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PubMed1988

Efficacy of perioperative cefamandole with postoperative cephalexin in the primary outpatient treatment of open wounds of the hand.

Eighty-seven patients participated in a prospective, double-blind, clinical study to determine the efficacy of preventive antibiotics in the management of common open traumatic hand wounds ranging in severity from single nail bed injuries with open fractures to moderately contaminated wounds involving tendon, bone, joint, and neurovascular structures. Under current medical practice, these wounds would be treated with antibiotics. Thirty-nine patients received intravenous cefamandole and oral cephalexin and 48 received intravenously and orally administered placebo. With an overall infection rate of 1.1%, there were no infections in the antibiotics group and only one (2.1%) infection in the placebo group. Aerobic cultures from 97 similar wounds were 53.6% positive predebridement and 50.5% positive postdebridement. There was no significant difference in rates of infection or imperfect wound healing between the two groups. The preventive antibiotics administered were not necessary in treating these wounds when accompanied by debridement, irrigation, and rapid primary repair in an operating room environment.

Adolescent↗
PubMed1991

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.

Cefaclor↗
PubMed2006

Delirium in an adolescent patient during treatment with cephalexin.

Although cephalosporins are generally safe, they have been reported to cause neurotoxic effects in some subjects. We report on a 16-year-old boy with no previous history of psychiatric illness, who developed symptoms of delirium during treatment of paronychia infection with cephalexin. Possible reasons for our patient's particular vulnerability to adverse drug effects in the central nervous system include his young age, a developmental delay, and an earlier head injury.

Adolescent↗
PubMed2005

Expression and purification of penicillin G acylase enzymes from four different micro-organisms, and a comparative evaluation of their synthesis/hydrolysis ratios for cephalexin.

Several genes for the enzyme penicillin G acylase, as isolated from four different micro-organisms (Alcaligenes facaelis, Escherichia coli, Kluyvera cryocrescens or Providencia rettgeri) were modified at their carboxy-termini to include His-tag fusions, then were expressed from the plasmid pET-24a(+) in E. coli JM109(DE3) cells. All fusion proteins were next purified to homogeneity in a single step by agar-based Co-IDA chromatography, and were then evaluated as catalysts for the synthesis of cephalexin by a kinetically controlled strategy. We find here that the penicillin G acylase enzyme from K. cryocrescens shows a higher intrinsic synthesis/hydrolysis ratio, when compared to three other enzymes from A. facaelis or P. rettgeri, or E. coli.

Alcaligenes faecalis↗
PubMed1977

Structure--activity relationships in cephalosporins prepared from penicillins. 2. Analogues of cephalexin substituted in the 3-methyl group.

A previously outlined general procedure for preparing various 3-substituted cephalosporins from the penicillin nucleus has been used, with modifications where required, to prepare a series of analogues of cephalexin with various substituents in the 3-methyl group. The 3-substituents most conducive to broad-spectrum antibacterial activity were 3-pyridylmethyl and m- or p-carboxybenzyl. The compounds were only poorly absorbed by the oral route in mice, but the 3-(carboxybenzyl) compounds gave more prolonged useful serum levels than the usual cephalosporins.

Animals↗
PubMed1996

Uptake characteristics of loracarbef and cephalexin in the Caco-2 cell culture model: effects of the proton gradient and possible presence of a distinctive second component.

The mechanisms of apical (AP) uptake of cephalexin (CEPH) and loracarbef (LOR) in the absence or presence of an (extemally imposed) proton gradient were determined using well-stirred diffusion chambers that minimize the effects of the unstirred water layer. The results indicated that, compared to AP uptake in the presence of an imposed proton gradient, AP uptake in the absence of an imposed proton gradient had higher K(m) values and lower Jmax values. Furthermore, when inhibition studies were performed in the absence of a proton gradient, only natural peptides were effective, whereas the peptide analogs (e.g., enalapril) were not. In addition to the effects of concentration and competitive inhibitors, the results also indicated that (1) the AP uptake of both drugs was decreased more than 60% by FCCP, regardless of whether the proton gradient was present or absent; (2) effects of protein kinase C promoter were dependent upon the presence of a proton gradient; and (3) AP uptake in the presence of an imposed proton gradient was not affected by feeding restriction, whereas AP uptake in the absence of an imposed proton gradient was. These results showed for the first time that two substrates with similar AP uptake characteristics in the presence of an imposed proton gradient may not share those characteristics in the absence of an imposed proton gradient. Taken together, these results suggest that the AP uptake component that functions in the absence of an imposed proton gradient is distinctly different from the one that functions in the presence of an imposed proton gradient. Data generated from the present study and those in the literature lend support to the hypothesis that this distinctive component represents the second binding site on the AP peptide transporter. However, an alternative hypothesis that there are two AP peptide transporters remains to be disapproved.

Caco-2 Cells↗
PubMed1983

Cefazolin and cephalexin kinetics in continuous ambulatory peritoneal dialysis.

We studied single-dose cefazolin (CFZ) and cephalexin (CPX) kinetics in continuous ambulatory peritoneal dialysis (CAPD) patients to establish therapeutic guidelines for two cephalosporins commonly used to treat peritonitis in these patients. CFZ, 10 mg/kg, was given intravenously and intraperitoneally, while CPX, 500 mg, was given orally. CFZ led to serum concentrations of 25 microgram/ml at 24 hr, with a half-life (t 1/2) of 33 hr. CAPD accounted for only 20% of total body clearance. When CFZ was given intraperitoneally, 74% of the dose was absorbed and similar serum concentrations had much the same t 1/2. CPX, on the other hand, had a serum t 1/2 of 8.6 hr and resulted in much lower peritoneal concentrations than CFZ. The kinetic principal of superposition provided a model for the prediction of plasma concentrations after repeated intraperitoneal doses of CFZ. The model predicts that a 10-mg/kg intraperitoneal loading dose, followed by 5-mg/kg doses in each exchange the first day and 2.5-mg/kg doses thereafter, will lead to steady-state plasma concentrations of 50 to 65 microgram/ml. The data suggest that CFZ needs be given only intraperitoneally at doses lower than those in current use. CPX probably adds little to the treatment of peritonitis.

Administration, Oral↗
PubMed1985

A new dosing regimen in renal insufficiency: application to cephalexin.

We describe a new method of drug dosage adjustment. The method simultaneously considers glomerular and tubular functions as parameters, because nonparallel decreases in both functions limit the use of the conventional endogenous creatinine clearance (CLCR) method for dosage adjustment. In the new method, CLCR and the 15-minute phenolsulfonphthalein (PSP15') test were used and applied to patients with renal insufficiency with cephalexin (CEX) as a model drug for renal tubular secretion. The results clearly demonstrate good control of plasma CEX concentrations by the CLCR-PSP15' method, whereas there were marked changes in plasma CEX levels with the CLCR method alone. Our method appears to be more useful for patients with renal impairment than the conventional CLCR method for CEX, which is mainly excreted in urine by renal tubular secretion. A nomogram for the CEX dosing interval is proposed for application to clinical practice.

Absorption↗
PubMed1981

Tobramycin-clindamycin versus cephalothin-cephalexin in the treatment of appendicular peritonitis.

Forty-seven children, ages 1 to 14 years, with appendicular peritonitis were randomly divided into two groups: 27 were treated with the combination tobramycin-clindamycin and 20 with cephalothin followed by cephalexin. The overall rate of complications was 32%. Patients who had had their symptoms for less than 48 hours before being admitted to hospital had significantly fewer complications than those whose symptoms had lasted longer. Patients treated with tobramycin-clindamycin had significantly fewer wound infections. As clindamycin is effective against anaerobes this observation supports the view that anaerobes play an important role in the infectious complications in peritonitis. In this series, 12 species of aerobes and eight species of anaerobes were cultured from peritoneal fluid. In eight patients only one species was isolated; in the remaining 39 patients 29 different combinations of bacteria were encountered. Early diagnosis and administration of antibiotics preoperatively or during surgery, including clindamycin, metronidazol or tinidazol is recommended in the treatment of children with appendicular peritonitis.

Adolescent↗
PubMed2004

Binding of transition metal ions [cobalt, copper, nickel and zinc] with furanyl-, thiophenyl-, pyrrolyl-, salicylyl- and pyridyl-derived cephalexins as potent antibacterial agents.

A method is described for the preparation of novel cephalexin-derived furanyl-, thiophenyl-, pyrrolyl-, salicylyl- and pyridyl-containing compounds showing potent antibacterial activity. The binding of these newly synthesized antibacterial agents with metal ions such as cobalt(II), copper(II), nickel(II) and zinc(II) has been studied and their inhibitory properties against various bacterial species such as Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae are also reported. These results suggest that metal ions to possess an important role in the designing of metal-based antibacterials and that such complexes are more effective against infectious diseases compared to the uncomplexed drugs.

Anti-Bacterial Agents↗
PubMed2004

Antifungal cobalt(II), copper(II), nickel(II) and zinc(II) complexes of furanyl-,thiophenyl-, pyrrolyl-, salicylyl- and pyridyl-derived cephalexins.

Some novel cephalexin-derived furanyl, thiophenyl, pyrrolyl, salicylyl and pyridyl Schiff's bases and their cobalt (II), copper (II), nickel (II) and zinc (II) complexes have been synthesized and studied for their antifungal properties against Trichophyton longifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solani and Candida glaberata. The presence of metal ions in the investigated Schiff's base complexes reported here lead to significant antifungal activity, whereas the parent ligands were generally less active.

Antifungal Agents↗
PubMed1975

An electron microscopic study of antagonism between cephalexin and erythromycin in Staphylococcus aureus.

This study concerns investigations at the cellular level of antagonism between cephalexin (CEX) and erythromycin (EM) with the aid of electron microscopes and a liquid scintillation counter. Exposure of Staphylococcus aureus 209-P to CEX and EM in combination was found to result in a marked antagonism between the two antibiotics in their effects on the growth of the organism. Observations under a scanning electron microscope revealed lysed cells in the presence of CEX alone but almost no lysis in the presence of a combination of CEX and EM. Observations under a transmission electron microscope, on the other hand, disclosed that nearly all of the cells exposed to 20 mug/ml of CEX were transformed into protoplasts with their morphological changes being most marked after 4 hr of exposure. When 1 mug/ml of EM was allowed to act alone, this exposure resulted in thickening of the cell walls. The combined use of CEX and EM, however, resulted in neither thickening of the cell walls as in the presence of EM alone nor in the formation of protoplasts as in the presence of CEX alone but merely produced the swelling of separating walls. Cellular uptake of 14C-L-lysine and N-acetylglucosamine-1-14C into the cell wall fraction and the protein fraction was affected by CEX and EM, respectively, when used alone or in combination.

Bacterial Proteins↗
PubMed1977

Fluorimetric assay of cephradine, cephalexin and cephaloglycin.

1 A simple, rapid and reproducible fluorimetric assay for cephradine, cephalexin and cephaloglycin is described. 2 The method involves addition of formaldehyde which catalyses the formation of fluorescent derivatives. 3 The structural similarities between the side chains of these antibiotics and their identical excitation and emission spectra suggest that they may be forming similar fluorescent derivatives.

Cephalexin↗
PubMed1975

Positive direct antiglobulin (Coombs') test caused by cephalexin administration in humans.

Of 71 patients showing a negative direct antiglobulin (Coombs') test (DAT) before administration of cephalexin (CEX) three developed a positive DAT after therapy with this drug (4 percent). No case of immunohemolytic anemia was observed. The sera of the patients with a positive DAT reacted with cephalothin-coated red cells producing high titers, with penicillin cells normal titers and with CEX cells low titers. Since the red cell eluates of these patients did not give significant reactions with red cells sensitized with CEX, cephalothin and penicillin, a nonimmunological mechanism for the development of the positive DAT in these patients has to be assumed.

Adolescent↗
PubMed1983

Bacteriuria in pregnancy treated with a single dose of cephalexin.

Of 87 women in whom bacteriuria was diagnosed on dip slides at between 9 and 22 weeks gestation only 51 (59%) had true bacteriuria in urine obtained by suprapubic aspiration. A single oral dose of cephalexin (3 g) was given to 37 of these patients, 10 were Indian and none of them had recurrence of infection after treatment, whereas 11 of the 27 (41%) 'indigenous' women again had bacteriuria within 2 weeks of treatment. None of the other 26 patients had recurrent bacteriuria in the pregnancy studied. Success of treatment was not related to renal concentrating ability nor, apart from ethnic group, were there other significant differences between successes and failures. Although single-dose treatment seems to be less effective in pregnancy than in the non-pregnant patients, it is an acceptable method of treatment provided that all treated patients are followed closely to detect those who do not respond and require further therapy.

Bacteriuria↗
PubMed1988

Stereospecific absorption and degradation of cephalexin.

Stereospecific absorption and degradation of two stereoisomers about the alpha-amino group at the 7-position of cephalexin (CEX) have been investigated in the rat intestine. The L-isomer (L-CEX) was not found to be present either in serum or urine after oral administration, but the D-isomer (D-CEX) was well absorbed. In contrast to the saturable uptake of D-CEX (Kt = 10.54 +/- 1.73 mM, pH = 6.0) by the in-vitro everted intestinal sac, no appreciable uptake of L-CEX was observed. However, L-CEX competitively inhibited the uptake of D-CEX by the in-vitro everted intestine and the inhibitory constant (Ki) of L-CEX was determined to be 0.67 +/- 0.09 mM. L-CEX was rapidly degraded in-vitro in the intestinal tissue homogenate, serum and urine, while there was no appreciable degradation of D-CEX. Analysis of the major metabolite of L-CEX by high-performance liquid chromatography identified it as 7-aminodeacetoxycephalosporanic acid (7-ADCA). Furthermore, 7-ADCA was detected in serum after oral administration of L-CEX, indicating significant absorption of L-CEX as well as D-CEX. The results obtained suggest that both L- and D-CEX can be absorbed through the intestinal brush-border membrane via the same mechanism, most likely through the dipeptide transport system, and that the affinity of L-CEX to the carrier system is higher than that of D-CEX.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed2006

Functional expression of stereoselective metabolism of cephalexin by exogenous transfection of oligopeptide transporter PEPT1.

Gastrointestinal absorption of the beta-lactam antibiotic cephalexin (CEX) is highly stereoselective: l- and d-CEX are both taken up by intestinal epithelial cells through the brush-border membrane, most likely via oligopeptide transporter PEPT1, but l-CEX is not found in serum or urine after administration p.o. because of its rapid intestinal metabolism, whereas d-CEX is well absorbed in the unchanged form. We examined the contribution of PEPT1 to the stereoselective uptake and metabolism of CEX. We observed stereoselective metabolism of CEX after exogenous transfection of PEPT1 alone into mammalian cell lines: l-CEX, but not d-CEX, was metabolized to 7-aminodesacetoxycephalosporanic acid (7-ADCA) in HeLa and human embryonic kidney 293 cells stably and transiently expressing human PEPT1, respectively, whereas such metabolism was minor in cells expressing the vector alone. The formation rate of 7-ADCA depended on the amount of PEPT1 cDNA transfected. l-CEX metabolism was rapid because only 7-ADCA was found inside and outside the cells during incubation with l-CEX. The characteristics of PEPT1-mediated metabolism of l-CEX were similar, but not identical, to those of PEPT1-mediated transport. PEPT1-mediated metabolism was also observed in permeabilized cells expressing PEPT1, in which PEPT1-mediated intracellular substrate accumulation was negligible, suggesting that the increase in l-CEX metabolism by PEPT1 transfection cannot be fully explained by an increase in uptake and subsequent exposure to intracellular hydrolases. The present findings show that stereoselectivity in CEX absorption can be fully explained in terms of PEPT1, implying that the l-CEX hydrolase is PEPT1 itself or is induced by PEPT1.

Anti-Bacterial Agents↗
PubMed1992

Kinetic interaction of biofilm cells of Staphylococcus aureus with cephalexin and tobramycin in a chemostat system.

Planktonic and young biofilm cells were completely eradicated after exposure of these cells to drug levels representing one loading and two maintenance doses of tobramycin and cephalexin. A very different picture was observed when antibiotic exposure was initiated on day 21. Complete eradication of the old biofilm cells was not observed even when the antibiotic exposure was continued for an extra 6 days. Regrowth of the organism was observed when the antibiotic exposure was terminated.

Cell Survival↗