Carbapenems

Carbapenems are also beta-lactam antibiotics. Carbapenems are set apart from general penicillins because of their effectiveness against beta-lactamase secreting organisms.  Carbapenems are reserved for resistant infections.  Carbapenems are cell wall inhibitors and work primarily by inhibition of transpeptidation of the cell wall, which decreases the cell wall strength and integrity.  Carbapenems also work on penicillin binding proteins to weaken the wall structure and also by promotion of autolysins.  

Resistance mechanisms have been noted to include carbapenemases, which inactivate the carbapenems.  Other resistance mechanisms are from reduced penetration of the cell wall, modified penicillin binding proteins, and efflux pumps.  

Hypersensitivity reactions can occur.  

Class Drugs

• Doripenem

• Ertapenem

• Meropenem

• Imipenem

Class Mechanism of Action

Three mechanisms of action:

• Cell wall inhibitor

Inhibits transpeptidation, which decreases cell wall strength/integrity

• Only effective against rapidly growing bacteria

• Inactivation of penicillin binding proteins (PBPs)

Bacteria have proteins on the surface that bind to carbapenems, resulting in morphologic changes to the bacteria and weakening the structure of the cell wall

• Certain bacteria can develop resistance to carbapenems by altering their surface proteins to decrease interaction of drug with bacteria

• Autolysins

Many bacteria naturally produce autolysins that usually assist in performing "maintenance" function for the bacteria by degrading the cell wall.  If new cell wall is not being produced in the presence of a carbapenem, the autolysins aid in destruction of the cell wall.

Class Applications

Treatment of gram negative and gram positive infections

Also effective against anaerobes

Class Adverse Effects

Resistance

• Beta-lactamase

Usually effective against ESBL (extended spectrum beta-lactamase)

• Carbapenemases are produced by some bacteria that inactivate carbapenems

• Decrease penetration of drug

Some organisms' cell membrane is resistant to penetration of the carbapenem, so the carbapenem cannot bind to PBPs.

• Efflux pumps

Pumps decrease intracellular concentration of drug

• Modified PBPs

Alterations of the binding proteins structure, limits ability of carbapenems to bind to the BPs.

Hypersensitivity

• Rashes, angioedema, anaphylaxis

Diarrhea

• Alteration of normal gut flora causes diarrhea

• Clostridium difficile can also cause a severe form of diarrhea with use of antibiotics

Drug Table

Drug Name	Application	Comments	Image
Doripenem			"Dora" "Pen"
Ertapenem	Not effective against enterococcus, P. aeruginosa, and acinetobacter		"Earth" "Pen"
Meropenem			"Mirror" "Pen"
Imipenem		Paired with cilastatin to inhibit metabolism	"Innie" "Pen"