Guarascio 4-5 Cephalosporins, Carbapenems, and Monobactam

General characteristics of cephalosporins

Time dependent (T > MIC) bactericidal activity

Generations: Gram positive → Gram negative

None reliably cover Enterococcus spp.

• Only difference from penicillins

Renal elimination and dose adjustment for renal dysfunction

Adverse drug reactions and interactions associated with cephalosporins are the same as penicillins except _____

C. difficile-associated diarrhea

• Maybe higher risk in third gen (minor)

Common first generation cephalosporins

Cefazolin (IV)

Cephalexin (PO)

Cefadroxil (PO)

Spectrum of first generation cephalosporins

Penicillinase-producing gram positive bacteria

Use for gram negative only if you have susceptibilities

First generation cephalosporins are DOC for _____

MSSA

Common second generation cephalosporins

Cefuroxime (IV)

Cefuroxime axetil (PO)

Cefprozil (PO)

Cefaclor (PO)

Cefoxitin (IV)

Cefotetan (IV)

Spectrum of second generation cephalosporins

Adds respiratory gram negative coverage

• Less than third gen

Less gram positive coverage than first gen

Cefoxitin and cefotetan are cephamycins with some anaerobic activity

• Often used as a one time dose for GI surgical prophylaxis

Common third generation cephalosporins (Group A)

Ceftriaxone (IV)

Cefotaxime (IV)

Spectrum of third generation cephalosporins (Group A)

Enhanced gram negative activity

Some with less gram negative activity

Third generation cephalosporins (Group A) are DOC for _____

S. pneumoniae

Third generation cephalosporins (Groups A and B) can be used to treat meningitis because they _____

Have good CSF penetration/get into the CNS well

Benefits of ceftriaxone

No renal dosing adjustments

Once daily administration for most indications

• Administered IM once for gonorrhea

Cefotaxime is superior to ceftriaxone in pediatrics due to _____ associated with ceftriaxone

Biliary sludging and precipitation with calcium-containing substances

Common third generation cephalosporin (Group B)

Ceftazidime (IV)

Spectrum of third generation cephalosporin (Group B)

Enhanced gram negative activity

Less gram positive activity

Covers P. aeruginosa

Lacks reliable Staphylococcus

Common PO third generation cephalosporins

Cefixime (PO)

Cepodoxime (PO)

Cefdinir (PO)

Spectrum of PO third generation cephalosporins

Enhanced gram negative activity

Some with less gram positive activity

No Pseudomonas aeruginosa coverage

Cefixime is less reliable for S. pneumoniae

PO third generation cephalosporins are mostly used for _____

Step-down therapy from IV third generation cephalosporins

Common fourth generation cephalosporin

Cefepime (IV)

Spectrum of fourth generation cephalosporin

Enhanced gram positive and gram negative activity

Enhanced SPACE and P. aeruginosa coverage

Broad spectrum

Does not cover anaerobes

Fourth generation cephalosporin is DOC for _____

Enterobacter spp.

• E in SPACE

• Has a resistance gene that is induced by third gen but NOT by fourth gen

Common fifth generation cephalosporin

Ceftaroline (IV)

Spectrum of fifth generation cephalosporin

Enhanced gram positive including MRSA and enhanced S. pneumoniae

• First and only beta-lactam to cover MRSA

Some gram negative coverage

No Pseudomonas aeruginosa coverage

FDA indications for CAP, SSTIs

ESBL organisms cannot be treated with _____

Conventional penicillins

Conventional cephalosporins

Aztreonam

ESBL organisms can be treated with _____

Carbapenems

Newer agents with newer gen beta-lactamase inhibitors

Non-beta-lactam antibiotics

Ceftolozane/tazobactam (Zerbaxa) is DOC for _____

Drug resistant Pseudomonas aeruginosa

Ceftazidime/avibactam (Avycaz) is DOC for _____

ESBL-producing organisms

Some carbapenemase-producing organisms

Cefepime/enmetazobactam (Exblifep) is DOC for _____

ESBL-producing organisms

Pseudomonas aeruginosa

Cefiderocol (Fetroja) is DOC for _____

Drug resistant SPACE organisms

• Pseudomonas

ESBL-producing organisms

Carbapenemase-producing organisms

Ceftobiprole (Zevtera) is DOC for _____

ESBL-producing organisms

Some carbapenemase-producing organisms

General characteristics of carbapenems

Similar to cephalosporins as well as:

• Highest seizure risk among beta-lactams

  • Mostly for inappropriate dosing in renal dysfunction

• Significant drug interaction with valproic acid derivatives (Depakote, Depakene)

  • Substantially decreases valproate levels → risk of breakthrough seizures

• Variable Enterococcus coverage (best with imipenem)

• Stable against most beta-lactamases including ESBL

Common carbapenems

Imipenem/cilastatin (IV)

Meropenem (IV)

Ertapenem (IV)

Doripenem (IV)

Spectrum of carbapenems

Broad spectrum gram positive and gram negative, anaerobe coverage

All except ertapenem have P. aeruginosa coverage

How does ertapenem differ from the other carbapenems?

Slightly narrower spectrum

Once daily administration

Characteristics of meropenem/vaborbactam (Vabomere)

First carbapenem/beta-lactamase inhibitor combination

Gram-negative focus including some carbapenemase producing organisms

FDA approval only for cUTI

Generally well tolerated → similar side effects to other beta-lactams

Characteristics of imipenem-cilastatin/relebactam (Recarbrio)

Gram negative focus including some carbapenemase producing organisms and carbapenem-resistant Pseudomonas aeruginosa

FDA approval for cUTI and intra-abdominal infections

Generally well tolerated → similar side effects to other beta-lactams

Common monobactam

Aztreonam (IV)

Spectrum of aztreonam

Gram negative ONLY including P. aeruginosa

• Lower susceptibility rates for P. aeruginosa than other antipseudomonal beta-lactams

Aztreonam is primarily used in patients with _____

Anaphylactic penicillin allergy or combined penicillin and cephalosporin allergy

Characteristics of sulbactam/durlobactam (Xacduro)

Combination of two beta-lactamase inhibitors

Treatment for HAP/VAP due to Acinetobacter baumannii

Generally well tolerated → similar side effects to other beta-lactams