C.9

Question 1

Cephalosporines

Answer 1

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

Question 2

Cephalosporins: True for all

Answer 2

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

Question 3

1st generation

Answer 3

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

Question 4

Cephalexin

Answer 4

ROA: p.o;
IND: UTIs, minor Staph infections, cellulitis, soft tissue abcess, respiratory tract infections (tonsillitis, pharyngitis)

Question 5

Cephazolin

Answer 5

ROA: only parentrally active;
IND: perioperative prophylaxis

Question 6

2nd generation

Answer 6

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

Question 7

Cefuroxime (-axetil)

Answer 7

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

Question 8

Cefoxitine

Answer 8

ROA: only parentral;
Penetration: no CNS penetration;
IND: high activity against anaerobic bacteria (incl. B.Fragilis);
Extra: semisynthetic cephamycin; Dose: 3Xdaily

Question 9

Cefixime

Answer 9

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

Question 10

Ceftriaxone

Answer 10

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

Question 11

Cefotaxime

Answer 11

ROA: parentral;
Kinetics: short T1/2;
IND: used in premature babies (H.influenza meningitis);
Dose: 3x1-2g

Question 12

Ceftazidime

Answer 12

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)

Question 13

Cefepime

Answer 13

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

Question 14

Ceftolozane +tazobactam

Answer 14

ROA: Parentral;
Penetration: can penetrate CNS;
IND: complicated UTI, targeted therapy against ESBL, and MBL (=carbapenepase) producing strains, more than 90% P.aeruginosa sensitivity

Question 15

Ceftarolin fosamil

Answer 15

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

Question 16

Cefiderocol

Answer 16

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

Question 17

Siderophore activity of cefiderocol

Answer 17

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.