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Cephalexin and penicillin in the treatment of group A beta-hemolytic streptococcal throat infections.

OBJECTIVE: To determine whether cephalexin or penicillin is more effective in the treatment of group A beta-hemolytic streptococcal tonsillopharyngitis in children. DESIGN: Randomized, double-blind, crossover study conducted from 1981 to 1984. SETTING: Seven pediatric practices in the United States, including private offices and pediatric clinics. PARTICIPANTS: Of the 654 patients, 525 children and adolescents with clinical evidence of tonsillitis or pharyngitis and throat cultures positive for group A beta-hemolytic streptococcal infection were evaluable. Eighty percent of patients completed the study; none were withdrawn because of adverse reaction. SELECTION CRITERIA: Children and adolescents who had acute illness suggestive of group A beta-hemolytic streptococcal infection were enrolled in the study. Treatment was continued if the throat culture was positive for group A beta-hemolytic streptococcal infection. INTERVENTIONS: Four doses of cephalexin and penicillin (27 mg/kg per day) were prescribed to be taken on an empty stomach for 10 days. MEASUREMENTS/MAIN RESULTS: Symptomatic clinical failure occurred in 8% of penicillin-treated patients and in 3% of cephalexin-treated patients. Bacteriologic failure rates were 11% in the penicillin treatment group and 7% in the cephalexin treatment group. The combined treatment failure rate of clinical relapse plus asymptomatic bacteriologic failure was 19% in the penicillin treatment group and 10% in the cephalexin treatment group. Paired antistreptolysin-O titer increased significantly in 62.3% of penicillin-treated patients and in 64.2% of cephalexin-treated patients. Similarly, anti-DNase B titers rose 52.2% in penicillin-treated patients and 52.4% in cephalexin-treated patients. CONCLUSION: Cephalexin is a more effective drug than penicillin in the treatment of group A beta-hemolytic streptococcal throat infection in children.

Adolescent

Ofloxacin versus cephalexin in the treatment of skin, skin structure, and soft-tissue infections in adults.

A multicenter study was conducted to compare the safety and efficacy of oral ofloxacin with that of cephalexin in microbiologic eradication of skin and skin-structure pathogens and the clinical treatment of skin and skin-structure infections. The subjects, 335 adult patients with acute localized infections of the skin, skin structure, or soft tissue, were randomly assigned to receive 400 mg of ofloxacin orally every 12 hours or 500 mg of cephalexin orally every six hours for 10 days. At admission, 398 aerobic pathogens were isolated, the most common being Staphylococcus aureus (160 isolates), Streptococcus pyogenes (49), coagulase-negative staphylococci (30), Staphylococcus epidermidis (25), and Pseudomonas aeruginosa (10). Of 317 isolates tested against ofloxacin, 96% were susceptible, and of 325 tested against cephalexin, 85% were susceptible (P less than 0.001). Microbiologic and clinical outcome were evaluated in 73 ofloxacin-treated patients and in 65 cephalexin-treated patients. The causative pathogens were eradicated in 95% of the ofloxacin group and in 92% of the cephalexin group. In the ofloxacin group, 75% were clinically cured and 23% improved, and in the cephalexin group, 74% and 23%, respectively. Drug-related adverse experiences were reported by 14% of the 161 ofloxacin-treated patients and by 11% of the 162 cephalexin-treated patients; gastrointestinal disturbances were reported by 8% and 7% and nervous system effects by 6% and 1%, respectively (P less than 0.05). It is concluded that both ofloxacin and cephalexin are safe and effective in the treatment of skin and soft-tissue infections.

Adolescent

Penetration of antibiotic into interstitial tissue fluid following parenteral administration of lysine cephalexin.

Serum and interstitial fluid levels of antibiotic have been measured at various times following i.m. administration of equivalent doses of lysine cephalexin and sodium ampicillin, in a cross-over design, to dogs fitted with s.c. implanted silastic "tissue cages" and the results subjected to pharmacokinetic analysis. Serum concentrations of cephalexin were consistently higher than those of ampicillin and elimination half-lives were calculated as 1.73 h and 0.87 h, respectively. The rate of appearance of cephalexin in the interstitial fluid (Ka 1.741 h-1 was faster than that for ampicillin (Ka 0.946 h-1) and the maximum concentration obtained also proved to be higher. The half-life of cephalexin in the interstitial fluid (6.79 h) was almost four times longer than that in serum whereas that of ampicillin (2.03 h) was only a little more than twice as long. As a consequence a greater concentration and retention in interstitial fluid was obtained with cephalexin at all times tested. Since the interstitial fluid levels of cephalexin were still relatively high 8-12 h after the administration of a single dose repeated administration of lysine cephalexin 2 or 3 times daily is expected to result in a beneficial accumulation of cephalexin in the interstitial fluid.

Ampicillin

Double-blind, double-dummy comparison of azithromycin and cephalexin in the treatment of skin and skin structure infections.

In this double-blind, randomised trial conducted in 22 centres in the USA, azithromycin given over five days, as a once-a-day regimen, (500 mg on day 1, 250 mg on days 2-5) was compared with cephalexin (500 mg b.i.d.) given for ten days in the treatment of patients with skin and skin structure infections. A total of 366 patients entered the study and 179 of these were eligible for the efficacy analysis. The overall clinical response to azithromycin was 94.0%, compared with 95.8% for cephalexin. The clinical cure rates were 53.0% for azithromycin and 59.4% for cephalexin; the respective improvement rates were 41.0% and 36.5%. Distribution of response (cured, improved, failed) was similar in each group (p = 0.37). The bacteriological eradication rate for azithromycin-treated patients was 94.2% and for cephalexin-treated patients was 90.3% (p = 0.34). Clinical and bacteriological response was similar in each group for all primary diagnoses. The two antibiotics were well tolerated, the overall incidence of side effects being 13.7% with approximately 60% due to gastrointestinal disturbances. In all but one case (cephalexin) the severity of the reported side effects was mild or moderate. Six patients withdrew from the study due to treatment-related events; five had been treated with azithromycin and one with cephalexin. In summary, a five-day, once-daily regimen of azithromycin was as effective as a ten-day, twice-daily regimen of cephalexin in the treatment of patients with skin and skin structure infections.

Abscess

Comparison of pharmacological and antimicrobial properties of cefadroxil and cephalexin.

Pharmacological and antimicrobial properties of cefadroxil, a new cephalosporin antibiotic, were compared with cephalexin. Absorption and excretion were studied in 20 healthy men. Peak concentrations of the drugs in serum were similar after ingestion of single 500-mg tablets. The concentration of cefadroxil in serum was more sustained than that of cephalexin. Levels of cefadroxil in serum after a dose of 1,000 mg were approximately twice those after a 500-mg dose through 6 h. Each drug administered in a dose of 500 mg every 6 h for 24 h resulted in concentrations in serum that were similar to a single dose without accumulation. Ninety-three percent of the cefadroxil and 85% of the cephalexin were excreted in urine after ingestions of single 500-mg tablets. The urine concentration of cefadroxil was more sustained than cephalexin. Minimal inhibitory and minimal bactericidal concentrations for clinical isolates were comparable with each drug. Cefadroxil compares favorably with cephalexin in this study. Sustained levels of cefadroxil in serum and urine suggest that this drug may be given at less frequent intervals than cephalexin.

Adult

Comparative efficacy of cephalexin and ampicillin for shigellosis and other types of acute diarrhea in infants and children.

Most ampicillin-resistant Shigella are susceptible to cephalexin. Randomized treatment with cephalexin or ampicillin was given to 154 infants and children with acute diarrhea. Rectal swab cultures revealed Shigella in 42%, Salmonella in 6%, enteropathogenic Escherichia coli in 2%, and no pathogen in 50%. Cephalexin failed to eradicate Shigella after 5 days of treatment in 76% of patients as contrasted with 28% of ampicillin-treated patients with susceptible organisms. Shigella persisted in 78% of ampicillin-treated patients with resistant organisms. Diarrhea lasted more than 5 days in 43% of cephalexin-treated patients, in 56% of the ampicillin group with resistant organisms, but in only 9% of ampicillin-treated patients with susceptible organisms. The failure of cephalexin was due to the relatively high minimal inhibitory concentrations and minimal bacterial concentrations of 5 or 10 mug/ml and, although serum concentrations were twice the minimal bacterial concentration, they were not sufficient to demonstrate killing by the serum dilution method. In vitro susceptibility or resistance of Shigella to ampicillin correlated with clinical success or failure. Cephalexin is not a suitable drug for treatment of shigellosis in patients with ampicillin-resistant organisms.

Ampicillin

Clinical comparison of cefuroxime axetil, cephalexin and cefadroxil in the treatment of patients with primary infections of the skin or skin structures.

This study was designed to compare the clinical and bacteriological efficacy of three oral cephalosporins, cefuroxime axetil, cephalexin and cefadroxil, in the treatment of patients with mild to moderate infections of the skin or skin structures. A total of 330 patients were enrolled at 10 centers and were randomly assigned to receive cefuroxime axetil 250 mg (n = 107), cephalexin 500 mg (n = 111) or cefadroxil 500 mg (n = 112), twice daily for 10 days. Patients were assessed for their clinical and bacteriological responses once during treatment (3-5 days) and twice after treatment (1-3 and 10-14 days). A total of 353 bacterial isolates were obtained: Staphylococcus aureus (41%), Staphylococcus epidermidis (33%) and Streptococcus pyogenes (5%). A satisfactory clinical outcome (cure or improvement) was achieved in 97% (89/92), 89% (80/90) and 94% (82/87) of the clinically evaluable patients treated with cefuroxime axetil, cephalexin or cefadroxil, respectively (p = 0.047, cefuroxime axetil vs. cephalexin). With respect to the eradication of the bacterial pathogens, a satisfactory outcome (cure or presumed cure) was obtained in 96% (69/72), 85% (60/71) and 93% (63/68) of bacteriologically evaluable patients treated with cefuroxime axetil, cephalexin and cefadroxil, respectively (p = 0.026, cefuroxime axetil vs. cephalexin). All three study drugs were well tolerated, with adverse events affecting the gastrointestinal system most commonly reported. There were no significant differences between treatment groups in the incidence of drug-related adverse events.

Adolescent

Ofloxacin versus cephalexin for treating skin and soft tissue infections.

Patients with acute localized skin or soft tissue infections were randomized to receive either ofloxacin (300 mg orally, b.i.d.) or cephalexin (500 mg orally, b.i.d.). Among 401 enrolled patients, 382 were evaluable for safety and 148 for microbiologic response. Microbiologic cure occurred in 93.4% of ofloxacin-treated patients and in 94.0% of those treated with cephalexin. Clinical cure or improvement, respectively, was found in 85.2% and 11.1% of patients treated with ofloxacin, and 83.6% and 14.9% of patients receiving cephalexin. Adverse effects (primarily associated with the gastrointestinal tract and central nervous system) were considered to be drug-related in 7.9% of those receiving ofloxacin and 4.8% of those receiving cephalexin. Thus, ofloxacin is as effective and well tolerated as cephalexin and a good alternate antibiotic for treating skin and skin structure infections caused by a variety of pathogens.

Cephalexin

Comparative human oral clinical pharmacology of cefadroxil, cephalexin, and cephradine.

At equivalent oral doses, cefadroxil has a longer serum half-life, slower urinary excretion rate, greater area under the serum level versus time curve than cephalexin or cephradine, and peak serum concentrations that are 75 to 80% those of cephalexin. The calculated, apparent in vivo volume of distribution of cefadroxil is greater than that of cephalexin. These properties infer greater persistence of cefadroxil in serum and urine and more prolonged in vivo bacterial exposure to cefadroxil than to cephalexin or cephradine. Neither cefadroxil nor cephalexin demonstrates drug accumulation on repeated administration. The serum levels achieved by cefadroxil are unaffected by food. The pharmacokinetic properties of cefadroxil are supportive of the development of clinical efficacy data which could indicate that cefadroxil could be administered at 12-h intervals.

Adult

Comparative double-blind study of cephalexin and co-trimoxazole in urinary tract infections.

Treatment with cephalexin 1 g twiec daily and cotrimoxazole 2 tablets twice daily was compared in a double-blind, randomised study of 100 women with urinary tract infections. CO-trimoxazole gave a significantly higher cure rate compared with cephalexin two and six weeks after the one-week course of treatment. The higher failure rate with cephalexin was not related to the age of the patient, presentation, pyelographic appearances, or type of organism in the initial infection. Among the failures all but one of the organisms were sensitive to cephalexin. With the dosage regimen and duration of treatment used in this study cotrimoxazole appears to be superior to cephalexin in the management of acute urinary infections.

Adult

Eradication of biofilm cells of Staphylococcus aureus with tobramycin and cephalexin.

The kinetics of growth and formation of biofilm by Staphylococcus aureus were investigated under iron-limited conditions in the chemostat. The population of planktonic cells reached 5.5 x 10(9) cells/mL 24 h after inoculation (D = 0.05 h-1) and remained constant throughout. The number of biofilm cells of S. aureus colonizing the silicone tubing increased exponentially from 6 x 10(4) to 2.7 x 10(7) cells/cm2 (6 days later) and continued to increase at a reduced rate to 2.7 x 10(8) cells/cm2 on day 13. Planktonic cells of S. aureus were susceptible to tobramycin and cephalexin. The planktonic cells could be successfully eradicated with a combination of 5 micrograms tobramycin plus 100 micrograms cephalexin per millilitre. Exposure of young biofilm cells of S. aureus to 5 micrograms tobramycin plus 100 micrograms cephalexin per millilitre resulted in a rapid loss of cell viability. The percentage of survival dropped to less than 0.0001% after exposure to these concentrations of antibiotics for 3 h. Old biofilm cells of S. aureus were found to be extremely resistant to these antibiotics. The cell viability was reduced to 0.09% after exposure to 10 micrograms tobramycin plus 100 micrograms cephalexin per millilitre. The results suggest that it is possible to eradicate S. aureus infection at the early stage with tobramycin plus cephalexin. Any delay in implementing antibiotic therapy is likely to result in the failure of the treatment. It is important to note that the concentrations of antibiotics required for the eradication of young biofilm cells must be determined for the treatment of device-associated infections.

Bacterial Adhesion

[Clinical experience with sustained release cephalexin (S-6437) in pediatrics (author's transl)].

S-6437 (Sustained release cephalexin granule for pediatric use) was studied with the following results: 1) Following the single oral administration of 25 mg/kg of S-6437 in 6 children 4 approximately 6 years old, the following blood levels (average) of cephalexin were obtained: 3.1 microgram/ml in one hour after the administration, 8.6 microgram/ml in 2 hours, 8.7 in 4 hours, 7.2 in 6 hours, 4.0 in 8 hours and 1.2 in 12 hours. Effective blood levels of cephalexin by S-6437 were maintained for longer period of time than those by regular cephalexine dry syrup. In 4 of 6 children receiving S-6437, cephalexin was scarcely detected in their blood in 12 hours after the administration. From this, it is not considered that S-6437 is accumulated in body. 2) S-6437 was administered to 38 patients including: 7 with pneumonia, 7 with acute bronchitis, 1 with suppurative lymphadenitis, 4 with acute pharyngitis, 15 with acute tonsillitis and 4 with acute urinary tract infections. Out of the 35 cases, 31 (88.6%) responded to S-6437, and 3 cases could not be evaluated. 3) Transient diarrhea in 2 patients, rash in 1 and elevation of serum GOT, GPT and LDH in 1 were observed. However, these side effects were improved by discontinuation of S-6437.

Age Factors

Cephalexin compared to ampicillin treatment of otitis media.

Cephalexin was compared to ampicillin for the treatment of otitis media in a randomized study. Bacteriologic diagnosis was sought by needle tympanocentesis in 179 children. No overall statistically significant differences were noted between the two groups; however, 20 patients who received cephalexin had a poor response to therapy whereas only five recipients of ampicillin responded poorly. A significant difference (P less than .05) between the two regimens was noted when Hemophilus influenzae was recovered. Fifty per cent of the children with H. influenzae otitis media who were treated with cephalexin responded poorly; no patients receiving ampicillin had a poor response. Our data suggest that the use of cephalexin monohydrate is not warranted for treatment of otitis media due to H. influenzae even when the isolate proves sensitive to this drug in vitro. In selected patients with otitis media caused by Staphylococcus aureus which is resistant to penicillin, cephalexin may provide effective treatment.

Ampicillin

Quantitative determination of cephalexin in cephradine by NMR spectroscopy.

An NMR method to determine quantitatively the presence of cephalexin in cephradine was developed. The method is applicable to the chemical itself as well as to capsules and oral suspension formulations. The determination is based on the NMR signal arising from the five aromatic protons of the cephalexin molecule. Integration of this signal relative to a signal from cephradine provides the data necessary to determine the percentage of cephalexin present. The precision at the 2% cephalexin levels is +/- 0.18%. The time required to carry out a single analysis is about 10 min, and five analyses can be done in about 0.5 hr.

Capsules

[Aqueous-and serum levels of cephalexin and penicillin V after oral application in man (author's transl)].

This clinical study implies orally administered cephalexin and penicillin V as agents with effective aqueous homor penetration in noninfected human eyes. Aqueous humor concentration of cephalexin increases up to 15% of the serum level 2 h after application. Administration of 1 g or 2 g cephalexin revealed no significant difference in aqueous humor concentration. So penetration of blood-aqueous-humor barrier can be regarded as a saturation process. Individual results of 92 cephalexin determinations are variant and not related to body weight or age of the patients.

Aged

[Subinhibitory activity of cefaclor and cephalexin (author's transl)].

The determination of the minimal inhibitory concentration (MIC), which is usually performed after 18 to 24 hours of incubation, results in the case of cefaclor in a false picture of the actual activity. Cefaclor is chemically so unstable that after 24 hours only 2-5% of the substance is microbiologically active. In order to compare the activity of cefaclor and cephalexin, the effect of subinhibitory concentrations of both antibiotics against Escherichia coli and Klebsiella pneumoniae strains was studied by means of turbidimetry. After eight hours the absolute inhibitory concentration of cefaclor was lower than that of cephalexin with both methods. At the same time the effect of subinhibitory concentrations of both antibiotics was equal. Automatic measurement over 20 hours showed at the end of the experiment a higher MIC, and also a higher subinhibitory range, for cefaclor than for cephalexin. In our opinion the absolute inhibitory concentration after eight hours should be the criterion used to evaluate the effectiveness of cefaclor and cephalexin, and not the MIC which is usually used. The eight-hour criterion should also be applied in clinical use.

Cefaclor

Cefaclor uptake by the proton-dependent dipeptide transport carrier of human intestinal Caco-2 cells and comparison to cephalexin uptake.

The human Caco-2 cell line spontaneously differentiates in culture to epithelial cells possessing intestinal enterocytic-like properties. These cells possess a proton-dependent dipeptide transport carrier that mediates the uptake of the cephalosporin antibiotic cephalexin (Dantzig, A.H. and Bergin, L. (1990) Biochim. Biophys. Acta 1027, 211-217). In the present study, the uptake of cefaclor was examined and found to be sodium-independent, proton-dependent, and energy-dependent. The initial rate of D-[3-phenyl-3H]cefaclor uptake was measured over a wide concentration range; uptake was mediated by a single saturable transport carrier with a Km of 7.6 mM and a Vmax of 7.6 nmol/min per mg protein and by a non-saturable component. Uptake was inhibited by dipeptides but not amino acids. The carrier showed a preference for the L-isomer. The effect of the presence of a 5-fold excess of other beta-lactam antibiotics was examined on the initial rates of 1 mM cefaclor and 1 mM cephalexin uptake. Uptake rates were inhibited by the orally absorbed antibiotics, cefadroxil, cefaclor, loracarbef, and cephradine and less so by the parenteral agents tested. The initial uptake rates of both D-[9-14C]cephalexin and D-[3-phenyl-3H]cefaclor were competitively inhibited by cephalexin, cefaclor, and loracarbef with Ki values of 9.2-13.2, 10.7-6.2, and 7.7-6.4 mM, respectively. Taken together, these data suggest that a single proton-dependent dipeptide transport carrier mediates the uptake of these orally absorbed antibiotics into Caco-2 cells, and provide further support for the use of Caco-2 cells as a cellular model for the study of the intestinal proton-dependent dipeptide transporter.

2,4-Dinitrophenol

Cefazolin and cephalexin levels in prostatic tissue and sera.

A study was carried out on 18 patients given cefazolin intramuscularly and 17 patients given cephalexin by mouth preoperatively prior to transurethral resection of the prostate. Prostatic tissue and serum levels of the two drugs were determined and contrasted with previously reported mean inhibitory concentrations. It was found that cefazolin was present in the sera and prostatic tissues in levels greater than was cephalexin and that cefazolin frequently exceeded the minimum inhibitory concentrations necessary for sensitive organisms to be affected, whereas cephalexin did not. Therefore, it would appear that cefazolin would be preferable to cephalexin in treatment of acute bacterial prostatitis.

Biological Availability