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PubMed2001

Flow-injection spectrophotometric determination of certain cephalosporins based on the formation of dyes.

A flow-injection spectrophotometric method is described for the determination of cefadroxil (I) and cefotaxime (II). The method is based on the hydrolysis of the cephalosporin with sodium hydroxide whereby the sulfide ion is produced. The latter is allowed to react with N,N-diethyl-p-phenylenediamine sulfate (N,N-DPPD) and Fe (III), and the blue color produced is measured at 670 nm (method A). Linear calibration graphs are obtained in the range 36.34-109.2 and 95.48-477.4 microgml(-1) for I and II, respectively. The experimental limits of detection (three times the noise signal) are 0.036 and 0.048 microgml(-1) for I and II, respectively. The total flow-rate is 5.3 ml min(-1) for both drugs. Alternately, the sulfide ion produced is allowed to react with p-phenylenediamine dihydrochloride (PPDD) and Fe (III), and the violet color produced is measured at 597 nm (method B). Linear calibration graphs are obtained in the range 0.5-400 and 0.5-450 microg ml(-1) for I and II, respectively. The limits of detection are 0.4 and 0.2 microg ml(-1) for I and II, respectively. The total flow-rate is 3 ml min(-1) for both drugs. The methods have been successfully applied to the analysis of some pharmaceutical formulations, particularly of the injection and capsule types. The relative standard deviation (RSD) (n = 10) at the 50 and 100 microg ml(-1) levels of I and II were 0.83-0.77 and 0.9-0.8% with N,N-DPPD and PPDD as reagents, respectively. Recoveries were quantitative; the results obtained agreed with those obtained by other reported methods.

Cefadroxil↗

PubMed2000

Simultaneous determination of the heat and the quantity of vapor sorption using a novel microcalorimetric method.

PURPOSE: In this study, instrumentation for measuring vapor sorption enthalpies and sorption uptakes simultaneously with an isothermal microcalorimeter is introduced. Various pharmaceutical model substances undergoing phase transitions when exposed to humid conditions (25 degrees C), were employed to evaluate the usefulness and sensitivity of the constructed experimental method. METHODS: The sample is placed in the sample vessel of a RH cell and the moisture content of the air flow is controlled. From the RH cell the air flow is conducted into a subsequent perfusion cell in which a saturated salt solution has been loaded. The RH cell and perfusion cells are positioned in the sample sides of two twin calorimetric units. Depending on the moisture content in the outlet flow leaving the preceding RH cell, the heat flow signal from the subsequent perfusion cell will vary. By means of blank measurement with identical settings, the rate of water sorption can be calculated and, by integration, the amount of sorbed water is obtained. RESULTS: Amorphous lactose and cefadroxil undergo recrystallization when the moisture level in the surroundings exceeds the threshold values specific to each compound. During the sorption phase, heat is evolved fairly linearly as a function of consumed moisture, and also after the recrystallization, the heats indicate linear behavior. The heat values for the desorption phase of amorphous lactose and the adsorption of crystalline lactose coincide. With the different anhydrous forms of theophylline, the hydration takes place more rapidly in the metastable form 1, and generally, the process is more energetic in form 1. In all cases, the gravimetric results agree with the water sorption uptakes calculated from the calorimetric data. CONCLUSIONS: The technique introduced offers a rapid and sensitive method to gain new insights into the transitions in which vapors are involved. In addition, different kinds of surfaces with various energetics can now be studied more closely.

Calorimetry↗

PubMed2001

No evidence for active peptide transport in forestomach epithelia of sheep.

The transport of peptides was studied with isolated preparations of rumen and omasum tissue of sheep by using the conventional Ussing-chamber method and isolated ruminal cells (REC). Mucosal addition of glycyl-L-glutamine, captopril (angiotensin converting enzyme inhibitor) or cefadroxil (beta-lactam antibiotic) did not change the short-circuit current (I(sc)), or tissue conductance (G(t)). The intracellular pH, pH(i), in isolated REC was not influenced by the addition of peptides to the buffer solution. These findings do not support the assumption of proton-coupled or electrogenic peptide transport. The determination of unidirectional flux rates of the peptide D-phenylalanyl-L-alanine (2,3-(3)H) showed that the flux rate in the serosal-mucosal direction, J(sm), was greater than J(ms), leading to a small net secretion of peptide. Transport was not significantly inhibited by the serosal addition of ouabain. Enhancing the paracelluIar permeability by an increase of osmotic pressure in the mucosal solution (FREYER and MARTENS, Proc. Soc. Nutr. Physiol. 8, 80, 1999) caused an increase of G(t) and significantly higher transport rates of peptide. The flux rates of peptides (in the nanomolar range) may therefore represent passive and possibly paracellular diffusion and are not of nutritional importance.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2000

Hospitalization due to Pasteurella multocida-infected animal bite wounds: correlation with inadequate primary antibiotic medication.

Over a 10-y period, patients hospitalized with Pasteurella-induced cat or dog bite-associated wound infection were analysed retrospectively with regard to preceding antibiotic medication. In 10/14 cases, hospitalization was necessitated in spite of prophylactic or therapeutic administration of oral antibiotics. In 1 case, phenoxymethylpenicillin and flucloxacillin had been prescribed. The other patients received flucloxacillin (7 patients), erythromycin, or cefadroxil (1 patient each), agents that are not consistently active against Pasteurella. In conclusion, hospitalization due to Pasteurella-induced animal bite-associated wound infection seemed to be related to the prescription of suboptimal oral antibiotic therapy at a preceding medical consultation.

Adolescent↗

PubMed2006

Treatment of lichen sclerosus with antibiotics.

Current therapy for lichen sclerosus centers on topical steroids, particularly clobetasol propionate. As some evidence suggests an infectious etiology owing to Borrelia, we studied the effect of penicillin and cephalosporin therapy on patients with lichen sclerosus who had responded poorly to treatment with potent topical corticosteroids. Fifteen patients with lichen sclerosus were treated for 3-21 months with either penicillin or cephalosporins in an observational study. Thirteen patients (nine women, four men) received penicillin, including intramuscular penicillin G benzathine suspension and/or oral penicillin V potassium, amoxicillin, or amoxicillin/clavulanate potassium. Two additional men received cephalosporins, either intramuscular ceftriaxone sodium or oral cefadroxil monohydrate. All patients showed a significant response, evident within a few weeks. Most striking was the rapid relief of pain, pruritus and burning. Four patients cleared completely, four experienced marked improvement, and the remaining seven had a favorable improvement of symptoms with incomplete clearing of lesions. We recommend treatment of lichen sclerosus with either intramuscular ceftriaxone every 3 weeks or intramuscular penicillin every 2-3 weeks. The addition of oral penicillin or cephalosporin presumably helps maintain antibiotic blood levels and may be a sufficient treatment in some cases.

Administration, Oral↗

PubMed1992

In vitro activities of Ro 40-6890 against 164 predominantly intestinal members of the families Enterobacteriaceae and Vibrionaceae.

The in vitro activities of Ro 40-6890, the active metabolite of a novel orally absorbable cephalosporin ester, Ro 41-3399, against 164 nonfastidious aerobic gram-negative rods of predominantly intestinal origin from patients with diarrhea were evaluated by the agar dilution method recommended by the National Committee for Clinical Laboratory Standards. Ro 40-6890 was inhibitory (MIC for 90% of isolates [MIC90], 0.12 micrograms/ml) against the majority of intestinal members of the families Enterobacteriaceae and Vibrionaceae (Vibrio spp., Aeromonas spp., and Plesiomonas shigelloides). The potency of Ro 40-6890 was very similar to that of cefotaxime (MIC90, 0.12 micrograms/ml) and distinctly higher than those of cefadroxil (MIC90, > or = 128 micrograms/ml) and amoxicillin-clavulanic acid (MIC90, 32 micrograms/ml-2 micrograms/ml).

Amoxicillin↗

PubMed2001

Intestinal peptide transport: ex vivo uptake studies and localization of peptide carrier PEPT1.

The nature of protein breakdown products and peptidomimetic drugs such as beta-lactams is crucial for their transmembrane transport across apical enterocyte membranes, which is accomplished by the pH-dependent high-capacity oligopeptide transporter PEPT1. To visualize oligopeptide transporter-mediated uptake of oligopeptides, an ex vivo assay using the fluorophore-conjugated dipeptide derivative D-Ala-Lys-N(epsilon)-7-amino-4-methylcoumarin-3-acetic acid (D-Ala-Lys-AMCA) was established in the murine small intestine and compared with immunohistochemistry for PEPT1 in murine and human small intestine. D-Ala-Lys-AMCA was accumulated by enterocytes throughout all segments of the murine small intestine, with decreasing intensity from the top to the base of the villi. Goblet cells did not show specific uptake. Inhibition studies revealed competitive inhibition by the beta-lactam cefadroxil, the angiotensin-converting enzyme inhibitor captopril, and the dipeptide glycyl-glutamine. Controls were performed using either the inhibitor diethylpyrocarbonate or an incubation temperature of 4 degrees C to exclude unspecific uptake. Immunohistochemistry for PEPT1 localized immunoreactivity to the enterocytes, with the highest intensity at the apical membrane. This is the first study that visualizes dipeptide transport across the mammalian intestine and indicates that uptake assays using D-Ala-Lys-AMCA might be useful for characterizing PEPT1-specific substrates or inhibitors.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1985

In vitro synergistic activity of some chinolinic compounds combined with beta-lactam antibiotics against gram-positive and gram-negative clinical isolates.

The antimicrobial activities of nalidixic acid-cephalexin (ratio 1:1) and cinoxacin-cefadroxil (ratio 1:2) combinations have been evaluated against 396 clinical isolates; many of them were nalidixic acid- or cinoxacin-resistant organisms (MIC greater than or equal to 100 micrograms/ml). We have also tested the nalidixic acid-amoxicillin combination (ratio 1:1) against 225 amoxicillin-resistant bacterial strains (MIC greater than or equal to 800 micrograms/ml). Synergy was found for 62-70% of the Enterobacteriaceae and nonfermenter bacilli tested and for 85-92% of the gram-positive bacterial strains. The 225 clinical isolates resistant to amoxicillin (MIC greater than or equal to 800 micrograms/ml) were synergistically inhibited by the nalidixic acid-amoxicillin combination.

Amoxicillin↗

PubMed1989

Use of cefuroxime in preventing postcesarean infection in high-risk patients.

Prophylactic antibiotic therapy is accepted for prevention of postceasarean infection in certain risk groups. Of the antibiotic regimens presented none appears superior. Patients having a cesarean section (CS) more than 6 h after membrane rupture were given three doses of cefuroxime (1.5 g every 8th hour) in a prospective study. This prophylaxis was as efficacious as a 7-day treatment with cefuroxime and cefadroxil. The infection rate was 21% which should be compared to approximately 50% when no prophylaxis was given. Patients with membrane rupture of less than 6 h and having a most urgent CS received the same 24-hour prophylaxis. No postoperative infection was recorded. Women having a CS with an ongoing uterine infection were treated with cefuroxime alone or combined with metronidazole. All but one (91%) had an uneventful recovery.

Bacterial Infections↗

PubMed1991

[Releasing properties of water soluble drug in internal water phase of W/O/W multiple emulsions].

A stable water/liquid paraffin system water-in-oil-in-water (W/O/W) multiple emulsion was prepared by the two-step procedure of emulsification using a variety of nonionic emulsifying agents, such as Span 80 and Tween 20. After comparison of the releasing properties of such water soluble drugs as cefadroxil, cephradine, 4-aminoantipyrine and antipyrine which were entrapped separately in the inner aqueous phase of the W/O/W multiple emulsion, a large difference was observed. It was ascertained that the difference in these releasing properties was due to no physical rupture by the microscopic observation and the results of the release test of W/O/W multiple emulsion with two kinds of drugs entrapped simultaneously in an inner aqueous phase. This reason was presumed to be dependent on permeation in the oily phase of the drug itself. It was proved that the differences of releasing properties tended to depend on the molecular weight and were closely related to the drug concentration of outer aqueous phase of W/O/W multiple emulsion containing the drug in both aqueous phases prepared as an experimental model. Therefore, two possible mechanisms for the releasing of drugs in W/O/W multiple emulsion may be interpreted as follows: the first is that the mixed and inversed micelles formed by Span 80 and Tween 20 agents in the oily phase act as a carrier of drugs, and the second is that drug molecules diffuse through small pore existing in very thin lamella of the emulsifying agents partially formed in the oil layer owing to the fluctuation of the thickness.

Ampyrone↗

PubMed1992

[Preparation of stable W/O/W type multiple emulsion containing water-soluble drugs and in vitro evaluation of its drug-releasing properties].

The stable water-in-oil-in-water (W/O/W) multiple emulsion was prepared by a two-step procedure for emulsification using glyceryl tricaprylate (Panasate-800) as the oil phase. The water-soluble drugs such as cefadroxil, cephradine, 4-aminoantipyrine, and antipyrine were selected and entrapped separately in the inner aqueous phase of W/O/W multiple emulsion. In consideration of parenteral administration, pH 7.4 phosphate buffered saline was used in both inner and outer aqueous phases. Moreover, these multiple emulsions could be significantly stable for a month at room temperature by the addition of hydrophilic polymer like gelatin and of amino acid like lysine to the inner aqueous phase.

Ampyrone↗

PubMed1987

Penicillin tolerance in beta-streptococci isolated from patients with tonsillitis.

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.

Cefadroxil↗

PubMed1991

[Importance of the antimicrobial mode of action of antibiotics for their combined effect with glycine in subinhibitory concentrations on microbial growth].

Following previous observations of an increase in microbial sensitivity to the bactericidal beta-lactams ampicillin and imipenem in the presence of glycine, the aim of the presented study was to examine if such an effect is due to the antimicrobial mode of action of an antibiotic and/or to its bactericidal or bacteriostatic capacity. Using growth curves as an experimental parameter the same synergistic glycine effect could be shown if tested concomitantly with a number of other antibiotics acting equally on bacterial cell wall formation as cefaclor, cefadroxil, or fosfomycin. This glycine effect is, therefore, associated with the antibiotic mode of action, but is independent of wether the antibiotics are beta-lactams or not (fosfomycin). In contrast, glycine had no particular effect in combination with antibiotics inhibiting protein synthesis (sisomicin, kanamycin, chloramphenicol, oxy-tetracycline) or nucleic acid polymerase activity (ciprofloxacin, cinoxacin; rifampicin being a certain exception) as well as with those acting on cytoplasmic and external membrane as polymyxin B. The synergistic effect of glycine and cell wall active antibiotics was interpreted predominantly by an action on carboxypeptidases.

Anti-Bacterial Agents↗

PubMed1991

[In vitro activity of cefuroxime against Moraxella (Branhamella) catarrhalis].

Minimal inhibitory concentrations of cefuroxime were determined by an agar dilution procedure and compared with erythromycin and four other beta-lactam antibiotics (amoxycillin, amoxycillin + clavulanate, cefadroxil, cefaclor) on 76 strains of Moraxella (Branhamella) catarrhalis. Sixty four of them produced a beta-lactamase. Results show that the beta-lactamase of Moraxella (Branhamella) catarrhalis abrogates the activity of amoxycillin (MIC 90% = 4 mg/l) meanwhile the combination of amoxycillin-clavulanate is inhibitory at low concentration (MIC 90% = 0.25 mg/l). There are no difference in MICs between strains producing or not producing beta-lactamase with erythromycin (MIC 90% = 0.25 mg/l). All the strains evaluated in this investigation, producing or not producing beta-lactamase have MIC 90% less than or equal to 2 mg/l for cefuroxime lower than those obtained for the two other cephalosporins.

Amoxicillin↗

PubMed1990

[Microbiological assay method of BMY-28100 and some other cephem antibiotic in serum and tissues. Development of new sample preparation with Evan's blue, a high albumin binding dye].

With a new simple sample pretreatment, microbiological assay methods for quantitative determination of BMY-28100 and some other cephem antibiotics in serum and tissues have been developed. Presented sample pretreatment was founded on the extraction with Evans' blue, a high serum protein binding dye, and the ultrafiltration using cellulose membrane (Millipore; MW cutoff is 10,000) to which Evans' blue was specifically absorbed. Regardless of sample media, antibiotic contents in filtrates were determined accurately using calibration curves based on standard solutions prepared with 1/15 M phosphate buffer, pH 7.4. Four cephems, ceftriaxone (CTRX), cefazolin (CEZ), BMY-28100 and cefadroxil (CDX) were examined in human serum and rat liver tissues. Corrections were made for antibiotic recoveries into 1/15 M phosphate buffer, pH 7.4. CTRX, CEZ, BMY-28100 and CDX in serum and tissues were recovered into buffer at rates of 98.4-101.6%, 97.6-102.0%, 99.8-101.4% and 97.5-98.2% of of spiked (theoretical) values, respectively regardless of antibiotic concentrations. Furthermore, these concentrations obtained using the present bioassay method were well in agreement with those obtained by the HPLC method. When BMY-28100 was administered to volunteers, concentrations of BMY-28100 in serum obtained by the present bioassay method were well in agreement with those obtained by the usual bioassay method which required the fresh human serum to prepare the standard solutions.

Animals↗

PubMed1985

[In vitro susceptibilities of causative organisms isolated from patients with primary respiratory tract infections to BRL 25000 (clavulanic acid/amoxicillin)].

The in vitro susceptibilities of various causative organisms recently isolated from patients with primary respiratory tract infections to BRL 25000 (a formulation of amoxicillin, 2 parts, and potassium clavulanate, 1 part), amoxicillin (AMPC), cefaclor (CCL), cephalexin (CEX), cefadroxil (CDX) and cefroxadine (CXD) were determined. beta-Lactamase producing strains were detected by nitrocefin chromogenic method and PCG acidometric method. The frequency of isolation of beta-lactamase production in strains of S. aureus, H. influenzae, B. catarrhalis and K. pneumoniae was 92%, 18%, 36% and 98%, respectively. Against S. aureus strains with MIC values to AMPC of less than or equal to 100 micrograms/ml and CEX of less than or equal to 25 micrograms/ml BRL 25000 showed MIC values in the range 0.39-6.25 micrograms/ml with inocula of 10(6) CFU/ml, while BRL 25000 required 12.5-100 micrograms/ml of concentrations for inhibition of the strains with MIC values to AMPC of greater than 100 micrograms/ml and CEX of greater than or equal to 25 micrograms/ml. Against S. pyogenes and S. pneumoniae BRL 25000 showed MIC values in the range less than 0.024-0.10 micrograms/ml with inocula of 10(6) CFU/ml, which is much more active than CCL, CEX, CDX and CXD and slight less active than AMPC. Against H. influenzae and B. catarrhalis BRL 25000 showed MIC values in the range 0.20-6.25 micrograms/ml with inocula of 10(6) CFU/ml, which showed most potent activity among the agents tested. The activity of BRL 25000 against K. pneumoniae was approximately equal to that of CCL and superior to that of AMPC, CEX, CDX and CXD.

Amoxicillin↗

PubMed1994

Transferable beta lactam resistance against cephalosporins in Salmonella typhimurium strains in India.

From 14 strains of S. typhimurium which were resistant to three cephalosporins (cephalexin, cefadroxil and sodium cefotaxime) the resistance plasmids were transferred to two different strains (Escherichia coli K12F-Lac-Rifr and S. typhimurium LT2). The plasmids were autotransferable and the donors as well as transconjugants showed high levels of MIC (80-320 micrograms/ml or more) against these antimicrobial agents. The resistance was demonstrated to be mediated by a 15 kilobase plasmid.

Cefadroxil↗

PubMed1995

Antimicrobial susceptibility of subgingival bacterial flora in dogs with gingivitis.

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.

Amoxicillin-Potassium Clavulanate Combination↗