7432-s and Otitis-Media

Ceftibuten is an extended-spectrum, cephem antimicrobial agent formulated for oral administration. Ceftibuten is absorbed by carrier-mediated processes and passive diffusion. The absorption of ceftibuten is described adequately by a first-order process. Following oral administration, peak serum ceftibuten concentrations are reached within 2 to 3 hours. Although the absolute bioavailability of ceftibuten in humans is not known, its relative bioavailability indicates that there is relatively rapid and complete absorption of the drug. Administration of ceftibuten with food may decrease the rate of absorption and, in the case of high fat meals, may decrease the extent of absorption by approximately 20 to 30%. The results of limited studies indicate that the drug distributes well into various body tissues and fluids, with relatively high concentrations being achieved in organs that receive a significant portion of the cardiac output. In adults with normal renal function or chronic renal failure, the apparent volume of distribution (Vd/F) for ceftibuten ranges from 0.2 to 0.4 L/kg and the total plasma clearance (CL/F) ranges from approximately 61 to 75 ml/min (3.7 to 4.5 L/h). Studies of ceftibuten elimination in adults have demonstrated positive linear correlation between CL/F and creatinine clearance. Following administration of a single dose of ceftibuten, approximately 67 to 94% of the drug has been recovered in the urine unchanged. The elimination half-life (t1/2 beta) of ceftibuten in adults with normal renal function is approximately 2.5 hours. Significant accumulation of ceftibuten does not occur with repeated administration. Despite the fact that the mean time taken to achieve maximal serum concentration (tmax) [1.1 to 2 hours] and t1/2 beta (2.1 hours) following administration of a single dose of ceftibuten to infants and children were similar to values previously reported in adults, the Vd/F (0.42 L/kg) and CL/F (3.1 ml/h/kg) were considerably greater in children younger than 5 years. Additionally, the apparent nonrenal clearance of ceftibuten in paediatric patients (52% of CL/F) was greater than reported for adults (approximately 32% of CL/F) with normal renal function. Thus, developmental differences appear to affect the pharmacokinetic profile of ceftibuten. Ceftibuten has a wide spectrum of antimicrobial activity against both Gram-positive and Gram-negative pathogens, and is stable to hydrolysis by a large number of beta-lactamases. Notable excep

Topics: Adolescent; Adult; Aging; Animals; Bacteria; Biological Availability; Ceftibuten; Cephalosporins; Child; Child, Preschool; Drug Interactions; Humans; Infant; Intestinal Absorption; Microbial Sensitivity Tests; Otitis Media; Pediatrics; Respiratory Tract Infections; Tissue Distribution

in recurrent acute otitis media (AOM) several alternative treatments are suggested, e.g. cephalosporins. Information about the optimal duration of treatment in recurrent AOM is sparse. The aim of the present study was to compare the efficacy of ceftibuten in 5 versus 10 days treatment in recurrent AOM in children.. this was a single-blind (doctor blinded), randomized, multicentre study with two parallel groups. Eleven investigators at six centres in the west of Sweden enrolled a total of 180 patients. Outpatients with a new clinical AOM within 1 month were randomized to 5 or 10 days treatment with ceftibuten, 9 mg/kg/day, as a single dose.. the mean age of the patients was 1.2 years (range 6 months-8 years). The patients had on average had three antibiotic treatments during the preceding 12 months. The recurrence rates in the 5- and 10-day groups were 21.4 and 4.5%, respectively, at first follow-up visit day 12 (P=0.001). The total recurrence rates between the two groups during the whole follow-up period of 40 days, 35 and 30%, respectively, did not differ significantly. The rate of recurrence did not correlate to nasopharyngeal findings of Streptococcus pneumoniae or Haemophilus influenzae. Pneumococci with decreased susceptibility to penicillin were found in 5% of all pneumococci, and beta-lactamase producing H. influenzae in 8%. Adverse events were reported less frequently in the 5- compared with the 10-day treatment group.. this study on young children with recurrent otitis media has shown no statistical difference between ceftibuten given once daily for 5 and 10 days as determined on day 40. The 10-day treatment was significantly better at early follow-up.

Topics: Acute Disease; Ceftibuten; Cephalosporins; Chi-Square Distribution; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Infant; Male; Microbial Sensitivity Tests; Otitis Media; Recurrence; Sweden; Treatment Outcome

The penetration of ceftibuten, an extended-spectrum oral cephalosporin, into middle ear fluid (MEF) was evaluated in pediatric patients during a course of daily oral doses of 9 mg/kg of body weight for 10 days. Plasma and MEF collected at 2, 4, 6, or 12 h after at least 3 days of dosing were analyzed for ceftibuten by a high-pressure liquid chromatography method, and the data were used to calculate pharmacokinetic parameters. Plasma and MEF had almost identical maximum concentrations (Cmax) of ceftibuten (14 micrograms/ml). These Cmax values in MEF during acute otitis media were well in excess of the MIC for 90% of the isolates of each of four major pathogens in this disease. The time to Cmax was longer in MEF (4 h) than in plasma (2 h). Excellent penetration (71%) of ceftibuten into MEF was observed on the basis of the area under the curve ratio (MEF/plasma). These data clearly indicate that ceftibuten penetrated well into the MEF to yield clinically effective concentrations.

Topics: Acute Disease; Ceftibuten; Cephalosporins; Child, Preschool; Chromatography, High Pressure Liquid; Ear, Middle; Humans; Infant; Otitis Media

Topics: Ceftibuten; Cephalosporins; Child; Humans; Male; Otitis Media; Therapeutic Equivalency

Ceftibuten is a new oral cephalosporin with an unusual stability to beta-lactamases that can hydrolyze other extended-spectrum cephalosporins. Using the chinchilla animal model, we compared the efficacy of ceftibuten (n = 33) with that of saline (n = 34), ampicillin (n = 32), and cefixime (n = 31) for the treatment of acute otitis media caused by beta-lactamase-producing nontypeable Hemophilus influenzae. Ceftibuten was superior to ampicillin regarding the time necessary to sterilize the middle ear (p < .001) and eliminate effusion (p < .001). The mean days of therapy required for bacteriologic cure were 2.57 for ceftibuten, 2.95 for cefixime, 7.95 for ampicillin, and 8.16 for saline. At the conclusion of therapy, chinchillas treated with ceftibuten had a significantly lower prevalence of positive cultures and middle ear effusion than did animals treated with ampicillin. No significant differences were observed between ceftibuten and cefixime. The results of this randomized, investigator-blinded experiment warrant further consideration of ceftibuten as a second-line agent for acute otitis media caused by ampicillin-resistant H influenzae.

Topics: Acute Disease; Ampicillin; Animals; Anti-Bacterial Agents; Cefixime; Cefotaxime; Ceftibuten; Cephalosporins; Chinchilla; Haemophilus Infections; Haemophilus influenzae; Otitis Media; Random Allocation