ΒETA LACTUM ANTIBIOTICS

Carbapenums and Monobactum

LECTURE BY DR. SAIQUA LASHARI

 CARBAPENEM

• 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.

• CLASSIFICATION
• Imipenem
• Meropenem
• Etrapenem
MECHANISM Imipenem
OF ACTION Spectrum:
 Aerobic & anaerobic microorganisms
ß- lactam antibiotics  Streptococci (including penicillin resistant S.
inhibit the key enzyme in
bacterial wall synthesis pneumoniae)
(transpeptidase).  Enterococci (except E-Faecium non- B-
They also appear to Lactamase producing penicillinresistant
activate one or more cell- strains)
wall autolytic enzymes,  Staphylococci
causing lysis of the
bacterium.
 Listeria
 Some MRSA
Imipenem
 Pseudomonas
Meropenem
 Acinetobacter
Etrapenem  Bacteroides (B. fragilis)
PHARMACOKINETICS
• Not absorbed orally ( poor absorption)
• The drug is hydrolyzed rapidly by
Dehydropeptidase-I found in the brush
border of the proximal renal tubule
• cilastatin (dehydropeptidase inhibitor) was
combined in equal amount with imipenem
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
Therapeutic uses
Urinary tract infections
Lower respiratory tract infections
Intra-abdominal infections
Gynecological infections
Skin and soft tissue, bones and joint
Adverse effects
infections
• Nausea and vomiting are most common (1% - 20%)
Cephalosporin-resistant nosocomial
• Seizures – 1.5% (esp. if high doses are given to
bacteria (Citrobacter Freundii, Enterobacter patients with CNS lesions and in those with renal
spp.) insufficiency)
• Hypersensitivity – seen in patients allergic to other
b- Lactam antibiotics.
MEROPENEM

Spectrum
• Newer drug
Similar to imipenem but it is good in
• Not sensitive to Dehydropeptidase vitro against some imipenem resistant P.
• cilastatin is not required aeruginosa, while less against gram +ve
cocci
In clinical experience both the drugs are
• Toxicity
therapeutically equivalent
• Similar to imipenem( i.e nausea and
vomiting)
• But less likely to cause seizures
ETRAPENEM

• 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 intraabdominal and pelvic
infections
 AZTREONAM (MONOBACTAM)

• 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
Spectrum PHARMACOKINETICS
• Differs from other B- Lactam antibiotics and
closely resembles to aminoglycosides Administered I/M or I/V
Peak conc. = 50mg/ml after 1g I/M
• Active only against gram –ve bacteria dose
• No activity against gram +ve bacteria and T ½ = 1.7 hrs prolonged to 6 hrs in
• anaerobic organism anephric patients
• However excellent against enterobacteriaceae Most of the drug is recovered
unchanged in urine
• and P. aeruginosa
Dose = 2g every 6 -8 hrs (reduced in
• H. influenza and gonococci (in vitro) renal patients)
 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

ADVERSE EFFECTS
• Usually well tolerated
• Patients with penicillins or cephalosporin allergy appear
not to react to aztreonam.