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The cross-reactivity between penicillins and cephalosporins can be influenced by different factors, which are not all well known. The chemical structure of the side chain may contribute to the cross-reactivity.
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There are only slight differences between the geometrical means of minimum inhibitory concentrations of (6R,7R)-7-[(R)-2-amino-2-2(p-hydroxyphenyl)-acetamido]-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid (cefadroxil, Bidocef) and cefalexin against gram-positive and gram-negative bacteria freshly isolated from clinical material. Enterococci are more susceptible to cefadroxil. Considering the different break point, cefadroxil is on the whole more effective than cefalexin, in particular so against Proteus mirabilis, Enterobacter, Citrobacter and Escherichia coli. With the aid of the described regression analysis a meaningful interpretation of the results of the cefadroxil agar diffusion test is possible.
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The pharmacokinetics of cefatrizine was studied in 15 patients with various degrees of renal impairment, after single oral administration of 500 mg. Cefatrizine elimination was reduced in parallel to renal function, as indicated by the significant correlations between apparent clearance (Cl/F) and creatinine clearance (Clcr), and between renal clearance (Clr) and creatinine clearance (Clcr). In patients with totally impaired renal function, the residual clearance (Cl/F) was 63 ml.min-1 per 1.73 m2. Comparisons with previously published data indicate that the apparent volume of distribution (V/F) of cefatrizine was lower in patients with impaired renal function than in young healthy volunteers, leading to increased peak concentrations (Cmax), but there was no relationship between V/F and Clcr. In patients with totally impaired renal function, the upper limit of cefatrizine elimination half-life was estimated to 5.5 h. The clinical significance of pharmacokinetic modifications observed in renal disease patients may only be realized through integration of pharmacodynamic characteristics of cefatrizine. The observed increase in Cmax and the lengthening of t1/2 could suggest a reduction of dosing frequency in patients with severe renal impairment.
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Beta-streptococci isolated from patients with acute tonsillitis were tested for penicillin tolerance defined as an MBC/MIC ratio greater than or equal to 16. 11/18 strains recovered from patients with clinical treatment failure were tolerant to penicillin in comparison with 0/15 strains from successfully treated patients. The MBC/MIC ratio was less than 16 for all strains versus cefadroxil but above that ratio for many strains versus clindamycin, doxycycline and erythromycin. We suggest that penicillin tolerance may be one reason to treatment failures in individuals with streptococcal tonsillitis and that other antibiotics could be used to treat these patients since penicillin tolerance is not correlated to a general increase in antibiotic resistance.
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Patients with CARTI were prospectively recruited from 30 primary hospitals from December 2007 to July 2010. Those who had used antimicrobials within previous 2 weeks were excluded from the study. The clinical information such as temperature, white blood cell (WBC) count and percentage of neutrophils was recorded, and throat swab or deep cough sputum was collected to isolate pathogens. The specimens were collected and couriered to the Zhongshan Hospital microbiology laboratory within 2 h for bacterial culture. The minimal inhibition concentrations (MIC) of penicillin G, amoxicillin, cephradine, cephalexin, cefadroxil, sulfamethoxazole/trimethoprim and azithromycin were determined using the agar dilution test.
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The presence of a proton-coupled electrogenic high-affinity peptide transporter in the apical membrane of tubular cells has been demonstrated by microperfusion studies and by use of brush border membrane vesicles. The transporter mediates tubular uptake of filtered di- and tripeptides and aminocephalosporin antibiotics. We have used expression cloning in Xenopus laevis oocytes for identification and characterization of the renal high-affinity peptide transporter. Injection of poly(A)+ RNA isolated from rabbit kidney cortex into oocytes resulted in expression of a pH-dependent transport activity for the aminocephalosporin antibiotic cefadroxil. After size fractionation of poly(A)+ RNA the transport activity was identified in the 3.0- to 5.0-kb fractions, which were used for construction of a cDNA library. The library was screened for expression of cefadroxil transport after injection of complementary RNA synthesized in vitro from different pools of clones. A single clone (rPepT2) was isolated that stimulated cefadroxil uptake into oocytes approximately 70-fold at a pH of 6.0. Kinetic analysis of cefadroxil uptake expressed by the transporter's complementary RNA showed a single saturable high-affinity transport system shared by dipeptides, tripeptides, and selected amino-beta-lactam antibiotics. Electrophysiological studies established that the transport activity is electrogenic and affected by membrane potential. Sequencing of the cDNA predicts a protein of 729 amino acids with 12 membrane-spanning domains. Although there is a significant amino acid sequence identity (47%) to the recently cloned peptide transporters from rabbit and human small intestine, the renal transporter shows distinct structural and functional differences.
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A three day oral antibiotic course was given to 71 elderly bacteriuric subjects with no or only moderate mobility problems. Seven of 17 men (41%) and 34 of 54 women (63%) had strongly positive antibody coated bacteria (ACB) in the urine. Following sensitivity tests and randomization one of the following agents was given: cefadroxil 1 g tid (13 subjects): co-trimoxazole 160/800 mg bd (23 subjects); or norfloxacin 400 mg bd (35 subjects). One week after therapy urines were negative in 13 men (76.5%) and 37 women (68.5%). Patients who were fully mobile and/or were ACB(-) responded better than those with moderate mobility problems or who were ACB(+). At six months, urines were negative in six (40%) of 15 men and 15 (33.3%) of 45 women. Two men and six women of these 21 subjects had a positive urine at one month. Of the three agents tested cefadroxil was less effective in women. The study indicates that a three day course will clear bacteriuria in about 70% of patients at one week, but only about 25% will remain free of infection at six months; these are usually patients with adequate mobility and normal renal function.
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The ecological effects on the commensal microflora in saliva and stool samples were studied during administration of two commonly used antibiotics: cefadroxil 500 mg b.i.d. for 10 days and phenoxymethylpenicillin 1 g b.i.d. for 10 days. Twenty healthy volunteers participated in the study. In the oropharyngeal microflora the aerobic microflora was significantly suppressed during administration of cefadroxil while no significant changes were noticed in the anaerobic microflora. Administration of phenoxymethylpenicillin caused a strong decrease in the number of viridans streptococci and an overgrowth of Neisseria cocci. The total numbers of anaerobic oropharyngeal microorganisms were suppressed during phenoxymethylpenicillin administration. In the intestinal microflora the variation in numbers of aerobic and anaerobic microorganisms was minor in both groups. The microflora became normalised 2 weeks after withdrawal of the drugs. It was concluded that peroral administration of cefadroxil to healthy volunteers resulted in minor ecological disturbances in the oropharyngeal and intestinal microflora, which were in the same range as for phenoxymethylpenicillin.
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Antigen detection tests (ADTs) were used by 64% of the pediatricians; 85% used throat cultures. Strategies for diagnosing streptococcal pharyngitis were throat culture alone (38%), consider positive ADTs definitive and use throat culture when ADTs are negative (42%), ADT alone (13%), ADT and throat culture for all patients with pharyngitis (5%), and no tests for GABHS performed (2%). Thirty-one percent usually or always treated with antibiotics before test results were available. Only 29% of these "early treaters" always discontinued antibiotics when tests did not confirm the presence of group A streptococci. The drug of choice for treatment was penicillin (73%); another 26% preferred a derivative of penicillin, particularly amoxicillin. Many pediatricians altered their management when a patient had recurrent streptococcal pharyngitis. Nearly half of the respondents would use a different antibiotic than they used for routine acute streptococcal pharyngitis. They most often changed to erythromycin (25%), cefadroxil (23%), or amoxicillin-clavulanate (20%). Follow-up throat culture was obtained by 51% of pediatricians after treatment of recurrent streptococcal pharyngitis. A patient with chronic carriage of GABHS and symptoms of pharyngitis would be treated with an antibiotic by 84%; most (62%) would use a penicillin. Other choices were cephalosporins (19%), erythromycin (12%), clindamycin (3%), or rifampin plus penicillin (3%). Tonsillectomy was recommended for symptomatic carriers by 31% of respondents. Carriers without symptoms were less likely to be treated with antibiotics (23%) or referred for tonsillectomy (21%).
Eleven new 7-[2-(dihydro-5-substituted-6-thioxo-2H-1,3,5-thiadiazine-3( 4H)-yl)-2- (4-hydroxyphenyl)acetamido]-3-methyl-3-cephem-4-carboxylic acid derivatives were synthesized by the reaction of cefadroxil monohydrate, formaldehyde and substituted potassium dithiocarbamate. Their structures have been elucidated by spectral data and elementary analysis. The title compounds were tested for antimicrobial activity in vitro against gram-positive bacteria (Staphylococcus aureus, Streptococcus faecalis), gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa) and yeast-like fungi (Candida albicans, C. parapsilosis, C. stellatoidea, C. pseudotropicalis) in comparison with cefadroxil monohydrate. The activity of compounds 1 and 10 against S. aureus (MBC: 37.5 micrograms/ml) and compound 1 against E. coli (MBC: 75 micrograms/ml) were found to be the same as cefadroxil monohydrate. Compounds 1 and 10 were more effective than cefadroxil monohydrate against S. faecalis with 25 and 37.5 micrograms/ml MBC values, respectively. None of the compounds and cefadroxil monohydrate proved to be effective against P. aeruginosa (MBC: greater than 100 micrograms/ml). While cefadroxil monohydrate had no activity against yeast-like fungi, compounds 9 and 10 were significantly effective against yeast-like fungi (MFC: 37.5 micrograms/ml).
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The efficacy of cefadroxil once daily and cefaclor given 3 times daily was compared in 250 pediatric patients with group A beta-hemolytic streptococcal pharyngitis. The duration of the therapy was 10 days. Therapeutic response was based on clinical responses at 24 h and 10 days and throat cultures on days 14, and 21 or 28. Five (5%) cefadroxil-treated patients and 12 (12%) cefaclor-treated patients were still culture-positive on day 14. When the patients were stratified according to major differences between treatment groups observed at baseline, a significant difference between the treatment groups in favor of cefadroxil was found on day 14 (p = 0.020) and days 21-28 (p = 0.043). These data were confirmed by the clinical findings; failure or clinical recurrence occurred in 4.6% of cefadroxil-treated patients versus 22.1% of cefaclor-treated patients. The patients complied with the recommended drug regimen, and none experienced any significant drug-related adverse reactions. The results of this study indicate that cefadroxil given once daily for streptococcal pharyngitis is an effective and well-tolerated antimicrobial agent, and suggest that the desirable pharmacokinetic properties of cefadroxil contribute to this efficacy.
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In a multicentre study 163 women with acute lower urinary tract infection were treated orally with either 125 mg cefuroxime axetil or 100 mg ofloxacin twice daily for three days. Both antimicrobial agents were generally well tolerated. Four patients in the group treated with cefuroxime axetil and two in the group treated with ofloxacin experienced adverse events. Clinical cure and improvement were registered in 56 of 66 (84.8%) and 59 of 62 (95.2%) of the evaluable patients treated with cefuroxime axetil and ofloxacin, respectively. Seven to nine days after therapy, bacteriuria (CFU < 10(3)/ml) had been eliminated in 53 of 66 (80.3%) and 57 of 64 (89.1%) of the evaluable patients receiving cefuroxime axetil and ofloxacin, respectively. The results were not statistically significantly different (p > 0.1). Pathogens present at baseline were eliminated by up to an MIC of 16 mg/l of cefuroxime axetil, independent of susceptibility to this agent. There was no difference with regard to efficacy and tolerance between patients treated with cefuroxime axetil and those treated with ofloxacin. On the basis of the MICs of six antimicrobial agents (cefuroxime, ofloxacin, cefadroxil, ampicillin, trimethoprim with and without sulfamethoxazole) determined for the pathogens isolated prior to therapy, resistance rates were lowest for cefuroxime (2.2%) and ofloxacin (3.4%).
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Two novel glucosinolates along with one known glucosinolate were isolated from Broccoli (Brassica oleracea L. var. italica) florets. Their structures were established mainly by 1D ((1)H and (13)C NMR), 2D NMR ((1)H-(1)H COSY, DEPT 135°, HSQC and HMBC), and Tandem MS-MS spectrometric data as 2-mercaptomethyl sulfinyl glucosinolate [(Z)-4-(methylsulfinyl)-N-(sulfooxy)-2-((2'S,3'R,4'S,5'S,6'R)-3',4',5'-trihydroxy-6'(hydroxylmethyl)-2'-mercapto tetrahydro-2H-pyran-2-yl) butane amide] 1, (Z)-1-((2S,5S)-5-hydroxytetra-hydro-2H-pyran-2-ylthio)-2-(1H-indol-3-yl) ethylidene amino sulfate 2 and a known cinnamoyl [6'-O-trans-(4″-hydroxy cinnamoyl)4-(methylsulphinyl)butyl glucosinolate] 3. Compound 1 exhibited scavenging activity against DPPH with an inhibitory concentration IC(50) of 20 mM, whereas compound 3 was a weak antioxidant when compared to the standard quercetin (5 mM) as a positive control. Both the compounds showed a significant and similar antimicrobial activity against Staphylococcus aureus with an IC(50) of <625 μg/mL when compared to antibiotic duricef. Against Salmonella typhimurium the IC(50) of 1 and 3 was determined as <625 μg/mL and <1250 μg/mL, respectively, when compared to ampicillin (IC(50) ≤ 39 μg/mL) as a positive control.
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An accurate, precise and sensitive HPLC assay was developed for the determination of amoxicillin in human plasma samples, to compare the bioavailability of two amoxicillin capsule (500mg) formulations (Amoxicilina from Brazil, as a test formulation and Amoxil from SmithKline Beecham Laboratories Ltda., Brazil, as a reference formulations) in 24 volunteers of both sexes.
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Owing to the frequent presence of many possible confounding factors, antimicrobial resistance to one drug does not always correlate well to the consumption of the same drug or closely related drugs. This study showed that the degree of antimicrobial consumption was significantly correlated to the incidence of multidrug-resistant E. coli.
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We conducted a prospective study of 214 consecutive subjects who had 307 nonimmediate reactions to penicillins (almost exclusively aminopenicillins) and had positive patch test and/or delayed-reading skin test responses to at least 1 penicillin reagent. To assess cross-reactivity with cephalosporins and aztreonam and the tolerability of such alternative β-lactams, all subjects underwent skin tests with cephalexin, cefaclor, cefadroxil, cefuroxime, ceftriaxone, and aztreonam. Subjects with negative responses were challenged with the alternative β-lactams concerned.
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The susceptibility of E. coli in France (166 isolates), Germany (133 isolates), Spain (169 isolates), Sweden (137 isolates), and the UK (124 isolates) was determined by disc diffusion according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints and methodology. Resistance rates were compared using Fisher's exact test, 2-tailed, with P < 0.05 indicating statistical significance.
Dogs with clinical signs of skin infection confirmed via bacteriologic culture were randomly allocated to receive a single SC injection of cefovecin (8 mg/kg [3.6 mg/lb]) followed by placebo administered PO twice daily for 14 days or cefadroxil (22 mg/kg [10 mg/lb]) administered PO twice daily for 14 days following a placebo injection. Two 14-day treatment courses were permitted. Treatment success was defined as reduction of clinical signs to mild or absent at the final assessment.
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A reversed-phase column liquid chromatographic method was developed for the assay of cefadroxil in bulk drugs and pharmaceutical preparations. An equation was derived showing a linear relationship between peak-area ratios of cefadroxil to dimethylphthalate (internal standard) and the cefadroxil concentration over a range of 0.02-0.8 mg/ml (r = 0.9999). Standard addition recoveries were generally greater than 97.7%. The coefficients of variation in the within-day assay were between 0.36 and 0.65, and in the between-day assay was 0.71%. The column liquid chromatographic assay results were compared with those obtained from a microbiological assay, which indicated that the proposed method is a suitable substitute for the microbiological method for potency assays and stability studies of cefadroxil preparations.
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Therapeutic use of cephaloridine, a beta-lactam antibiotic, in humans is associated with carnitine deficiency. A potential mechanism for the development of carnitine deficiency is competition between cephaloridine and carnitine for the renal reabsorptive process. OCTN2 is an organic cation/carnitine transporter that is responsible for Na(+)-coupled transport of carnitine in the kidney and other tissues. We investigated the interaction of several beta-lactam antibiotics with OCTN2 using human cell lines that express the transporter constitutively as well as using cloned human and rat OCTN2s expressed heterologously in human cell lines. The beta-lactam antibiotics cephaloridine, cefoselis, cefepime, and cefluprenam were found to inhibit OCTN2-mediated carnitine transport. These antibiotics possess a quaternary nitrogen as does carnitine. Several other beta-lactam antibiotics that do not possess this structural feature did not interact with OCTN2. The interaction of cephaloridine with OCTN2 is competitive with respect to carnitine. Interestingly, many of the beta-lactam antibiotics that were not recognized by OCTN2 were good substrates for the H(+)-coupled peptide transporters PEPT1 and PEPT2. In contrast, cephaloridine, cefoselis, cefepime, and cefluprenam, which were recognized by OCTN2, did not interact with PEPT1 and PEPT2. The interaction of cephaloridine with OCTN2 was Na(+)-dependent, whereas the interaction of cefoselis and cefepime with OCTN2 was largely Na(+)-independent. Furthermore, the Na(+)-dependent, OCTN2-mediated cellular uptake of cephaloridine could be demonstrated by direct uptake measurements. These studies show that OCTN2 plays a crucial role in the pharmacokinetics and therapeutic efficacy of certain beta-lactam antibiotics such as cephaloridine and that cephaloridine-induced carnitine deficiency is likely to be due to inhibition of carnitine reabsorption in the kidney.