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A sensitive, accurate and precise liquid chromatography (LC) method for the simultaneous determination of ceftazidime and pyridine in human plasma has been developed and validated. Acetonitrile (ACN) was employed to precipitate the proteins in the plasma samples. Chromatographic separation was performed with a Kinetex® C18 (150 mm × 3 mm, 2.6 µm) column with gradient elution. Ammonium formate 20 mM and ACN were mixed in a ratio of 98:2 (v/v) for mobile phase A and 85:15 (v/v) for mobile phase B. Both were adjusted to pH 4.5 with formic acid. The flow rate was 0.4 mL/min. UV detection was performed at 254 nm. Calibration curves were linear in the range from 0.3 to 225 μg/mL for ceftazidime and from 0.2 to 10 μg/mL for pyridine with correlation coefficients ≥ 0.999. Within- and between-run precision and accuracy were satisfactory with coefficients of variation (CV) ≤ 8.0% and deviations ≤ 7.0%, respectively. The method fulfilled all validation criteria prescribed by the European Medicines Agency guidelines. Next, it has been used successfully to analyze plasma samples of patients who received ceftazidime under intermittent and continuous administration. With intermittent administration, the concentration of the antibiotics reached a peak and then dropped quickly, which may be below the minimal inhibitory concentration (MIC). With continuous administration, the concentration of the antibiotics remained stable over 24 h, certainly above the MIC. Although the same tendency in ceftazidime concentration changes over time was observed, a difference in concentration amongst the patients was noticeable. The concentration of pyridine in plasma was negligible., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Portable infusion pumps are an interesting solution to continue outpatient parenteral antimicrobial therapy (OPAT) at the patient's home. However, the use of ceftazidime for such applications is challenging in view of its relatively poor stability in solution. In this study, elastomeric infusion pumps with 6 or 7 g of ceftazidime were deflated over 24 h in an oven at 33°C while ceftazidime and its degradation product, pyridine, were regularly monitored. Hereto, a fast and sensitive liquid chromatographic (LC) method has been developed using a Kinetex ® C18 (150 × 3 mm, 2.6 μm) column with gradient elution. Ammonium formate 20 mM and acetonitrile (ACN) were mixed in a ratio of 98:2 v/v for mobile phase A and 85:15 v/v for mobile phase B. Both were adjusted to pH 4.5 with formic acid. The flow rate was set at 0.4 mL/min. The solution with a starting dose of 6 g ceftazidime was found to be degraded 10% after an average of 19 h 11 min so that an administration of 6 g to the patient was not reached. For the solution with a starting dose of 7 g of ceftazidime, 10% degradation was observed after an average of 18 h 42 min. However, by starting from a higher dose, an average of 6.56 g of ceftazidime could be administered over 24 h. In addition, 1.0% of pyridine versus ceftazidime pentahydrate with sodium carbonate (=mixture for injection) was formed over 24 h., (© 2021 Wiley-VCH GmbH.)

Background: Effective antimicrobial treatment is key to reduce mortality associated with bacterial sepsis in patients on intensive care units (ICUs). Dose adjustments are often necessary to account for pathophysiological changes or renal replacement therapy. Extracorporeal membrane oxygenation (ECMO) is increasingly being used for the treatment of respiratory and/or cardiac failure. However, it remains unclear whether dose adjustments are necessary to avoid subtherapeutic drug levels in septic patients on ECMO support. Here, we aimed to evaluate and comparatively assess serum concentrations of continuously applied antibiotics in intensive care patients being treated with and without ECMO., Methods: Between October 2018 and December 2019, we prospectively enrolled patients on a pneumological ICU in southwest Germany who received antibiotic treatment with piperacillin/tazobactam, ceftazidime, meropenem, or linezolid. All antibiotics were applied using continuous infusion, and therapeutic drug monitoring of serum concentrations (expressed as mg/L) was carried out using high-performance liquid chromatography. Target concentrations were defined as fourfold above the minimal inhibitory concentration (MIC) of susceptible bacterial isolates, according to EUCAST breakpoints., Results: The final cohort comprised 105 ICU patients, of whom 30 were treated with ECMO. ECMO patients were significantly younger (mean age: 47.7 vs. 61.2 years; p < 0.001), required renal replacement therapy more frequently (53.3% vs. 32.0%; p = 0.048) and had an elevated ICU mortality (60.0% vs. 22.7%; p < 0.001). Data on antibiotic serum concentrations derived from 112 measurements among ECMO and 186 measurements from non-ECMO patients showed significantly lower median serum concentrations for piperacillin (32.3 vs. 52.9; p = 0.029) and standard-dose meropenem (15.0 vs. 17.8; p = 0.020) in the ECMO group. We found high rates of insufficient antibiotic serum concentrations below the pre-specified MIC target among ECMO patients (piperacillin: 48% vs. 13% in non-ECMO; linezolid: 35% vs. 15% in non-ECMO), whereas no such difference was observed for ceftazidime and meropenem., Conclusions: ECMO treatment was associated with significantly reduced serum concentrations of specific antibiotics. Future studies are needed to assess the pharmacokinetic characteristics of antibiotics in ICU patients on ECMO support.

Purpose: To determine in-use stability and sterility of fortified cefazolin, ceftazidime, vancomycin, amphotericin B, and methylprednisolone eye drops in a simulated inpatient setting with and without a mobile refrigerated container (MR)., Methods: Each drug was prepared and divided into 4 groups: 1) simulated patient use with the MR group: stored at 4°C and kept in the MR during drug administration, 2) simulated patient use without the MR (NoMR) group: stored at 4°C and no MR, 3) refrigerated control group: stored at 4°C, and 4) room temperature control group: stored at room temperature. Stability and sterility data were evaluated at days 0, 4, 7, 14, 21, and 28. Linear mixed-effects model and survival analysis were performed., Results: Median time to 10% loss of concentration for in-use medications (MR/NoMR groups) was >28/27.9, 22.2/22.2, 19.4/19.4, 10.18/<4, and >28/>28 days for cefazolin, ceftazidime, vancomycin, amphotericin B, and methylprednisolone, respectively. There was no significant difference in the predicted concentration loss per day among all groups for vancomycin and methylprednisolone (all P > 0.05). For the other study medications, all room temperature control groups, the cefazolin NoMR group, and the ceftazidime NoMR group had significantly greater predicted concentration loss per day compared with the refrigerated control groups (all P ≤ 0.02). Culture results were negative for all drugs throughout the study., Conclusions: The NoMR group showed that the drug significantly degraded rapidly for cefazolin, ceftazidime, and amphotericin B. Implementation of MR could decrease the predicted loss of concentration per day for cefazolin and ceftazidime. In vitro antimicrobial activity and sterility were retained for 28 days.

Objectives: Antibiotic therapy is of vital importance for the control of infectious exacerbations in cystic fibrosis (CF) patients. However, very little is known regarding the fraction of systemically administered antibiotics reaching the lower respiratory tract secretions. We developed and validated a method to measure the concentrations of piperacillin, ceftazidime, meropenem and aztreonam in CF sputum, and present the validation data., Methods: Ultra-performance LC coupled to tandem MS was used. A single sample can be measured in 2.5 min with multiple reaction monitoring in positive electrospray ionization mode. Deuterated internal standards were used and a concentration range of 0.7-160 mg/L was covered. The method was validated according to the EMA guideline on analytical method validation., Results: The boundaries within which a reliable measurement in CF sputum can be performed were determined. A few constraints are linked to the instability of the antibiotics in sputum. Piperacillin showed limited stability at room temperature and during freeze-thaw cycles. Autosampler instability was observed after 15 h for aztreonam at low concentrations., Conclusions: The method allows a reliable measurement of the selected antibiotics, if precautions are taken regarding the limited stability of piperacillin at room temperature. Due to freeze-thaw instability, piperacillin should always be analysed on the day of sampling. Quick review of the analytical data and reanalysis are needed as low concentrations of aztreonam are not stable in the autosampler., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

A rapid and simple method for the extraction and preconcentration of ceftazidime in aqueous samples has been developed using dispersive liquid-liquid microextraction followed by high-performance liquid chromatography analysis. The extraction parameters, such as the volume of extraction solvent and disperser solvent, salt effect, sample volume, centrifuge rate, centrifuge time, extraction time, and temperature in the dispersive liquid-liquid microextraction process, were studied and optimized with the experimental design methods. Firstly, for the preliminary screening of the parameters the taguchi design was used and then, the fractional factorial design was used for significant factors optimization. At the optimum conditions, the calibration curves for ceftazidime indicated good linearity over the range of 0.001-10 μg/mL with correlation coefficients higher than the 0.98, and the limits of detection were 0.13 and 0.17 ng/mL, for water and urine samples, respectively. The proposed method successfully employed to determine ceftazidime in water and urine samples and good agreement between the experimental data and predictive values has been achieved., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

An electrophoretic stacking method has been developed for monitoring the therapeutic level of the antibiotic ceftazidime in blood plasma and microdialysates taken from peripheral soft tissues of the lower limbs of patients with diabetic foot syndrome. The biological samples are treated by addition of acetonitrile in an amount of 75% v/v and injected into a capillary in a large volume; after turning on the separation voltage, the residual acetonitrile is forced out of the capillary by the application of hydrodynamic pressure. The clinical samples were separated in an optimised background electrolyte composed of 50 mM chloroacetic acid +20% v/v methanol +0.5% v/v INST coating solution. The attained LOD for ceftazidime equalled 0.42 μg mL -1 (0.8 μM) and the migration time equalled 3.75 min when using a 25 μm capillary with minimum length of 31.5 cm. The separation was controlled by a maximum voltage of +30 kV and the movement of the analyte was accelerated by a pressure of 50 mbar. The RSD values for intra-day repeatability of the migration time and peak area are 0.14% and 3.8%, respectively; the inter-day values equalled 0.25% for the migration time and 7.3% for peak area, respectively. Pharmacological studies revealed that ceftazidime passes from the blood circulation to the peripheral tissues of the lower limbs with an efficiency of 20%. The introduction of CE control of ceftazidime level in diabetic foot represents a very important improvement in achieving the targeted therapeutic effect., (Copyright © 2016 Elsevier B.V. All rights reserved.)

A novel and sensitive method for the determination of ceftazidime and cefepime in an active pharmaceutical ingredient (API) has been developed based on the fluorescence quenching of poly(ethylene glycol) (PEG)2000-capped carbon quantum dots (CQDs) prepared using a chemical oxidation method. The quenching of fluorescence intensity is proportional to the concentration of ceftazidime and cefepime over the range of 0.33-3.30 and 0.24-2.40 µg/mL, respectively. The mode of interaction between PEG2000-capped CQDs and ceftazidime/cefepime in aqueous solutions was investigated using a fluorescence, UV/Vis and Fourier transform infrared spectrometry (FTIR) at physiological pH. UV/Vis and FTIR spectra demonstrated that ground state compounds were formed through hydrophobic interaction the fluorescence quenching of CQDs caused by ceftazidime and cefepime. The quenching constants decreased with increases in temperature, which was consistent with static quenching., (Copyright © 2015 John Wiley & Sons, Ltd.)

Unlabelled: To find a more reasonable index to decide whether the universal quantitative NIR model needs to be updated and to develop a general method to update universal quantitative NIR models, the quantitative models for testing ceftazidime, water and arginine contents in ceftazidime for injection were taken as example. The study was performed by analyzing the similarity between new sample spectra and the training set spectra of the original models. At first, new samples of ceftazidime for injection were divided into five groups by cluster analysis. Then representative samples of each group were selected by sample selection strategy. Spectra of those samples were used to update the original quantitative models. The prediction deviation of the new ceftazidime powder injection samples by the models before and after updating was calculated. Decreasing the prediction deviation was regarded as the standard to decide if the updating was effective. At the same time, the correlation coefficient of new sample spectra and reference sample spectra was defined as the index to study the general method for model updating. (Reference sample refers to training set sample) Finally, the proposed method was validated by updating universal models for testing ceftazidime, water and arginine contents in ceftazidime powder injections. Results show that the correlation coefficient of new sample spectra and training set sample spectra of the original model was calculated within modeling wavelength range. It was proved that when correlation coefficient rT < 96.5%, the model needs to be updated. Accordingly, rT = 96.5% was set as the threshold. The quantitative models were updated by the method mentioned above. As a result, when testing ceftazidime for injection containing sodium carbonate using newly updated models, the average predicting deviation of ceftazidime contents decreased from 8.1% to 2.3%. And the average predicting deviation of water contents decreased from 2.2% to 0.3%. Meanwhile, with regard to samples containing arginine using the updated models, the average predicting deviation of ceftazidime contents decreased from 7.0% to 1.9%. The average predicting deviation of water contents decreased from 0.6% to 0.3%. And that of arginine contents de- creased from 2.3% to 0.4%., Conclusion: The newly updated models can be used for testing ceftazidime, water and arginine contens in ceftazidime for injection samples of domestic market. It is reasonable to set rT as the index to decide whether the model needs updating. Moreover, it is necessary to take PCA scores graph of new sample spectra and training set spectra of the original model into account. The proposed method for updating models can be used as a usual approach. And rT = 96.5% can be set as the threshold to determine whether the model needs to be updated.

A simple electrodeposition method is employed to construct a thin film modifier of palladium-gold nanoparticles (Pd-AuNPs) decorated multi-walled carbon nanotube (MWCNT) on the surface of glassy carbon electrode (GCE). Morphology and property of Pd-AuNPs-MWCNT have been examined by scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS). Electrochemical performance of Pd-AuNPs-MWCNT/GCE for detection of ceftazidime (CFZ) has been investigated by cyclic voltammetry (CV). This nanostructured film modified electrode effectively exhibited enhanced properties for detection of ceftazidime (CFZ). The effects of various experimental variables such as, the amount of casted MWCNT, time and potential of deposition of metal nanoparticles and the pH of the buffered solution on the electrode response are optimized. The proposed electrode showed a linear dynamic range of 0.05-50μM and the detection limit of 1nM for the CFZ. The modified electrode successfully supports the sensitive detection of trace amounts of the CFZ in pharmaceutical and clinical preparations., (© 2013.)

An HPLC method for the separation of seven cephalosporins [Cefepime (CEP), ceftazidime (CTA), ceftizaxime (CTI), ceftriaxone (CTR), cefotaxime (COT), cefixime (CIX) and cefoperazone (COP)] in human plasma and amniotic fluid has been developed. Optimization of the chromatographic method was performed in three steps: a series of initial experiments followed by two sets of experiments based on different experimental designs. The initial experiments were performed to decide the basic analytical requirements of the method. Then screening experiment fractional factorial design was used in order to decrease the number of parameters by eliminating parameters which having insignificant effect on responses. The parameters having significant effect were further optimized through a full factorial design. Having studied two responses (retention times and resolutions), a desirability function that assess the responses together, was used to find experimental conditions where the system generated desirable results. The desirable results were obtained with XTerra C18 (250 mm x 4.6mm, 5 microm i.d.) column, 40 mM phosphate buffer, pH 3.2, 18% MeOH, 0.85 mL min(-1) flow rate and 32 degrees C column temperature. Gradient elution with MeOH was applied. A simple and efficient solid-phase extraction was applied for the preparation of plasma and amniotic fluid samples. The validation parameters of the method were evaluated in accordance with ICH guideline. The method validated was applied to the analysis of CEP and COP in maternal venous, fetal venous and fetal arterial plasma, and to the analysis of CIX in maternal venous plasma and amniotic fluid.

A new UV spectrophotometric method was developed for quantitative evaluation of ceftazidime preparations. The UV detector was set at 255 nm. Beer's law is obeyed in the concentration range of 7.0-14.0 microg/mL. The method was found to be selective, linear, accurate, and precise in the specified ranges. Intra- and interday variability for the method were <2% relative standard deviation. Common excipients used as additives in pharmaceutical preparations do not interfere with the proposed method. This method was successfully used for quantification of ceftazidime in pure form and in pharmaceutical preparations.

Purpose: The data describing the compatibility of tobramycin and ceftazidime in icodextrin-based peritoneal dialysis (PD) solution is limited. The objective of this study was to assess the chemical stability of tobramycin and ceftazidime in icodextrin PD solution in polyvinyl chloride containers., Methods: Commercially available 2-L bags of icodextrin 7.5% PD solution were used for each sample. Nine tobramycin study samples were prepared by adding 80 mg tobramycin HCl to each bag. Nine ceftazidime samples were prepared by adding 1000 mg ceftazidime to each bag. Three bags of tobramycin-icodextrin solution were stored under each of the following conditions: refrigeration (4 degrees C), room temperature (25 degrees C), and body temperature (37 degrees C). Three bags of ceftazidime-icodextrin solution were also stored at each of the respective temperatures. Samples were withdrawn from each bag immediately after preparation and at predetermined intervals (1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, and 336 hours after preparation). Solutions were visually inspected for precipitation, cloudiness, and discoloration at each sampling interval. All samples were immediately frozen (-80 degrees C) after collection and stored prior to assay. Total concentrations of tobramycin and ceftazidime in dialysate fluid were determined by high-performance liquid chromatography. The last time point when tobramycin or ceftazidime concentration was >90% from baseline was used to denote stability., Results: All solutions were clear in appearance and no color change or precipitation was observed during the study. For tobramycin, under refrigeration, a mean of 94.6%+/-2.3% of the initial concentration remained at 336 hours (14 days); at room temperature, 90.5%+/-4.3% remained at 168 hours (7 days); at body temperature, 90.0%+/-8.1% remained at 24 hours. For ceftazidime, under refrigeration, a mean of 98.0%+/-0.3% of the initial concentration remained at 168 hours (7 days); at room temperature, 91.6%+/-2.0% remained at 48 hours; at body temperature, 93.9%+/-1.1% remained at 8 hours. Stability was not assessed beyond these respective time points., Conclusion: Premixed tobramycin-icodextrin PD solution remains stable for 336 hours (14 days) when refrigerated (4 degrees C) and for 168 hours (7 days) at room temperature (25 degrees C). Ceftazidime-icodextrin PD solution is stable for 168 hours and 48 hours, respectively, when stored at 4 degrees C and 25 degrees C. It is recommended that the bags be kept refrigerated whenever possible. Tobramycin-icodextrin solution stored at body temperature was stable up to 24 hours, and ceftazidime-icodextrin solutions up to 8 hours, permitting the practice of pre-warming solutions prior to administration.

A simple, accurate and rapid method for simultaneous analysis of vancomycin and ceftazidime in cerebrospinal fluid (CSF), utilizing high-performance liquid chromatography (HPLC), has been developed and thoroughly validated to satisfy strict FDA guidelines for bioanalytical methods. Protein precipitation was used as the sample pretreatment method. In order to increase the accuracy, tinidazole was chosen as the internal standard. Separation was achieved on a Diamonsil C18 column (200 mm x 4.6mm I.D., 5 microm) using a mobile phase composed of acetonitrile and acetate buffer (pH 3.5) (8:92, v/v) at room temperature (25 degrees C), and the detection wavelength was 240 nm. All the validation data, such as accuracy, precision, and inter-day repeatability, were within the required limits. The method was applied to determine vancomycin and ceftazidime concentrations in CSF in five craniotomy patients.

Two spectrophotometric methods for the determination of ceftazidime (CFZM) in either pure form or in its pharmaceutical formulations are described. The first method is based on the reaction of 3-methylbenzothiazolin-2-one hydrazone (MBTH) with ceftazidime in the presence of ferric chloride in acidic medium. The resulting blue complex absorbs at lambdamax 628 nm. The second method describes the reaction between the diazotized drug and N-(1-naphthyl)ethylenediamine dihydrochloride (NEDA) to yield a purple colored product with lambdamax at 567 nm. The reaction conditions were optimized to obtain maximum color intensity. The absorbance was found to increase linearly with increasing the concentration of CFZM; the systems obeyed the Beer's law in the range 2-10 and 10-50 microg mL-1 for MBTH and NEDA methods, resp. LOD, LOQ and correlation coefficient values were 0.15, 0.79 and 0.50, 2.61. No interference was observed from common excipients present in pharmaceutical formulations. The proposed methods are simple, sensitive, accurate and suitable for quality control applications.

A rapid, accurate, and sensitive high-performance liquid chromatographic (HPLC) method was developed and validated for the determination of ceftazidime in pharmaceuticals. The method validation parameters yielded good results and included range, linearity, precision, accuracy, specificity, and recovery. The excipients in the commercial powder for injection did not interfere with the assay. Reversed-phase chromatography was used for the HPLC separation on a Waters C18 (WAT 054275; Milford, MA) column with methanol-water (70 + 30, v/v) as the mobile phase pumped isocratically at a flow rate of 1.0 mL/min. The effluent was monitored at 245 nm. The calibration graph for ceftazidime was linear from 50.0 to 300.0 microg/mL. The values for interday and intraday precision (relative standard deviation) were <1%. The results obtained by the HPLC method were calculated statistically by analysis of variance. We concluded that the HPLC method is satisfactory for the determination of ceftazidime in the raw material and pharmaceuticals.

Good quality of antibiotic discs is a fundamental prerequisite to accurate antibiotic susceptibility tests. Capillary electrophoresis (CE) is a widely used method for quantitative analysis. Here, using ceftazidime as an example, we report an easy-to-perform strategy to determine ceftazidime content in discs. First, a serial of ceftazidime standard solutions was prepared to determine the detection linearity. Utilizing the background buffer containing 50 mmol/L Na2HPO4, 0.045 mmol/L beta-cyclodextrin and 3.15 mmol/L Tris (hydroxymethyl) aminomethane, ceftazidime of concentrations ranging from 1.875 to 60 microg/ml showed a linear response to detected peak areas. Subsequently, four kinds of ceftazidime discs were selected from different manufacturers. The discs were homogenized using 1 ml deionized water, and then detected by CE after filtration. The results showed that one kind of discs were of poor quality as further confirmed by disc diffusion tests using standard strains. This study proved the potential of CE as an easy choice to perform disc quality control under appropriate conditions.

Ceftazidime (CFZ) is a broad spectrum parenteral beta-lactam antibiotic of the cephalosporin family. This paper reports the development and validation of an agar diffusion microbiological assay using the cylinder-plate method for determination of CFZ in powder for injection. The validation carried out yielded good results in terms of linearity, precision, accuracy, selectivity, and robustness. The assay is based on the inhibitory effect of CFZ upon the strain of Pseudomonas aeruginosa ATCC 27853 used as the test microorganism. The results of the assays were treated statistically by analysis of variance and were found to be linear (correlation coefficient = 0.999998) in the selected range of 8.0-32.0 microg/mL; precise [repeatability: relative standard deviation (RSD) = 1.11%; intermediate precision: between-day RSD = 1.37% and between-analyst RSD = 1.41%]; and accurate. The selectivity of the bioassay was evaluated by analysis of degraded samples at 50 degrees C, and the results were compared with a pharmacopeial liquid chromatographic method at the time 0, 24, and 48 h. The results demonstrated the validity of the proposed bioassay, which allows reliable quantitation of CFZ in pharmaceutical samples and can be used as a useful alternative methodology for CFZ analysis in routine quality control.

A high performance liquid chromatographic (HPLC) method for the determination of ceftazidime and impurities in ceftazidime drug was developed and verified. An Alltima C18 column (250 mm x 4.6 mm, 5 microm) was used as the analysis column. Acetonitrile and phosphate buffer (22.6 g/L aqueous solution of ammonium dihydrogen phosphate, adjusted to pH 3.9 with 10% (v/v) phosphoric acid) were used as mobile phases with gradient elution at a flow rate of 1.3 mL/min. The column temperature was kept at 35 degrees C, and the detection wavelength was set at 255 nm. Fourteen impurities could be well separated. The assay exhibited a good linearity in the ceftazidime concentration range of 0.267-1069 microg/mL with a correlation coefficient of 1.0000. The limits of the quantitation and qualification of ceftazidime were 3.1 ng and 0.93 ng, respectively. The relative standard deviations (RSDs) of the interday and intraday (n=3) determinations at three concentration levels were 0.72% and 0.91%, respectively. At 4 degrees C ang under darkness, ceftazidime solution was stable for 24 h. The developed method is superior to the counterparts in British and Japanese pharmacopeias in the number of the impurities separated and detected.

A simple, sensitive, and specific biodiffusion assay for the antibacterial ceftazidime was developed using a strain of Staphylococcus epidermidis (ATCC 12228) as the test organism. Ceftazidime was measured in powder for injection at concentrations ranging from 100 to 400 microg/mL. The calibration graph for ceftazidime was linear (r2 = 1), and the method validation showed that it was precise (relative standard deviation = 0.415) and accurate. The results obtained by biodiffusion assay were statistically calculated by linear parallel model and by means of regression analysis and were verified using analysis of variance. It was concluded that the microbiological assay is satisfactory for in vitro quantification of the antibacterial activity of ceftazidime in pharmaceuticals.

Background and Objectives: Laser Raman spectroscopy is an inelastic light scattering technique able to characterize molecules in aqueous environments. The purpose of this work is to develop a non-contact and non-invasive spectroscopic method to identify and eventually quantify the presence of medicines (e.g., antibiotics) and physiological substances (e.g., glucose) in the aqueous humor of the eye., Study Design/materials and Methods: A new laser light delivery probe has been developed and adapted to a Raman spectroscopic system with the ability of favorable collection of the Raman light at 90 degrees scattering geometry while scanning the anterior chamber of the eye. Different amounts of ceftazidime, amphotericin B, and glucose had been injected in the aqueous humor of porcine eyes, maximum 24 hours after death and extraction, in-vitro. Raman measurements were excited with a visible (514.5 nm) laser beam at a power of 25 mW and an exposure/acquisition time of 1 second., Results: The specific collection optics and Raman analysis components used in the present work have resolved the Raman signatures of probed molecules and low concentrations of ceftazidime (0.9 mg/mL), amphotericin B (9 microg/mL), and glucose (2 mg/ml) separately injected in the anterior chamber of porcine eyes were detected in vitro., Conclusion: This special illumination design gives the opportunity of avoiding the direct exposure to the laser light of basic cordial tissues of the eye, like lens and retina, although an optimum collection of scattered light is accomplished. Concentrations close to the minimum inhibitory concentration (MIC) have been detected for ceftazidime and amphotericin b; the detection of glucose has been realized at concentrations close to the early pathological levels of patients with diabetes., (Copyright 2006 Wiley-Liss, Inc.)

Background: Peritonitis is the single most common complication in children maintained on continuous cycling peritoneal dialysis (CCPD) and a significant cause of morbidity. Recent consensus guidelines for the treatment of peritonitis in children receiving peritoneal dialysis recommend the combined intraperitoneal administration of ceftazidime with either a first-generation cephalosporin or vancomycin. The objective of this study is to determine whether a continuous maintenance dose of intraperitoneal ceftazidime in the absence of a loading dose would maintain adequate serum and dialysate concentrations to be effective in the treatment of peritonitis., Methods: Five ambulatory patients on CCPD therapy were studied with continuous intraperitoneal administration of ceftazidime (125 mg/L). Blood, dialysate, and urine samples were collected at specified intervals during a 24-hour period. Ceftazidime concentrations were measured by using a high-performance liquid chromatography assay., Results: Mean serum concentrations at completion of the short rapid cycles and at 24 hours were 28.92 +/- 13.64 and 23.92 +/- 11.93 microg/mL, respectively. Serum bioavailability at 24 hours was 74% +/- 6%. Mean dialysate concentrations at completion of the short rapid cycles and at 24 hours were 87.43 +/- 19.18 and 32.06 +/- 6.27 microg/mL, respectively. All 5 patients achieved serum and dialysate ceftazidime concentrations greater than the mean inhibitory concentration within 4 hours., Conclusion: In adolescent patients on CCPD therapy, a continuous maintenance dose of intraperitoneal ceftazidime in the absence of a loading dose achieves serum and dialysate levels greater than the mean inhibitory concentration of sensitive organisms within 4 hours that persist for 24 hours.

The influence of temperature and relative air humidity on the stability of ceftazidime in two different pharmaceutical preparations was investigated. The degradation of the substance studied was determined: (a) in dry air at 373, 378, 383, 388 and 393 K; (b) at air humidity RH = 76.4% at 323, 333, 343, 353 and 358 K; (c) in the humidity range 25.0 - 76.4% at 358 K. The decomposition of ceftazidime in these conditions is a first-order reaction relative to substance concentration. The kinetic and thermodynamic parameters of the degradation of ceftazidime were calculated and compared for the two pharmaceuticals. The study was conducted using the HPLC method on LiChrosorb RP-18 columns (250 x 4 mm) with 9% acetonitrile in 0.1 mole/L ammonium acetate as mobile phase and detection at 254 nm.

Cefepime has been examined for stability, potential liberation of degradation products and compatibility with other drugs under conditions mimicking its potential use by continuous infusion in cystic fibrosis and intensive care patients (5-12% w/v solutions; temperatures from 20 to 37 degrees C; 1 h contact at 25 degrees C with other drugs frequently co-administered by intravenous route to these types of patients). Ceftazidime was used as a comparator based on a previous normative study with this antibiotic for the same indications. Based on a limit of max. 10% degradation, cefepime can be considered stable for a maximum of 24 h at 25 degrees C, but for only approximately 14 h at 30 degrees C, and for <10 h at 37 degrees C. Cefepime released so far unidentified degradation products if maintained at >30 degrees C for >12 h as shown from a marked increase in pH and from the development of a strong red-purple colour. Incompatibilities were observed with erythromycin, propofol, midazolam, phenytoin, piritramide, theophylline, nicardipine, N-acetylcysteine and a concentrated solution of dobutamine. We conclude that: (i) cefepime cannot be used safely by continuous infusion if containers are kept for more than a few hours at 37 degrees C (as will be the case for cystic fibrosis patients if using portable pumps carried under clothes); (ii) caution must be exercised in intensive care patients if the temperature and co-administration of other drugs is not kept under tight control. The nature and safety of the cefepime degradation products need to be studied further.

The stability of ceftazidime in 5% dextrose injection and 0.9% sodium chloride injection when stored in a different disposable infusion device was determined. Solutions of ceftazidime 40 mg/ml were used to fill the drug administration devices. Stability was determined for both 5% dextrose injection and 0.9% sodium chloride injection solutions at 37 degrees C in four disposable infusion devices. Ceftazidime and its mean degradation product, pyridine, were simultaneously assayed in triplicate by a stability-indicating high-performance liquid chromatographic (HPLC) method. This method was simple, sensitive (limit of quantitation (LOQ), 2 ng injected for both compounds), rapid (run time was 7 min) and precise (mean recovery was 100.5+/-2.9 and 103.6+/-1.9% for pyridine and ceftazidime, respectively). The ceftazidime stability in the 5% dextrose solution was lower than in the 0.9% sodium chloride solution. When stored at 37 degrees C in a disposable infusion device, the stability of the ceftazidime is included in large hourly range, depending strongly on the manufacturer. The stability of ceftazidime exceed 19 h in none studied cases. The pyridine formed in 24 h was in the range of 100-400 mg depending on devices and infusions.

Cefotaxime sodium (CX) and Ceftazidime pentahydrate (CZ) are peptidomimetic cephalosporins (CPS) which exist as zwitterionic compounds at physiological pH and because of this reason they are not absorbed appreciably on peroral administration. The permeability of these compounds can be increased transiently by altering membrane characteristics of absorptive epithelium by use of sorption promoters (SPs). In present work a simple validated HPLC method utilizing isocratic mobile phase and having short retention times for CX and CZ is developed which can be used to monitor their concentrations in Kreb's Ringer Bicarbonate (KRB) solution in in vitro intestinal sac absorption model. The same was utilized to determine apparent permeability coefficients and absorption profiles of CPS by modified Wilson-Wiseman method. The CPS were analysed by the reverse phase HPLC method using Shim-pack C18 column. The mobile phase used was of isocratic composition with phosphate buffer (pH 7.0, 3.5 g/l of KH(2)PO(4) dissolved in 0.03 M Na(2)HPO(4).2H(2)O) and methanol in proportion 85:15 for CZ and 70:30 for CX. The flow rate was 1 ml/min and quantitative determinations were carried out at 254 nm at 25 degrees C. The method was found specific because none of the proposed SPs, components of KRB and intestinal sac artefacts interfered with the drug peaks. The drug concentration versus area under peak relationship was found to be linear in concentration range of 0.25-20.0 microg/ml. The recovery studies, intraday variation, interday variation and interanalyst variation were within statistical limits. The limit of detection (LOD) was 95.0 and 100.0 ng/ml for CZ and CX, respectively. The limit of Quantitation (LOQ) was 240.0 and 250.0 ng/ml for CZ and CX, respectively. The proposed method was found to be rapid and selective and hence applied for continuous monitoring of CPS in in vitro intestinal sac absorption studies.

A sensitive and rapid HPLC assay for the determination of the beta-lactam antibiotics ceftazidime and meropenem in serum and bronchial secretions is described. HPLC-integrated sample preparation allows direct injection of serum samples without any pretreatment. Sputum samples need only a simple homogenisation and volume measurement but no liquefying reagents are necessary. The inline extraction technique is realized by automatically switching from the extraction column to the analytical column. After the matrix passed the extraction column, the retained analyte is quantitatively transferred to the analytical column where separation by isocratic HPLC is performed. Ceftazidime and meropenem are detected according to their absorption maxima at 258 and 296 nm, respectively. The detection limit of both antibiotics is estimated to be better than 0.5 microg/ml in serum as well as in sputum samples. The described procedure allows determination of the antibiotics within 30-45 min, thereby facilitating drug monitoring in clinical routine.

The aim of this study was to evaluate, using high-performance liquid chromatography, the concentration of ceftazidime in agar released from an E test strip, sampling at the edge of the strip at different points (1, 2, 4, 8, 16, 32, 64, and 128 microg/ml) at 6, 15, and 24 h after its deposition on uninoculated plates. From 6 to 24 h, the ceftazidime concentration in agar increased at the graduations 1, 2, and 4 microg/ml (+140, +82, and +58%, respectively), remained fairly constant at 8 microg/ml (-1.9%), and decreased at 16, 32, 64, and 128 microg/ml (-25, -44, -36, and -58%, respectively). In the 6-24 h range, the ceftazidime concentrations between 16 and 1 microg/ml were +/-1 serial dilution of the values reported on the strip, confirming the accuracy of the E test in agar.

Objective: To assess the stability of an extemporaneously prepared ceftazidime eye-drop., Method: Ceftazidime was formulated at a concentration of 5% w/v as an eye drop, using Sno Tears, an artificial tear solution containing polyvinyl alcohol, as a vehicle. Two batches of the formulation were stored in 10 ml eye drop bottles at 7 and 25 degrees C for up to 14 days. Ceftazidime and pyridine, its degradation product, were determined at intervals by HPLC., Results: A yellow coloration was evident after 7 days at 7 degrees C and after 24 h at 25 degrees C. Ceftazidime lost approximately 35% after 7 days storage at 25 degrees C. At 7 degrees C, the mean time to 10% degradation, determined by linear regression, was 11 and 8 days for the two batches. However, the lower 95% confidence limits were 8 and 5 days, respectively. Pyridine levels increased during storage. The mass balance between ceftazidime remaining and pyridine formed was close to 100% during the early part of storage. By the end of storage, the balance had reduced to around 95% at 7 degrees C and 80% at 25 degrees C. This discrepancy may be due to sorption of pyridine to the butyl rubber bottle closure. The pH remained in the range 6-7 throughout the storage period., Conclusion: The formulation may be stored for 5 days in the refrigerator.

The stability of aqueous reconstituted ceftazidime injection vials containing ceftazidime pentahydrate blended with anhydrous sodium carbonate was investigated in different storage conditions (4 degrees C and 10 degrees C for 7 days in a refrigerator, 20 and 30 degrees C for 24 h) with validated HPLC and (micellar) CE methods. Stability indicating data were obtained for ceftazidime and two degradation products: pyridine and the delta2-ceftazidime isomer. Other degradation products were also identified (the complementarity of the two used experimental procedures was useful in such exercise) and characterized by their UV spectra and retention times. Stability data (7 days at 4 degrees C in a refrigerator and 18 h at room temperature) resulted in agreements with the manufacturers prescription and point out the need of a strict temperature control of the refrigerator's compartment used to store the reconstituted solution.

Ceftazidime is currently recommended as an alternative first-line agent in the treatment of peritonitis and for Pseudomonas peritonitis. The pharmacokinetics of intermittent intraperitoneal (i.p.) ceftazidime have been poorly characterized. This study was designed to characterize the pharmacokinetic disposition of a single dose of ceftazidime in anuric and non-anuric CAPD patients, over 48 hours. This was a prospective, open label, pharmacokinetic study. The study was conducted in an independent, outpatient dialysis center. Ten volunteer continuous ambulatory peritoneal dialysis (CAPD) patients with and without residual renal function, no peritonitis or antibiotics in the previous 4 weeks, and on CAPD for at least 2 months were recruited. Patients received a single dose of i.p. ceftazidime (15 mg/kg) in the first daytime exchange over a 6-hour dwell, after an overnight dwell. Serum, urine, and dialysate were collected over a 48-hour period. A high-pressure liquid chromatography (HPLC) assay was used to analyze ceftazidime in these samples. Pharmacokinetic parameters were calculated. Six of the 10 patients were non-anuric with a mean residual renal creatinine clearance of 2.9 +/- 1.6 mL/min. The mean +/- SD bioavailability was 72% +/- 14%, and the volume of distribution was 0.34 +/- 0.08 L/kg. The mean serum elimination half-life of 22 +/- 5 hours. The peritoneal clearance was 5.74 +/- 1.6 mL/min. No difference was detected between anuric and nonanuric patients. Mean plasma and dialysate concentrations at 24 hours were 24 +/- 6 microg/mL and 18 +/- 7 microg/mL, respectively, and were 12.0 +/- 3.6 microg/mL and 7.4 +/- 3.1 microg/mL at 48 hours, respectively. Once-daily i.p. dosing of ceftazidime achieves serum and dialysate levels greater than the MIC of sensitive organisms over 48 hours.

A micellar electrokinetic chromatographic method for the separation and quantification of ceftazidime, its delta2-isomer and pyridine (two ceftazidime related impurities) was developed and validated. Optimised conditions were obtained using an electrolyte system consisting of 25 mM sodium tetraborate, at pH 9.2, and 75 mM sodium dodecylsulphate. A limit of detection of 0.2 microg ml(-1) and a limit of quantitation of 0.6 microg ml(-1) were estimated for pyridine and delta2-isomer: this means that levels of < 0.1% of pyridine and delta2-isomer in ceftazidime can be determined. Calibration curves for all analytes were linear over the studied ranges with correlation coefficients >0.999. Good reproducibility for migration times and corrected peak areas were achieved (RSD % 0.3 and 1.0, respectively). The results demonstrate that the method is reproducible, accurate and appropriate for ceftazidime assay in pharmaceutical samples.

The direct quantification of antibiotics in agar allows one to study the quality of the agar matrix, the kinetics of diffusion and the bacteria-antibiotic interaction. Mueller-Hinton agar (MHA) plates from three manufacturers were tested using HPLC and the disc diffusion test of ceftazidime (CAZ). Notable differences in the chromatographic profiles of MHA plate extracts from OXOID, DID and Becton Dickinson (BD) were shown, with a higher CAZ concentration after 24 h a 6 mm in BD P. aeruginosa inoculated plates (5.1 +/- 1.7 micrograms/ml, n = 6) vs. OXOID and DID (1.6 +/- 0.3 micrograms/ml, n = 12). BD plates gave also a different inhibition zone diameter (26 +/- 0.5 mm, n = 3) with respect to DID and OXOID (29 +/- 0.5 mm, n = 3).

Twenty-five children with otitis media with effusion received ceftazidime 50 mg/kg intravenously before bilateral myringotomy with insertion of tympanostomy tubes. Concentrations of ceftazidime measured in serum and middle ear fluid exceeded 4 mg/L (i.e., largely above the minimal inhibitory concentrations for the gram-negative pathogens commonly recovered from children with otitis media) for at least 4 hours. Mean peak concentrations occurred 30 to 90 minutes after the injection and reached 11 to 14 mg/L. These results are in keeping with the clinical efficacy of ceftazidime in the treatment of chronic middle ear infections in children.

The antibacterial activity of ceftriaxone and ceftazidime against Gram-positive and Gram-negative bacteria, clinically isolated from patients hospitalized in intensive care unit, was compared in vitro. The study was performed using a dynamic model in which the human kinetics of the drugs after i.m. administration were simulated. The antibacterial activity was tested by determining viable colony forming units (CFU) of bacteria/ml. Kill curves were constructed by plotting the log CFU/ml versus time. Simultaneously with CFU detection, ceftriaxone and ceftazidime concentrations were assayed by HPLC. The results obtained show that ceftriaxone and ceftazidime exert the same killing activity against the highly sensitive strains tested. Against the less sensitive strains, both drugs have initial good killing activity followed by bacterial regrowth using ceftriaxone while no regrowth was observed using ceftazidime. These data indicate that both ceftazidime and ceftriaxone exhibit primarily time-dependent bacterial killing. Moreover, only unbound drug appears to be effective, so only free drug should be considered in the pharmacokinetic-pharmacodynamic interaction.

A simple competitive enzyme-linked immunoassay for the antibiotic ceftazidime and structurally similar beta-lactam antibiotics has been developed which can be performed directly on the surface of a cellulose nitrate filter used to capture the airborne drug during workplace monitoring for health and safety purposes. Post sampling analysis is performed on the filter retained within the air sampler. It involves two steps; the first a 10 min incubation in which the captured drug is dissolved and competes with drug immobilised within a protein conjugate on the surface of the filter for an enzyme-labelled antibody reagent, and the second, following washing under vacuum in situ, a 5 min incubation of substrate solution when colour develops on the spot at the location of the immobilised drug-protein conjugate. The intensity of the spot can be assessed visually within the sampler to ascertain the presence or absence of captured drug, or quantitative results can be obtained using an optical scanner. The intensity of the spots in linear from 10 ng to 1 microgram (r2 = 0.9996, n = 3) and the limit of detection is 1.9 ng of captured drug (10 ng for visual discrimination between this standard and the zero). The assay is precise with between-assay RSD values of < 4% over the linear range of the assay.

The ceftazidime concentration in agar plates inoculated with Pseudomonas aeruginosa was determined by high-performance liquid chromatography at fixed points (3, 6, 9, 12, and 15 mm) from the disk center and at fixed times (2, 4, 6, 16, and 24 h) to study the antibiotic kinetics of diffusion. A statistical difference between the concentrations determined in the presence of microorganisms and in uninoculated plates after 16 and 24 h was evidenced and was probably ascribable to the drug hydrolysis carried out by the induced beta-lactamase.

A pharmacokinetic profile of the antibiotic ceftazidime was established for perilymph, cerbrospinal fluid (CSF) and plasma in 12 guinea pigs using the technique of high-performance liquid chromatography. The mean peak levels of 13.35 mg/l in perilymph and 140.54 mg/l in plasma were reached within the first hour after a single intravenous dose of 100 mg/kg. The CSF mean peak level of 5.36 mg/l, however, was not attained until 3 h after injection. The half-life was about 4 h in perilymph, more than 6 h in CSF and less than 2 h in plasma. Six hours following administration, the perilymph drug concentration remained higher than the plasma level. The study indicates that ceftazidime has excellent penetration into perilymph. It is concluded that ceftazidime should be a very useful agent in the treatment of bacterial labyrinthitis caused by susceptible organisms.

Transplacental passage of ceftazidime was studied in 17 women with second-trimester pregnancy which had to be discontinued for medical causes. A single intramuscular injection of the antibiotic resulted in creation of therapeutically active concentrations in fetal blood and organs, amniotic fluid, and placenta. Transplacental passage of ceftazidime from the mother to the fetus was 19.12%, diffusions to the amniotic fluid 14.46%, diffusion to the placenta 48.46%. Ceftazidime may be effective for the prevention and therapy of fetal intrauterine infection and chorioamnionitis.

A simple and rapid enzyme linked immunosorbent assay (ELISA) method for the cephalosporin, ceftazidime, has been developed for the quantification of this antibiotic in solutions that have been eluted from filters following the capture of air samples in the workplace. The assay has the specificity, sensitivity and precision necessary for its use in determining airborne concentrations of ceftazidime in the workplace as part of an occupational health and hygiene programme.

The use of antibiotics in patients with severe acute pancreatitis (stage II and III) is indicated since bacterial complications are the most common cause of death in these patients. In the present study the penetration of ceftazidime into pancreatic juice, into healthy and chronically inflamed pancreatic tissue as well as into necrotic regions in cases of severe acute pancreatitis was investigated. A peak concentration of 12.9 +/- 5.9 mg/l was found 60 min after intravenous administration of 35 mg/kg of the drug, which is 32% of the corresponding serum levels. Pancreatic tissue concentrations varied between 9 and 79% of the corresponding serum levels, depending on the stage of inflammation. After five days of antibiotic treatment with doses of 2 g t.i.d., concentrations between 1.8 and 6.9 mg/kg were detected even in pancreatic necroses. This suggests that sufficient antibacterial levels of ceftazidime were present in all pancreatic compartments analyzed following administration of common therapeutic dosages. Therefore, from a pharmacokinetic point of view, ceftazidime could be a potentially effective drug for the treatment of pancreatitis.

The stability of ceftazidime solutions (100 and 200 mg/mL) in plastic syringes and glass vials under various storage conditions was examined. Solutions of ceftazidime 100 and 200 mg/mL in sterile water were placed in polypropylene plastic syringes or glass vials and stored (1) at 21-23 degrees C for up to 8 hours, (2) at 4 degrees C for up to 96 hours, (3) at -20 degrees C for 28 days and then 21-23 degrees C for up to 8 hours, (4) at -20 degrees C for 28 days and then 4 degrees C for up to 96 hours, (5) at -20 degrees C for 91 days and then 21-23 degrees C for up to 8 hours, or (6) at-20 degrees C for 91 days and then 4 degrees C for up to 96 hours. Samples were withdrawn from each syringe and vial at designated times and assayed by high-performance liquid chromatography. Solutions were judged to be stable if drug concentrations remained above 90% of the initial values. The number of particles in each container under each storage condition was also evaluated. Ceftazidime was stable under all storage conditions. In all containers, particulate matter was within USP specifications for small-volume injections, with no change in particle count as a result of the freezing and thawing. Ceftazidime in sterile water in either glass vials or plastic syringes is stable for 8 hours at room temperature or 96 hours at 4 degrees C when such storage occurs (1) immediately after constitution, (2) after 28 days of frozen storage, or (3) after 91 days of frozen storage.

The stability of ceftazidime (with arginine) and cefuroxime sodium was studied after storage in infusion-pump reservoirs at freezing and refrigerated temperatures and subsequent simulated administration over 24 hours at near-body temperature. Polyvinyl chloride reservoirs and glass vials were filled with ceftazidime (with arginine) or cefuroxime sodium at various concentrations, diluted in sterile water. Three reservoirs each of ceftazidime 30 and 60 mg/mL and of cefuroxime 22.5, 30, 45, and 60 mg/mL were stored for various times and at various temperatures. Three glass vials each of ceftazidime or cefuroxime 30 and 60 mg/mL were stored for 30 days at -20 degrees C, followed by 4 days at 3 degrees C and 24 hours at 30 degrees C. Samples obtained periodically during storage and during simulated administration were analyzed with high-performance liquid chromatography. Both drugs maintained at least 90% of their initial concentration under all of the test conditions except simulated administration at 30 degrees C, during which degradation accelerated. In portable infusion-pump reservoirs, ceftazidime 30 and 60 mg/mL and cefuroxime 30 and 60 mg/mL were stable for 30 days at -20 degrees C followed by 4 days at 3 degrees C; ceftazidime 30 and 60 mg/mL was stable for 10 days at 3 degrees C; and cefuroxime 22.5 and 45 mg/mL was stable for 7 days at 3 degrees C. However, the drugs may need to be administered over less than 24 hours when the pump reservoir is worn on the patient's body.

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)

Levels of ceftazidime (CAZ) in uninfected renal cysts of 25 patients were investigated. Seventeen patients received 2 g CAZ about 140 min prior to puncture of the cysts (group I), and eight patients were treated with 2 x 2 g CAZ one day before, and with a further dose of 2 g 2 h prior to puncture (group II). In eight cases (two of group I and six of group II) the concentration of the cyst fluid was also assessed at 4 h and 6 h after completion of the CAZ infusion. In group I, CAZ concentrations were 0.5 to 1.13, micrograms ml-1, mean 0.71; in group II CAZ concentrations were 3.6 to 6.7 micrograms ml-1, mean 5.55. At 4 h and 6 h after infusion the mean cyst concentrations were 4.4 and 2.9 micrograms ml-1, respectively.

Thirty-three patients who developed nosocomial pneumonia postoperatively were treated with ceftazidime, 4-6 g daily, over an average period of 7 days. Twenty-nine patients were evaluated; 13 (45%) patients were cured, five showed improvement, two relapsed, and one could not be assessed. X-rays of the chest showed no infiltrates in 17 out of the 29 cases (59%) after treatment. On the first day of treatment, ceftazidime concentrations in bronchial secretions of nine patients were estimated. The mean values of serum concentrations were: 15 min after infusion, 98 micrograms ml-1; 60 min, 63; 120 min, 44; 360 min, 20; 480 min, 13 micrograms ml-1. The mean values of the corresponding bronchial secretions were 2.9, 5.8, 10.2, 7.11 and 5.2 micrograms ml-1.

A procedure is described for the direct collection of bronchial or tracheal fluid samples on to paper discs. Using the procedure, the pharmacokinetics of ceftazidime in rabbit bronchial and tracheal fluids were compared with those in the respective wall tissue samples and in lung tissue. Concentrations appearing in lung tissue were approximately half those seen in bronchial or tracheal fluid or bronchial and tracheal wall tissue. Concentrations in these latter compartments were, in turn, four- to six-fold lower at all times than simultaneously-measured serum levels. The shape of the concentration/time curves were similar for all compartments sampled. The half life values were 63 to 64 min for respiratory tract concentrations and 59 min for serum levels. Percentage penetration from serum into the various compartments was 20.8% for bronchial fluid, 19.9% for tracheal fluid, 22.4% for bronchial wall, 20.0% for tracheal wall and 11.3% for lung tissue.