Carbapenems

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b-Lactam Antibiotics
Carbapenems
Dr. Salman Khan
Department of Pharmacology
LM&DC

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Carbapenems
Carbapenems are b- Lactams that
contain fused b- Lactam ring
system – different from penicillins.
It is unsaturated and contains a
carbon atom instead of the sulfur
atom.

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Classification
Imipenem
Meropenem
Etrapenem
Aztreonam (monobactam – monocyclic
b- Lactam compound)

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Imipenem
Mechanism of Action:
ۧ- lactam antibiotics inhibit the key
enzyme in bacterial wall synthesis.
(tanspeptidase)
€They also appear to activate one or more
cell-wall autolytic enzymes, causing lysis
of the bacterium.

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Imipenem
Spectrum:
–Aerobic & anaerobic micro-
organisms
•Streptococci (including
penicillin resistant S.
pneumoniae)

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Spectrum continued…
–Enterococci (except E-Faecium
non- b- Lactamase producing penicillin
resistant strains)
–Staphylococci
–Listeria
–Some MRSA

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Continued ..
–Pseudomonas
–Acinetobacter
–Bacteroides (B. fragilis)

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Pharmacokinetics
Not absorbed orally
The drug is hydrolyzed rapidly by
Dipeptidase found in the brush border of the
proximal renal tubule – because active drug
concentration in urine were very low,
cilastatin (dehydropeptidase inhibitor) was
synthesized and combined in equal amount
with imipenem

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Pharmacokinetics continued…
After I/V administration of 500mg
imipenem + cilastatin peak plasma
concentration is 33mg/ml. both have a
half life of 1 hour.
70 % of imipenem, if given in
combination with cilastatin, is
recovered as active drug in urine
Dosage should be modified in renal
insufficiency

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Adverse effects
Nausea and vomiting are most common
(1% - 20%)
Seizures – 1.5% (esp. if high doses are
given in to patients with CNS lesions and in
those with renal insufficiency)
Hypersensitivity – seen in patients allergic
to other b- Lactam antibiotics.

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Therapeutic uses
Urinary tract infections
Lower respiratory tract infections
Intra-abdominal infections
Gynecological infections
Skin and soft tissue, bones and joint
infections
Cephalosporin-resistant nosocomial
bacteria (Citrobacter Freundii, Enterobacter
spp.)

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Meropenem
Newer drug
Not sensitive to dipeptidase – cilastatin is
not required
Toxicity
Similar to imipenem
But less likely to cause seizures

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Meropenem
Spectrum
–Similar to imipenem but it is good in
vitro against some imipenem resistant P.
aeruginosa, while less against gram +ve
cocci
–In clinical experience both the drugs are
therapeutically equivalent

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Ertapenem
Larger serum half life – allows single daily
dose
Spectrum:
–Inferior activity against P. aeruginosa and
Acinetobacter spp.
–Good against gram +ve enterobacteriaceae &
anaerobes – makes it attractive for use in intra-
abdominal and pelvic infections

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Aztreonam
It is a monocyclic b- Lactam compound
(monobactam)
Mechanism:
–Interacts with penicillin-binding proteins of
susceptible micro-organisms and induces the
formation of long filamentous bacterial
structures
It is resistant to many of the b- Lactamases that
are elaborated by most gram-negative bacteria

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Aztreonam
Spectrum
–Differs from other b- Lactam antibiotics and
closely resembles to aminoglycosides
–Active only against gram –ve bacteria
–No activity against gram +ve bacteria and
anaerobic organism
–However excellent against enterobacteriaceae
and P. aeruginosa
–H. influenza and gonococci (in vitro)

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Pharmacokinetics
Administered I/M or I/V
Peak conc. = 50mg/ml after 1g I/M dose
T ½ = 1.7 hrs prolonged to 6 hrs in anephric
patients
Most of the drug is recovered unchanged in
urine
Dose = 2g every 6 -8 hrs (reduced in renal
patients)

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Adverse effects
Usually well tolerated
Patients with penicillins or
cephalosporin allergy appear not to
react to aztreonam (except
ceftazidine)

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Uses
Quite useful for treatment of gram negative
infections that normally would be treated
with a b- Lactam were it not for the history
of prior allergic reaction