The in vitro activity of loracarbef, penicillin V, cefaclor and cefadroxil against log and stationary phase cultures of group A streptococci was compared. MICs and MBCs were determined with the broth dilution method and by a modified agar plate dilution technique where the beta-lactams were inactivated after the MICs were determined allowing inhibited but not killed organisms to grow on further incubation. The MICs of loracarbef and the two cephalosporins were 16-32 times higher than those of penicillin V. In plate dilution the MBC/MIC ratios of all agents were < or = 2 for log phase cultures. With stationary phase cultures, especially in the broth dilution test, the MBC/MIC ratios of loracarbef and the two cephalosporins were > or = 32 for a large number of strains. The phenotype response of stationary phase cultures to beta-lactam antibiotics may not only be related to the physiological status of the streptococci, to the culture conditions and to the beta-lactam under test. The present investigation indicated that the phenotypic response was also an intrinsic property of certain strains.
We determined the in vitro susceptibilities of eight Borrelia burgdorferi isolates to five oral cephalosporins. MICs for B. burgdorferi 297 were 23 micrograms/ml (cephalexin), 45 micrograms/ml (cefadroxil), 91 micrograms/ml (cefaclor), 0.13 microgram/ml (cefuroxime), 0.8 microgram/ml (cefixime), and 0.02 microgram/ml (ceftriaxone). When B. burgdorferi isolates were exposed to concentrations twice the MIC of cefuroxime, cefixime, or ceftriaxone, at least 72 h of incubation was required to kill 99% of the organisms.
The aerobic and anaerobic flora from gingival pockets of 49 dogs with severe gingivitis and periodontitis were cultured. The susceptibility of each isolate to four antimicrobial agents currently approved for veterinary use in the USA (amoxicillin-clavulanic acid; clindamycin; cefadroxil; and enrofloxacin) was determined. Amoxicillin-clavulanic acid (Clavamox Pfizer Animal Health) had the highest in-vitro susceptibility against all isolates (96%), all aerobes (94%) and all anaerobes (100%) tested. For gram-negative aerobes, enrofloxacin (Baytril, Bayer Corp.) had the highest in-vitro susceptibility activity. For bacteria associated with treatment of gingivitis, which typically are mixed aerobic/anaerobic and gram-positive/gram-negative organisms, the antimicrobial of choice for clinical use based on these susceptibility tests is amoxicillin-clavulanic acid.
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We examined the effect of antibiotic therapy on the clinical course of group A beta-hemolytic streptococcal (GABHS) pharyngitis in 260 children. After a throat culture had been obtained, each child was evaluated for the presence of predetermined signs and symptoms, and was then randomized in a double-blind manner to receive penicillin V, cefadroxil, or placebo. Of the 194 children with throat cultures positive for GABHS, 68 received penicillin V, 70 received cefadroxil, and 56 received placebo. Approximately 18 to 24 hours later, each patient returned for reevaluation. Significantly fewer children who had received either penicillin or cefadroxil had persistence of each of the three objective signs and each of the three subjective symptoms than did children who had received placebo. In addition, the evaluating physician, parents, and patients all believed that significantly fewer of the patients given antibiotic failed to demonstrate overall clinical improvement.
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Allergic subjects with a selective response to amoxicillin were chosen according to the following criteria: history of an immediate allergic reaction to amoxicillin, negative skin test responses to benzylpenicilloyl and minor determinant mixture of benzylpenicillin, negative RAST response to benzylpenicilloyl, and good tolerance to benzylpenicillin and phenoxymethyl penicillin challenges. In addition, subjects had to have a positive skin test response to amoxicillin and/or positive RAST response to amoxicilloyl or, if these test results were negative, a positive challenge test response to amoxicillin. In vivo cross-reactivity to cefadroxil was assessed by giving oral cefadroxil at increasing doses from 5 to 500 mg. In vitro cross-reactivity was determined by RAST inhibition studies with amoxicilloyl RAST disks and the following monomeric conjugates in the fluid phase: amoxicillin-butylamine, cefadroxil-butylamine, and the side chain para-hydroxy-phenylglycine. Tolerance to cefamandole was determined by giving 100 mg and then 500 mg parenterally.
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A fast and simple high-performance liquid chromatographic procedure for the determination of cefatrizine, an orally active cephalosporin, in serum and urine is proposed. Reversed-phase liquid chromatography on the octoadecylsilane chemically bonded microparticulate packing, using methanol in 0.03 M sodium phosphate buffer (pH 5) as eluent, was used to separate and quantitate the antibiotic. The samples were analysed after deproteinization with trichloroacetic acid and injection of the clear supernatant. The accuracy and reproducibility of the procedure were investigated by determination of the cefatrizine content in spiked serum and urine samples, using cephradine as the internal standard.
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Eight Italian clinical centers carried out a controlled double-blind/double-dummy evaluation of the effectiveness of two different administration schedules of cefatrizine, an orally active cephalosporin. The first schedule provided for once-a-day administration of 1.5 gm of the drug, and the second one for twice-a-day administration of 0.75 gm. The trial included 160 patients affected by bacterial diseases of the respiratory apparatus. The two drug administration schedules were found to be equivalent in clinical and bacteriological results and in tolerability.
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Pharmacokinetics of cefadroxil, a new orally semisynthetic cephalosporin, was studied in 5 subjects with normal renal function and in 20 patients with varying degrees of renal insufficiency. All subjects received 1,000 mg per os in a single dose and the elimination phase was studied. In healthy subjects, elimination half-life (T1/2) was 1.39 +/- 0.06 h. Apparent volume of distribution was 0.305 liters/kg and area under the serum concentration versus time curve AUC was 82.94 +/- 19.98 microgram . h/ml. Peak level averaged 25.72 +/- 4.68 microgram . ml-1 and occurred at 1.20 +/- 0.45 h postingestion. 93.0 +/- 3.6% of the dose was recovered in urine during the first 24 h. Renal and serum clearance averaged 166.7 and 172.4 ml . min-1/1.73 m2, respectively. In patients with renal insufficiency, T1/2 increased to 25.49 h in severe chronic renal failure. Renal impairment did not significantly modify volume of distribution. During a 6- to 8-hour hemodialysis session, antibiotic serum concentrations decreased by 75.4 +/- 5.6%. Dosage schedules could be suggested on the basis of these pharmacokinetic results.
To compare the bioavailability of two cefadroxil capsule (500 mg) formulations (Cefadroxila from Eurofarma Laboratórios Ltd, Brazil, as test formulation and Cefamox from Bristol-Myers Squibb, Brazil S.A. as reference formulation) in 24 volunteers of both sexes.
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The apparent functional molecular mass of the kidney peptide/H(+)-symporter was determined by radiation inactivation in brush-border membrane vesicles (BBMV) of rat kidney cortex. Purified BBMV were irradiated at low temperatures with high energy electrons generated by a 10-MeV linear accelerator at doses from 0 to 30 megarads. Uptake studies were performed with [3H]cefadroxil, a beta-lactam antibiotic which serves as a substrate for the kidney peptide/H(+)-symporter. Inhibition of influx of [3H]cefadroxil into BBMV was used to determine the functional molecular mass of the transporter. Additionally, direct photoaffinity labeling of the transport- and/or binding proteins for [3H]cefadroxil in control and irradiated BBMV was performed to determine the molecular mass of the putative transporter by SDS-polyacrylamide gel electrophoresis. Initial rates of pH-gradient dependent uptake of [3H]cefadroxil decreased progressively as a function of radiation dose. The apparent radiation inactivation size (RIS) of the transport function was found to be 414 +/- 16 kDa. Direct photoaffinity labeling yielded labeled membrane proteins with apparent molecular masses of 130 kDa and 105 kDa, respectively. The proteins displayed different labeling characteristics with respect to incubation time, specificity and the response to irradiation. It appears that only a 105 kDa protein is directly involved in transport function since (a) only it showed a specific pH gradient dependent labeling pattern and (b) the covalent incorporation of [3H]cefadroxil into this protein decreased parallel to the loss of transport function in irradiated BBMV. The peptide/H(+)-symporter in kidney brush-border membranes therefore appears to have a monomer mass of 105 kDa and may function in an oligomeric arrangement.
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The average rates of antimicrobial resistance were low and did not increase between 2003 and 2012 in E. coli urinary isolates among Swedish nursing home residents. Antibiotic treatment during the previous month and hospitalisation during the previous six months predicted higher resistance rates.
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Four patients with anaphylaxis to cefaclor and 35 nonatopic controls never exposed to cefaclor were studied. Skin tests and oral challenges with this drug were performed. The specific IgE response to the antigenic determinant of cefaclor-human serum albumin (HSA) conjugate was compared in each patient. The serum specific IgE to cefaclor-HSA conjugate was detected using enzyme-linked immunosorbent assay (ELISA). Also, ELISA inhibition studies using various concentrations of cefaclor-HSA, HSA alone, and free cefaclor were performed, as were hapten inhibition studies using cefaclor, cephalexin, cefadroxil, ampicillin, ceftriaxone, and cefotaxime.
The pharmacokinetics of cefadroxil and cephalexin were examined following single oral doses of either 250, 500 or 1000 mg to a total of 36 healthy volunteers. The volunteers were divided into groups of 12 per dose-group and solution doses of cefadroxil or cephalexin were administered after an overnight fast according to a crossover design for the cephalosporins but not for doses. Serial blood and urine samples were collected from each individual and were analyzed for cefadroxil or cephalexin using validated HPLC assays with UV detection. The individual subject plasma concentration-time data for each cephalosporin were analyzed using noncompartmental methods. Profiles for cephalexin in plasma showed sharper and higher peaks than those for cefadroxil. Although values for the peak concentrations (Cmax) for cefadroxil were lower than that of cephalexin, the levels of cefadroxil in plasma and urine remained above the reported minimum inhibitory concentrations of susceptible organisms for longer period of time than those of cefalexin. The elimination half-life (t1/2) of cefadroxil (about 2 h) was significantly longer than that of cephalexin (about 1 h). The values for Cmax and AUC0-infinity values for both these cephalosporins showed dose-proportional increase, whereas t1/2, renal clearance (CLR) remained independent of dose. These observations confirm that cefadroxil and cephalexin obey linear pharmacokinetics. The CLr of both the cephalosporins were significantly higher than the average glomerular filtration rate at each dose level. The urinary recovery (% Xu) of each cephalosporin, accounted for over 80 per cent of the administered dose, and no significant differences in % Xu were observed between the two cephalosporins. These data suggest that the systemic availability of cefadroxil and cephalexin is similar at each dose level.
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Oral cefadroxil in doses of 0-6-1-8 g per day given on twice or three times daily schedules was effective in the treatment of thirty-six patients with infections such as abscesses, carbuncles, cellulitis, furunculosis and impetigo. Staphylococcus aureus strains and beta-haemolytic streptococci, alone or in combination, were cultured from lesions before treatment. In vitro studies with test discs showed that all the organisms were sensitive to cefadroxil, but twenty-three of twenty-nine S aureus strains and one of the seven streptococci strains were resistant to penicillin G. Pre- and post-treatment laboratory tests of renal, hepatic and haematopoietic functions produced no evidence of drug toxicity. The cefadroxil dosage effective in this study is lower than that recommended for currently available oral cephalosporins, which must be given on a four times daily schedule.