Carbapenems

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class of β-lactam antibiotics
Bacteriocidal at cell wall

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binds to bacterial penicillin binding proteins and interferes with bacterial cell wall integrity and synthesis.

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broad spectrum of antibacterial activity

Gram-positive and Gram-negative bacteria, and anaerobes, with the exception of intracellular bacteria (atypicals)

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are very similar to the penicillins (penams), but the sulfur atom in position 1 of the structure has been replaced with a carbon atom, and an unsaturation has been introduced—hence the name of the group, the carbapenems.

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highly resistant to most β-lactamases

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Imipenem / cilastatin ((Tienam))
Meropenem
Ertapenem (((INVANS )))
Doripenem

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New Delhi metallo-β-lactamase (shortened NDM-1)

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have poor oral bioavailability
they are administered intravenously in hospital
only ertapenem ((INVANZ)) can be given IM

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which one must be combined with cilastatin

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Imipenem

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Imipenem/cilastatin

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Tienam

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why with cilastatin

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Imipenem is rapidly degraded by the renal enzyme dehydropeptidase if administered alone (making it less effective)
other carbapenems not affected

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cilastatin

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a DHP-I inhibitor which increases half-life and tissue penetration of imipenem.

dehydropeptidase 1 enzyme

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But not meningitis (as it doesn't pass through the blood brain barrier), endocarditis

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The most common side effects of imipenem

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diarrhea, nausea, vomiting, skin rash, pruritus (itch) and injection site reactions

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Distributed rapidly and widely to most tissues and fluids,
low concentrations in CSF; crosses placenta; enters breast milk

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Big drug interaction with carbapenems?

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Decrease serum concentration of valproic acid. Loss of seizure control

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Carbapenems should be given cautiously in patients with?

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Seizures

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What is unique about Ertapenem?

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Does not cover P. aureginosa
and Acinetobacter

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New Delhi metallo-beta-lactimase (NDM-1)

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one member of a large gene family that encodes beta-lactamase enzymes called carbapenemases

was first detected in a Klebsiella pneumoniae / Escherichia coli

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polymyxin (((colistin)))
Tigecycline (((Tygacil)))

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Carbapenem pharmacokinetics

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parentral / IV
penetrate CSF and increased with meningitis exept
renal excreation
half life

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What is the half-life of the Carbapenems?

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Approximately 1 hour

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How are the Carbapenems eliminated from the body?

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Primarily eliminated by urinary excretion of unchanged drug.

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Are the Carbapenems removed by dialysis?

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mipenem and Meropenem are removed by hemodialysis and hemofiltration

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Clinical uses of Carbapenems?

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Adverse effects of Carbapenems

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What are the risk factors for neurotoxicity when treating with a Carbapenem?

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impaired renal function
improper dosing
age
previous CNS disorder
Concommitant agents that lower seizure threshhold.

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What is the Carbapenem of choice for treating patients that have an existing seizure disorder?

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Meropenem

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What is the only Carbapenem indicated in treating bacterial meningitis?

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Meropenem

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What are the adult IV/IM dosages of Ertapenem?

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1 g IV/IM daily

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What are the pediatric IV/IM dosages of Ertapenem?

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Not recommended in pediatric

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What are the adult IV dosages of Imipenem?

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What are the adult IV dosages or Meropenem?

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