Ceftazidime

Ceftazidime

Ceftazidime
Systematic (IUPAC) name
(6R,7R,Z)-7-(2-(2-aminothiazol-4-yl)-2-(2-carboxypropan-2-yloxyimino)acetamido)-8-oxo-3-(pyridinium-1-ylmethyl)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylate
Clinical data
Pronunciation
Trade names Fortaz, Tazicef
AHFS/Drugs.com
MedlinePlus
Pregnancy
category
  • AU: B1
  • US: B (No risk in non-human studies)
Legal status
Routes of
administration
Intravenous, intramuscular, inhalation (off-label only)
Pharmacokinetic data
Bioavailability 91% (IM)
Metabolism negligible
Biological half-life 1.6–2 hours
Excretion 90–96% renal
Identifiers
CAS Registry Number  Y
ATC code J01
PubChem CID:
DrugBank  Y
ChemSpider  Y
UNII  Y
ChEBI  Y
ChEMBL  N
Chemical data
Formula C22H22N6O7S2
Molecular mass 546.58 g/mol
 N   

Ceftazidime, sold under the brand names Fortaz and Tazicef,[1] is an antibiotic useful for the treatment of a number of bacterial infections. It is a third-generation cephalosporin.

As a class, cephalosporins have activity against Gram-positive and Gram-negative bacteria. The balance of activity tips toward Gram-positive organisms for earlier generations; later generations of cephalosporins have more Gram-negative coverage. Ceftazidime is one of the few in this class with activity against Pseudomonas. It is not active against methicillin-resistant Staphylococcus aureus.

Third-generation cephalosporins differ from earlier generations in the presence of a C=N-OCH3 group in their chemical structure (health system.[3]

Contents

  • Medical uses 1
    • Spectrum of activity 1.1
  • Side effects 2
    • Contraindications 2.1
    • Precautions 2.2
    • Pregnancy 2.3
  • Chemistry 3
  • See also 4
  • References 5

Medical uses

Ceftazidime is used to treat lower respiratory tract, skin, urinary tract, blood-stream, joint, and abdominal infections, and meningitis.[4] The drug is given intravenously (IV) or intramuscularly (IM) every 8–12 hours (two or three times a day), with dose and frequencing varying by the type of infection, severity, and/or renal function of the patient. Ceftazidime is also commonly prescribed off-label for nebulization in Cystic Fibrosis patients for the suppression of Pseudomonas in the lungs as well as the treatment of pulmonary exacerbations. Those with kidney disease are dosed less frequently.[4]

Ceftazidime is the first-line treatment for the tropical infection, melioidosis, an important cause of sepsis in Asia and Australia.[5] [6]

Labeled indications include the treatment of patients with:

  • Pseudomonas aeruginosa infections
  • other Gram-negative, aerobic infections
  • neutropenic fever[1]

Spectrum of activity

Clinically relevant organisms against which ceftazidime has activity include:

  • Gram-negative aerobes, such as Enterobacter, E. coli, H. influenzae, Klebsiella, Proteus, Pseudomonas, and N. meningitidis
  • Gram-positive aerobes, such as group B streptococci, Streptococcus pneumoniae, and Streptococcus pyogenes
  • Anaerobes, such as Bacteroides[4]

The following represents MIC susceptibility data for a few clinically significant pathogens:

  • Escherichia coli - 0.015 µg/mL - 512 µg/mL
  • Pseudomonas aeruginosa - ≤0.03 µg/mL - 1024 µg/mL [7]

Side effects

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, such as 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.[4]

Another source reported, in addition, blood tests of patients may show 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%), or increased alkaline phosphatase (4%).[1]

Contraindications

Ceftazidime is contraindicated in patients with a known allergy to ceftazidime or to any other cephalosporin antibiotic.[4]

Precautions

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.[1] No dose adjustment is needed for those with liver disease.

Pregnancy

Ceftazidime falls under the pregnancy category B.[1] 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, no high-quality research studies of the effects of the drug in pregnant women were conducted.[4]

Chemistry

In addition to the syn-configuration of the pyridinium moiety increases water-solubility. Ceftazidime shares the same variable R-group side chain with aztreonam, a monobactam antibiotic; the two drugs share a similar spectrum of activity, including activity against Pseudomonas.

See also

References

  1. ^ a b c d e Lexicomp Online, Lexi-Drugs, Hudson, Ohio: Lexi-Comp, Inc.; 2014; April 20, 2014. http://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/6560
  2. ^ Sharma M, Pathak S, Srivastava P (October 2013). "Prevalence and antibiogram of Extended Spectrum β-Lactamase (ESBL) producing Gram negative bacilli and further molecular characterization of ESBL producing Escherichia coli and Klebsiella spp". J Clin Diagn Res 7 (10): 2173–7.  
  3. ^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014. 
  4. ^ a b c d e f Ceftazidime for Injection(R) [package insert]. Schaumburg, IL: Sagent; 2012. PDF of insert
  5. ^ White NJ (2003). "Melioidosis". Lancet 361 (9370): 1715–722.  
  6. ^ White, N. J.; Dance, D. A.; Chaowagul, W; Wattanagoon, Y; Wuthiekanun, V; Pitakwatchara, N (1989). "Halving of mortality of severe melioidosis by ceftazidime". Lancet 2 (8665): 697–701.  
  7. ^ http://www.toku-e.com/Assets/MIC/Ceftazidime%20pentahydrate.pdf