Carbapenems Flashcards
Structure
B-lactam ring + 5-membered ring
Carbon analogs of B-lactams
Hydroxyethyl group in the trans configuration at position 6 as compared to acylamino group in the cis configuration of penicillin and cephalosporins
MOA
Bactericidal–>Time-dependent except against Enterococcus
Inhibit cell wall synthesis by covalently binding to PBPs that are involved in biosysnthesis
MOR
Decreased permeability due to alterations to outer membrane porins
Hydrolysis of carbapenem antibiotics by B-lactamase or carbapenemases (KPC, OXA, others)
Alterations in PBPs lead to decreased affinity
Spectrum of activity
Most broad-spectrum antibiotics
Activity against Gram (+) AND Gram (-) aerobes AND anaerobes
Distribution
Widely distributed in various body tissues
Only low concentrations of imipenem diffuse into the CSF following IV administration
Meropenem penetrates into the CSF better than imipenem and ertapenem
Elimination
Eliminated unchanged in the kidneys by glomerular filtration and tubular secretion
ALL CARBAPENEMS REQUIRE DOSE ADJUSTMENTS IN RENAL INSUFFICIENCY
Imipenem undergoes hydrolysis by DHP–>Cilastatin is a DHP-1 inhibitor
T1/2= 1 hour
T1/2 (ertapenem)= 4 hours
Gram (+) aerobes
imipenem and doripenem exhibit the best activity
MSSA
Gram (-) aerobes
doripenem and meropenem exhibit the best activity
carbapenems display activity against B-lactamase producing strains that display resistance to other B-lactam antibiotics
DOC for ESBL and AmpC producing bacteria
Meropenem-vaborbactam and imipenem-relebactam also have activity against KPC-producing Enterobacterales
PSEUDOMONAS AERUGINOSA
EXCEPT ERTAPENEM
Anaerobes
ALL carbapenems display excellent activity against Gram (+) and Gram (-) anaerobes including:
ADA (Peptostreptococcus, peptococcus, and Clostridium)
BDA
What do the carbapenems not have activity against?
MRSA
Clostridium difficile
Atypical bacteria
Clinical uses
Polymicrobial infections such as intraabdominal infections or skin infections in diabetic patients
Empiric therapy for nosocomial infections
Infections due to resistant Gram (-) bacteria, especially organisms that produce ESBL or type 1/class C/AmpC B-lactamase enzymes
Complicated UTI’s caused by KPC producing Enterobacterales: Meropenem-vaborbactam and impipenem-relebactam
Adverse effects
Hypersensitivity: cross-reactivity can occur in patients who have a history of penicillin allergy
GI: N/V/D
CNS–> direct toxic effect
- SEIZURES higher in imipenem
Risk factors for development of seizures–> preexisting CNS disorders, high doses > 2 g of imipenem, renal dysfunction
