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Clinical pharmacokinetics of theophylline during co-treatment with cefaclor.

The effect of cefaclor on the steady state pharmacokinetics of theophylline was investigated in healthy young adults by comparing the pharmacokinetic parameters as found during a nine days course of theophylline alone and as obtained during co-medication with the antibiotic cefaclor. The pharmacokinetic parameters obtained on Day 9 during the two periods of drug treatment accounted for the following figures respectively: minimum plasma concentration 5.0 +/- 1.7 mg X 1(-1) (mean +/- SD) and 6.0 +/- 2.0 mg X 1(-1); maximum plasma concentration 9.7 +/- 2.6 mg X 1(-1) and 9.0 +/- 2.6 mg X 1(-1); time to peak 3.2 +/- 0.4 h and 3.9 +/- 0.8 h; AUC 132.54 +/- 41.73 mg X 1(-1) X h and 126.90 +/- 40.45 mg X 1(-1) X h; half-life of elimination 6.6 +/- 1.6 h and 7.1 +/- 1.2 h; clearance 0.059 +/- 0.011 1 X h-1 X kg-1 and 0.063 +/- 0.014 1 X h-1 X kg-1; volume of distribution 0.54 +/- 0.09 1 X kg-1 and 0.64 +/- 0.17 1 X kg-1. Only the values for cmax and tmax after cefaclor co-treatment were slightly, but significantly (p less than 0.05) different from the values found after administration of theophylline alone. As the volume of distribution and the clearance were not affected by cefaclor, it is concluded that both drugs can be given concomitantly without any dosage adjustment of theophylline.

Adult↗

No effect of cefaclor on theophylline pharmacokinetics.

The effect of the antibiotic drug cefaclor on steady state pharmacokinetics of theophylline was studied in healthy adults by comparing the pharmacokinetic parameters as found during a 9 days course of theophylline alone and as obtained during comedication with cefaclor. Theophylline plasma concentrations were measured by means of HPLC analysis. On the ninth day of each of the 2 periods of drug administration, a concentration-time curve was evaluated. It showed no influence of cefaclor on volume of distribution and clearance of theophylline and only a slight, but significant (p less than 0.05) influence on the values for Cmax and tmax after cefaclor co-treatment. It is concluded that both drugs can be given concomitantly without any dosage adjustment of theophylline.

Adult↗

Comparison of cefaclor and ampicillin in the treatment of shigellosis.

Fifty-four children with acute diarrhoea were treated orally with 50 mg/kg/day of either ampicillin in 4 divided doses, or with cefaclor in 3 divided doses for 5 days. Shigella was isolated from the stool of 28 patients, 6 of whom were hospitalized. All isolates, including ampicillin-resistant strains, were susceptible in vitro to cefaclor. For ampicillin-sensitive infections, the clinical response and clearing of Shigella from stools appeared to occur more rapidly in patients treated with ampicillin than in those treated with cefaclor. In areas where ampicillin resistance is a problem, cefaclor appears not to be a drug of choice for the treatment of Shigella.

Ampicillin↗

Comparative efficacy of cefadroxil and cefaclor in the treatment of skin and soft-tissue infections.

A ten-day, randomized, open-label study was conducted to compare the efficacy of 1,000 mg of cefadroxil once daily and 250 mg of cefaclor TID in 200 black patients with skin and soft-tissue infections caused by microorganisms sensitive to these cephalosporins. Statistically, the clinical results with each drug were not significantly different: 91% efficacy with cefadroxil and 95% efficacy with cefaclor. The important difference between cefadroxil and cefaclor is the remarkably longer half-life of cefadroxil, which makes once-a-day dosing possible and offers greater patient convenience and the likelihood of better compliance. In an analysis of compliance, only 2% of the patients in the cefadroxil group (20 capsules given to each patient) returned unused capsules; 77% in the cefaclor group (30 capsules given to each patient) returned unused capsules.

Adult↗

Cefaclor in the treatment of susceptible infections in infants and children.

Cefaclor is a new oral cephalosporin with in vitro activity against a wide variety of organisms including S. aureus, S. pneumoniae, S. pyogenes and H. influenzae (including ampicillin-resistant strains). Seventy-nine patients ranging in age from 2 months to 14 years with soft tissue infections (17 cases), otitis media (17), and streptococcal pharyngitis (45) were studied. They received cefaclor orally at a dose of 40 mg/kg per day in three or four divided doses for a minimum of five days. Results were generally good with favourable clinical and bacteriological responses obtained in 90% of cases. Most patients became afebrile within 48 hours after starting cefaclor. Two patients with H. influenzae cellulitis and bacteraemia defervesced within 24 hours and their blood cultures became negative promptly. Hepatic, renal and haematopoietic studies showed no adverse reactions except for an occasional increase in the eosinophil count with no clinical counterpart of hypersensitivity. Pharmacokinetic studies revealed that following a 10 mg/kg oral dose, peak serum levels of 8 micrograms/ml were observed at one hour, followed by a rather rapid tapering off so that at the end of four hours, virtually no cefaclor was detectable in serum.

Adolescent↗

A comparison of cefaclor and tetracycline in the treatment of bacterial bronchitis.

Cefaclor and tetracycline were compared in a single-blind study designed to treat patients with acute bacterial bronchitis and acute exacerbations of chronic bronchitis. Twenty-five pathogens (including 19 of Haemophilus influenzae and four of Streptococcus pneumoniae) were obtained from sputum samples of 48 patients. No pathogen could be cultured from the sputum of 23 patients. All of these pathogens were susceptible to cefaclor, while 12 (63%) of the 19 H influenzae isolates and three of the four S pneumoniae isolates were resistant to tetracycline. When the susceptibility of the 25 isolates to other commonly used antibacterials was tested, 18 isolates of H influenzae were resistant to erythromycin and one was resistant to ampicillin. (One H influenzae isolate was not tested for erythromycin susceptibility.) The four isolates of S pneumoniae were susceptible to erythromycin and ampicillin. Satisfactory results were achieved in 21 of the 23 patients receiving cefaclor. After four to six days of cefaclor therapy, the other two patients were diagnosed as having bronchopneumonia, and parenteral antibiotic therapy was instituted. Of the 25 patients assigned to the tetracycline regimen, three with resistant H influenzae had unsatisfactory clinical responses and required parenteral antibiotic therapy for recovery. Although patients were randomly assigned to therapy, only three of the 16 patients infected with tetracycline-resistant organisms were assigned to the tetracycline group, and all three failed to respond to treatment. Had the patients been more evenly distributed according to susceptibilities, it is possible that more treatment failures would have occurred in the group receiving tetracycline.

Adult↗

Treatment of skin and skin structure infections: a comparative study of Augmentin and cefaclor.

Sixty-four patients were entered into a double-blind study of Augmentin and cefaclor. Pathogenic bacteria were recovered from twenty-one patients who received Augmentin and seventeen patients who received cefaclor. The primary diagnoses were pyodermas and impetigo, as well as cellulitis, folliculitis, infected skin structure, and infected surgical sites. Eighty-one percent of the Augmentin-treated patients were classified as successfully treated, based on clinical and bacteriologic criteria, as were eighty-nine percent of the patients treated with cefaclor. Side effects were minimal in both groups; no laboratory abnormalities were found. Both Augmentin and cefaclor are useful oral antimicrobial agents in the treatment of infections of the skin and skin structure.

Adult↗

Nasopharyngeal carriage of Haemophilus influenzae type b: attempted eradication by cefaclor or rifampin.

The efficacy of cefaclor and rifampin in eradicating Haemophilus influenzae type b (HITB) from the nasopharynx of day care center and household contacts of children with HITB meningitis was evaluated. In 38/50 children treated with cefaclor, the carrier state persisted, a failure rate of 76%. Although cefaclor failed to eradicate HITB from many carriers, an appreciable reduction in the intensity of colonization following treatment was noticed. When rifampin was used in 17 children who had failed to respond to cefaclor, persistence of the carrier state with HITB was found in only two children, a failure rate of only 12%. During the study, two episodes of invasive HITB disease were documented to be acquired from sources other than the index cases or from children who were screened, which suggested the need to reevaluate the usually recommended strategy to screen for carriage and to treat only the immediate contacts 6 years of age and younger. Furthermore, the most appropriate agent for eradicating nasopharyngeal carriage of HITB awaits additional studies.

Adult↗

Clinical and bacteriological evaluation of cefaclor and tetracycline in acute episodes of bacterial bronchitis.

This report describes a single-blind, comparative evaluation of cefaclor and tetracycline therapy for acute episodes of bacterial bronchitis due to Hemophilus influenzae or Streptococcus pneumoniae. One therapeutic failure occurred in the 25 patients receiving cefaclor, and four occurred in the 26 patients receiving tetracycline. The latter failures were due to tetracycline-resistant organisms. Sputum cultures yielded 39 isolates of S pneumoniae and 11 of H influenzae. None of the isolates were resistant to cefaclor. In contrast, the incidence of resistance to tetracycline was 38% (18 of 48 isolates). All of the nine isolates of H influenzae tested were resistant to tetracycline; five of 11 H influenzae isolates were resistant to ampicillin, four of four were resistant to erythromycin, and five strains were resistant to multiple agents. These findings suggest that traditional therapy of bacterial bronchitis may be unsatisfactory in a substantial proportion of patients. The high cure rate and the absence of resistance found in the present study indicate that cefaclor is preferable to tetracycline in the treatment of bacterial bronchitis.

Bacterial Infections↗

Metabolism of (14C) cefaclor, a cephalosporin antibiotic, in three species of laboratory animals.

The metabolic fate of the orally effective cephalosporin antibiotic cefaclor (Lilly 99638) has been studied in rats, mice, and dogs. Cefaclor is efficiently absorbed from the gastrointestinal tract as the intact antibiotic. In rats and mice, cefaclor, for the most part, escapes metabolism in the body and is eliminated unchanged as unaltered antibiotic, primarily by renal excretion. In dogs, however, cefaclor is more labile to metabolism and only a portion of the administered antibiotic is eliminated unchanged via the kidney.

Animals↗

In vitro activity of cefaclor, a new orally administered cephalosporin antibiotic.

The in vitro antibacterial activity of cefaclor, cephalothin, and cephalexin against 261 clinical isolates of Staphylococcus aureus and Enterobacteriaceae was compared. Cefaclor and cephalexin were about equally active against S. aureus. Cefaclor was the most active cephalosporin against Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae. The effect on the antimicrobial activity using a relatively high and low inoculum was pronounced for cefaclor when compared with that of cephalothin.

Bacteria↗

Cefaclor: in vitro spectrum of activity and beta-lactamase stability.

The in vitro activity of cefaclor against 556 clinical isolates of gram-positive and gram-negative bacteria was compared with that of other cephalosporins. Cefaclor had activity similar to that of cephalexin against gram-positive bacteria. It showed greater activity against Haemophilus strains than did cephalexin and inhibited beta-lactamase-producing Haemophilus isolates. Cefaclor was more active than cephalexin or cephalothin against Escherichia coli, Salmonella, and Shigella isolates but did not act against Serratia, Acinetobacter, indole-positive Proteus, or Bacteroides isolates. Cefaclor was resistant to type III (TEM) beta-lactamases but was destroyed by type I beta-lactamases and, to a lesser degree, by type IV and type V beta-lactamases.

Amidohydrolases↗

Susceptibility of Staphylococcus aureus to cefaclor and cephalothin: laboratory and clinical studies.

In vitro susceptibility tests of 201 strains of Staphylococcus aureus by agar dilution revealed 90% to be susceptible to 8 mug or less of cefaclor per ml. Strains from hospitalized children and adults were more often resistant than those from patients with bullous impetigo. Cephalothin was more active than cefaclor against all strains tested. Results with disk tests, including those strains examined from the clinical investigation, revealed some discrepancies in identifying strains more resistant to cefaclor. In clinical studies, cefaclor proved quite effective for the treatment of bullous impetigo. Of 73 patients, 90% were cured and 7% improved after completing 5 or more days of treatment. Prompt improvement was noted among most patients seen 3 to 5 days after treatment was begun. One patient experienced mild diarrhea. There were no other adverse or toxic manifestations attributable to therapy.

Adolescent↗

Pharmacokinetics of cefaclor and cephalexin: dosage nomograms for impaired renal function.

The pharmacokinetics of cefaclor and cephalexin were characterized in patients with creatinine clearances ranging from 0 to 147 ml/min. Each of 24 fasted subjects received a single 500-mg oral dose of cefaclor, and 13 of these subjects later received 500 mg of cephalexin. Serum and urine levels of the antibiotics were measured by bioassay. The serum half-lives were highly correlated with corrected creatinine clearance (cefaclor r = 0.92, cephalexin r = 0.94). Linear regression estimates of the half-life of cefaclor were 2.3 h in the anephric patient and 40 min in the patient with a corrected creatinine clearance of 100 ml/min. For cephalexin, corresponding half-lives were 15.4 h and 58 min. We present a dosage nomogram for calculating the appropriate adjustments to the loading dose based on patient weight and maintenence dose based on corrected creatinine clearance.

Adult↗

[Treatment of bronchitis with cefaclor (Panoral) (author's transl)].

14 patients from the Allergy Unit of an outpatient clinic suffering from acute exacerbation of chronic bronchitis and 13 outpatients with acute bronchitis were treated with 250 mg cefaclor (Panoral) 3 times daily per os for 5 days. 59% of the organisms isolated from cefaclor-sensitive sputum at the time of prominent clinical symptoms were resistent to tetracycline, 53% of them were resistant to penicillin, and 37% were resistant to ampicillin. 12 out of the 14 patients with acute exacerbation of chronic bronchitis became asymptomatic, and no organisms could be detected in the sputum of 13 out of the same 14 patients two days after cessation of cefaclor treatment. In 12 out of the 13 patients with acute bronchitis, the acute clinical symptoms disappeared and in 11 out of the 13 patients the initial sputum organisms were two days after stopping cefaclor treatment.

Bronchitis↗

Comparative evaluation of cefuroxime axetil and cefaclor for treatment of acute bacterial maxillary sinusitis.

Cefuroxime axetil, a new beta-lactamase-stable cephalosporin, was compared with cefaclor for the treatment of acute bacterial maxillary sinusitis in 106 adult patients. Direct sinus aspirations for quantitative bacterial culture were done for all patients before treatment; aspiration was repeated for most patients after treatment. Pretreatment sinus aspirates were positive for 63 of 134 sampled sinuses. Of specimens yielding at least 10(4) CFU/mL, Haemophilus influenzae (38%) and Streptococcus pneumoniae (37%) were the most common pathogens. Ten (42%) of 24 strains of H influenzae, 2 (40%) of 5 Haemophilus parainfluenzae, and all 3 isolates (60%) of Branhamella catarrhalis produced beta-lactamase. Cefuroxime axetil, 250 mg twice a day, was compared with cefaclor, 500 mg three times a day. Among culture-positive sinuses, bacteriologic cure was achieved in 36 (95%) of 38 sinuses and 15 (71%) of 21 sinuses treated with cefuroxime axetil and cefaclor, respectively. The overall frequencies of adverse events were similar between drugs, although cefuroxime axetil was associated with more frequent diarrhea. Cefuroxime axetil was an effective therapy for the treatment of acute bacterial maxillary sinusitis in adults.

Acute Disease↗

The efficacy of cefaclor vs amoxicillin on recovery after tonsillectomy in children.

Tonsillectomy and adenoidectomy continues to be one of the most commonly performed operations in the pediatric age group. The morbidity from tonsillectomy can be severe and includes throat and ear pain, fever, lethargy, and poor oral intake. A previous study at the Children's Hospital of Philadelphia (Pa) demonstrated the efficacy of amoxicillin therapy in minimizing some of these postoperative symptoms. However, some children continue to have a prolonged recovery even while receiving this antibiotic regimen. Because of these children and the high incidence of Staphylococcus found in tonsillar core tissue, a randomized, prospective study was undertaken at the Children's Hospital of Philadelphia to evaluate the efficacy of cefaclor vs amoxicillin in patients recovering from tonsillectomy. The patients received either ampicillin or cefazolin intravenously at the time of surgery and for 12 to 24 hours postoperatively. When oral intake was adequate, they received either amoxicillin or cefaclor orally for 7 additional postoperative days. Intraoperative cultures of the oropharynx and tonsillar tissue were obtained, as well as cultures of the tonsillar fossa 7 to 14 days postoperatively. The patients were evaluated for severity and duration of postoperative symptoms as well as complications. The results of this study showed no difference between the two groups of patients. We conclude that there is no justification for routine use of cefaclor over amoxicillin in the posttonsillectomy patient.

Amoxicillin↗

HPTLC assay of cephalexin and cefaclor in pharmaceuticals.

A simple and reliable HPTLC method for the simultaneous determination of cephalexin and cefaclor is developed and validated. The methanol-ethyl acetate-acetone-water (5:2.5:2.5:1.5 v/v/v/v) solvent system is used for the quantitative evaluation of chromatograms. The chromatographic zones, corresponding to the spots of cephalexin and cefaclor on the silica gel plates, are scanned in the reflectance/absorbance mode at 265 nm. The method is found to be reproducible and convenient for the quantitative analysis of cephalexin and cefaclor in its dosage forms.

Cefaclor↗