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Pronunciation:

(SEF tay zi deem)

U.S. Brand Names:

Ceptaz® [DSC]; Fortaz®; Tazicef®

Generic Available:

Canadian Brand Names:

Fortaz®

Use:

Treatment of documented susceptible Pseudomonas aeruginosa infection and infections due to other susceptible aerobic gram-negative organisms; empiric therapy of a febrile, granulocytopenic patient

Pregnancy Risk Factor:

Lactation:

Enters breast milk (small amounts)/use caution (AAP rates "compatible")

Contraindications:

Hypersensitivity to ceftazidime, any component of the formulation, or other cephalosporins

Warnings/Precautions:

Modify dosage in patients with severe renal impairment; prolonged use may result in superinfection; use with caution in patients with a history of penicillin allergy especially IgE-mediated reactions (eg, anaphylaxis, urticaria). May cause antibiotic-associated colitis or colitis secondary to C. difficile.

Adverse Reactions:

1% to 10%:

Gastrointestinal: Diarrhea (1%)

Local: Pain at injection site (1%)

Miscellaneous: Hypersensitivity reactions (2%)

<1%: Anaphylaxis, angioedema, asterixis, BUN increased, candidiasis, creatinine increased, dizziness, encephalopathy, eosinophilia, erythema multiforme, fever, headache, hemolytic anemia, hyperbilirubinemia, jaundice, leukopenia, myoclonus, nausea, neuromuscular excitability, paresthesia, phlebitis, pruritus, pseudomembranous colitis, rash, Stevens-Johnson syndrome, thrombocytosis, toxic epidermal necrolysis, transaminases increased, vaginitis, vomiting

Reactions reported with other cephalosporins include seizure, urticaria, serum-sickness reactions, renal dysfunction, interstitial nephritis, toxic nephropathy, elevated BUN, elevated creatinine, cholestasis, aplastic anemia, hemolytic anemia, pancytopenia, agranulocytosis, colitis, prolonged PT, hemorrhage, superinfection

Overdosage/Toxicology:

Symptoms of overdose include neuromuscular hypersensitivity and convulsions. Many beta-lactam containing antibiotics have the potential to cause neuromuscular hyperirritability or convulsive seizures. Hemodialysis may be helpful to aid in removal of the drug from blood; otherwise, treatment is supportive or symptom-directed.

Drug Interactions:

Increased effect: Probenecid may decrease cephalosporin elimination; aminoglycosides: in vitro studies indicate additive or synergistic effect against some strains of Enterobacteriaceae and Pseudomonas aeruginosa

Increased toxicity: Aminoglycosides and furosemide may increase nephrotoxic potential

Stability:

Reconstituted solution and I.V. infusion in NS or D5W solution are stable for 24 hours at room temperature, 10 days when refrigerated, or 12 weeks when frozen; after freezing, thawed solution is stable for 24 hours at room temperature or 4 days when refrigerated; 96 hours under refrigeration, after mixing

Compatibility:

Stable in D5NS, D5W, NS, sterile water for injection; variable stability (consult detailed reference) in peritoneal dialysis solutions

Y-site administration: Compatible: Acyclovir, allopurinol, amifostine, aminophylline, aztreonam, ciprofloxacin, diltiazem, docetaxel, enalaprilat, esmolol, etoposide phosphate, famotidine, filgrastim, fludarabine, foscarnet, gatifloxacin, gemcitabine, granisetron, heparin, hydromorphone, labetalol, linezolid, melphalan, meperidine, morphine, ondansetron, paclitaxel, propofol, ranitidine, remifentanil, tacrolimus, teniposide, theophylline, thiotepa, vinorelbine, zidovudine. Incompatible: Alatrofloxacin, amphotericin B cholesteryl sulfate complex, amsacrine, doxorubicin liposome, fluconazole, idarubicin, midazolam, pentamidine, warfarin. Variable (consult detailed reference): Cisatracurium, sargramostim, vancomycin.

Compatibility in syringe: Compatible: Hydromorphone.

Compatibility when admixed: Compatible: Ciprofloxacin, clindamycin, fluconazole, linezolid, metronidazole, ofloxacin. Incompatible: Aminophylline, ranitidine. Variable (consult detailed reference): Vancomycin.

Mechanism of Action:

Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.

Pharmacodynamics/Kinetics:

Distribution: Widely throughout the body including bone, bile, skin, CSF (higher concentrations achieved when meninges are inflamed), endometrium, heart, pleural and lymphatic fluids

Protein binding: 17%

Half-life elimination: 1-2 hours, prolonged with renal impairment; Neonates <23 days: 2.2-4.7 hours

Time to peak, serum: I.M.: ~1 hour

Excretion: Urine (80% to 90% as unchanged drug)

Dosage:

Infants and Children 1 month to 12 years: I.V.: 30-50 mg/kg/dose every 8 hours; maximum dose: 6 g/day

Adults: I.M., I.V.: 500 mg to 2 g every 8-12 hours

Urinary tract infections: 250-500 mg every 12 hours

Dosing interval in renal impairment:

Clcr 30-50 mL/minute: Administer every 12 hours

Clcr 10-30 mL/minute: Administer every 24 hours

Clcr<10 mL/minute: Administer every 48-72 hours

Hemodialysis: Dialyzable (50% to 100%)

Continuous arteriovenous or venovenous hemodiafiltration effects: Dose as for Clcr 30-50 mL/minute

Administration:

Any carbon dioxide bubbles that may be present in the withdrawn solution should be expelled prior to injection; administer around-the-clock to promote less variation in peak and trough serum levels; ceftazidime can be administered deep I.M. into large mass muscle, IVP over 3-5 minutes, or I.V. intermittent infusion over 15-30 minutes; do not admix with aminoglycosides in same bottle/bag; final concentration for I.V. administration should not exceed 100 mg/mL

Monitoring Parameters:

Observe for signs and symptoms of anaphylaxis during first dose

Test Interactions:

Positive direct Coombs', false-positive urinary glucose test using cupric sulfate (Benedict's solution, Clinitest®, Fehling's solution), false-positive serum or urine creatinine with Jaffé reaction

Dietary Considerations:

Sodium content of 1 g: 2.3 mEq

Patient Education:

Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. Do not take any new medication during therapy unless approved by prescriber. This medication is administered by infusion or injection. Report immediately any redness, swelling, burning, or pain at injection/infusion site; itching or hives; or difficulty swallowing or breathing. Maintain adequate hydration (2-3 L/day of fluids) unless instructed to restrict fluid intake. May cause false test results with Clinitest®; use of another type of glucose testing is preferable. May cause diarrhea (yogurt, boiled milk, or buttermilk may help). Report unresolved diarrhea; opportunistic infection (vaginal itching or drainage; sores in mouth; blood, pus, or mucus in stool or urine); easy bleeding or bruising; rash; or respiratory difficulty. Breast-feeding precaution: Consult prescriber if breast-feeding.

Additional Information:

With some organisms, resistance may develop during treatment (including Enterobacter spp and Serratia spp); consider combination therapy or periodic susceptibility testing for organisms with inducible resistance

Dental Health: Effects on Dental Treatment:

No significant effects or complications reported

Dental Health: Vasoconstrictor/Local Anesthetic Precautions:

No information available to require special precautions

Mental Health: Effects on Mental Status:

May cause nervousness; case reports of euphoria, delusion, illusions, and depersonalization with cephalosporins

Mental Health: Effects on Psychiatric Treatment:

May rarely cause neutropenia; use caution with clozapine and carbamazepine

Oncology: Emetic Potential:

Very low (<10%)

Oncology: Vesicant:

Dosage Forms:

[DSC] = Discontinued product

Infusion, as sodium [premixed iso-osmotic solution] (Fortaz®): 1 g (50 mL); 2 g (50 mL)

Injection, powder for reconstitution:

Ceptaz® [DSC]: 10 g [L-arginine formulation]

Fortaz®: 500 mg, 1 g, 2 g, 6 g [contains sodium carbonate]

Tazicef®: 1 g, 2 g, 6 g [contains sodium carbonate]

International Brand Names:

Biotum® (PL); Cef-4® (TH); Cefazima® (BR); Ceffotan® (CO); Cefodime® (TH); Cefortam® (PT); Ceftazidima Ahimsa® (AR); Ceftazidima® (AR); Ceftazidima Biocrom® (AR); Ceftazidima Fabra® (AR); Ceftazidima Gen Med® (AR); Ceftazidima Klonal® (AR); Ceftazidima Northia® (AR); Ceftazidima Richet® (AR); Ceftazidime Hexpharm® (ID); Ceftazidim-ratiopharm® (DE); Ceftazidim Sandoz® (SE); Ceftidin® (IN); Ceftim® (IT); Ceftum® (ID); Cetazime® (RO); Cetazum® (ID); Crima® (AR); Forcas® (YU); Fortam® (CH, ES); Fortaz® (BR, CA); Fortum® (AR, AT, AU, BD, BG, CL, CR, CZ, DE, DK, DO, EC, FR, GB, GT, HK, HN, HU, ID, IE, IL, IN, KW, MX, NL, NO, NZ, PA, PL, RO, RU, SE, SG, SI, SV, TH, TR, YU, ZA); Fortumset® (FR); Forzid® (TH); Glazidim® (BE, FI, IT, LU); Iesetum® (TR); Izadima® (CO, MX); Kefadim® (BE, BR, CZ, GB, LU, RO); Kefamin® (ES); Kefazim® [inj.] (AT); Kefzim® (CL, ZA); Mirocef® (HR, SI); Panzid® (IT); Pharodime® (ID); Pluseptic® (AR); Spectrum® (IT); Starcef® (IT); Tagal® [inj.] (MX); Taxifur® [inj.] (MX); Taxime® (SG); Tazicef® (RU); Thidim® (ID); Tinacef® (AR); Zefidim® (ID); Zeftam M H® (TH); Zibac® (ID); Zytaz® (IN)

References

Davies SP, Lacey LF, Kox WJ, et al, "Pharmacokinetics of Cefuroxime and Ceftazidime in Patients With Acute Renal Failure Treated by Continuous Arteriovenous Haemodialysis,"Nephrology, Dialysis, Transplantation, 1991, 6(120):971-6.

Donowitz GR and Mandell GL, "Beta-Lactam Antibiotics,"N Engl J Med, 1988, 318(7):419-26 and 318(8):490-500.

Klein NC and Cunha BA, "Third-Generation Cephalosporins,"Med Clin North Am, 1995, 79(4):705-19.

Marshall WF and Blair JE, "The Cephalosporins,"Mayo Clin Proc, 1999, 74(2):187-95.

McCracken GH Jr, Threlkeld N, and Thomas ML, "Pharmacokinetics of Ceftazidime in Newborn Infants,"Antimicrob Agents Chemother, 1984, 26(4):583-4.

Rains CP, Bryson HM, and Peters DH, "Ceftazidime. An Update of Its Antibacterial Activity, Pharmacokinetic Properties and Therapeutic Efficacy,"Drugs, 1995, 49(4):577-617.

Robinson DG, Cookson TL, and Frisafe JA, "Concentration Guidelines for Parenteral Antibiotics in Fluid-Restricted Patients,"Drug Intell Clin Pharm, 1987, 21(12):985-9.

Sirgo MA and Norris S, "Ceftazidime in the Elderly: Appropriateness of Twice-Daily Dosing,"DICP Ann Pharmacother, 1991, 25(3):284-8.

Slaker RA and Danielson B, "Neurotoxicity Associated With Ceftazidime Therapy in Geriatric Patients With Renal Dysfunction,"Pharmacotherapy, 1991, 11(4):351-2.

Stea S, Bachelor T, Cooper M, et al, "Disposition and Bioavailability of Ceftazidime After Intraperitoneal Administration in Patients Receiving Continuous Ambulatory Peritoneal Dialysis,"J Am Soc Nephrol, 1996, 7(11):2399-402.

Vlasses PH, Bastion WA, Behal R, et al, "Ceftazidime Dosing in the Elderly: Economic Implications,"Ann Pharmacother, 1993, 27(7-8):967-71.

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