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1.
J Dairy Res ; 88(1): 64-68, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33731240

ABSTRACT

Our objective was to evaluate the efficacy of intramammary administration, at drying-off, of a Panax ginseng extract (PGe) combined with cephalexin (Ceph) on the post-calving bacteriological cure rate of pre-existing intramammary infections (IMI) and on the occurrence of new IMI during the dry period. In addition, milk yield and somatic cell count (SCC) in the post-treatment lactation were evaluated. One hundred and eight late-lactation cows were randomly divided into two experimental groups and were treated at drying-off with Ceph alone or PGe combined with Ceph.Cure rates for IMI present at drying-off were similar for both treatments (OR = 0.95, 95% CI = 0.33-2.74). Cure rates for Staphylococcus aureus were lower (OR = 15.4, 95% CI = 1.66-142.52) in quarters treated with PGe + Ceph than in those treated with Ceph alone. Intramammary infusion of PGe + Ceph at drying-off had no effect on preventing new dry period IMI (OR = 0.75, 95% CI = 0.38-1.51), compared with infusion of Ceph alone. Milk production and SCC in the ensuing lactation were not affected by PGe + Ceph treatment. In conclusion, addition of PGe to dry cow therapy did not show any advantage over the use of dry cow therapy alone.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Cephalexin/administration & dosage , Mastitis, Bovine/drug therapy , Panax/chemistry , Plant Extracts/administration & dosage , Animals , Cattle , Cell Count/veterinary , Drug Therapy, Combination/veterinary , Female , Lactation , Mammary Glands, Animal/drug effects , Mastitis, Bovine/prevention & control , Milk/cytology , Staphylococcal Infections/drug therapy , Staphylococcal Infections/veterinary , Staphylococcus aureus
2.
Pediatr Infect Dis J ; 39(6): 523-525, 2020 06.
Article in English | MEDLINE | ID: mdl-32398570

ABSTRACT

Osteoarticular infections are one of the more common invasive bacterial infections encountered in children. There exist significant practice variations in both the diagnosis and treatment of such infections. However, the practice of transitioning from parenteral therapy to oral antibiotics has been well validated by several studies. For methicillin-sensitive Staphylococcus aureus (MSSA), cephalexin is often recommended. Prospective, controlled data regarding optimal dosing of cephalexin in pediatric osteomyelitis are not available. We sought to review our retrospective, uncontrolled data on four times daily (QID) versus three times daily (TID) dosing of cephalexin for pediatric osteoarticular infections. Children ≥1 month to <18 years of age admitted to Rady Children's Hospital-San Diego with a diagnosis of osteomyelitis or septic arthritis between January 1, 2002, and November 30, 2007, were identified and previously reported. Only patients with culture-positive MSSA infections are included in this report. Demographic and clinical data were manually extracted from the electronic medical record. Fifty-nine patients were treated with cephalexin and had records available for review through our electronic medical record. Thirty-eight patients (64.4%) were treated QID, and 21 patients (35.6%) were treated TID. Clinical cure was achieved in all patients with only one adverse event occurring in the QID group. In this retrospective chart review of children with osteoarticular infections caused by MSSA treated with cephalexin, similar clinical outcomes were found with QID versus TID dosing.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Arthritis, Infectious/drug therapy , Cephalexin/administration & dosage , Osteomyelitis/drug therapy , Staphylococcal Infections/drug therapy , Administration, Oral , Adolescent , Anti-Bacterial Agents/therapeutic use , Arthritis, Infectious/microbiology , Cephalexin/therapeutic use , Child , Child, Preschool , Drug Administration Schedule , Electronic Health Records , Female , Humans , Infant , Male , Methicillin Resistance , Microbial Sensitivity Tests , Osteomyelitis/microbiology , Prospective Studies , Retrospective Studies , Staphylococcal Infections/microbiology , Staphylococcus aureus/drug effects
4.
Drug Metab Dispos ; 47(3): 173-183, 2019 03.
Article in English | MEDLINE | ID: mdl-30593545

ABSTRACT

It is difficult to predict the pharmacokinetics and plasma concentration-time profiles of new chemical entities in humans based on animal data. Some pharmacokinetic parameters, such as clearance and volume of distribution, can be scaled allometrically from rodents, mammals, and nonhuman primates with good success. However, it is far more challenging to predict the oral pharmacokinetics of experimental drug candidates. In the present study, we used in situ estimates of intestinal permeability, obtained in silico and from rat, wild-type (WT), and humanized PepT1 (huPepT1) mice, to predict the systemic exposure of cefadroxil, an orally administered model compound, under a variety of conditions. Using the GastroPlus simulation software program (Simulations Plus, Lancaster, CA), we found that the C max and area under the plasma concentration-time curve from time zero to the last measurable concentration of cefadroxil were better predicted using intestinal permeability estimates (both segmental and jejunal) from huPepT1 than from WT mice, and that intestinal permeabilities based on in silico and rat estimates gave worse predictions. We also observed that accurate predictions were possible for cefadroxil during oral dose escalation (i.e., 5, 15, and 30 mg/kg cefadroxil), a drug-drug interaction study (i.e., 5 mg/kg oral cefadroxil plus 45 mg/kg oral cephalexin), and an oral multiple dose study [i.e., 500 mg (6.7 mg/kg) cefadroxil every 6 hours]. Finally, the greatest amount of cefadroxil was absorbed in duodenal and jejunal segments of the small intestine after a 5 mg/kg oral dose. Thus, by combining a humanized mouse model and in silico software, the present study offers a novel strategy for better translating preclinical pharmacokinetic data to oral drug exposure during first-in-human studies.


Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Cefadroxil/pharmacokinetics , Intestinal Mucosa/metabolism , Models, Biological , Peptide Transporter 1/genetics , Administration, Oral , Animals , Anti-Bacterial Agents/administration & dosage , Area Under Curve , Cefadroxil/administration & dosage , Cephalexin/administration & dosage , Cephalexin/pharmacology , Computer Simulation , Drug Evaluation, Preclinical/methods , Drug Interactions , Duodenum/metabolism , Humans , Jejunum/metabolism , Mice , Mice, Transgenic , Peptide Transporter 1/metabolism , Permeability , Rats , Software
5.
J Dairy Sci ; 95(6): 3448-53, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22612980

ABSTRACT

A combination of kanamycin and cefalexin was licensed in Europe in 2008 to treat bovine clinical mastitis. Preliminary broth and disk clinical breakpoints for this antibiotic combination have been proposed for Staphylococcus aureus, Streptococcus dysgalactiae, Streptococcus uberis, and Escherichia coli. This study indicates that these proposed breakpoints also hold for coagulase-negative staphylococci (CNS), a group of bacteria frequently isolated in milk samples from cows with clinical mastitis. The data show that clinical bovine mastitis isolates of CNS from Europe have a high degree of susceptibility to the kanamycin/cefalexin combination, with minimal resistance to either agent alone. The use of the available kanamycin and cefalexin combination disk for testing the susceptibility of bovine mastitis isolates of Staph. aureus, Strep. uberis, Strep. dysgalactiae, and E. coli is also reliable for use in the testing of CNS, as disk results correlated with broth minimum inhibitory concentrations. The study reports, for the first time, the approved Clinical Laboratory Standards Institute quality control ranges for the kanamycin/cefalexin combination and wild-type cutoff values for major bacterial pathogens implicated in bovine mastitis.


Subject(s)
Cephalexin/therapeutic use , Kanamycin/therapeutic use , Mastitis, Bovine/drug therapy , Staphylococcal Infections/veterinary , Staphylococcus aureus/drug effects , Animals , Cattle , Cephalexin/administration & dosage , Disk Diffusion Antimicrobial Tests/veterinary , Drug Combinations , Escherichia coli/drug effects , Escherichia coli Infections/drug therapy , Escherichia coli Infections/microbiology , Escherichia coli Infections/veterinary , Female , Kanamycin/administration & dosage , Mastitis, Bovine/microbiology , Microbial Sensitivity Tests/veterinary , Pneumococcal Infections/drug therapy , Pneumococcal Infections/microbiology , Pneumococcal Infections/veterinary , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Streptococcus pneumoniae/drug effects
6.
Br J Clin Pharmacol ; 73(3): 422-7, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22023069

ABSTRACT

AIMS: To investigate the effect of zinc sulfate on pharmacokinetics of cephalexin when administered concurrently or at strategically spaced dosing times designed to avoid the potential interaction in healthy volunteers. METHODS: In this study, all subjects (n= 12) were randomized to receive the following four treatments, separated by a wash-out period of 7 days: cephalexin 500mg alone, concomitantly with zinc 250mg, 3h after zinc 250mg or 3h before zinc 250mg. RESULTS: All subjects completed the study safely. Zinc supplements administered concurrently with cephalexin significantly decreased the peak serum concentration (C(max) ), area under the plasma concentration-time curve from zero to infinity (AUC(0-∞) ) and the time for which the plasma concentration of the drug remained above the minimal inhibitory concentration of the pathogenic organism (T > MIC) of cephalexin [mean percentage decrease (95% confidence intervals) of 31.05% (22.09-40.01%), 27.40% (18.33-36.47%) and 22.33% (12.51-32.16%), respectively; P < 0.05] compared with administration of cephalexin alone. Also, administration of zinc 3h before cephalexin decreased the C(max) , AUC(0-∞) and T > MIC of the drug compared with administration of cephalexin alone [mean percentage decrease (95% confidence intervals) of 11.48% (3.40-19.55%), 18.12% (9.63-26.60%) and 23.75% (14.30-33.20%), respectively; P < 0.05]. In contrast, the pharmacokinetics of cephalexin was not notably altered by administration of zinc 3h after cephalexin dosing (P > 0.05). CONCLUSIONS: The significant interaction between zinc and cephalexin might affect the clinical outcome of cephalexin therapy. The dosing recommendation is that zinc sulfate can be safely administered 3h after a cephalexin dose.


Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Cephalexin/pharmacokinetics , Zinc Sulfate/pharmacology , Administration, Oral , Adult , Anti-Bacterial Agents/administration & dosage , Biological Availability , Cephalexin/administration & dosage , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Interactions , Humans , Male , Zinc Sulfate/administration & dosage
7.
J Colloid Interface Sci ; 361(1): 115-21, 2011 Sep 01.
Article in English | MEDLINE | ID: mdl-21658706

ABSTRACT

Water/propylene glycol/sucrose laurate/ethoxylated mono-di-glyceride/isopropyl myristate/peppermint oil U-type microemulsions were used to solubilize cephalexin. Microemulsion dilution and interfacial factors contributing to the cephalexin solubilization were evaluated. Cephalexin solubilization capacity increases with the increase in the aqueous phase volume fraction (φ) up to 0.4 then decreases. Electrical conductivity of drug loaded and drug free microemulsions increases with φ. The hydrodynamic radius measured by dynamic light scattering of the oil-in-water loaded microemulsions decreases with temperature. The microemulsions were characterized by the volumetric parameters, density, excess volume, ultrasonic velocity and isentropic compressibility. The microemulsion densities increase with φ up to 0.8 then decrease. The excess volume decreases with φ up to 0.8 then stabilizes. Ultrasonic velocities increase with the increase in φ while isentropic compressibility decreases. Analysis of the volumetric parameters enabled the characterization of structural transition along the microemulsion phase region. The presence of water-in-oil, bicontinuous and oil-in-water microemulsions, at aqueous phase volume fractions below 0.2, between 0.3 and 0.7 and above 0.8, respectively were found. Interfacial properties and dynamic structure of the monolayer for drug loaded and drug free microemulsions, were studied by electron paramagnetic resonance spectroscopy employing the nitroxide spin probe 5-doxylstearic acid. The rigidity of the interface was affected by the water content and also the presence of cephalexin.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Cephalexin/administration & dosage , Drug Delivery Systems , Emulsions/chemistry , Administration, Cutaneous , Diffusion , Electric Conductivity , Electron Spin Resonance Spectroscopy , Mentha piperita , Phase Transition , Plant Oils/chemistry , Propylene Glycol/chemistry , Solubility , Sucrose/analogs & derivatives , Sucrose/chemistry , Water/chemistry
8.
Antibiot Khimioter ; 49(8-9): 21-4, 2004.
Article in Russian | MEDLINE | ID: mdl-15727141

ABSTRACT

The aim of the study was to lower the immunosuppressory, prooxidant and hepatotoxic effects of rifampicin and cephalexin by their immobilization in erythrocyte vehicles. The experiments were performed on Wistar rats with the use of rifampicin, cephalexin and lysozyme (ZAO Ferane) and hemodes (6% aqueous saline solution of low molecular polyvinylpyrrolidone, mol. wt. 12600+/-2700). Rifampicin- and cephalexin-entrapped erythrocytes were prepared. Spectrophotometric procedures for quantitative assay of the immobilized antibiotics were developed. The impact of the solution concentration and incubation time on the level of the antibiotic entrapping was studied. The erythrocyte vehicles were shown to be able to entrap the antibiotics for 9 days and to preserve their stability for 24 hours. It was observed that the increase of the immunosuppressory, prooxidant and hepatotoxic effects of the antibiotics administered without the vehicles to the laboratory animals infected by staphylococci was dose-dependent. The use of the antibiotics entrapped in the erythrocyte vehicles stimulated the immune reactivity of the animals and normalized the indices of lipid peroxidation, the antioxidant system, cytolysis and cholestasis.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Cephalexin/administration & dosage , Drug Carriers , Erythrocytes , Rifampin/administration & dosage , Adjuvants, Immunologic/administration & dosage , Adjuvants, Immunologic/therapeutic use , Animals , Anti-Bacterial Agents/therapeutic use , Antioxidants/administration & dosage , Antioxidants/therapeutic use , Cephalexin/therapeutic use , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Hepatocytes/metabolism , Injections, Intramuscular , Liver/drug effects , Liver/metabolism , Lymphocyte Count , Rats , Rats, Wistar , Rifampin/therapeutic use , Spleen/immunology , Staphylococcus aureus
9.
J Vet Pharmacol Ther ; 22(5): 308-13, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10597534

ABSTRACT

The pharmacokinetics of cephalexin, a first generation cephalosporin, were investigated in dogs using two formulations marketed for humans, but also often employed by practitioners for pet therapy. Cephalexin was administered to five dogs intravenously and intramuscularly as a sodium salt and by the oral route as a monohydrate. The dosage was always 20 mg/kg of active ingredient. A microbiological assay with Sarcina lutea as the test organism was adopted to measure cephalexin concentrations in serum. The mean residence time (MRT) median values after intravenous (i.v.), intramuscular (i.m.) and oral administration (p.o.) were 86 min, 200 min, and 279 min, respectively. After i.m. and oral dosing the peak serum concentrations (24.2 +/- 1.8 micrograms/mL and 20.3 +/- 1.7 micrograms/mL, respectively) were attained at 90 min in all dogs and bioavailabilities were 63 +/- 10% and 57 +/- 5%, respectively. The time course of the cephalexin serum concentrations after oral administration was best described by a model incorporating saturable absorption kinetics of the Michaelis-Menten type: thus in the gastrointestinal tract of dogs a carrier mediated transport for cephalexin similar to that reported in humans, may exist. The predicted average serum concentrations of cephalexin after repeated i.m. and oral administration indicated that, in order to maintain the therapeutic concentrations, the 20 mg/kg b.w. dosage should be administered every 6-8 h.


Subject(s)
Cephalexin/pharmacokinetics , Cephalosporins/pharmacokinetics , Absorption , Administration, Oral , Animals , Area Under Curve , Biological Availability , Cephalexin/administration & dosage , Cephalexin/blood , Cephalosporins/administration & dosage , Cephalosporins/blood , Chemistry, Pharmaceutical , Dogs , Female , Half-Life , Injections, Intramuscular , Injections, Intravenous , Male , Metabolic Clearance Rate , Regression Analysis , Sarcina/drug effects
11.
Infection ; 16 Suppl 1: S62-4, 1988.
Article in English | MEDLINE | ID: mdl-3286518

ABSTRACT

30/30 patients with lower UTI were enrolled in a randomized study to compare ciprofloxacin (250 mg/b.i.d.) and cefalexin (1 g/t.i.d.). In addition, 59 patients with cefalexin-resistant bacterial strains were treated in an open study arm. Ciprofloxacin showed convincingly better clinical and bacteriological efficacy than cefalexin. Both antibiotics were well tolerated. Ciprofloxacin has proved to be superior to cefalexin in the treatment of lower UTI.


Subject(s)
Bacterial Infections/drug therapy , Cephalexin/therapeutic use , Ciprofloxacin/therapeutic use , Urinary Tract Infections/drug therapy , Adult , Cephalexin/administration & dosage , Ciprofloxacin/administration & dosage , Clinical Trials as Topic , Humans , Random Allocation
12.
South Med J ; 75(2): 143-6, 1982 Feb.
Article in English | MEDLINE | ID: mdl-7036355

ABSTRACT

Eighteen adult cancer patients with 21 episodes of staphylococcal bacteremia were treated with sequential intravenous and oral antimicrobial agents. Adequacy of antimicrobial therapy was monitored with serum antibacterial activity studies. The mean duration of intravenous and oral therapy was nine and 25 days, respectively. Clinical and bacteriologic cures were achieved in all cases except one, in which relapse occurred after only 16 days of therapy. One patient had staphylococcal endocarditis and one had staphylococcal pneumonia. Four patients died of causes unrelated to staphylococcal bacteremia after 12, 21, 27, and 40 days of therapy, respectively. Initial intravenous therapy followed by oral antimicrobial agents to complete treatment, monitored with serum antibacterial activity studies, is effective therapy for patients with cancer and staphylococcal bacteremia.


Subject(s)
Cephalosporins/administration & dosage , Nafcillin/administration & dosage , Neoplasms/complications , Sepsis/drug therapy , Staphylococcal Infections/drug therapy , Administration, Oral , Cefazolin/administration & dosage , Cephalexin/administration & dosage , Cephalothin/administration & dosage , Clinical Trials as Topic , Dicloxacillin/administration & dosage , Humans , Injections, Intravenous , Microbial Sensitivity Tests , Sepsis/complications , Staphylococcal Infections/complications
13.
Surg Clin North Am ; 55(6): 1439-44, 1975 Dec.
Article in English | MEDLINE | ID: mdl-1198300

ABSTRACT

The use of the term "prophylactic antibiotics" is probably not appropriate because we are in fact treating contaminated wounds. Only broad spectrum antibiotics that can be expected to be effective against coagulase-positive Staphylococcus aureus should be selected for antibiotic therapy in open fractures. We have found cephalothin-cephalexin therapy to be effective in significantly reducing the infection rate. However, the final selection of antibiotic treatment should be determined by the previous experience of organisms isolated and sensitivity studies done from open fracture wounds in each institution. These organisms will vary from hospital to hospital.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacterial Infections/prevention & control , Fractures, Bone/complications , Fractures, Open/complications , Wound Infection/prevention & control , Cephalexin/administration & dosage , Cephalexin/therapeutic use , Cephalothin/administration & dosage , Cephalothin/therapeutic use , Debridement , Humans , Microbial Sensitivity Tests , Penicillins/administration & dosage , Penicillins/therapeutic use , Prospective Studies , Streptomycin/administration & dosage , Streptomycin/therapeutic use , Therapeutic Irrigation
15.
Antimicrob Agents Chemother ; 6(4): 501-6, 1974 Oct.
Article in English | MEDLINE | ID: mdl-4157353

ABSTRACT

The effectiveness of cephalexin, an oral cephalosporin using a dosage equivalent to available capsular dosage forms, was studied in relation to the effectiveness of phenoxymethyl penicillin and benzathine penicillin in the treatment of 128 patients with beta-hemolytic streptococcal pharyngitis, all but six of whom had group A streptococci isolated from throat cultures. Approximately one-half, 66 patients, received cephalexin for 10 days; 34 patients received phenoxymethyl penicillin for 10 days; and 28 patients had a single injection of benzathine penicillin. There were four treatment failures determined bacteriologically post-therapy, two in the cephalexin treatment group and one each in the oral penicillin and intramuscular penicillin groups. Similar cure rates of 96.7, 97.1, and 96.4% were computed for the respective treatment regimens. Whereas intramuscular benzathine penicillin remains the regimen of choice in most instances, cephalexin appeared to be as effective as oral penicillin in the elimination of group A streptococci from the pharynx when oral treatment was desired for streptococcal pharyngitis.


Subject(s)
Cephalexin/administration & dosage , Penicillin G Benzathine/administration & dosage , Penicillin V/administration & dosage , Pharyngitis/drug therapy , Streptococcal Infections/drug therapy , Administration, Oral , Adolescent , Antistreptolysin , Bacteriological Techniques , Cephalexin/adverse effects , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Injections, Intramuscular , Male , Microbial Sensitivity Tests , Pharyngitis/microbiology , Titrimetry
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