Ceftazidime

ADMINISTRATION ROUTES:

IV, IM

ALTERNATIVE NAMES:

Fortum

ICU INDICATIONS:

1. Treatment of infections caused by susceptible organisms (especially Pseudomonas)
2. Empiric treatment of hospital acquired pneumonia

PRESENTATION AND ADMINISTRATION:

IV:

500 mg, 1 gm and 2 gm vials of powder

Add appropriate volume of water for injection to a vial then shake well until all powder is dissolved. Prepare the solutions as follows:

Inject slowly over 3-5 minutes. Store at room temperature

Compatible with:

Normal saline, glucose and sodium chloride, 5% dextrose, Hartmanns

IM:

Reconstitute with 0.5% lignocaine adding 1.5 mL to a 500 mg vial, or 3 mL to a 1 gm vial. Do not give single doses of more than 1 gm via this route.

DOSAGE:

IV:

1-2 gm TDS

DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:

Dose in renal impairment

Dose in renal replacement therapy

DOSAGE IN PAEDIATRICS:

25-50 mg/kg TDS

CLINICAL PHARMACOLOGY:

Ceftazidime is a 3rd generation cephalosporin. It has a bactericidal action resulting from inhibition of cell wall synthesis.

A wide range of gram-negative organisms is susceptible to ceftazidime in vitro, including strains resistant to gentamicin and other aminoglycosides. In addition, ceftazidime has been shown to be active against gram-positive organisms (although it is not 1st line for these infections). Ceftazidime has been shown to be active against the following organisms both in vitro and in clinical infections:

Gram-Negative Aerobes:

• Citrobacter spp. (including Citrobacter freundii and Citrobacter diversus)
• Enterobacter spp. (including Enterobacter cloacae and Enterobacter aerogenes)
• Escherichia coli
• Haemophilus influenzae (including ampicillin-resistant strains)
• Klebsiella spp. (including Klebsiella pneumoniae)
• Neisseria meningitidis
• Proteus mirabilis
• Proteus vulgaris
• Pseudomonas spp. (including Pseudomonas aeruginosa)
• Serratia spp.

Gram-Positive Aerobes:

• Staphylococcus aureus (including penicillinase- and non-penicillinase-producing strains)
• Streptococcus agalactiae (group B streptococci)
• Streptococcus pneumoniae
• Streptococcus pyogenes (group A beta-haemolytic streptococci)

Anaerobes:

Bacteroides spp. (Note: many strains of Bacteroides fragilis are resistant)

Ceftazidime and the aminoglycosides have been shown to be synergistic in vitro against Pseudomonas aeruginosa and the enterobacteriaceae. Ceftazidime is not active in vitro against methicillin-resistant staphylococci, Streptococcus faecalis and many other enterococci, Listeria monocytogenes, Campylobacter spp., or Clostridium difficile

CONTRAINDICATIONS:

1. Hypersensivity to cephalosporins

WARNINGS:

Anaphylaxis

Cephalosporins are a common cause of anaphylactic reactions and cross reactivity with penicillins may occur

Pseudomembranous colitis

Pseudomembranous colitis has been reported with nearly all antibacterial agents, including cefotaxime, 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

Risk of seizures in patients with renal failure

Elevated levels of ceftazidime in patients with renal insufficiency can lead to seizures, encephalopathy, coma, asterixis, neuromuscular excitability, and myoclonia (see PRECAUTIONS).

PRECAUTIONS:

General:

Prescribing ceftazidime in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Positive direct Coombs' tests have been reported during treatment with the cephalosporin antibiotics. It should be recognised that a positive Coombs' test may be due to the drug.

High and prolonged serum ceftazidime concentrations can occur from usual dosages in patients with transient or persistent reduction of urinary output because of renal insufficiency. The total daily dosage should be reduced when ceftazidime is administered to patients with renal insufficiency. Elevated levels of ceftazidime in these patients can lead to seizures, encephalopathy, coma, asterixis, neuromuscular excitability, and myoclonus.

If patients fail to respond to monotherapy, an aminoglycoside or similar agent should be considered.

Laboratory Tests:

No tests additional to usual ICU tests are required

Drug/Laboratory Test Interactions: None of note

IMPORTANT DRUG INTERACTIONS IN ICU:

None of note

ADVERSE REACTIONS:

Body as a Whole:

Fever, candidiasis (including oral thrush), angioedema and anaphylaxis

Haematological System:

Haemolytic anaemia, eosinophilia, positive Coombs test, thrombocytosis, leukopaenia, neutropaenia, agranulocytosis, thrombocytopaenia, and lymphocytosis

Urogenital System:

increased creatinine

Digestive System:

Diarrhoea, nausea, vomiting, and abdominal pain, slight elevations in one or more of the hepatic enzymes

Nervous System:

Seizures encephalopathy, coma, asterixis, neuromuscular excitability, myoclonus, headache, dizziness, and paraesthesia

Skin:

Pruritus, rash, Toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme

Cephalosporin-Class Adverse Reactions:

In addition to the adverse reactions listed above that have been observed in patients treated with cefaclor, the following reactions and altered laboratory tests have been reported for cephalosporin-class antibiotics: fever, abdominal pain, superinfection, renal dysfunction, toxic nephropathy, haemorrhage, false positive test for urinary glucose, elevated bilirubin, elevated LDH, and pancytopaenia.

Several cephalosporins have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced. If seizures associated with drug therapy occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated