime
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Ceftaroline | This is the only ceph that covers MRSA! Better than using Vanco b/c less Side effects
It has increased affinity for PBP 2x and 2a
for Streptococcus pneumoniae and Staphylococcus aureus
(back up for Strept. pneumo if resistant to Ceftriaxone)
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Ceftaroline | Covers CAP, so Strept Pneumo & H. Influenza, but doesn't cover atypicals such as legionella, chlamydia, & mycoplasma in CAP.
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How to Tx CAP? | Usually with 2 drugs (Cephs + macrolide or quinolone to manage the atypicals)
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