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RavLect12: Cephs


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
Mech of resistance to Cephs Beta-lactamase including ESBL’s Altered cell wall penetration limiting access to targets PBP affinity alteration
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!
1st Gen Cephs cefazolin (Ancef) cephalexin (Keflex)/cephradine cefadroxil
1st Gen Cephs: SoA Mainly G+ cocci, eg. Staphylococcus and Streptococcus
Ancef (cefazolin) frequently used IV as a pre-operative prophylaxis antibiotic against skin organisms or general penicillin or methicillin susceptible S. aureus
Cephs PK Cleared renally, requiring adjustment Concentration INdependent (all b-lactams are)
Ceftriaxone (Rosephin) doses Gonorrhea: 125-250mg IM x 1 dose (w/ Azith for Chlamydia) Meningitis: 2g BID IV Pneumonia: 1-2g QD
2nd Gen Cephs cefaclor cefprozil cefuroxime cefoxitin* cefotetan* *most freq used, these are cephamycins
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)
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
Cefotetan ADRs MTT group in structure causes bleeding risk (not good for ptx with GI ulcers) & ETOH intolerance (not good for alcoholics!).
Cefoxitin Like Cefotetan (same SoA) except no bleeding risk or ETOH problem b/c lack of MTT group. However, less stable (shorter half-life)
Cefuroxime Classic true Ceph in 2nd gen Must be taken with food for absorption! for Strept. pneumonia & H. influenza for upper RT infection
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
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
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.
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.
Cefixime PO. Used in children's RT or ear infections.
Which of the cephs are taken with food to increase absorption? • Cefuroxime • Cefditoren • Cefpodoxime (Vantin)
Cefpodoxime like an oral cefotaxime. Take with food.
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
4th Gen Ceph Cefepime
Cefepime Zwitterionic: rapid outer membrane passage of gram negative organisms for Pseudomonas & S. pneumoniae generally reserved for SPACE & ICU infections
2 cephs for pseudomonas  Ceftazidine  Cefepime
2 cephs for IAB infections  Cefoxitin  Cefotetan
2 cephs for hospitalized patients with CAP (a bunch will cover RT) or meningitis  Ceftriaxone  Cefotaxime
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)
Ceftaroline Covers CAP, so Strept Pneumo & H. Influenza, but doesn't cover atypicals such as legionella, chlamydia, & mycoplasma in CAP.
How to Tx CAP? Usually with 2 drugs (Cephs + macrolide or quinolone to manage the atypicals)
Created by: cheeoh