Erdman Carbapenems

Question 1

Carbapenems general info

Answer 1

Beta lactam ring and 5-membered ring like PCN (house with garage), except have a Carbon instead of sulfa
**hydroxy-ethyl group in trans position off of the garage is likely the cause of the intense beta lactamase stability

Agents are imipenem, meropenem, ertapenem, and doripenem

Question 2

Resistance methods

Answer 2

some beta lactamase “carbapenamases”, decreased permeability (porins in gram -), and alterations in PBPs (MRSA is not susceptible to any carbapenems) (no real activity against PRSP).

Mostly stable against beta lactamases

Question 3

Spectrum of activity

Answer 3

Most broad spectrum agents available!!
Gram - and Gram + aerobes and anaerobes
(Impenem and doripenem are best towards gram +)

Question 4

Gram +

Answer 4

several, but only species of enterococcus is faecalis (static)

MSSA

Question 5

Gram -

Answer 5

HENPECKSSS,
Acinetobacter spp (not erta)

Pseudomonas aeruginosa is covered EXCEPT by ertapenem**

Can get synergy response if use a carbapenem with (aminoglycosides) either gentamicin, tobramycin, or amikacin

Question 6

Gram + anaerobes

Answer 6

many, but NOT clostridium DIFFICILE species

Question 7

Gram - anaerobes

Answer 7

several, ESPECIALLY bacteroides sp

Question 8

NOT effective against

Answer 8

MRSA
PRSP (lacking in vivo activity)
Vancomycin resistant enterococcus
C diff
atypical bacteria
nocardia (atypical)

Question 9

CSF coverage

Answer 9

Meropenem is the best and really only one used due to concentrations attained in CSF

Question 10

Elimination

Answer 10

All are primarily eliminated by kidney (dose adjust)

**Imipenem undergoes hydrolysis by DHP in renal brush to a nephrotoxic metabolite, so it is comarketed with cilastatin. Cilastatin is a DHP inhibitor, NOT a beta lactamase inhibitor

Short half lives(1hr), except for ertapenem which has a half life of 4 hours (allows once daily dosing)

Question 11

Clinical uses

Answer 11

empiric therapy for hospital acquired infections
polymicrobial infections
infections due to B-lactamase producers (SPICE, SPACE, ESBL, others)
If pseudomonas is suspected, do NOT use ertapenem

Question 12

Hypersensitivity

Answer 12

3% of population is allergic
same 5-15% cross reactivity to PCN
use same general guidelines with types of reactions

Question 13

CNS effects

Answer 13

confusion, dizziness, seizure (neuro toxicity) - much less prevalent now that renal adjustment happens.

RISK FACTORS - preexisting CNS disorders, high doses, and renal insufficiency)

Question 14

Agent requiring use with cilastatin

Answer 14

Imipenem

Cilastatin is a dhp inhibitor that prevents the drug from being broken down.

Question 15

Agent that does not cover pseudomonas

Answer 15

Ertapenem

Question 16

Agent with best CSF perfusion

Answer 16

Meropenem.

Question 17

Half life with one exception

Answer 17

Each has a 1hr half life that requires multiple dosing, except ertapenem which allows for once a day dosing.