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PubMed2005

Pharmacokinetics of intraperitoneal cefazolin and ceftazidime coadministered to CAPD patients.

PURPOSE: Guidelines for empiric treatment of PD-related peritonitis published in 2000 recommend concurrent intraperitoneal (IP) cefazolin and ceftazidime. The pharmacokinetics (PK) of these agents combined have not been studied. This study was designed to determine the PK of combined IP cefazolin and ceftazidime in CAPD patients. DESIGN: Prospective PK study in seven non-infected CAPD patients. PROCEDURES: Patients had a peritoneal equilibration test (PET), then received one IP dose of cefazolin and ceftazidime (15 mg/kg each) co-administered over a 4-hour dwell, then performed three CAPD exchanges over the next 16 hours. Serum and dialysate samples collected over the 20-hour study period were assayed for drug concentrations by HPLC. OUTCOME MEASURES: PK parameters. STATISTICAL METHODS: Correlations were tested between PET and PK parameters using the Pearson-product correlation coefficient. MAIN FINDINGS: Serum cefazolin and ceftazidime levels exceeded the minimum inhibitory concentrations for susceptible organisms (8 mg/L) throughout the 20 hour study period. Mean cefazolin and ceftazidime PK parameters included: bioavailability, 71% and 63%; elimination rate constant, 0.031 and 0.045 h -1 ; total clearance, 5.8 and 16.0 ml/min; peritoneal clearance, 1.6 and 3.9 ml/min; renal clearance, 2.3 and 3.9 ml/min, respectively. Predictive equations suggest that 1000 mg IP of cefazolin and of ceftazidime every 24 hours would produce average steady-state trough serum cefazolin and ceftazidime concentrations of 70 +/- 52 mg/L and 17 +/- 7 mg/L, respectively. There was no correlation between PET and PK parameters. CONCLUSIONS: Co-administration did not adversely affect the PK of either agent. IP cefazolin and ceftazidime (15 mg/kg) produced adequate serum and dialysate concentrations in CAPD patients for 20 hours. PK predictions suggest that most patients would achieve adequate cefazolin and ceftazidime concentrations with 1000 mg IP once-daily. Anuric patients and those with significant residual renal function may require a more individualized approach.

Adult↗
PubMed1985

Serum bactericidal activity of ceftazidime increased by netilmicin.

Cephalosporins are often used in combination with aminoglycoside antibiotics in the treatment of gram-negative infections. Although ceftazidime possesses activity against gram-negative bacteria, especially against Pseudomonas, combined use with aminoglycosides is useful. In this study, 12 healthy volunteers (6 men, 6 women; mean age 21.5 yr) received a single dose of ceftazidime 1 g iv and one week later ceftazidime 1 g iv with netilmicin 100 mg iv. Both antibiotics were infused over five minutes. Concentrations of ceftazidime were determined by high performance liquid chromatography. Serum bactericidal activity (SBA) was evaluated against seven microorganisms isolated from clinical specimens. The mean peak serum level of ceftazidime was 113.4 micrograms/ml. At eight hours, we observed a concentration of 2.6 micrograms/ml. The total clearance was 126 ml/min, while the renal clearance was 100 ml/min. Ceftazidime exhibited a half-life of 1.9 hours. Up to ten hours, the SBA of ceftazidime against Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, and Salmonella typhi was greater than 1:8 in more than 90 percent of samples. At one hour, ceftazidime exhibited a SBA of 1:4 for Staphylococcus aureus, and 1:16 for Pseudomonas aeruginosa. With the addition of netilmicin, median SBA against Staph. aureus and P. aeruginosa were 1:32 and 1:64, respectively, at one hour. Netilmicin enhanced the SBA of ceftazidime. The combination was not effective against Streptococcus faecalis.

Adult↗
PubMedDate not supplied

Ceftazidime dosing in the elderly: economic implications.

OBJECTIVE: This study evaluated the prevalence and resulting costs of ceftazidime dosing in excess of product labeling recommendations in elderly hospitalized patients. Ceftazidime is a beta-lactam antibiotic excreted via glomerular filtration. According to product labeling, ceftazidime dosing can frequently be decreased in the elderly because glomerular filtration declines with age. METHODOLOGY: A multicenter, retrospective utilization audit involving 11 US academic medical centers examined 221 medical records of patients 65 years of age or older receiving ceftazidime (any brand, any indication). The creatinine clearance of each patient was estimated using the Cockcroft-Gault formula. RESULTS: Renal insufficiency, defined as an estimated creatinine clearance of less than 50 mL/min, was present in 111 of the patients (50 percent). Ceftazidime dosing in excess of product labeling recommendations was noted in 75 of those 111 (68 percent). The cost of excess ceftazidime dosing for those 75 patients (i.e., extra drug acquisition, preparation, administration) was $13,822.50. CONCLUSIONS: Although the dosage of ceftazidime required in a specific patient is based on many factors, ceftazidime is frequently overdosed in the elderly because renal function is not considered. Ceftazidime dose-adjustment in the elderly, based on the estimated creatinine clearance, can lead to cost savings. In the US, where hospital reimbursement by Medicare is based on diagnosis, institutions can realize direct cost savings.

Academic Medical Centers↗
PubMed1985

Ceftazidime. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use.

Ceftazidime is a new 'third generation' cephalosporin administered intravenously or intramuscularly. Similarly to other third generation cephalosporins it has a broad spectrum of in vitro activity against Gram-positive and Gram-negative aerobic bacteria, is particularly active against Enterobacteriaceae (including beta-lactamase-positive strains) and is resistant to hydrolysis by most beta-lactamases. Importantly, in vitro ceftazidime is presently the most active cephalosporin available against Pseudomonas aeruginosa, but it is less active against Staphylococcus aureus than first and second generation cephalosporins. Only larger comparative trials are likely to discern any statistically significant differences in clinical efficacy which may exist between ceftazidime and other antibiotics, but ceftazidime appears to be similar in efficacy to 'standard' comparative drugs in lower respiratory tract infections and complicated and/or chronic urinary tract infections among debilitated or hospitalised patients. Thus, in patients having Gram-negative infections at these sites and in whom the potential toxicity of the aminoglycosides is a concern, ceftazidime may be a valuable alternative in that it apparently lacks serious side effects and does not require routine drug plasma concentration monitoring. In fibrocystic patients having acute respiratory tract infections, ceftazidime is highly effective at both reducing symptoms of infection and temporarily reducing the sputum counts of Pseudomonas species. However, in these patients resistance to ceftazidime may develop, as seen with other beta-lactam antibiotics. In the treatment of fever of unknown origin or documented infections in immunocompromised adults and children, ceftazidime appears to be similar in efficacy to various 2- or 3-drug combinations. Nevertheless, the coadministration of an antibiotic having greater efficacy against Gram-positive bacteria should be considered in immunocompromised patients. Results from a small number of comparative trials suggest that ceftazidime may be as effective as the aminoglycosides in intra-abdominal, obstetric and gynaecological, and skin and soft tissue infections. However, further clinical experience, particularly a few well designed comparative studies, is needed to clarify the comparative efficacy in these conditions as well as in septicaemia/bacteraemia, meningitis, and bone and joint infections.

Aging↗
PubMed2002

An in vitro study of ceftazidime and vancomycin concentrations in various fluid media: implications for use in treating endophthalmitis.

PURPOSE: To investigate the precipitation process of a mixture of vancomycin and ceftazidime by equilibrium dialysis and determine its subsequent effect on the level of free antibiotics for treatment of endophthalmitis. METHODS: Concentrations of vancomycin and ceftazidime in an equilibrium dialysis chamber were measured during the equilibrium process by high-performance liquid chromatography. Normal saline (NS), balanced salt solution (BSS), and vitreous were used separately as the medium of dialysis. RESULTS: Precipitation of ceftazidime occurred at 37 degrees C but not at room temperature and did not affect the pH of the medium. It formed precipitate on its own or when mixed with vancomycin in all the three media of NS, BSS, and vitreous. More precipitation was formed if ceftazidime was initially prepared in BSS than in NS. After 168 hours in the dialysis chambers, ceftazidime prepared in NS precipitated to 54% of that in vitreous, compared with 88% if prepared in BSS. At 48 hours, ceftazidime prepared in NS decreased from an initial concentration of 137.5 to 73.4 microg/mL in vitreous medium and to 6.3 microg/mL if prepared in BSS. Precipitation of vancomycin was negligible. CONCLUSIONS: Based on this in vitro investigation, ceftazidime precipitates in vitreous at body temperature, regardless of the presence of vancomycin. NS is preferred to BSS as a preparation medium for antibiotics for intravitreal injection, because the extent of ceftazidime precipitation is less. However, due to precipitation, the concentration of free ceftazidime in vitreous may not be sufficiently high for antibacterial activity against most common organisms.

Anti-Bacterial Agents↗
PubMed1992

A comparison of imipenem to ceftazidime with or without amikacin as empiric therapy in febrile neutropenic patients.

BACKGROUND: Neutropenic patients with cancer are traditionally treated with empiric antibiotic combinations when they become febrile. The availability of broad-spectrum antibiotics such as ceftazidime and imipenem has made it possible to initiate therapy with a single agent (monotherapy). The objectives of this trial were to compare ceftazidime and imipenem as single agents for the therapy of febrile episodes in neutropenic patients and to ascertain whether the addition of an aminoglycoside (amikacin) to either of these agents would provide an advantage. METHODS: A prospective clinical trial was conducted in which eligible neutropenic patients with cancer were randomized to one of four treatment arms: ceftazidime alone; imipenem alone; ceftazidime plus amikacin; and imipenem plus amikacin. Efficacy analysis was done for 750 assessable episodes. A multivariate logistic-regression analysis was also performed to examine the unique contribution of various prognostic factors. RESULTS: The overall response rates were 76% with imipenem plus amikacin, 72% with imipenem, 71% with ceftazidime plus amikacin, and 59% with ceftazidime alone. Single-organism gram-positive infections occurred in 101 of 750 episodes. Without a change in antibiotics, the response rates were 50% with imipenem, 40% with imipenem plus amikacin, 39% with ceftazidime plus amikacin, and 38% with ceftazidime. Most responded to vancomycin or other antibiotics, and the mortality associated with gram-positive infections was only 5%. Regardless of the antibiotic regimen, the majority of uncomplicated gram-negative infections responded to therapy and the majority of complicated gram-negative infections failed to respond. Multivariate logistic-regression analysis showed that recovery of the neutrophil count was the most favorable prognostic factor in a patient's response to infection, whereas the presence of gram-positive infection, acute leukemia, pulmonary or enteric infection, and therapy with ceftazidime were unfavorable factors. CONCLUSIONS: Single-agent therapy with imipenem is as effective as more conventional combination antibiotic therapy for the empirical treatment of febrile episodes in neutropenic patients with cancer.

Adolescent↗
PubMed1991

Stability of ceftazidime and amino acids in parenteral nutrient solutions.

The stability of ceftazidime was studied under conditions simulating administration via a Y-injection site into a primary infusion of parenteral nutrient (PN) solution; the stabilities of ceftazidime and amino acids when the drug was added directly to PN solutions were also studied. Three PN solutions containing 25% dextrose were used; the amino acid contents were 0, 2.5%, and 5%. Ceftazidime with sodium carbonate was used to prepare stock solutions of ceftazidime 40 mg/mL in both 0.9% sodium chloride injection and 5% dextrose injection; to simulate Y-site injection, samples were added to the three PN solutions to achieve ceftazidime concentrations of 10 and 20 mg/mL, or 1:1 and 1:3 ratios of drug solution to PN solution. Samples of these admixtures were assayed by high-performance liquid chromatography (HPLC) initially and after room-temperature (22 degrees C) storage for one and two hours. Additional solutions were prepared by adding sterile water for injection to ceftazidime with sodium carbonate; drug solutions were added to each PN solution in polyvinyl chloride bags to achieve ceftazidime concentrations of 1 and 6 mg/mL. The samples were assayed by HPLC for ceftazidime concentration after storage at 22 degrees C for 3, 6, 12, 24, and 36 hours and at 4 degrees C for 1, 3, 7, and 14 days. Amino acid stability was analyzed in admixtures containing 5% amino acids and ceftazidime 6 mg/mL after 24 and 48 hours at 22 degrees C and after 7 and 10 days at 4 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1989

Single- and multiple-dose pharmacokinetics of ceftazidime in infected patients with varying degrees of renal function.

To determine the single- and multiple-dose ceftazidime kinetics, we administered ceftazidime, 2 gm intravenous bolus every 12 hours, to 14 infected Chinese patients with various degrees of renal function. Blood samples were drawn in serial after the first and 7th dose and serum ceftazidime concentrations were measured by high pressure liquid chromatography. Ceftazidime concentration-time data were fitted to a two-compartment model with a nonlinear regression program. Ceftazidime kinetics was unaltered by repeated dosing. Both total body clearance and elimination rate constant of ceftazidime decrease significantly in proportion to the creatinine clearance estimated by Bjornsson's method. Renal insufficiency did not modify the steady-state volume of distribution (Vdss) of ceftazidime which, however, appeared to be larger than those reported previously. This larger Vdss may be explained by acute infection process, confinement to bed, and increased extracellular fluid volume as a result of hypoalbuminemia. Our study indicates the estimated creatinine clearance as a useful guide to ceftazidime dosage adjustment and also emphasizes the clinical relevance of conducting kinetic studies of antibiotics in infected patients.

Adult↗
PubMed1993

Pharmacokinetics of intravenous and intraperitoneal ceftazidime in chronic ambulatory peritoneal dialysis.

The pharmacokinetics of ceftazidime have been investigated in eight patients with chronic renal failure undergoing continuous ambulatory peritoneal dialysis. Each subject was given ceftazidime 1 g intravenously and 1 g intraperitoneally at an interval of 1 week. Ceftazidime was assayed by high-pressure liquid chromatography. After intravenous administration, the pharmacokinetic parameters of ceftazidime were: elimination plasma half-life (t1/2 beta) = 24.6 +/- 4.6 hours; apparent volume of distribution (V(area)): 0.37 +/- 0.09 1/kg, total plasma clearance (CL): 11.9 +/- 3.3 mL/minute, peritoneal clearance (CLp): 1.7 +/- 0.3 mL/minute. Over 72 hours, only 15.6 +/- 4.7% of the dose was eliminated by the peritoneal route. After intraperitoneal administration, ceftazidime appeared in the plasma rapidly, and the peak plasma concentration of 24.5 +/- 5.2 mg/L was achieved at the fourth hour; the elimination half-life (t1/2ke) was 20.8 +/- 1.7 hours. The absorption of ceftazidime from the peritoneal space was 74.1 +/- 7.4%. These data suggest that ceftazidime has bidirectional exchange characteristics through the peritoneal membrane. A single 1-g intraperitoneal dose led to serum and dialysate concentrations of ceftazidime above the minimum concentrations for susceptible pathogen germs for 24 hours.

Adult↗
PubMed1988

Pharmacokinetics and tissue concentrations of ceftazidime in burn patients.

The pharmacokinetics and tissue concentrations of ceftazidime have been investigated in 8 patients with severe burns (20-80% of body surface area) undergoing skin transplantation 2 to 21 days after injury. Two prophylactic doses of ceftazidime were administered as 1 g i.v. bolus injections with an 8 h interval. Blood, urine, burn blister fluid and tissue were frequently sampled and drug concentrations were analyzed by HPLC. The kinetics of ceftazidime was the same after each dose. In these patients the pharmacokinetics of ceftazidime was greatly altered from that in other patients and there was much interindividual variation. The mean ceftazidime elimination half-life, apparent volume of distribution and total clearance were: 2.7 h, 30.91 (0.38 1.kg-1) and 139 ml.min-1, respectively. A linear correlation was found between creatinine clearance and the renal clearance of the ceftazidime, the mean values being 108 and 95 ml.min-1, respectively. No correlation was found between creatinine clearance and the total clearance of ceftazidime. The mean percentage urine recovery was 69% of the dose. Tissue and burn blister fluid concentrations were above the MIC, and ranged from 40.0 to 3.1 mg.kg-1. A substantial increase in the apparent volume of distribution and non-renal clearance of ceftazidime was observed, probably due to increased capillary permeability and drug loss through the wound surface replacement of prior to surgery and subsequently to lost and blood fluid.

Adult↗
PubMed1987

[Ceftazidime versus cefotaxime in the therapy of severe infections in intensive care patients].

In a randomized controlled, clinical study the efficacy of ceftazidime at a dosage of 2 g b. i. d. was compared to that of cefotaxime at a dosage of 2 g t. i. d. or more in the treatment of pneumonia or peritonitis in intensive care patients. 61 of 67 assessable cases were evaluable. In the ceftazidime group ten out of 11 patients with pneumonia and 17 out of 20 with peritonitis showed a clinical success. In the cefotaxime group 15 out of 19 patients with pneumonia and eight out of 11 with peritonitis were clinically cured or improved. With ceftazidime an overall success was achieved in 87% of the patients (27 out of 31) and with cefotaxime in 77% of the patients (23 out of 30). Two patients in the cefotaxime group developed a reinfection. Five of the patients treated with cefotaxime and four of those treated with ceftazidime were therapeutical failures. Escherichia coli, Pseudomonas, Klebsiella, Enterobacter and Proteus species as well as Staphylococcus aureus and enterococci were the most frequent organisms isolated prior to therapy. Following ceftazidime therapy 30 of the 32 gram-negative species were eliminated, whereas in the cefotaxime group the number of gram-negative species isolated was reduced from 28 to ten. Gram-positive species isolated in ten cases prior to therapy, were still present in seven cases after ceftazidime therapy and the number of gram-positive organisms was reduced from 19 to ten following treatment with cefotaxime. In one patient therapy with ceftazidime was stopped due to urticaria. Reversible leukopenia was observed in a patient treated with ceftazidime and a cholestatic reaction in a patient treated with cefotaxime. In both groups a slight elevation of transaminases was seen.

Bacteria↗
PubMed2003

Population pharmacokinetics of ceftazidime in burn patients.

AIM: The aim of this study was to characterize, via a population pharmacokinetic approach, the pharmacokinetics of ceftazidime in burn patients who were not in the acute post-injury phase. METHODS: The development of the pharmacokinetic model was based on data from therapeutic drug monitoring (41 patients, 94 samples). The estimation of population pharmacokinetic parameters and the selection of covariates (age, gender, body weight, size of burn and creatinine plasma concentration) that could affect the pharmacokinetics were performed with a nonlinear mixed effect modelling method. RESULTS: No relationship between covariates and the pharmacokinetic parameters was established with the exception of an inverse-linear relationship between creatinine plasma concentration and ceftazidime total clearance. The total clearance of ceftazidime was 2.72 l h-1[coefficient variation (CV) = 56.3%] and the distribution volume of the central compartment was 0.28 l kg-1 (CV = 13.2%) The transfer rate constants (k12, k 21) between the central and peripheral compartments were 0.06718 h-1 (CV = 87.2%) and 0.001823 h-1 (CV = 82.7%), respectively. From these parameters, the total ceftazidime volume of distribution (10.64 l kg-1) was calculated. CONCLUSION: The population parameters were different from those obtained in a previous study performed in fewer patients and in the early period after burn injury. In our study, the lower ceftazidime clearance could be explained by the relative decrease in ceftazidime elimination in relation to the burn area, and the higher ceftazidime volume of distribution in the presence of interstitial oedema, which could act as a reservoir from which ceftazidime returns slowly to the circulation.

Adult↗
PubMed1987

Ceftazidime combined with a short or long course of amikacin for empirical therapy of gram-negative bacteremia in cancer patients with granulocytopenia.

To determine whether combination antibiotic therapy including a short course of an aminoglycoside was as effective and less toxic than a conventional long course of the combination for the empirical therapy of gram-negative bacteremia in patients with cancer and granulocytopenia, we conducted a randomized multicenter trial comparing ceftazidime plus a short course (three days) of amikacin, ceftazidime plus a long course (nine days) of amikacin, and azlocillin plus a long course (nine days) of amikacin. Single-organism gram-negative bacteremia occurred in 129 of 872 evaluable patients. Without a change in antibiotics, the response rates were 81 percent with ceftazidime and long-course amikacin, 48 percent with ceftazidime and short-course amikacin (P = 0.002), and 40 percent with azlocillin and long-course amikacin (P less than 0.001). Among patients with fewer than 100 granulocytes per cubic millimeter throughout therapy, the response rates were 6 percent with ceftazidime and short-course amikacin and 50 percent with ceftazidime and long-course amikacin (P = 0.03). Linear logistic-regression analysis showed that therapy with ceftazidime and long-course amikacin was the most favorable prognostic factor of the response to infection, whereas the presence of leukemia or shock was the least favorable. We conclude that ceftazidime should be given in combination with a conventional full course of an aminoglycoside (amikacin) when used for the empirical treatment of gram-negative bacteremia in cancer patients with granulocytopenia.

Adolescent↗
PubMed1996

Selection and characterization of amino acid substitutions at residues 237-240 of TEM-1 beta-lactamase with altered substrate specificity for aztreonam and ceftazidime.

Recently, natural variants of TEM-1 beta-lactamase with amino acid substitutions at residues 237-240 have been identified that have increased hydrolytic activity for extended-spectrum antibiotics such as ceftazidime. To identify the sequence requirements in this region for a given antibiotic, a random library was constructed that contained all possible amino acid combinations for the 3-residue region 237-240 (ABL numbering system) of TEM-1 beta-lactamase. An antibiotic disc diffusion method was used to select mutants with wild-type level activity or greater for the extended-spectrum cephalosporin ceftazidime and the monobactam aztreonam. Mutants that were selected for optimal ceftazidime hydrolysis contained a conserved Ala at position 237, a Ser for Gly substitution at position 238, and a Lys for Glu at position 240. Mutants selected for aztreonam hydrolysis exhibited a Gly for Ala substitution at position 237, a Ser for Gly substitution at position 238, and a Lys/Arg for Glu at position 240. The role of the A237G substitution in differentiating between ceftazidime and aztreonam was further investigated by kinetic analysis of the A237G, E240K, G238S:E240K, and A237G:G238S:E240K enzymes. The A237G single mutant and the G238S:E240K double mutant exhibited increases in catalytic efficiency for both ceftazidime and aztreonam. However, the triple mutant A237G:G238S:E240K, displayed a 12-fold decrease in catalytic efficiency for ceftazidime but a 3-fold increase for aztreonam relative to the G238S:E240K double mutant. Thus, the A237G substitution increases ceftazidime hydrolysis when present alone but antagonizes ceftazidime hydrolysis when it is combined with the G238S:E240K substitutions. In contrast, the A237G substitution acts additively with the G238S:E240K substitutions to increase aztreonam hydrolysis.

Amino Acid Sequence↗
PubMed1983

Serum bactericidal activity of cefoperazone and ceftazidime at increasing dosages against Pseudomonas aeruginosa.

Serum bactericidal activity (SBA) greater than or equal to 1:8 correlates with the clinical effectiveness of antibiotics. Ten healthy young volunteers received iv on separate days cefoperazone 1, 2, or 3 g and ceftazidime 1, 2, or 3 g. The serum levels 1 and 6 h after the administration of cefoperazone 1, 2 and 3 g were respectively 52 and 7 mg/l, 122 and 13 mg/l, 190 and 22 mg/l. The serum levels of ceftazidime 1, 2 and 3 g, after 1 h and 6 h were 28 and 8, 56 and 9, 78 and 13 mg/l. The SBA was determined against seven strains of Pseudomonas aeruginosa with MBC of 1.6-12.5 mg/l of cefoperazone and 0.8-6.2 mg/l of ceftazidime. Increased dosage of cefoperazone and ceftazidime led to a significant increase in the SBA's greater than or equal to 1:8 at 1 h (P less than 0.01). In sera obtained 1 h and 6 h after the injection of the antibiotics, 97% and 51% of the strains were inhibited by ceftazidime 2 g, while 1 g was inhibitory on 84% (1 h) and 8% (6 h) of the strains. Ceftazidime 1 g produced SBA's greater than or equal to 1:8 significantly more often than did cefoperazone 3 g (P less than 0.01) at 1 h. The rate of killing with all ceftazidime regimens was similar and slightly higher than that of any cefoperazone regimen. Ceftazidime seems more effective than cefoperazone against Ps. aeruginosa; however, increased MBC values were observed during killing curves studies with both drugs.

Adult↗
PubMed1983

Studies on absorption, distribution, metabolism and excretion of ceftazidime in Japan.

Ceftazidime achieved mean serum levels of 54.6 and 119.7 mg/l at 5 min and 0.9 and 1.9 mg/l at 8 h after an intravenous bolus injection of 0.5 and 1 g in healthy male adult volunteers, showing a dose-related increase in serum levels. Serum half-lives were in the range from 1.6 to 1.7 h. About 90% of the given dose was excreted in the urine during the first 24 h. Following a 1-h intravenous drip infusion of 1 and 2 g, ceftazidime attained peak serum levels of 69.5 and 150.8 mg/l at the end of the infusion. Eighty-three and 90%, respectively, of the given doses were excreted in the urine during 24 h after the administration of 1 and 2 g of ceftazidime. When serum levels were compared after intravenous bolus injections of 1 g of ceftazidime and 1 g of cefoperazone in a crossover fashion, results were very similar for both compounds, but the 24-h urinary recovery rate was about three times higher with ceftazidime than with cefoperazone. An intravenous injection of 1 g ceftazidime resulted in peak biliary levels about 4 h after administration, longer than that of ceftizoxime compared in a crossover fashion, and subsequently fairly high levels were maintained for a longer time. Ceftazidime penetrated gall bladder tissues at concentrations sufficient to inhibit most of the pathogenic bacteria. In the urine collected from healthy volunteers 1 h after an intravenous injection of 1 g ceftazidime, no active metabolite was detected.

Adult↗
PubMed1983

Ceftazidime treatment of chronic Pseudomonas aeruginosa respiratory tract infection in cystic fibrosis.

Two open randomized cross-over studies were undertaken comparing ceftazidime to tobramycin and ceftazidime to tobramycin plus carbenicillin in 13 and 15 cystic fibrosis (CF) patients, respectively, with chronic bronchopulmonary Pseudomonas aeruginosa infection. The difference in lung function improvement was statistically better in terms of FEV1 and FVC for the ceftazidime group in the study versus tobramycin plus carbenicillin. Patients receiving ceftazidime showed a tendency for a greater long-term benefit in lung function as measured at 1 and 2 months after treatment than patients receiving the other antibiotics. Development of resistance against both ceftazidime and carbenicillin was seen regularly and was not prevented by combination therapy with tobramycin. No resistance developed when tobramycin was used as monotherapy. Serum concentration curves for ceftazidime fitted a two compartment first order open model in CF patients and showed a distribution volume of 40% of the body weight and a final serum half-life of 1.8 h. One case of Type III hypersensitivity reaction was seen during ceftazidime treatment. Ceftazidime seems to be an effective and safe antibiotic in the treatment of Ps. aeruginosa bronchopulmonary infection in CF patients, although these bacteria could not be eradicated.

Adolescent↗
PubMed1985

Penetration of beta-lactam antibiotics into cardiac vegetations, aorta and heart muscle in experimental Staphylococcus aureus endocarditis: comparison of ceftazidime, cefuroxime and methicillin.

The penetration of ceftazidime, cefuroxime and methicillin into cardiac vegetations, normal aorta wall tissue, heart muscle and heart muscle tissue fluid was measured in rabbits with Staphylococcus aureus (853E) endocarditis. After a 100 mg/kg intramuscular injection, ceftazidime attained significantly higher peak concentrations than cefuroxime and methicillin in all compartments with the exception of aorta where no difference was observed between ceftazidime and methicillin. The half life of ceftazidime in each compartment (50-65 min) was approximately twice that of cefuroxime and methicillin. The area under the concentration/time curve for ceftazidime in vegetations over a post dosing 6 h period was approximately five times greater than that for cefuroxime and three times that for methicillin. Ceftazidime remained for a longer time period in all compartments, however cefuroxime persisted the longest at supra-MIC concentrations in all compartments except serum. Compared to cefuroxime and methicillin where vegetation and aorta tissue levels were similar, ceftazidime attained peak levels in vegetations which were more than double those found in aorta tissue. Analysis of the percentage penetration from serum into vegetation, suggested that the higher concentrations of ceftazidime in vegetation tissue were probably not a function of increased fluid content relative to undamaged aorta but were more likely caused by an intrinsically better penetrating capacity for vegetation tissue.

Animals↗