Antibiotic prophylaxis by low-dose cefaclor in children with vesicoureteral reflux.

Sulfamethoxazole/trimethoprim (SMX/TMP) and nitrofurantoin are the most frequently used agents for prophylaxis to reduce the risk of recurrent urinary tract infections (UTIs) in children with vesicoureteral reflux (VUR). Nitrofurantoin, however, is not available in Japan and increasing resistance of organisms to SMX/TMP has recently raised doubts about its effectiveness as a prophylactic agent. This study was conducted to investigate whether antibiotic prophylaxis using low-dose cefaclor can effectively reduce the risk of recurrent UTIs. Thirty-nine children (31 male, 8 female) with primary VUR were enrolled. Ages varied from 0.5 to 111 months (mean 10.6 months). A prophylactic dose of 5-10 mg cefaclor per kg per day was given 1-3 times daily depending on the patient's age. Mean duration of prophylactic treatment was 15.5 months. Eleven children (ten male, one female) developed breakthrough UTIs during a total of 606 months treatment (or about one further infection in 55 months). Resistance to cefaclor was noted in three organisms: Enterococcus spp., Morganella spp., and Pseudomonas spp. Evidence of antibacterial activity was present in the morning urine samples from all of seven children tested. Cefaclor was well accepted and tolerated by all subjects. None withdrew from the study because of side effects. These results suggest that cefaclor can be an alternative choice for prophylactic treatment because of its safety, good compliance and low rates of resistant Escherichia coli.

Determination of cefaclor by selective sample enrichment/clean-up on silica gel bonded polyelectrolyte in ion-exchange column chromatography.

A silica gel-bound cationic polyelectrolyte, poly[N-chloranil N,N,N',N'- tetramethylethylene diammonium dichloride], modified as ion-exchanger capable of molecular recognition of beta-lactam antibiotic, was used in solid phase extraction through column chromatography for a sample clean-up and enrichment of analyte from a dilute solution. The optimum and selective sorption conditions for a model antibiotic, cefaclor, were established. The high selectivity of polymer at pH 9.5 and flow rate as high as 5 ml/min were observed for the quantitative sorption of cefaclor. The desorption by 0.1 N HCl at flow rate of 0.1 ml/min and subsequent heating at 80 degrees C for 2 h allowed the antibiotic to be detected as corresponding oxazolone form in UV-spectrophotometric and differential pulse adsorptive stripping voltammetric measurements. The potential of the suggested approach was illustrated by estimating cefaclor in urine and blood plasma samples.

Indirect polarographic and cathodic stripping voltammetric determination of cefaclor as an alkaline degradation product.

Cefaclor is not reducible at a mercury electrode, but it can be determined polarographically and by cathodic stripping voltammetry as its initial alkaline degradation product which is obtained in high yield by hydrolysis of cefaclor in Britton-Robinson (B-R) buffer pH 10 at 50 degrees C for 30 min (reduction peak at pH 10, -0.70 V). Differential pulse polarographic calibration graphs are linear up to at least 1 x 10(-4) mol/l(-1). Recoveries of 93% of the cefaclor (n = 3) were obtained from urine spiked with 38.6 microg/ml(-1) using this polarographic method with 1 ml urine made up to 10 ml with pH 10 buffer. Using cathodic stripping voltammetry and accumulating at a hanging mercury drop electrode at - 0.2 V for 30 s, linear calibration graphs were obtained from 0.35 to 40 microg/ml(-1) cefaclor in B-R buffer pH 10. A relative standard deviation of 4.2% (eta = 5) was obtained, and the limit of detection was calculated to be 2.9 ng/ml(-1). Direct determination of cefaclor in human urine (1 ml of urine was made up to 10 ml with pH 10 buffer) spiked to 0.39 microg/ml(-1) was made (recovery 98.6%).

High-performance liquid chromatographic determination of loracarbef, a potential metabolite, cefaclor and cephalexin in human plasma, serum and urine.

A high-performance liquid chromatographic (HPLC) method is reported for the determination of a new carbacephem antibiotic, loracarbef, a hydroxylated analogue, and two cephalosporins, cefaclor and cephalexin, in plasma, serum, and urine. The antibiotics are extracted from plasma by means of C18 solid-phase cartridges. Urine samples are diluted with water and directly injected on the HPLC system. The HPLC system utilizes a Supelcosil LC-18-DB (250 mm x 4.6 mm I.D.) reversed-phase column and ultraviolet detection at 265 nm. The limit of quantitation is 0.5 micrograms/ml for each compound. Excellent correlation of plasma concentrations is shown between results determined by HPLC and those obtained by microbiological agar-well diffusion assays. Stability studies of loracarbef in human plasma show the antibiotic to be stable for at least 24 h at room temperature and for at least twelve months at -20 degrees C.

[Comparative pharmacokinetics of oral cephalosporins: cephalexin, cefaclor and cefadroxil (author's transl)]. / Vergleichende Pharmakokinetik oraler Cephalosporine: Cephalexin, Cefaclor und Cefadroxil.

In a randomized crossover study, the pharmacokinetics of two new cephalosporin antibiotics, cefaclor (CCL), and cefadroxil (CDX), were determined after oral administration of 1000 mg (capsules) on an empty stomach in 12 normal subjects in comparison to cephalexin (CEX). Serum concentrations were measured during a period of 8 h and urine recovery during 24 h. The significant parameters of bioavailability of an orally administered substance were determined. The maximum serum concentrations (ymax) were 38.8 +/- 8.1 mg/l (CEX), 34.6 +/0 7.8 mg/l (CCL), 33.0 +/- 5.4 mg/l (CDX); the areas under the curve were 93.0 +/- 14.8 h . mg/l (CEX), 74.5 +/- 9.9 h . mg/l (CCL), and 108.5 +/- 18.4 h . mg/l (CDX). In a further crossover study with 6 subjects, 1000 mg CEX and CDX were given during a standard breakfast. The ymax of CEX decreased to 23.1 +/- 6.6 mg/l in contrast to CDX with an unchanged ymax of 32.7 +/- 3.4 mg/l.

[Pharmacokinetics of cefaclor and initial therapeutical experience (author's transl)]. / Zur Pharmakokinetik von Cefaclor und erste therapeutische Erfahrungen.

Twelve normal volunteers in the fasting state were given 1000 mg cefaclor, and the serum and urine concentrations over 8 h and 24 h respectively were measured. The average peak serum concentration was 34.6 +/- 7.8 mg/l, this value being reached after 65.2 +/- 11.1 min; the half-life was 42.5 +/- 8.3 min. In another six volunteers the absorption of 500 mg of 'cefaclor following administration in the fasting state and after a test breakfast was studied. The peak serum concentrations after administration in the fasting state were 16.1 +/- 3.2 mg/l, and after a meal 12.5 +/- 1.9 mg/l; the areas under the curve did not differ. The low recovery rate of cefaclor in urine observed in this series of investigations could be partly explained by the inactivation of the substance in urine. Cefaclor was administered therapeutically to 23 patients, most of whom were suffering from bronchopulmonary infections and chronic pyelonephritis. The results of therapy were good in four patients, satisfactory in 13 patients and unsatisfactory in three patients. Intolerance was rare.

[Assay of cefaclor in serum and urine (including stability test) using high pressure liquid chromatography (author's transl)]. / Zum Nachweis von Cefaclor im Serum und Urin (einschliesslich Stabilitaätsprüfung) mit Hilfe der Hochdruckflüssigkeitschromatographie.

Using high pressure liquid chromatography (reverse phase method) a study was made of the stability of cefaclor dissolved in sodium citrate buffer, normal serum and urine and stored for different periods of time at 4 degrees C and 37 degrees C. In sodium citrate buffer (pH 4.0) and in urine (pH 6.0) no appreciable loss of activity of cefaclor occurred at either 4 degrees C or 37 degrees C, even after longer periods of storage (up to 24 h). Serum containing cefaclor stored at 37 degrees C lost about 4% of the active cefaclor after 30 min, 13% after 1 h and 20% after 2 h; no cefaclor could be detected after 24 h. The loss was lower during storage of serum containing cefaclor at 4 degrees C, and after 24 h 60% of the initial concentration of active cefaclor was found. Using a lichrosorb-NH2 column, it could be demonstrated that after 24 h storage of serum containing cefaclor, only phenylglycine, but not amino-chloro-cephem-carboxylic acid or cefaclor was present. After oral administration of 1 g cefaclor, cefaclor was present in the serum and urine of adult volunteers and only small amounts of phenylglycine and amino-chloro-cephem-carboxylic acid.

[Thin layer and high pressure liquid chromatography investigations with cefaclor in urine and serum (author's transl)]. / Dünnschicht- und Hochdruck-Flüssigkeitschromatographie mit Cefaclor in Urin und Serum.

After oral administration of 500 mg cefaclor, antibacterially active metabolites could not be detected in human urine using thin layer chromatography followed by bioautography. Degradation products of cefaclor could also not be detected in the serum of human volunteers (n = 10) using high pressure liquid chromatography with a reversed phase system. Cefaclor was eluated as a single and homogenous peak with a retention period of 2.9 min. High pressure liquid chromatography for the measurement of cefaclor serum levels and a technique for preparation of serum samples are described. After administration of 500 mg cefaclor to volunteers (n = 10), the average peak serum concentration of 9.8 mg/l, determined by high pressure liquid chromatography, was observed after one hour. Four hours later the serum level was 0.3 mg/l. Using microbiological methods no statistically significant difference was obtained in comparison with the chromatography results. Some of the sera stored at -75 degrees C for four weeks showed a substantial loss of activity of cefaclor.