Imipenem

ADMINISTRATION ROUTES:

IV

ALTERNATIVE NAMES:

Primaxin

ICU INDICATIONS:

1. Treatment of infections caused by susceptible organisms
2. Broad spectrum cover of hospital-acquired infections (particularly in the setting of intra-abdominal sepsis)

PRESENTATION AND ADMINISTRATION:

IV:

Injection (vial) 500 mg imipenem and 500 mg cilastatin (powder)

Add 10 mL of compatible IV fluid to the powder in each 500 mg vial. Shake to form a suspension (which must be further diluted before IV infusion). Transfer this suspension to the IV fluid container.

• For 500 mg, dilute with 100 mL of compatible IV fluid. Agitate until clear. Infuse over 20 minutes.
• For 1 gm, dilute with 250 mL of compatible IV fluid. Agitate until clear. Infuse over 40-60 minutes.

If the patient develops nausea during infusion, the rate of infusion may be slowed.

Compatible with the following IV fluids:

Normal saline, 5% glucose and 0.15% KCl, 5% or 10% glucose, 5% and 10% Mannitol, Glucose and sodium chloride

DOSAGE:

IV:

500 mg - 1 gm QID

DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:

Dose in renal impairment

Dose in renal replacement therapy

DOSAGE IN PAEDIATRICS:

IV:

15 - 25 mg/kg QID

CLINICAL PHARMACOLOGY:

Imipenem is a carbapenem antibiotic. The bactericidal activity of imipenem results from the inhibition of cell wall synthesis.

Imipenem has a high degree of stability in the presence of beta-lactamases (both penicillinases and cephalosporinases produced by gram-negative and gram-positive bacteria). It is a potent inhibitor of betalactamases from certain gram-negative bacteria which are inherently resistant to most beta-lactam antibiotics such as Pseudomonas aeruginosa, Serratia spp., and Enterobacter spp.

Imipenem has in vitro activity against a wide range of gram-positive and gram-negative organisms. In vitro tests show imipenem to act synergistically with aminoglycoside antibiotics against some isolates of Pseudomonas aeruginosa. Imipenem has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections.

Aerobes, Gram-Positive:

• Enterococcus faecalis (Note: Imipenem is inactive in vitro against Enterococcus faecium)
• Staphylococcus aureus including penicillinase-producing strains
• Staphylococcus epidermidis including penicillinase-producing strains (Note: Methicillin- resistant staphylococci should be reported as resistant to imipenem)
• Streptococcus agalactiae (Group B streptococci)
• Streptococcus pneumoniae
• Streptococcus pyogenes

Aerobes, Gram-Negative:

• Acinetobacter spp.
• Citrobacter spp.
• Enterobacter spp.
• Escherichia coli
• Gardnerella vaginalis
• Haemophilus influenzae
• Haemophilus parainfluenzae
• Klebsiella spp.
• Morganella morganii
• Proteus vulgaris
• Providencia rettgeri
• Pseudomonas aeruginosa (Note: Imipenem is inactive in vitro against Xanthomonas (Pseudomonas) maltophilia and some strains of P. cepacia.)
• Serratia spp., including S. marcescens

Anaerobes, Gram-Positive:

• Bifidobacterium spp.
• Clostridium spp.
• Eubacterium spp.
• Peptococcus spp.
• Peptostreptococcus spp.
• Propionibacterium spp.

Anaerobes, Gram-Negative:

• Bacteroides spp., including B. fragilis
• Fusobacterium spp.

CONTRAINDICATIONS:

1. Hypersensitivity to carbapenems

WARNINGS:

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving therapy with beta-lactams. These reactions are more apt to occur in patients with a history of sensitivity to multiple allergens.

there have been reports of patients with a history of penicillin hypersensitivity who have experienced severe hypersensitivity reactions when treated with another beta-lactam. Before initiating therapy with imipenem, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, other beta-lactams, and other allergens.

PRECAUTIONS:

General:

Seizures and other CNS adverse experiences, such as confusional states and myoclonic activity, have been reported during treatment with imipenem. Pseudomembranous colitis has been reported with nearly all antibacterial agents, including imipenem-cilastatin sodium, and may range in severity from mild to life threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhoea subsequent to the administration of antibacterial agents.

Laboratory Tests:

No tests in addition to routine ICU tests are required

Drug/Laboratory Test Interactions:

None noted

IMPORTANT DRUG INTERACTIONS IN ICU:

Generalised seizures have been reported in patients who received ganciclovir and imipenem. These drugs should not be used concomitantly unless the potential benefits outweigh the risks.

ADVERSE REACTIONS:

Body as a whole:

Polyarthralgia, asthenia/weakness, drug fever

Gastrointestinal:

Pseudomembranous colitis, diarrhoea, nausea, vomiting, haemorrhagic colitis, hepatitis (including fulminant hepatitis), jaundice, gastroenteritis, abdominal pain, glossitis, tongue papillar hypertrophy, staining of the teeth and/or tongue, heartburn, pharyngeal pain, increased salivation

Haematologic:

Pancytopaenia, bone marrow depression, thrombocytopaenia, neutropaenia, leukopaenia, haemolytic anaemia

Central Nervous System:

Seizures, encephalopathy, tremor, confusion, myoclonus, paraesthesia, vertigo, headache, psychic disturbances including hallucinations

Respiratory:

Chest discomfort, dyspnoea, hyperventilation, thoracic spine pain

Cardiovascular:

Palpitations, tachycardia

Skin:

Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, angioneurotic oedema, flushing, cyanosis, hyperhidrosis, skin texture changes, candidiasis, pruritus vulvae

Renal:

Acute renal failure, oliguria/anuria, polyuria, urine discolouration