CEFTAZIDIME Injection

・Single infections

・Mixed infections caused by two or more susceptible organisms

・Severe infections in general

・Respiratory tract infections

・Ear, nose and throat infections

・Urinary tract infections

・Skin and soft tissue infections

・Gastrointestinal, biliary and abdominal infections

・Bone and joint infections

・Dialysis: infections associated with haemo- and peritoneal dialysis and with continuous ambulatory peritoneal dialysis (CAPD). In meningitis it is recommended that the results of a sensitivity test are known before treatment with ceftazidime as a single agent. It may be used for infections caused by organisms resistant to other antibiotics including aminoglycosides and many cephalosporins. When appropriate, however, it may be used in combination with an aminoglycoside or other beta-lactam antibiotic for example, in the presence of severe neutropenia, or with an antibiotic active against anaerobes when the presence of bacteroides fragilis is suspected. In addition, ceftazidime is indicated in the perioperative prophylaxis of transurethral prostatectomy.

Dosage and administration

+Adults:

 - Most uses: 1g 8hourly Or 2g 12hourly

 - Severe infections and infections in neutropenic patients: 2g 8hourly Or 3g 12hourly

 - UTI: 500mg 12hourly Or 1g 12hourly

 - Prophylaxis for prostatectomy: 1g at induction. +/- 1g at catheter removal

 - Cystic  fibrosis: 100-150mg/kg/day in three divided doses, not to exceed 9g/day

+Elderly:

 - All infections, especially in those >80years: not to exceed 3g daily total

+Infants >2months and children:

 - Most uses: 30-100mg/kg/day in two or three divided doses

 - Severe infections: up to 150mg/kg/day (max 6g total per day) in three divided doses

+Neonates and infants <2month:

 - Most uses: 25-60mg/kg/day in two divided doses

Ceftazidime is contraindicated in patients with known hypersensitivity to cephalosporins.

The most common adverse reactions are local reactions following intravenous injection, allergic reactions, and effects on the gastro-intestinal tract.

Local effects: Phlebitis or thrombophlebitis, and pain and/or inflammation at the site of injection.

Hypersensitivity: Pruritus, rash, urticaria, erythema multiforme and fever. Toxic epidermal necrolysis and Stevens Johnson syndrome have been reported rarely. Angioedema and anaphylaxis (bronchospasm and/or hypotension) have been reported very rarely.

Gastro-intestinal: Diarrhoea (diarrhoea may sometimes be a symptom of pseudomembranous colitis, nausea, vomiting and abdominal pain). Very rarely, oral thrush or colitis.

Central nervous system: Headache, dizziness, paraesthesiae and bad taste. There have been reports of neurological sequelae, including tremor, myoclonia, convulsions, encephalopathy and coma in patients with renal impairment in whom the dose of ceftazidime has not been appropriately reduced.

Genito-urinary: Candidiasis and vaginitis.

Blood and lymphatic system disorders (usually transient): Eosinophilia, positive Coombs’ test without haemolysis, haemolytic anaemia, thrombocytosis and very rarely leucopenia, neutropenia, agranulocytosis, and thrombocytopenia.

Hepatobiliary: Slight elevations in one or more hepatic enzymes: (AST(SGOT), ALT(SGPT), LDH, GGT and alkaline phosphates), hepatitis. Very rarely, clinically apparent jaundice has been reported.

Renal and urinary disorders: Elevations of blood urea, blood urea nitrogen and/or serum creatinine have been observed occasionally. Rare cases of interstitial nephritis have been reported in patients treated with ceftazidime. Acute renal tubular necrosis may occur with ceftazidime.

Psychiatric disorders: Confusion and hallucinations.

Aminoglycoside antibiotics and diuretics: Nephrotoxicity has been reported following concomitant administration of cephalosporins and aminoglycoside antibiotics or potent diuretics, such as furosemide. Renal function should be carefully monitored, especially if higher dosages of the aminoglycosides are to be administered of if therapy is prolonged, because of the potential nephrotoxicity of aminoglycoside antibiotics.

Antibiotics: In vitro, chloramphenicol has been shown to be antagonistic with respect to ceftazidime and other cephalosporins. The clinical relevance of this finding is unknown, but if concurrent administration of ceftazidime with chloramphenicol is proposed, the possibility of antagonism should be considered.

There is no experimental evidence of embryopathic or teratogenic effects attributable to ceftazidime but, as with all drugs, it should be administered with caution during the early months of pregnancy and in early infancy. Use in pregnancy requires that the anticipated benefit be weighed against the possible risks.

Ceftazidime is excreted in human milk in low concentrations and consequently caution should be exercised when ceftazidime is administered to a nursing mother.

Hypersensitivity reactions:

Before therapy with ceftazidime is instituted, careful inquiry should be made for a history of hypersensitivity reactions to ceftazidime, cephalosporins, penicillins or other drugs. If an allergic reaction to ceftazidime occurs, discontinue the drug. Serious hypersensitivity reactions may require epinephrine (adrenaline), hydrocortisone, antihistamine or other emergency measures.

Renal function:

Cephalosporin antibiotics at high dosage should be given with caution to patients receiving concurrent treatment with nephrotoxic drugs, e.g. aminoglycoside antibiotics, or potent diuretics such as furosemide, as these combinations are suspected of affecting renal function adversely. Clinical experience with ceftazidime has shown that this is not likely to be a problem at the recommended dose levels. There is no evidence that ceftazidime adversely affects renal function at normal therapeutic doses; however, as for all antibiotics eliminated via the kidneys, it is necessary to reduce the dosage according to the degree of reduction in renal function to avoid the clinical consequences of elevated antibiotic levels, e.g. neurological sequelae, which have occasionally been reported when the dose has not been reduced appropriately.

Overgrowth of non-susceptible organisms:

As with other broad spectrum antibiotics, prolonged use of ceftazidime may result in the overgrowth of non-susceptible organisms (e.g. Candida, Enterococci and Serratia spp) which may require interruption of treatment of adoption of appropriate measures. Repeated evaluation of the patient’s condition is essential.

Ceftazidime is a semi-synthetic antibacterial agent of the cephalosporin class which is resistant to most beta-lactamases and is active against a wide range of gram-positive and gram-negative bacteria. Ceftazidime inhibits bacterial cell wall synthesis following attachment to penicillin binding proteins (PBPs). This results in the interruption of cell wall (peptidoglycan) biosynthesis, which leads to bacterial cell lysis and death.