|Systematic (IUPAC) name|
|Trade names||Fortaz, Tazicef|
|Pregnancy cat.||B1 (AU) B (US)|
|Legal status||Prescription Only (S4) (AU)|
|Mol. mass||546.58 g/mol|
|(what is this?)|
Ceftazidime (brand names: Fortaz, Tazicef) // is a third-generation cephalosporin antibiotic used for treating patients with infections. As a class, the third-generation cephalosporins mostly share the moderate activity of earlier generations against Gram-(+) bacteria such as streptococci, and share their lack of activity against more difficult Gram-(+) bacteria such as methacillin-resistant Staphylococcus aureus and Enterococci. They exhibit broader activity against Gram-(-) bacteria such as Escherichia coli, Klebsiella pneumoniae, and Haemophilus influenzae that are important causes of urinary tract infections, abdominal infections, pneumonia, and meningitis. As such, they are commonly used in first-line therapy of serious and/or hospital-acquired infections and as second-line therapy for infections acquired in the community. This difference in part reflects greater expectations that hospital-acquired infections will be resistant to older, narrower spectrum antibiotics.
Third-generation cephalosporins differ from earlier generations in the presence of a C=N-OCH3 group in their chemical structure. This group provides improved stability against certain beta lactamase enzymes produced by Gram-(-) bacteria. These enzymes rapidly destroy earlier generation cephalosporins by catalyzing the opening of the four member ring. With widespread use of third generation cephalosporins, some Gram-(-) bacteria have developed the ability to produce extended-spectrum beta-lactamases (ESBLs) that are able to hydrolyze third-generation cephalosporins. Infections caused by ESBL-producing Gram-(-) bacteria are of particular concern in hospitals and other healthcare facilities.
Like other third-generation cephalosporins, it has broad-spectrum activity against Gram-positive and Gram-negative bacteria. Unlike most third-generation agents, it is active against Pseudomonas aeruginosa, however it has weaker activity against Gram-positive microorganisms and is not used for such infections.
The drug is given intravenously (IV) or intramuscularly (IM) every 8–12 hours (2-3 times a day), with dose and frequencing varying by the type of infection, severity, and/or renal function of the patient. Those with kidney disease are dosed less frequently.
Labeled indications include the treatment of patients with:
- Pseudomonas aeruginosa infections
- other Gram-negative, aerobic infections
- neutropenic fever
Ceftazidime is contraindicated in patients with a known allergy to ceftazidime or to any other cephalosporin antibiotic.
Ceftazidime is mainly eliminated by the kidneys into the urine. As such, drug levels in the blood may build up in persons with kidney injury or kidney disease. This includes those on dialysis. In these cases of renal impairment, the drug is dosed less frequently.
No dose adjustment is needed for those with liver disease.
Ceftazidime is generally well-tolerated. When side effects do occur, they are most commonly local effects from the intravenous line site, allergic reactions, and gastrointestinal symptoms. According to one manufacturer, in clinical trials, allergic reactions including itching, rash, and fever, happened in fewer than 2% of patients. Rare but more serious allergic reactions, like toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme have been reported with this class of antibiotics, including Ceftazidime. Gastrointestinal symptoms, including diarrhea, nausea, vomiting, and abdominal pain, were reported in fewer than 2% of patients.
Another source reports that in addition, patients may also have alterations in these blood tests:
- Increased eosinophils (8%)
- Increased lactate dehydrogenase (6%)
- Increased gamma-glutamyl transferase (5%)
- Positive direct Coombs test (4%)
- Increased platelets (thrombocythemia) (2%)
- Increased ALT (7%), increased AST (6%), increased alkaline phosphatase (4%)
Use in Pregnancy
According to the manufacturer, research studies in mice and rats showed no evidence of harm to the fetus, even at up to 40 times the human dose of ceftazidime. Importantly though, there were no high-quality research studies of the effects of the drug in pregnant women.
Spectrum of Activity
In addition to the syn-configuration of the imino side chain, compared to other third-generation cephalosporins, the more complex moiety (containing two methyl and a carboxylic acid group) confers extra stability to β-lactamase enzymes produced by many Gram-negative bacteria. The extra stability to β-lactamases increases the activity of ceftazidime against otherwise resistant Gram-negative organisms including Pseudomonas aeruginosa. The charged pyridinium moiety increases water-solubility.
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