Comparison of the concentrations of ceftazidime in the serum of newborn infants after intravenous and intramuscular administration.

The concentrations of ceftazidime in serum were studied in 16 preterm and term neonates to whom a single dose of 50 mg/kg had been administered intramuscularly or intravenously. After intramuscular injection, concentrations of ceftazidime in serum were comparable to those obtained with the intravenous dose, although they were more variable. Peak serum levels ranging from 50 to 102 micrograms/ml were reached 30 to 60 min after intramuscular injection. The concentrations declined monoexponentially after the peak, with a mean half-life of 3.8 +/- 1.1 h. Concentrations of ceftazidime in serum declined biexponentially after intravenous injection, with a terminal half-life of 4.7 +/- 1.5 h.     

Comparison of ceftazidime and cefamandole pharmacokinetics and blister fluid concentrations.

Eight healthy male volunteers received 1 g of either ceftazidime or cefamandole as an intravenous infection. Serial blood samples were taken over the next 8 h. Urine samples were collected over 24 h. Levels of these antibiotics were measured in the fluid of blisters resulting from application of cantharides. The concentration of ceftazidime in serum at 0.25 h after intravenous injection was 83.3 micrograms/ml. The serum half-lives for the respective drugs were 1.8 and 0.8 h. The mean apparent volume of distribution of ceftazidime (13.6 liters) was greater than that of cefamandole (9.8 liters). Plasma clearance was 111 ml/min for ceftazidime and 216 ml/min for cefamandole. The maximum blister fluid concentration of ceftazidime was 45.9 micrograms/ml, and that of cefamandole was 22.1 micrograms/ml. The relative availability of each drug in blister fluid compared with serum was similar.     

Intraoperative concentrations of ofloxacin in serum, bile fluid, and gallbladder wall tissue.

To evaluate concentrations of ofloxacin in serum, bile fluid, and gallbladder wall tissue after intravenous administration, patients greater than or equal to 16 years old diagnosed with acute cholecystitis were randomly assigned to receive ofloxacin (400 mg) intravenously every 12 h or ceftazidime (2 g) intravenously every 8 h. Doses of each regimen were given preoperatively. Serum, bile fluid, and gallbladder wall tissue samples of consecutive patients in the ofloxacin group were obtained intraoperatively. The samples were frozen at -70 degrees C until analyzed by high-pressure liquid chromatography. Twenty-three patients (6 males and 17 females) were evaluated. The mean (+/- the standard deviation) ofloxacin concentrations in serum, bile fluid, and gallbladder wall tissue were 2.9 +/- 2.4 and 6.0 +/- 7.9 micrograms/ml and 3.1 +/- 2.9 micrograms/g, respectively. The mean number of doses each patient received before surgery was 5.3 +/- 3.0, and the mean delta time (time elapsed between last antibiotic administration and when intraoperative samples were obtained) was 9.6 +/- 7.5 h. The mean tissue-to-serum ratio was 1.2 +/- 0.5, and the mean bile-to-serum ratio was 2.3 +/- 1.4. The mean serum ofloxacin concentrations were not statistically different from the concentrations in bile (P = 0.1) and tissue (P = 0.7) at the mean delta time. The study revealed that concentrations of ofloxacin in serum, bile fluid, and gallbladder tissue after intravenous dosing were adequate against susceptible organisms found in the biliary tract.     

High-pressure liquid chromatographic analysis of ceftazidime in serum and urine.

A rapid and sensitive high-pressure liquid chromatographic procedure was developed for quantitative analysis of a new semisynthetic cephalosporin, ceftazidime, in serum and urine. A good linear relationship was established between peak height and the amount of ceftazidime injected over a concentration range of 1.9 to 30 micrograms/ml. Recovery was approximately 90% at concentrations of 3, 15, and 30 micrograms/ml. The method is specific for ceftazidime, with no interference noted from 11 other beta-lactam antibiotics tested. The assay is accurate, reproducible, and useful for pharmacokinetic studies in humans as demonstrated in two subjects.     

Effect of ceftazidime on systemic cytokine concentrations in rats

The effect of a single dose of ceftazidime on circulating concentrations of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) in a rat model of sepsis was studied. IL-6 concentrations were significantly elevated (100 to 200 times the baseline) 6 h after ceftazidime administration in both septic and nonseptic (control) rats. TNF-alpha concentrations increased significantly in nonseptic (approximately 40 times the baseline) rats but not septic (approximately 2 to 3 times the baseline) rats. Ceftazidime administration was not associated with an increase in endotoxin concentrations. These findings suggest that ceftazidime modulation of proinflammatory cytokine concentrations may be independent of its antimicrobial properties.     

Comparison of ex-vivo serum bactericidal activity of cefepime,ceftazidime and cloxacillin against Staphylococcus aureus

Cefepime (1 g), ceftazidime (1 g), and cloxacillin (2 g) were administered intravenously to 10 volunteers each. After infusion of a single dose over 30 min, blood samples were obtained at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 h (for ceftazidime at 0.5 and 4 h) after dosing. Drug levels were determined by the bioassay method. Serum bactericidal activity against five clinical isolates of cloxacillin-susceptible Staphylococcus aureus were determined by the microdilution method according to the National Committee for Clinical Laboratory Standards guidelines. The mean peak serum level was 76.88 ± 24.71 mg/L for cefepime, 42.8 ± 15.98 mL/L for ceftazidime, and 92.81 ± 24.7 mg/L for cloxacillin. Concentrations of cefepime were detected during the whole testing period (mean trough level, 1.43 ± 0.9 mg/L at 12 h), whereas concentrations of cloxacillin were measurable up to 5 h after administration (mean trough level, 0.90 ± 0.97 mg/L). The mean peak reciprocal bactericidal titers were 29.41 for cefepime, 5.6 for ceftazidime, and 377 for cloxacillin. Effective bactericidal titers were detected as long as 5 h for cefepime (∼40% of the dosing interval) and 3 h for cloxacillin (at least 50% of the dosing interval). For ceftazidime, serum bactericidal activity was markedly lower compared with that of cefepime. Although cefepime has demonstrated an improved antistaphylococcal bactericidal activity compared with ceftazidime, it was somewhat lower than that of cloxacillin.     

Comparative pharmacokinetics and serum bactericidal activities of SCE-2787 and ceftazidime.

Ceftazidime and the new SCE-2787 are parenteral cephalosporins with a broad antimicrobial spectrum. Pharmacokinetics, serum bactericidal activities, and side effects were investigated in a randomized crossover study. A total of 12 healthy volunteers received a 20-min infusion of 1.5 g of SCE-2787 or 2.0 g of ceftazidime. Serum and urine concentrations were determined by the bioassay method and by high-pressure liquid chromatography (HPLC). The mean (+/- standard deviation) drug concentrations in serum at the end of infusion of SCE-2787 and ceftazidime were 124.4 +/- 23.8 and 233.1 +/- 54.1 mg/liter, respectively. The urine recovery of SCE-2787 was 87.8% +/- 5.5% of dose in 24 h and for ceftazidime was 85.8% +/- 6.3% of dose in 24 h. Metabolites of SCE-2787 could not be detected by HPLC in serum or urine. Pharmacokinetic parameters were calculated both with a noncompartmental analysis and on the basis of an open two-compartment model (drugs are administered into and eliminated from a central compartment only. However, reversible drug distribution from the central space occurs simultaneously into one peripheral space). The area under the concentration time curve from 0 h to infinity of SCE-2787 was 197.9 +/- 25.4 mg.h/liter, and that of ceftazidime was 334.2 +/- 40.0 mg.h/liter. SCE-2787 had a mean terminal half-life in the elimination phase of 109.0 +/- 15.3 min, while that of ceftazidime was 99.0 +/- 13.4 min. The volume of distribution at steady state of SCE-2787 was 17.1 +/- 1.6 liters/70 kg, and that of ceftazidime was 122.9 +/- 1.3 liters/70 kg. The mean residence time of SCE-2787 was 136.4 +/- 15.4 min, and that of ceftazidime was 122.9 +/- 12.7 min. The renal clearance per. 1.73 m2 of SCE-2787 was 103.1 +/- 12.3 ml/min, and that of ceftazidime was 80.6 +/- 13.2 ml/min. The serum bactericidal activities were measured with the microdilution method of Stratton and Reller (L. B. Reller and C. W. Stratton, J. Infect. Dis. 136:196-204, 1977) against 40 clinically isolated strains. One hour after administration, we measured mean reciprocal bactericidal titers of SCE-2787 and ceftazidime, respectively, against Escherichia coli of 388 and 243, against Klebsiella pneumoniae of 395 and 138, against Pseudomonas aeruginosa of 13.0 and 12.7, and against Staphylococcus aureus of 32.2 and 4.0. No severe side effects were observed in this single drug administration.     

Serum concentrations and excretion of bile acids in cirrhosis.

Bile acid concentrations in serum, and urinary and faecal excretion of bile acids have been studied in ten patients with liver cirrhosis as a consequence of alcohol abuse. Eight of the patients were categorized as Child group A, whereas the remaining two patients comprised Child group C. Individual bile acids were isolated and identified by gas chromatography coupled to mass spectrometry. Total fasting serum bile acid concentrations were elevated in all patients, but not correlated to conventional tests of liver function. Eight of the patients had increased urinary excretion of bile acids. Faecal bile acid-excretion was highly variable between patients, and also between Child's group A and C patients. Total fasting serum bile acid concentrations were not correlated to either urinary, faecal, or total bile acid excretion (= synthesis of bile acids) or to the ratio between urinary and faecal excretion of bile acids. The daily synthesis of bile acids showed a large overlap between Child's group A and C patients. The percentage of chenodeoxycholic acid and its metabolites relative to total daily excretion of bile acids did not correlate, indicating that the synthesis pathways for the primary bile acids does not systematically change in relation to the rate of synthesis. We conclude that even in mild cirrhosis, serum bile acid concentrations are elevated. However, no consistent changes in synthesis of bile acids or synthesis pathways was observed in such patients.     

Comparison of lung tissue concentrations of nebulized ceftazidime in ventilated piglets: ultrasonic versus vibrating plate nebulizers

OBJECTIVE: To compare the efficiency of an Aeroneb Pro vibrating plate and an Atomisor MegaHertz ultrasonic nebulizer for providing ceftazidime distal lung deposition. DESIGN: In vitro experiments. One gram of cetazidime was nebulized in respiratory circuits and mass median aerodynamic diameter of particles generated by ultrasonic and vibrating plate nebulizers was compared using a laser velocimeter. In vivo experiments. Lung tissue concentrations and extrapulmonary depositions were measured in ten anesthetized ventilated piglets with healthy lungs that received 1 g of ceftazidime by nebulization with either an ultrasonic (n = 5), or a vibrating plate (n = 5) nebulizer. SETTING: A two-bed Experimental Intensive Care Unit of a University School of Medicine. INTERVENTION: Following sacrifice, 5 subpleural specimens were sampled in dependent and nondependent lung regions for measuring ceftazidime lung tissue concentrations by high-performance liquid chromatography. MEASUREMENTS AND RESULTS: Mass median aerodynamic diameters generated by both nebulizers were similar with more than 95% of the particles between 0.5 and 5 mum. Lung tissue concentrations were 553 +/- 123 [95% confidence interval: 514-638] mug g(-1) using ultrasonic nebulizer, and 452 +/- 172 [95% confidence interval: 376-528] mug g(-1) using vibrating plate nebulizers (NS). Extrapulmonary depositions were, respectively, of 38 +/- 5% (ultrasonic) and 34 +/- 4% (vibrating plate) (NS). CONCLUSIONS: Vibrating plate nebulizer is comparable to ultrasonic nebulizers for ceftazidime nebulization. It may represent a new attractive technology for inhaled antibiotic therapy.     

Radioimmunoassay of bile acids in serum.

We developed four radioimmunoassay procedures for the determination of glycine-conjugated bile acids in serum. Antibodies to two primary bile acids, cholylgycine and chenodeoxycholylglycine, and to two secondary bile acids, sulfolithocholylglycine and deoxycholylglycine, were raised in rabbits after the acids were covalently linked to albumin by use of the carbodiimide reaction. Assay sensitivity for each of these bile acids is in the picomole range with the standard curve extending from 10-80 pmol. The concentration of bile acids in serum increased in various states of liver disease and its measurement appears to be an extremely sensitive indicator of liver function.     

Serum and sputum concentrations of ceftazidime in patients with cystic fibrosis

The pharmacokinetic parameters of ceftazidime were assessed in six cystic fibrotic patients during eight courses administered for acute exacerbations of pulmonary infection. In order to assess the initial and steady state concentrations of ceftazidime at a dose of 35 mg/kg and to determine the levels found after a higher dose, each ten day course of ceftazidime consisted of eight doses of 35 mg/kg followed by 22 doses of 50 mg/kg, all administered at 8-hourly intervals. Samples of blood and sputum were collected following the 1st, 8th and 9th doses for ceftazidime assay. The mean peak serum concentrations of ceftazidime were 97, 110 and 147 mg/l respectively with corresponding mean concentrations in sputum of 2.7, 2.6 and 1.6 mg/l. The mean clearance rate was calculated on a two compartment model to be 197 ml/min/50 kg lean body mass, the mean volume of distribution was 281/50 kg lean body mass and the mean half life was 1.57 h. There were large inter-patient differences in the pharmacokinetic parameters, however, which suggests that the clinical condition of the patient affects the pharmacokinetics of ceftazidime in cystic fibrosis. In all the patients, even after the doses of 50 mg/kg, the trough serum concentrations were low. Samples of blood were also collected for adverse effects before, during and after each course; there was no evidence of renal, hepatic or haematological changes in response to the drug.     

Comparison of cefoperazone and cefoxitin concentrations in serum and pelvic tissue of abdominal hysterectomy patients.

Cefoperazone and cefoxitin concentrations were determined in serum and pelvic tissue samples obtained at various intervals after a 2-g intramuscular dose. These levels were determined in 59 women scheduled for elective abdominal hysterectomy. Concentrations were measured by a new high-pressure liquid chromatography method which correlated with the microbiological assay. The mean times (+/- standard deviation) of specimen collection were 188.5 +/- 61 and 185.5 +/- 55 min for cefoperazone and cefoxitin, respectively. The mean serum levels (+/- standard deviation) were 60.8 +/- 18.0 and 14.6 +/- 8.6 micrograms/ml, respectively. For cefoperazone, the mean pelvic tissue concentration was 19.8 micrograms/g. The mean pelvic tissue concentration for cefoxitin was 7.8 micrograms/g. The ratio of tissue concentration to serum concentration varied from 0.220 to 0.469 for cefoperazone and from 0.176 to 1.031 for cefoxitin. Although the serum and tissue concentrations of cefoperazone were much higher than those of cefoxitin, a greater portion of cefoxitin remained in the tissue. The tissue levels of both cefoperazone and cefoxitin were above the minimum inhibitory concentration of most sensitive pathogens several hours after a single prophylactic dose of either antibiotic.     

毛细管电泳法检测药敏纸片内头孢他啶含量

目的毛细管电泳法评价药敏纸片内头孢他啶含量。方法采用毛细管电泳方法（CE）对2种国产和2种进口头孢他啶（CAZ）药敏纸片内的头孢他啶含量进行检测。结果2种进口纸片内的CAZ含量比较稳定,2种国产纸片的CAZ均一性略差。利用3种标准菌株对4种纸片的各10次抑菌环直径结果进行比较发现,一种纸片的结果有一次超过允许范围。结论毛细管电泳法分析发现进口的头孢他啶纸片的质量较稳定。CE分析较适合临床实验室对药敏纸片有效药物含量进行监测。     

Comparison of ceftazidime with cefamandole for therapy of community-acquired pneumonia.

Ceftazidime and cefamandole were compared in the treatment of pneumonia. The median MIC of ceftazidime for all Streptococcus pneumoniae (n = 17) and Haemophilus influenzae (n = 10) isolates was 0.125 microgram/ml. All other isolates were inhibited by less than 0.5 microgram of ceftazidime per ml, with the exception of a group B streptococcus (MIC = 4 micrograms/ml). Satisfactory clinical responses were observed in 91% (20 of 22) of cefamandole-treated patients and 85% (17 of 20) of ceftazidime-treated patients.     

Comparison of a radioimmunoassay and a microbiological assay for measurement of serum vancomycin concentrations.

A newly developed radioimmunoassay was used to measure the concentration of vancomycin in 137 specimens of serum from patients being treated with this antibiotic. Of these sera, 84 were also analyzed with a microbiological assay technique for vancomycin. Duplicate determinations were done with each of the techniques. Individual values and averaged values for both methods were used for statistical analyses. The correlation coefficients between all possible combinations of radioimmunoassay and microbiological assay results for the 84 sera were greater than or equal to 0.99 (P less than 0.01). Values for the regression coefficients of radioimmunoassay results on microbiological assay results ranged from 0.98 +/- 0.01 to 1.03 +/- 0.01. The mean percent deviation of radioimmunoassay versus microbiological assay results was -1.56 +/- 0.60. A one-way analysis of variance demonstrated that the use of different standard curves for each batch of specimens assayed by microbiological assay did not significantly influence the results (P = 0.07). The microbiological assay and the radioimmunoassay for measurement of serum vancomycin levels yielded essentially identical results.     

Amikacin sulfate levels in human serum and bile.

Amikacin levels in blood and bile were measured in 10 patients who underwent cholecystectomy and T-tube drainage. Each patient received 500 mg of amikacin intravenously 12 h preoperatively, during surgery, and every 12 h thereafter for four more doses. Average levels of amikacin in bile were 8.3 micrograms/ml at 1 h after the intraoperative dose, with a bile/serum ratio of 0.44. Postoperative doses at 1 h produced levels in bile of 3.8 to 4.2 micrograms/ml, with a bile/serum ratio of 0.15 to 0.22. Levels in bile decreased at a rate lower than levels in blood, and bile/serum ratios increased from 0.54 at 2 h to 0.93 at 12 h. Amikacin accumulated in bile at 6 h after the intravenous dose.     

Comparison of the pharmacokinetics of ceftazidime and moxalactam and their microbiological correlates in volunteers.

We compared ceftazidime with moxalactam, a commonly utilized, currently available drug. The microbiological activities of ceftazidime and moxalactam were studied. In addition, single-dose pharmacokinetics and serum bactericidal activity 1 and 6 h after a 2.0-g, 30-min infusion of each drug were determined in a crossover study in human volunteers. In vitro, both drugs had MICs for 90% of the isolates of less than 1.0 microgram/ml against the common members of the family Enterobacteriaceae and of 8.0 micrograms/ml against Staphylococcus aureus. Against Pseudomonas aeruginosa ceftazidime was more active than moxalactam, the respective MICs for 90% of the isolates being 8 and 128 micrograms/ml. Mean half-lives were 1.75 (+/- 0.21) h for ceftazidime and 2.5 (+/- 0.38) h for moxalactam. The serum bactericidal titers for both compounds against Escherichia coli and Klebsiella pneumoniae were high. Titers against S. aureus 6 h after infusion were negative. The mean (geometric) serum bactericidal titer of ceftazidime against 31 strains of P. aeruginosa (1:44) was higher than that of moxalactam (1:3.4).