After IV administration of 500-mg and 1-g doses of ceftazidime over 5 minutes to normal adult male volunteers, mean peak serum concentrations of 45 and 90 mcg/mL, respectively, were achieved. After IV infusion of 500-mg, 1-g, and 2-g doses of ceftazidime over 20 to 30 minutes to normal adult male volunteers, mean peak serum concentrations of 42, 69, and 170 mcg/mL, respectively, were achieved. The average serum concentrations following IV infusion of 500-mg, 1-g, and 2-g doses to these volunteers over an 8-hour interval are given in Table 1.
|Ceftazidime||Serum Concentrations (mcg/mL)|
|IV Dose||0.5 hr||1 hr||2 hr||4 hr||8 hr|
The absorption and elimination of ceftazidime were directly proportional to the size of the dose. The half-life following IV administration was approximately 1.9 hours. Less than 10% of ceftazidime was protein bound. The degree of protein binding was independent of concentration.
There was no evidence of accumulation of ceftazidime in the serum in individuals with normal renal function following multiple IV doses of 1 and 2 g every 8 hours for 10 days.
Following intramuscular (IM) administration of 500-mg and 1-g doses of ceftazidime to normal adult volunteers, the mean peak serum concentrations were 17 and 39 mcg/mL, respectively, at approximately 1 hour. Serum concentrations remained above 4 mcg/mL for 6 and 8 hours after the IM administration of 500-mg and 1-g doses, respectively. The half-life of ceftazidime in these volunteers was approximately 2 hours.
The presence of hepatic dysfunction had no effect on the pharmacokinetics of ceftazidime in individuals administered 2 g intravenously every 8 hours for 5 days. Therefore, a dosage adjustment from the normal recommended dosage is not required for patients with hepatic dysfunction, provided renal function is not impaired.
Approximately 80% to 90% of an IM or IV dose of ceftazidime is excreted unchanged by the kidneys over a 24-hour period. After the IV administration of single 500-mg or 1-g doses, approximately 50% of the dose appeared in the urine in the first 2 hours. An additional 20% was excreted between 2 and 4 hours after dosing, and approximately another 12% of the dose appeared in the urine between 4 and 8 hours later. The elimination of ceftazidime by the kidneys resulted in high therapeutic concentrations in the urine.
The mean renal clearance of ceftazidime was approximately 100 mL/min. The calculated plasma clearance of approximately 115 mL/min indicated nearly complete elimination of ceftazidime by the renal route. Administration of probenecid before dosing had no effect on the elimination kinetics of ceftazidime. This suggested that ceftazidime is eliminated by glomerular filtration and is not actively secreted by renal tubular mechanisms.
Since ceftazidime is eliminated almost solely by the kidneys, its serum half-life is significantly prolonged in patients with impaired renal function. Consequently, dosage adjustments in such patients as described in the DOSAGE AND ADMINISTRATION section are suggested.
Therapeutic concentrations of ceftazidime are achieved in the following body tissues and fluids.
|Tissue or Fluid||Dose/Route||No. of Patients||Time of Sample|
|Average Tissue or Fluid Level|
(mcg/mL or mcg/g)
|Urine||500 mg IM||6||0 to 2 hr||2,100|
|2 g IV||6||0 to 2 hr||12,000|
|Bile||2 g IV||3||90 min||36.4|
|Synovial fluid||2 g IV||13||2 hr||25.6|
|Peritoneal fluid||2 g IV||8||2 hr||48.6|
|Sputum||1 g IV||8||1 hr||9|
|Cerebrospinal fluid||2 g q8hr IV||5||120 min||9.8|
|(inflamed meninges)||2 g q8hr IV||6||180 min||9.4|
|Aqueous humor||2 g IV||13||1 to 3 hr||11|
|Blister fluid||1 g IV||7||2 to 3 hr||19.7|
|Lymphatic fluid||1 g IV||7||2 to 3 hr||23.4|
|Bone||2 g IV||8||0.67 hr||31.1|
|Heart muscle||2 g IV||35||30 to 280 min||12.7|
|Skin||2 g IV||22||30 to 180 min||6.6|
|Skeletal muscle||2 g IV||35||30 to 280 min||9.4|
|Myometrium||2 g IV||31||1 to 2 hr||18.7|
Mechanism of Action
Ceftazidime is a bactericidal agent that acts by inhibition of bacterial cell wall synthesis. Ceftazidime has activity in the presence of some beta-lactamases, both penicillinases and cephalosporinases, of Gram-negative and Gram-positive bacteria.
Mechanism of Resistance
Resistance to ceftazidime is primarily through hydrolysis by beta-lactamase, alteration of penicillin-binding proteins (PBPs), and decreased permeability.
Interaction with Other Antimicrobials
In an in vitro study, antagonistic effects have been observed with the combination of chloramphenicol and ceftazidime.
Ceftazidime has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section:
- Citrobacter species
- Enterobacter species
- Escherichia coli
- Klebsiella species
- Haemophilus influenzae
- Neisseria meningitidis
- Proteus mirabilis
- Proteus vulgaris
- Pseudomonas aeruginosa
- Serratia species
- Staphylococcus aureus
- Streptococcus pneumoniae
- Streptococcus pyogenes
- Streptococcus agalactiae
- Bacteroides species (Note: many isolates of Bacteroides species are resistant)
The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following microorganisms exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for ceftazidime. However, the efficacy of ceftazidime in treating clinical infections due to these microorganisms has not been established in adequate and well-controlled clinical trials.
- Acinetobacter species
- Citrobacter diversus
- Citrobacter freundii
- Providencia species (including Providencia rettgeri)
- Salmonella species
- Shigella species
- Haemophilus parainfluenzae
- Morganella morganii
- Neisseria gonorrhoeae
- Yersinia enterocolitica
- Staphylococcus epidermidis
- Clostridium species (Not including Clostridium difficile)
- Peptostreptococcus species