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Chapter: Clinical Pharmacology: Anti-infective drugs


Carbapenems are a class of beta-lactam antibacterials that in-cludes: · ertapenem · imipenem-cilastatin sodium (a combination drug) · meropenem.



Carbapenems are a class of beta-lactam antibacterials that in-cludes:


·                 ertapenem


·                 imipenem-cilastatin sodium (a combination drug)


·                 meropenem.


The Broadway of antibacterials


The antibacterial spectrum of activity for imipenem-cilastatin is broader than that of any other antibacterial studied to date. Be-cause of this broad spectrum of activity, it’s used for serious or life-threatening infection, especially gram-positive and gram-negative health-care acquired infections. Broad-spectrum antibac-terials cover many organisms; narrow-spectrum antibacterials are effective against a select few organisms.



The pharmacokinetic properties of carbapenems vary slightly.

Distribution, metabolism, and excretion


Imipenem must be given with cilastatin because imipenem alone is rapidly metabolized in the tubules of the kidneys, rendering it ineffective. After parenteral administration, imipenem-cilastatin is distributed widely. It’s metabolized by several mechanisms and ex-creted primarily in urine.Ertapenem is completely absorbed after I.V. administration and is more highly protein-bound than the other two carbapen-ems. It’s metabolized by hydrolysis and excreted mainly in urine.

Mostly unchanged

After parenteral administration, meropenem is distributed widely, including to the CNS. Metabolism is insignificant; 70% of the drug is excreted unchanged in urine.



Imipenem-cilastatin, ertapenem, and meropenem are bactericidal. They exert antibacterial activity by inhibiting bacterial cell-wall synthesis.



Imipenem has the broadest spectrum of activity of currently avail-able beta-lactam antibiotics.


§    It’s effective against aerobic gram-positive species, such as Streptococcus, S. aureus, and S. epidermidis.


§    It inhibits most Enterobacter species.


§    It also inhibits P. aeruginosa (including strains resistant to piperacillin and ceftazidime) and most anaerobic species, includ-ing B. fragilis.

Lone ranger

Imipenem may also be used alone to treat serious health-care ac-quired infections and infections in immunocompromised patients caused by mixed aerobic and anaerobic organisms.


Don’t forget the other carbapenems


Meropenem is indicated for the treatment of intra-abdominal in-fections as well as for the management of bacterial meningitis caused by susceptible organisms.


§    Ertapenem’s spectrum of activity includes intra-abdominal, skin, urinary tract, and gynecologic infections as well as commu-nity-acquired pneumonias caused by a variety of gram-positive, gram-negative, and anaerobic organisms.

Drug interactions


Carbapenems may interact with these drugs.


·                 Taking probenecid with imipenem-cilastatin increases the serum level of cilastatin, but only slightly increases the serum lev-el of imipenem.


·                 Probenecid may cause meropenem and ertapenem to accumu-late to toxic levels.


·                 The combination of imipenem-cilastatin and an aminoglycosideacts synergistically against E. faecalis, Staphylococcus aureusand Listeria monocytogenes. (See Adverse reactions to car-bapenems.)


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