Carbapenems Flashcards
Cilastatin is
DHP1 inhibitor
Carbapenems came from
imipenem
Carbapenem base structure
beta-lactam ring fused with a 5 C ring and sulfur is not in the ring
CARBapenems
presence of many carbons
Modifications at C3 and C4
improve stability, spectrum of activity, and lower epileptogenic potential
Imipenem is vulnerable to
renal DHP1 and has epileptogenic potential
Meropenem benefits:
stable to renal DHP1 (improved bt 1 beta methyl group on C4), less epileptogenic potential, and increased gram - activity
Carbapenem MOA:
bind to and inactivate multiple PBP resulting in inhibition of cell wall synthesis and initiating autolysis
Carbapenem spectrum of activity varies depending on
affinity to PBP
Doripenem 1/2 life
short
Doripenem elimination
renal 70%
Imipenem/cilastatin 1/2 life
short
Imipenem/cilastatin elimination
renal 70%
Meropenem 1/2 life
short
Meropenem elimination
renal 70%
Carbapenem tissue penetration
peritoneal fluid urine lung bone CSF dosing is different for meningitis
Carbapenem CSF penetration
very low with no inflammation and not the best with inflammation but meropenem would work the best out of all of them
Carbapenems are bactericidal/bacteriostatic
bactericidal
What PD property is used for carbapenems?
% Time> MIC
Carbapenems have the _____ % Time >Mic requirement
shortest
What is the % requirement for carbapenems to have bactericidal activity?
40%
Carbapenem spectrum coverage
dark purple: streptococcus, s. pneumoniae, viridans, MSSA/MSSE, E. faecalis
dark red: Neisseria, h. influenzae, m. catarrhalis, E. coli, klebsiella, p. mirabilis, morganella, enterobacter, citrobacter, serratia, p. aeruginosa, acinetobacter
anaerobes: ++ oral and gut
Misc: stable against ESBL and AmpC, activity against mycobacterium, inactive against s. maltophilia
Carbapenems do not cover
MRSA/MRSE and e. faecium
Common carbapenems include
doripenem, imipenem/cilastatin, meropenem
Ertapenem is unique because
it has anionic character that results in decreased penetration into porin channels found in pseudonomas
Ertapenem also has
increased protein binding and increased 1/2 life
Ertapenem does not cover
acinetobacter, p. aeruginosa, MRSA, enterococcus
Ertapenem 1/2 life
medium/long 4 hours
Ertapenem elimination
renal
Hemodialysis can remove ___% of Ertapenem
30
Ertapenem spectrum coverage
dark purple: streptococcus, s. pneumoniae, viridans, MSSA/MSSE
dark red: Neisseria, h. influenzae, m. cattarhalis, E. coli, klebsiella, p. mirabilis, Morganella, enterobacter, citrobacter, serratia
anaerobe: ++ (oral and gut)
Misc: stable against ESBL and AmpC, inactive against S. maltophilia
Carbapenem resistance
- stable from hydrolysis from numerous beta lactamases
- enterobacteriaceae/acinetobacter inactivate the drug by carbapenem-hydrolyzing enzymes
- pseudonomas decreased outer membrane permeability (altered porin channels) and active efflux
- mutant or acquired altered PBPs
Addition of beta-lactamase inhibitor to carbapenems advantage:
expands coverage
Meropenem/vaborbactam advantage:
expanded activity against CRE (KPCs)
Vaborbactam does/does not enhance activity against pseudomonas aeruginosa or acinetobacter that are resistant to carbapenems due to efflux or porin mutations
does NOT
Imipenem/cilastatin/relebactam advantage:
- expanded activity against CRE (KPCs and some OXA-type) and carbapenem resistant pseudomonas aeruginosa
- may have a role in treatment of nontuberculous mycobacterial infections
Adverse events related to to carbapenems
CNS GI hepatic renal skin hematologic anaphylaxis
Drug interactions with carbapenems
-effect on valproic acid (loss of seizure control)
should consider alternative antibacterial or anticonvulsant
-probenecid interferes with tubular secretion of all carbapenems
Antipseudomonal Carbapenem indications
- ESBL/AmpC infections
- strong propensity for selecting for resistant organisms (increasing incidence of carbapenem-resistant enterobacteriaceae)
- should be considered in cefepime or pipercilln/tazobactam resistant gram - bacilli
- clinical worsening while receiving extended spectrum penicillin or cephalosporins
Ertapenem dosing
QD, eases transition to home
Ertapenem indications
stable against ESBL and AmpC beta-lactamases
intra-ab infections
skin/skin structure infections
CA pneumonia
UTI
pelvic infections
surgical prophylaxis in colorectal surgery
Antipseudomonal carbapenems include
doripenem, morepenem, imipenem/cilastatin
Carbapenem/beta lactamase inhibitor indications
- expanded activity against carbapenem-resistant enterobacteriaceae (CRE)
- utilization is driven by susceptibility profile and should be used as definitive therapy
Carbapenem/beta lactamase inhibitor drugs are
EXPENSIVE
Carbapenems are broad/narrow spectrum
broad
