C.9 Flashcards
Cephalosporines
1st generation: Cephalexin, Cephazolin,
2nd generation: Cefuroxime (-axetil), Cefoxitine,
3rd generation: Cefixime, Ceftriaxone, Ceftazidime, Cefotaxime,
4th generation: Cefepime, Ceftolozane+tazobactam
5th generation: Ceftarolin fosamil, cefiderocol
Cephalosporins: True for all
MOA: inhibit PBP→ no cell wall formation;
Bactericidal;
Ineffective against: E.faecalis, L. monocytogenes, anaerobes (exceptions- peptococci, peptostreptococci);
Classification: 5 generations, with the higher generation- better activity against G(-) bacteria, decreased activity against G(+) bacteria, better penetration, 5th generation- active against MRSA!;
SEs: Allergy (less than with penicillins), GI SEs (nausea, diarrhea, dysbacteriosis), local iriitation (when given I.M), Hematologic SEs (anemia, thrombocytopenia), methylthiotetrazole substitution (vit.K epoxide reductase ↓→hypoprothrombinemia →bleeding disorders), neurotoxicity (seizures), superinfections (resistant bacteria may overgrow)→ risk of fungal superinfection
1st generation
Spectrum: G(+)cocci (→ streptococci, pneumococci, staphylococci), anaerobes (pepto-, streptopeptococci), G(-) rods (→E.coli, Klebsiella, Proteus);
Not active against: MRSA, MRSE, P. aeruginosa, indole-positive proteus, Enterobacter, Serratia, Acinetobacter;
Penetration: no CNS penetration
Cephalexin
ROA: p.o;
IND: UTIs, minor Staph infections, cellulitis, soft tissue abcess, respiratory tract infections (tonsillitis, pharyngitis)
Cephazolin
ROA: only parentrally active;
IND: perioperative prophylaxis
2nd generation
Spectrum: same as 1st gen.
with extended G(-) coverage, less active against G(+) bacteria, +H.influenza, Moraxella catarrhalis;
Not active against: E.faecalis, L. monocytogenes, P. aeroginosa;
Kinetics: more stable to β-lactamase
Cefuroxime (-axetil)
ROA: p.o;
Penetration: can penetrate to CNS;
-Cefuroxime-axetil: Ester prodrug of Cefuroxime, better BA p.o;
IND: good activity against G(+) cocci, extended G(-) coverage (H.influenza, E.coli, Klebsiella), community aquired pneumonia;
Dose: Cefuroxime- 3X1.5g, Cefuroxime-axetil- 2X0.5g
Cefoxitine
ROA: only parentral;
Penetration: no CNS penetration;
IND: high activity against anaerobic bacteria (incl. B.Fragilis);
Extra: semisynthetic cephamycin; Dose: 3Xdaily
Cefixime
ROA: p.o;
Spectrum: good G(-) coverage
-(exception: Pseudomonas, lactamase producing enterobacter);
IND: 1st line against N.gonorrhoae (sgl dose p.o-400mg);
Dose: given 2X0.4g;
Penetration: low level in the brain
Ceftriaxone
ROA: parentral;
Kinetics: long T1/2, hepatic elimination;
Contra-IND: premature babies→can displace bilirubin from albumin→jaundice;
IND: meningitis (NOT Listeria), pneumonia, otitis, severe UTI, Cholecystitis, abdominal infections (with metronidazole), gonorrhoeae, syphilis, endocarditis, disseminated Lyme disease
Cefotaxime
ROA: parentral;
Kinetics: short T1/2;
IND: used in premature babies (H.influenza meningitis);
Dose: 3x1-2g
Ceftazidime
ROA: Parentral;
Spectrum: extended G(-) coverage (incl. Citrobacter, S. Marcescens, N.gonorrhoeae, Haemophilus, Pseudomonas);
IND: severe infections, incl. those caused by Pseudomonas (usually in combo with Aminoglycosides)
Cefepime
Spectrum: like 3rd gen. but coverage is further extended→ P. aeruginosa, more resistant to hydrolysis by lactamases, H.influenza and Nisseria, good activity against S.aureus and S. pneumoniae;
Kinetics: administered i.v, penetrates well into CSF, Excreted by the kidneys;
Dose: 2x1-2g i.v;
IND: for serious life threatening infections
Ceftolozane +tazobactam
ROA: Parentral;
Penetration: can penetrate CNS;
IND: complicated UTI, targeted therapy against ESBL, and MBL (=carbapenepase) producing strains, more than 90% P.aeruginosa sensitivity
Ceftarolin fosamil
Extra: prodrug, active metabolite →Ceftarolin;
IND: active against MRSA, skin & soft tissue infections, community aquired pneumonia;
Spectrum: G(-) spectrum is similar to ceftriaxone;
ROA: i.v
Cefiderocol
IND: complicated UTIs (with/without pyelonephritis);
MOA (extra): it is a siderophore that is able to undergo activ transport into the bacterial cell through iron channels;
Spectrum: effective against ESBL and carbapenemase producing bacteria, G(-) bacteria (incl. E.Coli, K.pneumoniae, P. aeruginosa;
ROA: i.v;
Elimination: mostly excreted by urine;
T1/2: 2-3h
Siderophore activity of cefiderocol
Unlike other β-lactams, cefiderocol contains a chlorocatechol group which allows it to chelate iron. Once bound to ferric iron cefiderocol is able to undergo active transport into bacterial cells through iron channels in the outer cell membrane such as those encoded by the cirA and fiu genes in E. coli or the PiuA gene in P. aeruginosa. Once inside the cell, cefiderocol binds to and inhibits PBP3 with high affinity thereby preventing the linking of peptodoglycan layers via the pentapeptide bridge.
